id
int64 37.5k
3.5M
| image
unknown | bboxes
sequence | tokens
sequence | ner_tags
sequence |
---|---|---|---|---|
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] | [
"EXPERIMENTAL",
"and",
"MOLECULAR",
"MEDICINE,",
"Vol.",
"44,",
"No.",
"2,",
"130-137,",
"February",
"2012",
"Identification",
"of",
"novel",
"peptides",
"that",
"stimulate",
"human",
"neutrophils",
"Geon",
"Ho",
"Bae1*,",
"Ha",
"Young",
"Lee1,2*,",
"Young",
"Su",
"Jung1,2,",
"Jae",
"Woong",
"Shim1,",
"Sang",
"Doo",
"Kim1,2,",
"Suk-Hwan",
"Baek3,",
"Jae",
"Young",
"Kwon1,",
"Joon",
"Seong",
"Park4",
"and",
"Yoe-Sik",
"Bae1,2,5",
"1Department",
"of",
"Biological",
"Sciences",
"Sungkyunkwan",
"University",
"Suwon",
"440-746,",
"Korea",
"2Mitochondria",
"Hub",
"Regulation",
"Center",
"College",
"of",
"Medicine,",
"Dong-A",
"University",
"Busan",
"602-714,",
"Korea",
"3Department",
"of",
"Biochemistry",
"and",
"Molecular",
"Biology",
"Yeungnam",
"University",
"Daegu",
"705-030,",
"Korea",
"4Department",
"of",
"Hematology-Oncology",
"Ajou",
"University",
"School",
"of",
"Medicine",
"Suwon",
"443-721,",
"Korea",
"5Corresponding",
"author:",
"Tel,",
"82-31-290-5914;",
"Fax,",
"82-31-290-7015;",
"E-mail,",
"yoesik@skku.edu",
"*These",
"authors",
"contributed",
"equally",
"to",
"this",
"work.",
"http://dx.doi.org/10.3858/emm.2012.44.2.008",
"Accepted",
"14",
"November",
"2011",
"Available",
"Online",
"16",
"November",
"2011",
"Abbreviations:",
"FPR,",
"formyl",
"peptide",
"receptor;",
"GMMWAI,",
"Gly-",
"Met-Met-Trp-Ala-Ile-CONH2;",
"IP3,",
"inositol-1,4,5-triphosphate;",
"MMHWAM,",
"Met-Met-His-Trp-Ala-Met-CONH2;",
"MMHWFM,",
"Met-Met-His-Trp-Phe-Met-CONH2;",
"PLC,",
"phospholipase",
"C;",
"PS-SPCL,",
"positional",
"scanning",
"synthetic",
"peptide",
"combinatorial",
"library;",
"PTX,",
"pertussis",
"toxin",
"Abstract",
"Neutrophils",
"play",
"a",
"key",
"role",
"in",
"innate",
"immunity,",
"and",
"the",
"identification",
"of",
"new",
"stimuli",
"that",
"stimulate",
"neutrophil",
"activity",
"is",
"a",
"very",
"important",
"issue.",
"In",
"this",
"study,",
"we",
"iden-",
"tified",
"three",
"novel",
"peptides",
"by",
"screening",
"a",
"synthetic",
"hexapeptide",
"combinatorial",
"library.",
"The",
"identified",
"pep-",
"tides",
"GMMWAI,",
"MMHWAM,",
"and",
"MMHWFM",
"caused",
"an",
"increase",
"in",
"intracellular",
"Ca2+",
"in",
"a",
"concentration-de-",
"pendent",
"manner",
"via",
"phospholipase",
"C",
"activity",
"in",
"human",
"neutrophils.",
"The",
"three",
"peptides",
"acted",
"specifically",
"on",
"neutrophils",
"and",
"monocytes",
"and",
"not",
"on",
"other",
"non-leu-",
"kocytic",
"cells.",
"As",
"a",
"physiological",
"characteristic",
"of",
"the",
"peptides,",
"we",
"observed",
"that",
"the",
"three",
"peptides",
"induced",
"chemotactic",
"migration",
"of",
"neutrophils",
"as",
"well",
"as",
"stimu-",
"lated",
"superoxide",
"anion",
"production.",
"Studying",
"receptor",
"specificity,",
"we",
"observed",
"that",
"two",
"of",
"the",
"peptides",
"(GMMWAI",
"and",
"MMHWFM)",
"acted",
"on",
"formyl",
"peptide",
"re-",
"ceptor",
"(FPR)1",
"while",
"the",
"other",
"peptide",
"(MMHWAM)",
"act-",
"ed",
"on",
"FPR2.",
"Since",
"the",
"three",
"novel",
"peptides",
"were",
"specif-",
"ic",
"agonists",
"for",
"FPR1",
"or",
"FPR2,",
"they",
"might",
"be",
"useful",
"tools",
"to",
"study",
"FPR1-",
"or",
"FPR2-mediated",
"immune",
"response",
"and",
"signaling.",
"Keywords:",
"calcium;",
"chemotaxis;",
"neutrophils;",
"pep-",
"tide",
"library;",
"peptides;",
"receptors,",
"formyl",
"peptide",
"Introduction",
"Neutrophils",
"play",
"an",
"important",
"role",
"in",
"the",
"regulation",
"of",
"immune",
"responses,",
"especially",
"in",
"the",
"innate",
"immune",
"response",
"(Kumar",
"and",
"Sharma,",
"2010).",
"Neutrophils",
"are",
"recruited",
"to",
"infected",
"areas",
"or",
"sites",
"of",
"injury",
"according",
"to",
"a",
"chemoattractant",
"gradient",
"(Borregaard,",
"2010;",
"Kumar",
"and",
"Sharma,",
"2010).",
"Recruited",
"neutrophils",
"can",
"be",
"activated",
"by",
"extra-",
"cellular",
"stimuli,",
"resulting",
"in",
"the",
"production",
"of",
"several",
"reactive",
"oxygen",
"species",
"(Dahlgren",
"and",
"Karlssson,",
"1999;",
"Walther",
"et",
"al.,",
"2000;",
"Tiffany",
"et",
"al.,",
"2001).",
"It",
"is",
"a",
"critical",
"aspect",
"of",
"resting",
"neutrophils",
"that",
"they",
"must",
"be",
"activated",
"for",
"host",
"defense.",
"The",
"activation",
"of",
"neutrophils",
"can",
"be",
"induced",
"by",
"various",
"different",
"stimuli,",
"including",
"pathogen-derived",
"molecules",
"and",
"several",
"chemoattractants",
"(Walther",
"et",
"al.,",
"2000;",
"Tiffany",
"et",
"al.,",
"2001;",
"Sabroe",
"et",
"al.,",
"2003;",
"Kobayashi,",
"2008).",
"Among",
"these,",
"chemo-",
"attractants,",
"including",
"several",
"chemokines",
"that",
"regulate",
"the",
"activities",
"of",
"neutrophils,",
"have",
"received",
"much",
"attention",
"over",
"the",
"last",
"decade.",
"These",
"chemoattractants",
"bind",
"to",
"specific",
"cell",
"surface",
"receptors,",
"which",
"are",
"coupled",
"to",
"pertussis",
"toxin",
"(PTX)-sensitive",
"G-protein(s),",
"resulting",
"in",
"intracel-",
"lular",
"Ca2+",
"mobilization,",
"cell",
"migration,",
"exocytosis,",
"adhesion,",
"and",
"generation",
"of",
"bioactive",
"lipids",
"and/or",
"reactive",
"oxygen",
"species",
"(Walther",
"et",
"al.,",
"2000;",
"Tiffany",
"et",
"al.,",
"2001;",
"Kobayashi,",
"2008).",
"Keeping",
"in",
"mind",
"the",
"important",
"roles",
"of",
"chemoattractants",
"in",
"Copyright",
"ⓒ",
"2012",
"by",
"the",
"The",
"Korean",
"Society",
"for",
"Biochemistry",
"and",
"Molecular",
"Biology",
"This",
"is",
"an",
"open-access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://creativecommons.org/licenses/",
"by-nc/3.0)",
"which",
"permits",
"unrestricted",
"non-commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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"role",
"in",
"addition",
"to",
"being",
"neuroprotective",
"and",
"pro-regenerative.",
"To",
"further",
"characterise",
"the",
"role",
"of",
"galanin",
"following",
"nerve",
"injury,",
"a",
"novel",
"transgenic",
"line",
"was",
"created",
"using",
"the",
"binary",
"transgenic",
"tet-off",
"system,",
"to",
"overexpress",
"galanin",
"in",
"galaninergic",
"tissue",
"in",
"a",
"suppressible",
"manner.",
"The",
"double",
"transgenic",
"mice",
"express",
"significantly",
"more",
"galanin",
"in",
"the",
"DRG",
"one",
"week",
"after",
"sciatic",
"nerve",
"section",
"(axotomy)",
"compared",
"to",
"WT",
"mice",
"and",
"this",
"overexpression",
"is",
"suppressible",
"upon",
"administration",
"of",
"doxycycline.",
"Phenotypic",
"analysis",
"revealed",
"markedly",
"attenuated",
"allodynia",
"when",
"galanin",
"is",
"overexpressed",
"and",
"an",
"increase",
"in",
"allodynia",
"following",
"galanin",
"suppression.",
"This",
"novel",
"transgenic",
"line",
"demonstrates",
"that",
"whether",
"galanin",
"expression",
"is",
"increased",
"at",
"the",
"time",
"of",
"nerve",
"injury",
"or",
"only",
"after",
"allodynia",
"is",
"established,",
"the",
"neuropeptide",
"is",
"able",
"to",
"reduce",
"neuropathic",
"pain",
"behaviour.",
"These",
"new",
"findings",
"imply",
"that",
"administration",
"of",
"a",
"galanin",
"agonist",
"to",
"patients",
"with",
"established",
"allodynia",
"would",
"be",
"an",
"effective",
"treatment",
"for",
"neuropathic",
"pain.",
"Findings",
"The",
"29",
"(30",
"in",
"human)",
"amino",
"acid",
"neuropeptide",
"galanin",
"has",
"a",
"wide",
"distribution",
"in",
"both",
"the",
"peripheral",
"and",
"cen-",
"tral",
"nervous",
"systems.",
"The",
"galanin",
"peptide",
"shares",
"homol-",
"ogy",
"with",
"only",
"two",
"other",
"known",
"peptides,",
"galanin-like",
"peptide",
"(GALP)",
"[1]",
"and",
"the",
"GALP",
"splice",
"variant",
"alarin",
"[2].",
"Galanin",
"is",
"expressed",
"at",
"low",
"levels",
"in",
"~5%",
"of",
"small",
"diameter",
"C-fibre",
"neurons",
"in",
"the",
"intact",
"adult",
"rodent",
"dor-",
"sal",
"root",
"ganglia",
"(DRG)",
"[3-5].",
"Higher",
"levels",
"of",
"the",
"pep-",
"tide",
"are",
"detected",
"in",
"the",
"primary",
"afferent",
"terminals",
"of",
"the",
"spinal",
"cord",
"(lamina",
"II),",
"the",
"dorsal",
"horn",
"inter-neurons",
"[6],",
"and",
"in",
"a",
"number",
"of",
"brain",
"regions",
"known",
"to",
"modu-",
"late",
"nociception,",
"including",
"the",
"arcuate",
"nucleus",
"and",
"peri-",
"aqueductal",
"grey",
"[7,8].",
"Galanin",
"levels",
"are",
"strongly",
"and",
"persistently",
"increased",
"in",
"the",
"DRG",
"and",
"dorsal",
"horn",
"of",
"the",
"spinal",
"cord",
"as",
"well",
"as",
"in",
"many",
"regions",
"of",
"the",
"central",
"nervous",
"system",
"following",
"nerve",
"injury.",
"Axotomy",
"of",
"motor",
"nerves",
"elevates",
"galanin",
"mRNA",
"levels",
"by",
"6-10",
"fold",
"in",
"the",
"dorsal",
"motor",
"nucleus",
"of",
"the",
"vagus",
"and",
"nucleus",
"*",
"Correspondence:",
"d.wynick@bris.ac.uk",
"Department",
"of",
"Physiology",
"and",
"Pharmacology",
"and",
"Clinical",
"Sciences",
"at",
"South",
"Bristol,",
"School",
"of",
"Medical",
"Sciences,",
"University",
"Walk,",
"University",
"of",
"Bristol,",
"Clifton,",
"Bristol,",
"BS8",
"1TD,",
"UK",
"ambiguus",
"[9]",
"and",
"a",
"similar",
"increase",
"is",
"found",
"in",
"the",
"facial",
"nucleus",
"following",
"facial",
"nerve",
"axotomy",
"[10].",
"Galanin",
"levels",
"in",
"the",
"central",
"nervous",
"system",
"are",
"also",
"upregulated",
"in",
"many",
"disease",
"states",
"and",
"in",
"rodent",
"models",
"of",
"these",
"pathological",
"conditions,",
"including",
"Alzheimer’s",
"disease",
"[11],",
"stroke",
"induced",
"ischemia",
"[11,12]",
"and",
"in",
"multiple",
"sclerosis",
"[13].",
"However,",
"the",
"most",
"potent",
"upregulation",
"occurs",
"in",
"the",
"DRG",
"following",
"peripheral",
"nerve",
"axotomy",
"when",
"galanin",
"is",
"rapidly",
"up-regulated",
"by",
"up",
"to",
"120-fold",
"and",
"is",
"expressed",
"in",
"40-50%",
"of",
"sensory",
"neurons",
"[14].",
"A",
"much",
"smaller",
"increase",
"in",
"galanin",
"expression",
"is",
"observed",
"in",
"the",
"dorsal",
"horn",
"after",
"peripheral",
"nerve",
"injury",
"[15]",
"implying",
"that",
"much",
"of",
"the",
"neuropeptide",
"is",
"anterogradely",
"transported",
"to",
"the",
"site",
"of",
"injury.",
"Following",
"the",
"descrip-",
"tion",
"of",
"galanin",
"expression",
"increasing",
"after",
"nerve",
"injury,",
"the",
"role",
"of",
"galanin",
"in",
"nociception",
"and",
"neuropathic",
"pain",
"has",
"been",
"the",
"subject",
"of",
"a",
"substantial",
"body",
"of",
"research.",
"Studies",
"of",
"intact",
"and",
"nerve",
"injured",
"animals",
"have",
"described",
"a",
"bell-shaped",
"response",
"curve",
"after",
"intrathecal",
"infusion",
"of",
"galanin",
"and",
"galanin",
"agonists",
"[16-18]",
"with",
"inhibition",
"of",
"nociceptive",
"responses",
"at",
"high",
"doses",
"[19,20].",
"To",
"further",
"define",
"the",
"role",
"played",
"by",
"galanin",
"in",
"nocicep-",
"tion,",
"we",
"have",
"previously",
"generated",
"and",
"characterised",
"©",
"2010",
"Pope",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Post",
"Clinical",
"Sarcoma",
"Research",
"2012,",
"2:20",
"http://www.clinicalsarcomaresearch.com/content/2/1/20",
"R",
"E",
"V",
"I",
"E",
"W",
"CLINICAL",
"SARCOMA",
"RESEARCH",
"Open",
"Access",
"Mouse",
"models",
"of",
"sarcomas:",
"critical",
"tools",
"in",
"our",
"understanding",
"of",
"the",
"pathobiology",
"Sean",
"M",
"Post",
"Abstract",
"Sarcomas",
"are",
"neoplastic",
"malignancies",
"that",
"typically",
"arise",
"in",
"tissues",
"of",
"mesenchymal",
"origin.",
"The",
"identification",
"of",
"novel",
"molecular",
"mechanisms",
"leading",
"to",
"sarcoma",
"formation",
"and",
"the",
"establishment",
"of",
"new",
"therapies",
"has",
"been",
"hampered",
"by",
"several",
"critical",
"factors.",
"First,",
"this",
"type",
"of",
"cancer",
"is",
"rarely",
"observed",
"in",
"the",
"clinic",
"with",
"fewer",
"than",
"15,000",
"newly",
"cases",
"diagnosed",
"each",
"year",
"in",
"the",
"United",
"States.",
"Another",
"complicating",
"factor",
"is",
"that",
"sarcomas",
"are",
"extremely",
"heterogeneous",
"as",
"they",
"arise",
"in",
"a",
"multitude",
"of",
"tissues",
"from",
"many",
"different",
"cell",
"lineages",
"(e.g.",
"bone",
"(osteosarcoma),",
"fat",
"(liposarcoma),",
"and",
"muscle",
"(myosarcoma)).",
"The",
"scarcity",
"of",
"clinical",
"samples",
"coupled",
"with",
"its",
"inherent",
"heterogeneity",
"creates",
"a",
"challenging",
"experimental",
"environment",
"for",
"clinicians",
"and",
"scientists.",
"Faced",
"with",
"these",
"challenges,",
"there",
"has",
"been",
"extremely",
"limited",
"advancement",
"in",
"treatment",
"options",
"available",
"to",
"patients",
"as",
"compared",
"to",
"other",
"cancers.",
"In",
"order",
"to",
"glean",
"insight",
"into",
"the",
"pathobiology",
"of",
"sarcomas,",
"scientists",
"are",
"now",
"using",
"in",
"vivo",
"mouse",
"models",
"whose",
"genomes",
"have",
"been",
"specifically",
"tailored",
"to",
"carry",
"gene",
"deletions,",
"gene",
"amplifications,",
"and",
"point",
"mutations",
"commonly",
"observed",
"in",
"human",
"sarcomas.",
"The",
"use",
"of",
"these",
"model",
"organisms",
"has",
"been",
"successful",
"in",
"increasing",
"our",
"knowledge",
"and",
"understanding",
"of",
"how",
"alterations",
"in",
"relevant",
"oncogenic,",
"tumor",
"suppressive,",
"and",
"signaling",
"pathways",
"directly",
"impact",
"sarcomagenesis.",
"It",
"is",
"the",
"goal",
"of",
"many",
"in",
"the",
"biological",
"community",
"that",
"the",
"use",
"of",
"these",
"mouse",
"models",
"will",
"serve",
"as",
"powerful",
"in",
"vivo",
"tools",
"to",
"further",
"our",
"understanding",
"of",
"sarcomagenesis",
"and",
"potentially",
"identify",
"new",
"therapeutic",
"strategies.",
"Keywords:",
"Sarcoma,",
"Mouse",
"models,",
"p53,",
"Retinoblastoma",
"(Rb),",
"Translocation",
"Background",
"Sarcomas",
"are",
"a",
"rare",
"form",
"of",
"cancer",
"with",
"less",
"than",
"15,000",
"new",
"cases",
"diagnosed",
"each",
"year",
"in",
"the",
"United",
"States.",
"Though",
"rare,",
"sarcomas",
"are",
"highly",
"debilitating",
"malignan-",
"cies",
"as",
"they",
"are",
"often",
"associated",
"with",
"significant",
"morbidity",
"and",
"mortality.",
"Sarcomas",
"are",
"biologically",
"very",
"heteroge-",
"neous",
"as",
"evidenced",
"by",
"the",
"fact",
"that",
"these",
"cancers",
"arise",
"from",
"a",
"plethora",
"of",
"different",
"tissues",
"and",
"cell",
"types.",
"They",
"are",
"classically",
"defined",
"by",
"their",
"tissue",
"of",
"origin",
"and",
"are",
"add-",
"itionally",
"stratified",
"by",
"their",
"histopathology",
"or",
"patient’s",
"age",
"at",
"diagnosis",
"[1,2].",
"While",
"these",
"classifications",
"have",
"proven",
"useful,",
"modern",
"biological",
"and",
"clinical",
"techniques",
"have",
"the",
"ability",
"to",
"further",
"stratify",
"sarcomas",
"based",
"on",
"their",
"genetic",
"profile",
"[1,3,4].",
"Cytogenetic",
"and",
"karyotype",
"analyses",
"have",
"revealed",
"two",
"divergent",
"genetic",
"profiles",
"in",
"sarcomas.",
"The",
"first",
"and",
"most",
"simple",
"genetic",
"profile",
"is",
"the",
"observation",
"of",
"translocation",
"events",
"in",
"sarcomas",
"with",
"an",
"otherwise",
"Correspondence:",
"spost@mdanderson.org",
"Department",
"of",
"Leukemia,",
"M.D.",
"Anderson",
"Cancer",
"Center,",
"1515",
"Holcombe",
"Blvd,",
"Houston,",
"TX",
"77030,",
"USA",
"normal",
"diploid",
"karyotype.",
"On",
"the",
"other",
"hand,",
"most",
"sarco-",
"mas",
"display",
"a",
"more",
"complex",
"genetic",
"phenotype,",
"suggest-",
"ing",
"genomic",
"instability",
"plays",
"an",
"important",
"role",
"in",
"many",
"sarcomas.",
"Historical",
"perspective",
"Much",
"of",
"our",
"current",
"knowledge",
"regarding",
"sarcoma",
"biol-",
"ogy",
"has",
"been",
"ascertained",
"through",
"experimentation",
"using",
"high",
"dose",
"irradiation,",
"viral",
"infections,",
"in",
"vitro",
"cell",
"line",
"studies,",
"and",
"xenografts",
"models.",
"One",
"of",
"the",
"earliest",
"animal",
"studies",
"investigated",
"the",
"impact",
"of",
"the",
"Rous",
"sarcoma",
"virus",
"on",
"the",
"development",
"of",
"soft",
"tissue",
"sarcomas",
"[5].",
"Our",
"knowledge",
"regarding",
"radiation-induced",
"sarcomagenesis",
"largely",
"stems",
"from",
"the",
"observation",
"of",
"women",
"occupation-",
"ally",
"exposed",
"to",
"radium",
"and",
"animal",
"models",
"subjected",
"to",
"high",
"dose",
"radiation",
"developed",
"sarcomas",
"[6,7].",
"While",
"the",
"plight",
"of",
"these",
"patients",
"and",
"the",
"subsequent",
"animal",
"experi-",
"ments",
"led",
"to",
"the",
"identification",
"of",
"a",
"cause",
"and",
"effect",
"for",
"some",
"sarcomas,",
"these",
"observations",
"were",
"unable",
"to",
"identify",
"the",
"molecular",
"events",
"responsible",
"for",
"sarcomagenesis.",
"©",
"2012",
"Post;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Int.",
"J.",
"Mol.",
"Sci.",
"2012,",
"13,",
"6800-6819;",
"doi:10.3390/ijms13066800",
"OPEN",
"ACCESS",
"International",
"Journal",
"of",
"Molecular",
"Sciences",
"ISSN",
"1422-0067",
"www.mdpi.com/journal/ijms",
"Opinion",
"The",
"Kiss-and-Run",
"Model",
"of",
"Intra-Golgi",
"Transport",
"Alexander",
"A.",
"Mironov",
"*",
"and",
"Galina",
"V.",
"Beznoussenko",
"*",
"IFOM",
"Foundation,",
"FIRC",
"Institute",
"of",
"Molecular",
"Oncology",
"(IFOM-IEO",
"Campus),",
"Via",
"Adamello",
"16,",
"20139,",
"Milan,",
"Italy",
"*",
"Authors",
"to",
"whom",
"correspondence",
"should",
"be",
"addressed;",
"E-Mails:",
"alexandre.mironov@ifom-ieo-campus.it",
"(A.A.M.);",
"galina.beznusenko@ifom-ieo-campus.it",
"(G.V.B.);",
"Tel.:",
"+39-02-574-303-869",
"(A.A.M.);",
"Fax:",
"+39-02-574-303-231",
"(A.A.M.).",
"Received:",
"9",
"April",
"2012;",
"in",
"revised",
"form:",
"9",
"May",
"2012",
"/",
"Accepted:",
"22",
"May",
"2012",
"/",
"Published:",
"5",
"June",
"2012",
"Abstract:",
"The",
"Golgi",
"apparatus",
"(GA)",
"is",
"the",
"main",
"station",
"along",
"the",
"secretory",
"pathway.",
"Mechanisms",
"of",
"intra-Golgi",
"transport",
"remain",
"unresolved.",
"Three",
"models",
"compete",
"with",
"each",
"other",
"for",
"the",
"right",
"to",
"be",
"defined",
"as",
"the",
"paradigm.",
"The",
"vesicular",
"model",
"cannot",
"explain",
"the",
"following:",
"(1)",
"lipid",
"droplets",
"and",
"aggregates",
"of",
"procollagen",
"that",
"are",
"larger",
"than",
"coatomer",
"I",
"(COPI)-dependent",
"vesicles",
"are",
"transported",
"across",
"the",
"GA;",
"and",
"(2)",
"most",
"anterograde",
"cargoes",
"are",
"depleted",
"in",
"COPI",
"vesicles.",
"The",
"compartment",
"progression/maturation",
"model",
"has",
"the",
"following",
"problems:",
"(1)",
"most",
"Golgi-resident",
"proteins",
"are",
"depleted",
"in",
"COPI",
"vesicles;",
"(2)",
"there",
"are",
"no",
"COPI",
"vesicles",
"for",
"the",
"recycling",
"of",
"the",
"resident",
"proteins",
"in",
"the",
"trans-most-Golgi",
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"explain",
"the",
"transport",
"of",
"large",
"cargo",
"aggregates.",
"Keywords:",
"intra-Golgi",
"transport;",
"Golgi",
"apparatus;",
"vesicular",
"model;",
"cisterna",
"maturation;",
"kiss-and-run",
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] | [
"Martin-Gallego",
"et",
"al.",
"Nanoscale",
"Research",
"Letters",
"2011,",
"6:610",
"http://www.nanoscalereslett.com/content/6/1/610",
"N",
"A",
"N",
"O",
"E",
"X",
"P",
"R",
"E",
"S",
"S",
"Open",
"Access",
"Thermal",
"conductivity",
"of",
"carbon",
"nanotubes",
"and",
"graphene",
"in",
"epoxy",
"nanofluids",
"and",
"nanocomposites",
"Mario",
"Martin-Gallego1,",
"Raquel",
"Verdejo1,",
"Mohamed",
"Khayet2,",
"Jose",
"Maria",
"Ortiz",
"de",
"Zarate2,",
"Mohamed",
"Essalhi2",
"and",
"Miguel",
"Angel",
"Lopez-Manchado1*",
"Abstract",
"We",
"employed",
"an",
"easy",
"and",
"direct",
"method",
"to",
"measure",
"the",
"thermal",
"conductivity",
"of",
"epoxy",
"in",
"the",
"liquid",
"(nanofluid)",
"and",
"solid",
"(nanocomposite)",
"states",
"using",
"both",
"rodlike",
"and",
"platelet-like",
"carbon-based",
"nanostructures.",
"Comparing",
"the",
"experimental",
"results",
"with",
"the",
"theoretical",
"model,",
"an",
"anomalous",
"enhancement",
"was",
"obtained",
"with",
"multiwall",
"carbon",
"nanotubes,",
"probably",
"due",
"to",
"their",
"layered",
"structure",
"and",
"lowest",
"surface",
"resistance.",
"Puzzling",
"results",
"for",
"functionalized",
"graphene",
"sheet",
"nanocomposites",
"suggest",
"that",
"phonon",
"coupling",
"of",
"the",
"vibrational",
"modes",
"of",
"the",
"graphene",
"and",
"of",
"the",
"polymeric",
"matrix",
"plays",
"a",
"dominant",
"role",
"on",
"the",
"thermal",
"conductivities",
"of",
"the",
"liquid",
"and",
"solid",
"states.",
"PACS:",
"74.25.fc;",
"81.05.Qk;",
"81.07.Pr.",
"Keywords:",
"carbon",
"nanotubes,",
"graphene,",
"nanocomposites,",
"nanofluids,",
"thermal",
"conductivity",
"Introduction",
"Due",
"to",
"the",
"increasing",
"importance",
"of",
"energy",
"dissipation",
"in",
"the",
"electronic",
"industry,",
"thermal",
"conductivity",
"of",
"cured",
"epoxy",
"resins",
"has",
"been",
"widely",
"investigated",
"over",
"the",
"years.",
"One",
"strategy",
"to",
"improve",
"the",
"thermal",
"transport",
"of",
"epoxy",
"resins",
"has",
"been",
"the",
"addition",
"of",
"highly",
"conductive",
"fillers,",
"such",
"as",
"carbon-based",
"or",
"metallic",
"fillers",
"[1].",
"However,",
"the",
"effect",
"of",
"such",
"additions",
"on",
"either",
"the",
"uncured",
"sys-",
"tem",
"or",
"the",
"cure",
"reaction",
"of",
"resins",
"has",
"not",
"yet",
"been",
"fully",
"established.",
"The",
"thermal",
"conductivity",
"of",
"the",
"uncured",
"liquid",
"resin",
"plays",
"an",
"important",
"role",
"to",
"define",
"the",
"vari-",
"ables",
"involved",
"in",
"the",
"transformation",
"process,",
"such",
"as",
"time,",
"applied",
"heat,",
"or",
"cooling",
"time,",
"which",
"will",
"then",
"have",
"a",
"profound",
"effect",
"on",
"the",
"cross-link",
"density",
"and",
"hence,",
"on",
"the",
"final",
"properties",
"of",
"the",
"system.",
"Thus,",
"we",
"aimed",
"at",
"studying",
"the",
"effect",
"of",
"two",
"types",
"of",
"carbon-based",
"nanofil-",
"lers,",
"in",
"particular,",
"nanotubes",
"and",
"graphene",
"sheets,",
"on",
"the",
"thermal",
"conductivity",
"of",
"an",
"uncured",
"liquid",
"epoxy",
"resin.",
"There",
"have",
"been",
"considerable",
"interest",
"and",
"effort",
"in",
"the",
"transport",
"properties",
"of",
"carbon",
"nanotube",
"[CNT]",
"*",
"Correspondence:",
"lmanchado@ictp.csic.es",
"1Instituto",
"de",
"Ciencia",
"y",
"Tecnologia",
"de",
"Polimeros,",
"ICTP-CSIC,",
"Juan",
"de",
"la",
"Cierva",
"3,",
"Madrid,",
"28006,",
"Spain",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"filled",
"polymer",
"nanocomposites",
"[2,3].",
"Electrical",
"conduc-",
"tivity",
"of",
"epoxy",
"nanocomposites",
"increases",
"by",
"several",
"orders",
"of",
"magnitude",
"with",
"CNT",
"concentration",
"[4];",
"this",
"effect",
"can",
"be",
"explained",
"by",
"the",
"established",
"percolation",
"theory",
"[5]",
"with",
"the",
"shift",
"from",
"an",
"insulator",
"into",
"a",
"con-",
"ductive",
"material",
"when",
"a",
"critical",
"concentration",
"of",
"the",
"conductive",
"filler",
"is",
"reached,",
"commonly",
"known",
"as",
"perco-",
"lation",
"threshold.",
"However,",
"the",
"thermal",
"conductivity",
"has",
"shown",
"at",
"best",
"linear",
"enhancements",
"with",
"nanotube",
"con-",
"tent",
"with",
"a",
"lack",
"of",
"thermal",
"percolation.",
"The",
"main",
"reason",
"for",
"this",
"fact",
"is",
"the",
"relatively",
"small",
"thermal",
"conductivity",
"ratio",
"(Kcnt/Kmatrix)",
"by",
"comparison",
"with",
"the",
"correspond-",
"ing",
"ratio",
"of",
"electrical",
"conductivities",
"[6].",
"Graphene",
"is",
"a",
"two-dimensional",
"carbon",
"nanofiller",
"with",
"a",
"one-atom-thick",
"sheet",
"of",
"sp2",
"bonded",
"carbon",
"atoms",
"that",
"are",
"densely",
"packed",
"in",
"a",
"honeycomb",
"crystal",
"lattice",
"[7,8].",
"Single",
"layer",
"graphene",
"is",
"predicted",
"to",
"have",
"a",
"remarkable",
"performance,",
"such",
"as",
"high",
"thermal",
"conductivity",
"of",
"5,000",
"W/mK,",
"which",
"corresponds",
"to",
"the",
"upper",
"bound",
"of",
"the",
"highest",
"values",
"reported",
"for",
"single-walled",
"carbon",
"nano-",
"tube",
"bundles",
"[9],",
"high",
"electrical",
"conductivity",
"of",
"up",
"to",
"6,000",
"S/cm",
"[10],",
"and",
"superior",
"mechanical",
"properties",
"with",
"Young’s",
"modulus",
"of",
"1",
"TPa",
"and",
"ultimate",
"strength",
"of",
"130",
"GPa",
"[11].",
"In",
"addition",
"to",
"these",
"outstanding",
"properties,",
"the",
"recent",
"developments",
"on",
"graphene",
"synthesis",
"routes",
"and",
"©",
"2011",
"Martin-Gallego",
"et",
"al;",
"licensee",
"Springer.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"DAF-12",
"Regulates",
"a",
"Connected",
"Network",
"of",
"Genes",
"to",
"Ensure",
"Robust",
"Developmental",
"Decisions",
"Daniel",
"Hochbaum1.,",
"Yue",
"Zhang2.,",
"Carsten",
"Stuckenholz3,",
"Paul",
"Labhart4,",
"Vassili",
"Alexiadis5,",
"Rene´",
"Martin6,7,",
"Hans-Joachim",
"Kno¨",
"lker7,",
"Alfred",
"L.",
"Fisher1*",
"1",
"Division",
"of",
"Geriatric",
"Medicine,",
"Department",
"of",
"Medicine,",
"University",
"of",
"Pittsburgh,",
"Pittsburgh,",
"Pennsylvania,",
"United",
"States",
"of",
"America,",
"2",
"Department",
"of",
"Radiation",
"Oncology,",
"Beth",
"Israel",
"Deaconess",
"Medical",
"Center,",
"Harvard",
"Medical",
"School,",
"Boston,",
"Massachusetts,",
"United",
"States",
"of",
"America,",
"3",
"Division",
"of",
"Hematology/Oncology,",
"Department",
"of",
"Medicine,",
"University",
"of",
"Pittsburgh,",
"Pittsburgh,",
"Pennsylvania,",
"United",
"States",
"of",
"America,",
"4",
"Active",
"Motif,",
"Carlsbad,",
"California,",
"United",
"States",
"of",
"America,",
"5",
"Biocept,",
"San",
"Diego,",
"California,",
"United",
"States",
"of",
"America,",
"6",
"ChiroBlock",
"GmbH,",
"Wolfen,",
"Germany,",
"7",
"Department",
"Chemie,",
"Technische",
"Universita¨t",
"Dresden,",
"Dresden,",
"Germany",
"Abstract",
"The",
"nuclear",
"receptor",
"DAF-12",
"has",
"roles",
"in",
"normal",
"development,",
"the",
"decision",
"to",
"pursue",
"dauer",
"development",
"in",
"unfavorable",
"conditions,",
"and",
"the",
"modulation",
"of",
"adult",
"aging.",
"Despite",
"the",
"biologic",
"importance",
"of",
"DAF-12,",
"target",
"genes",
"for",
"this",
"receptor",
"are",
"largely",
"unknown.",
"To",
"identify",
"DAF-12",
"targets,",
"we",
"performed",
"chromatin",
"immunoprecipitation",
"followed",
"by",
"hybridization",
"to",
"whole-genome",
"tiling",
"arrays.",
"We",
"identified",
"1,175",
"genomic",
"regions",
"to",
"be",
"bound",
"in",
"vivo",
"by",
"DAF-12,",
"and",
"these",
"regions",
"are",
"enriched",
"in",
"known",
"DAF-12",
"binding",
"motifs",
"and",
"act",
"as",
"DAF-12",
"response",
"elements",
"in",
"transfected",
"cells",
"and",
"in",
"transgenic",
"worms.",
"The",
"DAF-12",
"target",
"genes",
"near",
"these",
"binding",
"sites",
"include",
"an",
"extensive",
"network",
"of",
"interconnected",
"heterochronic",
"and",
"microRNA",
"genes.",
"We",
"also",
"identify",
"the",
"genes",
"encoding",
"components",
"of",
"the",
"miRISC,",
"which",
"is",
"required",
"for",
"the",
"control",
"of",
"target",
"genes",
"by",
"microRNA,",
"as",
"a",
"target",
"of",
"DAF-12",
"regulation.",
"During",
"reproductive",
"development,",
"many",
"of",
"these",
"target",
"genes",
"are",
"misregulated",
"in",
"daf-12(0)",
"mutants,",
"but",
"this",
"only",
"infrequently",
"results",
"in",
"developmental",
"phenotypes.",
"In",
"contrast,",
"we",
"and",
"others",
"have",
"found",
"that",
"null",
"daf-12",
"mutations",
"enhance",
"the",
"phenotypes",
"of",
"many",
"miRISC",
"and",
"heterochronic",
"target",
"genes.",
"We",
"also",
"find",
"that",
"environmental",
"fluctuations",
"significantly",
"strengthen",
"the",
"weak",
"heterochronic",
"phenotypes",
"of",
"null",
"daf-12",
"alleles.",
"During",
"diapause,",
"DAF-12",
"represses",
"the",
"expression",
"of",
"many",
"heterochronic",
"and",
"miRISC",
"target",
"genes,",
"and",
"prior",
"work",
"has",
"demonstrated",
"that",
"dauer",
"formation",
"can",
"suppress",
"the",
"heterochronic",
"phenotypes",
"of",
"many",
"of",
"these",
"target",
"genes",
"in",
"post-",
"dauer",
"development.",
"Together",
"these",
"data",
"are",
"consistent",
"with",
"daf-12",
"acting",
"to",
"ensure",
"developmental",
"robustness",
"by",
"committing",
"the",
"animal",
"to",
"adult",
"or",
"dauer",
"developmental",
"programs",
"despite",
"variable",
"internal",
"or",
"external",
"conditions.",
"Citation:",
"Hochbaum",
"D,",
"Zhang",
"Y,",
"Stuckenholz",
"C,",
"Labhart",
"P,",
"Alexiadis",
"V,",
"et",
"al.",
"(2011)",
"DAF-12",
"Regulates",
"a",
"Connected",
"Network",
"of",
"Genes",
"to",
"Ensure",
"Robust",
"Developmental",
"Decisions.",
"PLoS",
"Genet",
"7(7):",
"e1002179.",
"doi:10.1371/journal.pgen.1002179",
"Editor:",
"Stuart",
"K.",
"Kim,",
"Stanford",
"University",
"Medical",
"Center,",
"United",
"States",
"of",
"America",
"Received",
"November",
"26,",
"2010;",
"Accepted",
"May",
"23,",
"2011;",
"Published",
"July",
"21,",
"2011",
"Copyright:",
"2011",
"Hochbaum",
"et",
"al.",
"This",
"is",
"an",
"open-access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"author",
"and",
"source",
"are",
"credited.",
"Funding:",
"This",
"work",
"was",
"supported",
"by",
"NIH",
"grant",
"AG028977",
"to",
"ALF",
"(http://grants.nih.gov/grants/oer.htm),",
"a",
"pilot",
"project",
"from",
"Pittsburgh",
"Claude",
"D",
"Pepper",
"Older",
"Americans",
"Independence",
"Center",
"P30",
"AG024827",
"(http://www.pepper.pitt.edu/),",
"and",
"a",
"pilot",
"grant",
"from",
"the",
"University",
"of",
"Pittsburgh",
"Institute",
"Of",
"Aging",
"(http://www.",
"aging.pitt.edu/).",
"The",
"funders",
"had",
"no",
"role",
"in",
"study",
"design,",
"data",
"collection",
"and",
"analysis,",
"decision",
"to",
"publish,",
"or",
"preparation",
"of",
"the",
"manuscript.",
"Competing",
"Interests:",
"The",
"authors",
"have",
"declared",
"that",
"no",
"competing",
"interests",
"exist.",
"*",
"E-mail:",
"afisher@pitt.edu",
".",
"These",
"authors",
"contributed",
"equally",
"to",
"this",
"work.",
"Introduction",
"From",
"bacteria",
"to",
"humans,",
"organisms",
"sense",
"environmental",
"cues",
"and",
"reprogram",
"life",
"history",
"by",
"altering",
"gene",
"expression",
"patterns.",
"In",
"the",
"nematode",
"C.",
"elegans,",
"the",
"nuclear",
"receptor",
"DAF-12",
"alters",
"life",
"history",
"in",
"response",
"to",
"the",
"environment.",
"During",
"development,",
"when",
"conditions",
"are",
"unfavorable,",
"due",
"to",
"starvation,",
"crowding",
"or",
"high",
"temperature,",
"daf-12",
"promotes",
"diapause",
"and",
"formation",
"of",
"dauer",
"larvae",
"[1–3].",
"In",
"favorable",
"conditions,",
"the",
"DAF-12",
"receptor",
"is",
"activated",
"by",
"a",
"group",
"of",
"steroidal",
"carboxylic",
"acids,",
"termed",
"dafachronic",
"acids",
"(DA)",
"[4–6],",
"produced",
"from",
"cholesterol",
"via",
"a",
"multi-step",
"pathway",
"involving",
"the",
"daf-36",
"Rieske-like",
"oxygenase",
"and",
"the",
"daf-9",
"cytochrome",
"P450",
"enzyme",
"[7–9].",
"The",
"activation",
"of",
"DAF-",
"12",
"by",
"DA",
"leads",
"to",
"bypass",
"of",
"dauer",
"arrest",
"and",
"expression",
"of",
"later",
"larval",
"developmental",
"and",
"reproductive",
"programs",
"[10].",
"On",
"the",
"other",
"hand,",
"in",
"unfavorable",
"conditions,",
"DA",
"is",
"not",
"produced,",
"and",
"DAF-12",
"binds",
"to",
"the",
"co-repressor",
"DIN-1",
"promoting",
"dauer",
"programs",
"[11].",
"DAF-12",
"is",
"also",
"required",
"for",
"the",
"normal",
"lifespan",
"of",
"worms",
"[12–14]",
"and",
"for",
"the",
"increased",
"longevity",
"of",
"germline",
"ablated",
"animals",
"[7,15,16].",
"DAF-12",
"also",
"alters",
"life",
"history",
"by",
"regulation",
"of",
"the",
"heterochronic",
"circuit.",
"The",
"heterochronic",
"pathway",
"in",
"C.",
"elegans",
"determines",
"specific",
"cell",
"fate",
"programs",
"for",
"each",
"larval",
"stage",
"[17].",
"Several",
"daf-12",
"alleles,",
"especially",
"those",
"in",
"phenotypic",
"class",
"1,",
"have",
"heterochronic",
"phenotypes",
"[10].",
"These",
"mutants",
"repeat",
"L2",
"programs",
"instead",
"of",
"progressing",
"to",
"L3",
"programs,",
"resulting",
"in",
"excessive",
"hypodermal",
"seam",
"cell",
"division",
"in",
"the",
"L3",
"stage",
"and",
"defects",
"in",
"distal",
"tip",
"cell",
"migration",
"in",
"the",
"L4",
"stage",
"[1,10].",
"The",
"heterochronic",
"phenotypes",
"depend",
"on",
"the",
"activity",
"of",
"the",
"co-repressor",
"din-1,",
"as",
"daf-12(rh61);din-1",
"mutants",
"develop",
"normally",
"[11].",
"In",
"part,",
"DAF-12",
"regulates",
"the",
"heterochronic",
"circuit",
"by",
"controlling",
"expression",
"of",
"let-7",
"family",
"miRNAs",
"[18,19],",
"which",
"are",
"necessary",
"to",
"promote",
"L3",
"and",
"adult",
"programs",
"through",
"the",
"down-regulation",
"of",
"the",
"heterochronic",
"genes",
"hbl-1",
"and",
"lin-41",
"respectively",
"[20,21].",
"DAF-12",
"might",
"also",
"affect",
"the",
"heterochronic",
"circuit",
"via",
"dauer",
"formation,",
"as",
"many",
"heterochronic",
"phenotypes",
"are",
"suppressed",
"in",
"post",
"dauer",
"development",
"[22–25].",
"PLoS",
"Genetics",
"|",
"www.plosgenetics.org",
"1",
"July",
"2011",
"|",
"Volume",
"7",
"|",
"Issue",
"7",
"|",
"e1002179"
] | [
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] | [
"Kislov",
"et",
"al.",
"Implementation",
"Science",
"2011,",
"6:64",
"http://www.implementationscience.com/content/6/1/64",
"D",
"E",
"B",
"A",
"T",
"E",
"Implementation",
"Science",
"Open",
"Access",
"Collaborations",
"for",
"Leadership",
"in",
"Applied",
"Health",
"Research",
"and",
"Care:",
"lessons",
"from",
"the",
"theory",
"of",
"communities",
"of",
"practice",
"Roman",
"Kislov*,",
"Gill",
"Harvey",
"and",
"Kieran",
"Walshe",
"Abstract",
"Background:",
"The",
"paper",
"combines",
"the",
"analytical",
"and",
"instrumental",
"perspectives",
"on",
"communities",
"of",
"practice",
"(CoPs)",
"to",
"reflect",
"on",
"potential",
"challenges",
"that",
"may",
"arise",
"in",
"the",
"process",
"of",
"interprofessional",
"and",
"inter-organisational",
"joint",
"working",
"within",
"the",
"Collaborations",
"for",
"Leaderships",
"in",
"Applied",
"Health",
"Research",
"and",
"Care",
"(CLAHRCs)–partnerships",
"between",
"the",
"universities",
"and",
"National",
"Health",
"Service",
"(NHS)",
"Trusts",
"aimed",
"at",
"conducting",
"applied",
"health",
"research",
"and",
"translating",
"its",
"findings",
"into",
"day-to-day",
"clinical",
"practice.",
"Discussion:",
"The",
"paper",
"discusses",
"seminal",
"theoretical",
"literature",
"on",
"CoPs",
"as",
"well",
"as",
"previous",
"empirical",
"research",
"on",
"the",
"role",
"of",
"these",
"communities",
"in",
"healthcare",
"collaboration,",
"which",
"is",
"organised",
"around",
"the",
"following",
"three",
"themes:",
"knowledge",
"sharing",
"within",
"and",
"across",
"CoPs,",
"CoP",
"formation",
"and",
"manageability,",
"and",
"identity",
"building",
"in",
"CoPs.",
"It",
"argues",
"that",
"the",
"multiprofessional",
"and",
"multi-agency",
"nature",
"of",
"the",
"CLAHRCs",
"operating",
"in",
"the",
"traditionally",
"demarcated",
"organisational",
"landscape",
"of",
"the",
"NHS",
"may",
"present",
"formidable",
"obstacles",
"to",
"knowledge",
"sharing",
"between",
"various",
"professional",
"groupings,",
"formation",
"of",
"a",
"shared",
"‘collaborative’",
"identity,",
"and",
"the",
"development",
"of",
"new",
"communities",
"within",
"the",
"CLAHRCs.",
"To",
"cross",
"multiple",
"boundaries",
"between",
"various",
"professional",
"and",
"organisational",
"communities",
"and",
"hence",
"enable",
"the",
"flow",
"of",
"knowledge,",
"the",
"CLAHRCs",
"will",
"have",
"to",
"create",
"an",
"effective",
"system",
"of",
"‘bridges’",
"involving",
"knowledge",
"brokers,",
"boundary",
"objects,",
"and",
"cross-disciplinary",
"interactions",
"as",
"well",
"as",
"address",
"a",
"number",
"of",
"issues",
"related",
"to",
"professional",
"and",
"organisational",
"identification.",
"Summary:",
"The",
"CoP",
"approach",
"can",
"complement",
"traditional",
"‘stage-of-change’",
"theories",
"used",
"in",
"the",
"field",
"of",
"implementation",
"research",
"and",
"provide",
"a",
"basis",
"for",
"designing",
"theory-informed",
"interventions",
"and",
"evaluations.",
"It",
"can",
"help",
"to",
"illuminate",
"multiple",
"boundaries",
"that",
"exist",
"between",
"professional",
"and",
"organisational",
"groups",
"within",
"the",
"CLAHRCs",
"and",
"suggest",
"ways",
"of",
"crossing",
"those",
"boundaries",
"to",
"enable",
"knowledge",
"transfer",
"and",
"organisational",
"learning.",
"Achieving",
"the",
"aims",
"of",
"the",
"CLAHRCs",
"and",
"producing",
"a",
"sustainable",
"change",
"in",
"the",
"ways",
"applied",
"health",
"research",
"is",
"conducted",
"and",
"implemented",
"may",
"be",
"influenced",
"by",
"how",
"effectively",
"these",
"organisations",
"can",
"navigate",
"through",
"the",
"multiple",
"CoPs",
"involved",
"and",
"promote",
"the",
"development",
"of",
"new",
"multiprofessional",
"and",
"multi-organisational",
"communities",
"united",
"by",
"shared",
"practice",
"and",
"a",
"shared",
"sense",
"of",
"belonging–an",
"assumption",
"that",
"needs",
"to",
"be",
"explored",
"by",
"further",
"empirical",
"research.",
"Introduction",
"Since",
"being",
"identified",
"as",
"a",
"mechanism",
"through",
"which",
"knowledge",
"is",
"held,",
"transferred,",
"and",
"created,",
"the",
"commu-",
"nities",
"of",
"practice",
"(CoP)",
"approach",
"has",
"become",
"increas-",
"ingly",
"influential",
"within",
"management",
"research",
"and",
"practice",
"[1].",
"Originally",
"developed",
"by",
"Lave",
"and",
"Wenger",
"[2]",
"in",
"a",
"study",
"of",
"situated",
"learning,",
"the",
"CoP",
"theory",
"is",
"*",
"Correspondence:",
"roman.kislov@postgrad.mbs.ac.uk",
"Manchester",
"Business",
"School,",
"The",
"University",
"of",
"Manchester,",
"Booth",
"Street",
"West,",
"Manchester,",
"M15",
"6PB,",
"UK",
"currently",
"being",
"used",
"to",
"analyse",
"and",
"facilitate",
"knowledge",
"sharing",
"in",
"a",
"wide",
"range",
"of",
"organisational",
"environments,",
"including,",
"but",
"not",
"limited",
"to,",
"business",
"sector,",
"education,",
"information",
"technology",
"(IT)",
"and",
"healthcare",
"organisa-",
"tions.",
"In",
"the",
"healthcare",
"sector,",
"CoPs",
"have",
"been",
"argued",
"to",
"play",
"a",
"role",
"in",
"the",
"generation",
"of",
"social,",
"human,",
"organi-",
"sational,",
"professional,",
"and",
"patient",
"capital,",
"thus",
"being",
"potentially",
"useful",
"for",
"enhancing",
"care,",
"providing",
"learning",
"opportunities,",
"analysing",
"practice,",
"problem-solving,",
"shar-",
"ing",
"knowledge,",
"and",
"generating",
"ideas",
"[3].",
"©",
"2011",
"Kislov",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Hindawi",
"Publishing",
"Corporation",
"Gastroenterology",
"Research",
"and",
"Practice",
"Volume",
"2010,",
"Article",
"ID",
"453563,",
"13",
"pages",
"doi:10.1155/2010/453563",
"Review",
"Article",
"Contribution",
"of",
"Gut",
"Bacteria",
"to",
"Liver",
"Pathobiology",
"Gakuhei",
"Son,1",
"Michael",
"Kremer,2",
"and",
"Ian",
"N.",
"Hines1,",
"3",
"1",
"Division",
"of",
"Gastroenterology",
"and",
"Hepatology,",
"Department",
"of",
"Medicine,",
"University",
"of",
"North",
"Carolina,",
"Chapel",
"Hill,",
"NC",
"27599,",
"USA",
"2",
"Department",
"of",
"Surgery,",
"University",
"of",
"Heidelberg,",
"69120,",
"Heidelberg,",
"Germany",
"3",
"Department",
"of",
"Nutrition",
"and",
"Dietetics,",
"College",
"of",
"Human",
"Ecology,",
"East",
"Carolina",
"University,",
"110",
"Rivers",
"Building,",
"Greenville,",
"NC",
"27858-4353,",
"USA",
"Correspondence",
"should",
"be",
"addressed",
"to",
"Ian",
"N.",
"Hines,",
"hinesi@euc.edu",
"Received",
"16",
"April",
"2010;",
"Accepted",
"17",
"June",
"2010",
"Academic",
"Editor:",
"Ekihiro",
"Seki",
"Copyright",
"©",
"2010",
"Gakuhei",
"Son",
"et",
"al.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Emerging",
"evidence",
"suggests",
"a",
"strong",
"interaction",
"between",
"the",
"gut",
"microbiota",
"and",
"health",
"and",
"disease.",
"The",
"interactions",
"of",
"the",
"gut",
"microbiota",
"and",
"the",
"liver",
"have",
"only",
"recently",
"been",
"investigated",
"in",
"detail.",
"Receiving",
"approximately",
"70%",
"of",
"its",
"blood",
"supply",
"from",
"the",
"intestinal",
"venous",
"outflow,",
"the",
"liver",
"represents",
"the",
"first",
"line",
"of",
"defense",
"against",
"gut-derived",
"antigens",
"and",
"is",
"equipped",
"with",
"a",
"broad",
"array",
"of",
"immune",
"cells",
"(i.e.,",
"macrophages,",
"lymphocytes,",
"natural",
"killer",
"cells,",
"and",
"dendritic",
"cells)",
"to",
"accomplish",
"this",
"function.",
"In",
"the",
"setting",
"of",
"tissue",
"injury,",
"whereby",
"the",
"liver",
"is",
"otherwise",
"damaged",
"(e.g.,",
"viral",
"infection,",
"toxin",
"exposure,",
"ischemic",
"tissue",
"damage,",
"etc.),",
"these",
"same",
"immune",
"cell",
"populations",
"and",
"their",
"interactions",
"with",
"the",
"infiltrating",
"gut",
"bacteria",
"likely",
"contribute",
"to",
"and",
"promote",
"these",
"pathologies.",
"The",
"following",
"paper",
"will",
"highlight",
"recent",
"studies",
"investigating",
"the",
"relationship",
"between",
"the",
"gut",
"microbiota,",
"liver",
"biology,",
"and",
"pathobiology.",
"Defining",
"these",
"connections",
"will",
"likely",
"provide",
"new",
"targets",
"for",
"therapy",
"or",
"prevention",
"of",
"a",
"wide",
"variety",
"of",
"acute",
"and",
"chronic",
"liver",
"pathologies.",
"1.",
"Introduction",
"Receiving",
"approximately",
"70%",
"of",
"its",
"blood",
"supply",
"from",
"the",
"portal",
"vein",
"which",
"is",
"the",
"direct",
"venous",
"outflow",
"of",
"the",
"intestine,",
"the",
"liver",
"is",
"continually",
"exposed",
"to",
"gut-derived",
"factors",
"including",
"bacteria",
"and",
"bacterial",
"components.",
"To",
"combat",
"this",
"influx,",
"the",
"liver",
"contains",
"a",
"large",
"number",
"of",
"resident",
"immune",
"cells",
"including",
"macrophages",
"(i.e.,",
"the",
"Kupffer",
"cell),",
"lymphocytes,",
"natural",
"killer",
"cells,",
"dendritic",
"cells,",
"and",
"B",
"cells.",
"Together,",
"these",
"immune",
"cell",
"populations",
"in",
"conjunction",
"with",
"other",
"nonparenchymal",
"cells",
"including",
"endothelial",
"cells",
"and",
"stellate",
"cells",
"orchestrate",
"a",
"controlled",
"and",
"organized",
"response",
"to",
"these",
"potentially",
"highly",
"inflammatory",
"factors.",
"However,",
"when",
"normal",
"liver",
"physiology",
"is",
"disrupted",
"and",
"inflammatory",
"cells",
"are",
"activated,",
"gut-derived",
"factors",
"likely",
"augment",
"or",
"exacerbate",
"certain",
"liver",
"diseases",
"leading",
"to",
"enhanced",
"tissue",
"damage",
"and",
"propagation",
"of",
"inflammation.",
"Thus,",
"understanding",
"the",
"mechanisms",
"both",
"of",
"control",
"and",
"of",
"activation",
"by",
"gut-derived",
"factors",
"as",
"well",
"as",
"the",
"functionality",
"of",
"the",
"gut",
"barrier",
"are",
"critical",
"to",
"the",
"development",
"of",
"new",
"therapeutic",
"modalities",
"to",
"treat",
"or",
"prevent",
"acute",
"and",
"chronic",
"liver",
"diseases",
"such",
"as",
"viral",
"hepatitis,",
"alcoholic",
"liver",
"disease,",
"and/or",
"liver",
"cancer.",
"The",
"current",
"paper",
"will",
"provide",
"an",
"overview",
"of",
"gut",
"bacterial",
"populations,",
"gut",
"barrier",
"function,",
"and",
"the",
"potential",
"interactions",
"of",
"gut",
"bacteria",
"with",
"acute",
"and",
"chronic",
"liver",
"disease.",
"2.",
"The",
"Gut",
"Microbiome",
"The",
"human",
"intestine",
"provides",
"residence",
"to",
"1",
"×",
"1013",
"bac-",
"teria,",
"a",
"number",
"which",
"dwarfs",
"the",
"total",
"number",
"of",
"cells",
"in",
"the",
"human",
"body",
"(1",
"×",
"1012)",
"[1,",
"2].",
"Referred",
"to",
"as",
"commensal",
"bacteria,",
"these",
"microorganisms",
"play",
"a",
"crucial",
"role",
"in",
"human",
"physiology",
"and",
"metabolism,",
"providing",
"key",
"metabolic",
"functions",
"during",
"absorption",
"and",
"waste",
"breakdown",
"[3].",
"Moreover,",
"they",
"also",
"contribute",
"to",
"gut",
"epithelial",
"cell",
"responses",
"including",
"proliferation",
"and",
"differentiation",
"and",
"play",
"a",
"key",
"role",
"in",
"barrier",
"development",
"and",
"function",
"[4].",
"It",
"is",
"clear,",
"however,",
"that",
"these",
"same",
"luminal",
"contents",
"may",
"also",
"contribute",
"to",
"intestinal",
"pathology",
"in",
"the",
"setting",
"of",
"colitis",
"where",
"immune",
"cell",
"dysfunction,",
"barrier",
"disruption,",
"and/or"
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] | [
"BMC",
"Genetics",
"Software",
"CapsID:",
"a",
"web-based",
"tool",
"for",
"developing",
"parsimonious",
"sets",
"of",
"CAPS",
"molecular",
"markers",
"for",
"genotyping",
"Jonathan",
"Taylor1",
"and",
"Nicholas",
"J",
"Provart*2",
"BioMed",
"Central",
"Open",
"Access",
"Address:",
"1Department",
"of",
"Computer",
"Science,",
"University",
"of",
"Toronto,",
"40",
"St",
"George",
"Street,",
"Toronto,",
"ON",
"M5S",
"2E4,",
"Canada",
"and",
"2Centre",
"for",
"the",
"Analysis",
"of",
"Genome",
"Evolution",
"and",
"Function,",
"Department",
"of",
"Cell",
"and",
"Systems",
"Biology,",
"University",
"of",
"Toronto,",
"25",
"Willcocks",
"Street,",
"Toronto,",
"ON",
"M5S",
"3B2,",
"Canada",
"Email:",
"Jonathan",
"Taylor",
"-",
"jonathan.taylor@utoronto.ca;",
"Nicholas",
"J",
"Provart*",
"-",
"nicholas.provart@utoronto.ca",
"*",
"Corresponding",
"author",
"Published:",
"10",
"May",
"2006",
"BMC",
"Genetics",
"2006,",
"7:27",
"doi:10.1186/1471-2156-7-27",
"This",
"article",
"is",
"available",
"from:",
"http://www.biomedcentral.com/1471-2156/7/27",
"Received:",
"03",
"March",
"2006",
"Accepted:",
"10",
"May",
"2006",
"©",
"2006",
"Taylor",
"and",
"Provart;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"Genotyping",
"may",
"be",
"carried",
"out",
"by",
"a",
"number",
"of",
"different",
"methods",
"including",
"direct",
"sequencing",
"and",
"polymorphism",
"analysis.",
"For",
"a",
"number",
"of",
"reasons,",
"PCR-based",
"polymorphism",
"analysis",
"may",
"be",
"desirable,",
"owing",
"to",
"the",
"fact",
"that",
"only",
"small",
"amounts",
"of",
"genetic",
"material",
"are",
"required,",
"and",
"that",
"the",
"costs",
"are",
"low.",
"One",
"popular",
"and",
"cheap",
"method",
"for",
"detecting",
"polymorphisms",
"is",
"by",
"using",
"cleaved",
"amplified",
"polymorphic",
"sequence,",
"or",
"CAPS,",
"molecular",
"markers.",
"These",
"are",
"also",
"known",
"as",
"PCR-RFLP",
"markers.",
"Results:",
"We",
"have",
"developed",
"a",
"program,",
"called",
"CapsID,",
"that",
"identifies",
"snip-SNPs",
"(single",
"nucleotide",
"polymorphisms",
"that",
"alter",
"restriction",
"endonuclease",
"cut",
"sites)",
"within",
"a",
"set",
"or",
"sets",
"of",
"reference",
"sequences,",
"designs",
"PCR",
"primers",
"around",
"these,",
"and",
"then",
"suggests",
"the",
"most",
"parsimonious",
"combination",
"of",
"markers",
"for",
"genotyping",
"any",
"individual",
"who",
"is",
"not",
"a",
"member",
"of",
"the",
"reference",
"set.",
"The",
"output",
"page",
"includes",
"biologist-friendly",
"features,",
"such",
"as",
"images",
"of",
"virtual",
"gels",
"to",
"assist",
"in",
"genotyping",
"efforts.",
"CapsID",
"is",
"freely",
"available",
"at",
"http://bbc.botany.utoronto.ca/capsid.",
"Conclusion:",
"CapsID",
"is",
"a",
"tool",
"that",
"can",
"rapidly",
"provide",
"minimal",
"sets",
"of",
"CAPS",
"markers",
"for",
"molecular",
"identification",
"purposes",
"for",
"any",
"biologist",
"working",
"in",
"genetics,",
"community",
"genetics,",
"plant",
"and",
"animal",
"breeding,",
"forensics",
"and",
"other",
"fields.",
"Background",
"DNA",
"sequences",
"from",
"different",
"varieties",
"or",
"accessions",
"of",
"a",
"given",
"species",
"are",
"becoming",
"available",
"through",
"a",
"number",
"of",
"sequencing",
"projects.",
"Single",
"nucleotide",
"polymorphisms",
"(SNPs),",
"together",
"with",
"insertion/deletions",
"(InDels),",
"are",
"the",
"most",
"common",
"type",
"of",
"polymorphism",
"in",
"the",
"genomes",
"studied",
"so",
"far.",
"Large",
"sets",
"of",
"predicted",
"SNPs",
"are",
"publicly",
"available",
"for",
"the",
"human",
"genome",
"(SNP",
"Consortium,",
"http:/",
"/snp.cshl.org),",
"and",
"for",
"some",
"genetic",
"model",
"organisms,",
"including",
"Caenorhabditis",
"elegans",
"[1],",
"Drosophila",
"mela-",
"nogaster",
"[2],",
"and",
"Arabidopsis",
"thaliana",
"[3].",
"In",
"addition,",
"the",
"generation",
"of",
"short",
"stretches",
"of",
"DNA",
"sequence",
"informa-",
"tion",
"for",
"non-model",
"organisms,",
"e.g.",
"from",
"ribosomal",
"sequences,",
"is",
"becoming",
"increasingly",
"economical.",
"Approx-",
"imately",
"30–40%",
"of",
"SNPs",
"alter",
"restriction",
"endonuclease",
"recognition",
"sites",
"and",
"these",
"are",
"commonly",
"referred",
"to",
"as",
"snip-SNPs",
"[1].",
"Restriction",
"enzyme",
"digestion",
"pattern",
"poly-",
"morphism",
"may",
"be",
"used",
"to",
"create",
"cleaved",
"amplified",
"poly-",
"morphic",
"sequence",
"(CAPS)",
"markers",
"(also",
"known",
"as",
"PCR-",
"RFLP",
"markers),",
"which",
"are",
"codominant",
"molecular",
"markers",
"that",
"amplify",
"a",
"short",
"genomic",
"sequence",
"around",
"the",
"poly-",
"morphic",
"endonuclease",
"restriction",
"site",
"[4].",
"They",
"are",
"easily",
"Page",
"1",
"of",
"5",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"Sustained",
"Fixation",
"Induced",
"Changes",
"in",
"Phoria",
"and",
"Convergence",
"Peak",
"Velocity",
"Eun",
"H.",
"Kim1,",
"Vincent",
"R.",
"Vicci2,",
"Sang",
"J.",
"Han1,",
"Tara",
"L.",
"Alvarez1*",
"1",
"Department",
"of",
"Biomedical",
"Engineering,",
"New",
"Jersey",
"Institute",
"of",
"Technology,",
"Newark,",
"New",
"Jersey,",
"United",
"States",
"of",
"America,",
"2",
"Department",
"of",
"Vision,",
"Private",
"Practice,",
"Westfield,",
"New",
"Jersey,",
"United",
"States",
"of",
"America,",
"3",
"Department",
"of",
"Vision",
"Rehabilitation,",
"Kessler",
"Institute,",
"West",
"Orange,",
"New",
"Jersey,",
"United",
"States",
"of",
"America",
"Abstract",
"Purpose:",
"This",
"study",
"sought",
"to",
"investigate",
"the",
"influence",
"of",
"phoria",
"adaptation",
"on",
"convergence",
"peak",
"velocity",
"from",
"responses",
"located",
"at",
"different",
"initial",
"vergence",
"positions.",
"Methods:",
"Symmetrical",
"4u",
"convergence",
"step",
"responses",
"and",
"near",
"dissociated",
"phoria",
"(measured",
"at",
"40",
"cm",
"from",
"the",
"subject’s",
"midline)",
"were",
"recorded",
"from",
"six",
"subjects",
"with",
"normal",
"binocular",
"vision",
"using",
"an",
"infrared",
"limbus",
"tracking",
"system",
"with",
"a",
"haploscope.",
"Two",
"different",
"sustained",
"fixations",
"(1u",
"and",
"16u",
"convergent",
"rotation",
"along",
"the",
"subject’s",
"midline)",
"were",
"used",
"to",
"study",
"whether",
"phoria",
"had",
"an",
"influence",
"on",
"the",
"peak",
"velocity",
"of",
"convergence",
"responses",
"located",
"at",
"two",
"initial",
"vergence",
"positions",
"(1u",
"or",
"‘far’",
"steps",
"and",
"12u",
"or",
"‘near’",
"steps).",
"Results:",
"Phoria",
"was",
"significantly",
"adapted",
"after",
"a",
"sustained",
"fixation",
"task",
"at",
"near",
"(16u)",
"and",
"far",
"(1u)",
"(p,0.002).",
"A",
"repeated",
"measures",
"ANOVA",
"showed",
"that",
"convergence",
"far",
"steps",
"were",
"significantly",
"faster",
"than",
"the",
"near",
"steps",
"(p,0.03).",
"When",
"comparing",
"convergence",
"steps",
"with",
"the",
"same",
"initial",
"vergence",
"position,",
"steps",
"measured",
"after",
"near",
"phoria",
"adaptation",
"were",
"faster",
"than",
"responses",
"after",
"far",
"adaptation",
"(p,0.02).",
"A",
"regression",
"analysis",
"demonstrated",
"that",
"the",
"change",
"in",
"phoria",
"and",
"the",
"change",
"in",
"convergence",
"peak",
"velocity",
"were",
"significantly",
"correlated",
"for",
"the",
"far",
"convergence",
"steps",
"(r",
"=",
"0.97,",
"p",
"=",
"0.001).",
"A",
"weaker",
"correlation",
"was",
"observed",
"for",
"the",
"near",
"convergence",
"steps",
"(r",
"=",
"0.59,",
"p",
"=",
"0.20).",
"Conclusion:",
"As",
"a",
"result",
"of",
"sustained",
"fixation,",
"phoria",
"was",
"adapted",
"and",
"the",
"peak",
"velocity",
"of",
"the",
"near",
"and",
"far",
"convergence",
"steps",
"was",
"modified.",
"This",
"study",
"has",
"clinical",
"considerations",
"since",
"prisms,",
"which",
"evoke",
"phoria",
"adaptation,",
"can",
"be",
"prescribed",
"to",
"help",
"alleviate",
"visual",
"discomfort.",
"Future",
"investigations",
"should",
"include",
"a",
"systematic",
"study",
"of",
"how",
"prisms",
"may",
"influence",
"convergence",
"and",
"divergence",
"eye",
"movements",
"for",
"those",
"prescribed",
"with",
"prisms",
"within",
"their",
"spectacles.",
"Citation:",
"Kim",
"EH,",
"Vicci",
"VR,",
"Han",
"SJ,",
"Alvarez",
"TL",
"(2011)",
"Sustained",
"Fixation",
"Induced",
"Changes",
"in",
"Phoria",
"and",
"Convergence",
"Peak",
"Velocity.",
"PLoS",
"ONE",
"6(6):",
"e20883.",
"doi:10.1371/journal.pone.0020883",
"Editor:",
"Joel",
"M.",
"Miller,",
"Smith-Kettlewell",
"Eye",
"Research",
"Institute,",
"United",
"States",
"of",
"America",
"Received",
"February",
"2,",
"2011;",
"Accepted",
"May",
"11,",
"2011;",
"Published",
"June",
"17,",
"2011",
"Copyright:",
"2011",
"Kim",
"et",
"al.",
"This",
"is",
"an",
"open-access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"author",
"and",
"source",
"are",
"credited.",
"Funding:",
"This",
"work",
"was",
"supported",
"in",
"part",
"by",
"a",
"CAREER",
"award",
"from",
"the",
"National",
"Science",
"Foundation",
"(BES-0447713).",
"No",
"additional",
"external",
"funding",
"was",
"received",
"for",
"this",
"study.",
"The",
"funders",
"had",
"no",
"role",
"in",
"study",
"design,",
"data",
"collection",
"and",
"analysis,",
"decision",
"to",
"publish,",
"or",
"preparation",
"of",
"the",
"manuscript.",
"Competing",
"Interests:",
"The",
"authors",
"have",
"declared",
"that",
"no",
"competing",
"interests",
"exist.",
"*",
"E-mail:",
"tara.l.alvarez@njit.edu",
"Introduction",
"Vergence,",
"a",
"binocular",
"eye",
"movement,",
"is",
"responsible",
"for",
"attaining",
"visual",
"information",
"located",
"at",
"different",
"distances.",
"The",
"two",
"primary",
"inputs",
"to",
"the",
"vergence",
"system",
"are",
"retinal",
"blur",
"and",
"disparity[1].",
"Retinal",
"blur",
"is",
"the",
"defocusing",
"of",
"images",
"which",
"stimulates",
"the",
"accommodative",
"vergence",
"system,",
"whereas",
"dispar-",
"ity",
"is",
"the",
"difference",
"between",
"where",
"a",
"new",
"target",
"is",
"projected",
"onto",
"the",
"retina",
"and",
"the",
"fovea.",
"Disparity",
"stimulates",
"the",
"disparity-",
"vergence",
"system",
"and",
"allows",
"a",
"person",
"to",
"perceive",
"and",
"maintain",
"a",
"single",
"binocular",
"vision.",
"The",
"eyes",
"may",
"rotate",
"inward",
"(conver-",
"gence)",
"or",
"outward",
"(divergence)",
"to",
"project",
"the",
"line",
"of",
"sight",
"onto",
"the",
"same",
"point",
"of",
"interest.",
"Through",
"the",
"use",
"of",
"different",
"instruments,",
"one",
"can",
"study",
"accommodative-vergence",
"or",
"dispar-",
"ity-vergence",
"independently.",
"A",
"haploscope",
"can",
"systematically",
"change",
"where",
"an",
"object",
"is",
"projected",
"onto",
"the",
"retina",
"while",
"maintaining",
"a",
"fixed",
"focal",
"length.",
"Hence,",
"when",
"using",
"a",
"haploscope,",
"any",
"changes",
"within",
"eye",
"movements",
"can",
"be",
"assumed",
"to",
"be",
"associated",
"with",
"the",
"disparity-vergence",
"system",
"since",
"the",
"retinal",
"blur",
"stimulus",
"is",
"constant.",
"When",
"a",
"binocular",
"stimulus",
"is",
"eliminated,",
"such",
"as",
"when",
"one",
"eye",
"is",
"occluded",
"while",
"the",
"other",
"eye",
"is",
"fixating",
"on",
"a",
"target",
"located",
"along",
"midline,",
"the",
"occluded",
"eye",
"will",
"decay",
"to",
"its",
"dissociated",
"phoria",
"level.",
"Near-dissociated",
"phoria",
"is",
"quantified",
"when",
"the",
"viewing",
"or",
"non-",
"occluded",
"eye",
"is",
"fixated",
"on",
"a",
"target",
"located",
"at",
"40",
"cm",
"from",
"the",
"subject’s",
"midline.",
"Phoria",
"can",
"be",
"classified",
"as",
"orthophoria,",
"esophoria",
"or",
"exophoria,",
"which",
"are",
"the",
"absence,",
"nasal",
"or",
"temporal",
"rotation",
"of",
"the",
"occluded",
"eye,",
"respectively.",
"Phoria",
"adaptation",
"is",
"a",
"persistent",
"modification",
"in",
"the",
"eye",
"alignment",
"which",
"can",
"be",
"due",
"to",
"a",
"prolonged",
"exposure",
"to",
"a",
"binocular",
"stimulus",
"at",
"different",
"spatial",
"depths.",
"A",
"rich",
"history",
"exists",
"in",
"the",
"literature",
"that",
"describes",
"model-",
"representation",
"of",
"the",
"neural",
"control",
"of",
"disparity-vergence",
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"Mochizuki,3",
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"1",
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"Correspondence",
"should",
"be",
"addressed",
"to",
"Masayuki",
"Obatake,",
"mobatake@nagasaki-u.ac.jp",
"Received",
"25",
"April",
"2011;",
"Accepted",
"10",
"August",
"2011",
"Academic",
"Editor:",
"E.",
"N.",
"Myers",
"Copyright",
"©",
"2011",
"Masayuki",
"Obatake",
"et",
"al.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
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"is",
"properly",
"cited.",
"Tracheoinnominate",
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"a",
"potentially",
"fatal",
"complication",
"for",
"patients",
"who",
"depend",
"on",
"tracheostomy",
"or",
"tracheoesophageal",
"diversion.",
"Since",
"the",
"bleeding",
"from",
"a",
"TIF",
"is",
"often",
"difficult",
"to",
"control,",
"preventative",
"procedures",
"are",
"recommended",
"to",
"avoid",
"this",
"complication.",
"An",
"11-year-old",
"girl",
"with",
"hypoxic-ischemic",
"encephalopathy",
"and",
"scoliosis",
"developed",
"tracheal",
"stenosis",
"caused",
"by",
"compression",
"from",
"the",
"innominate",
"artery.",
"Respiratory",
"control",
"with",
"intubation",
"through",
"the",
"tracheal",
"stenosis",
"was",
"needed,",
"and",
"the",
"patient",
"was",
"at",
"high",
"risk",
"for",
"developing",
"a",
"TIF.",
"She",
"underwent",
"ligation",
"of",
"the",
"innominate",
"artery",
"at",
"tracheostomy.",
"Subsequent",
"tracheostomy",
"revealed",
"a",
"widened",
"tracheal",
"lumen",
"and",
"no",
"further",
"complications.",
"Prophylactic",
"ligation",
"of",
"the",
"innominate",
"artery",
"and",
"creation",
"of",
"tracheostomy",
"might",
"be",
"considered",
"as",
"a",
"valid",
"option",
"for",
"patients",
"at",
"high",
"risk",
"of",
"developing",
"TIF.",
"1.",
"Introduction",
"Neurologically",
"impaired",
"children",
"often",
"require",
"tracheostomy",
"or",
"tracheoesophageal",
"diversion",
"for",
"long-term",
"mechanical",
"ventilation.",
"Under",
"these",
"circumstances,",
"numerous",
"compli-",
"cations",
"such",
"as",
"tracheal",
"wall",
"damage,",
"tracheal",
"granulation,",
"and",
"tracheoinnominate",
"fistula",
"(TIF)",
"have",
"been",
"reported",
"[1–3].",
"TIF",
"is",
"a",
"serious",
"and",
"often",
"fatal",
"complication.",
"Since",
"the",
"survival",
"rate",
"is",
"reported",
"to",
"be",
"less",
"than",
"30%",
"even",
"with",
"surgical",
"intervention",
"[4,",
"5],",
"preventive",
"measures",
"are",
"recommended",
"to",
"avoid",
"TIF.",
"We",
"report",
"a",
"case",
"of",
"ligation",
"of",
"the",
"innominate",
"artery",
"before",
"tracheostomy",
"in",
"a",
"patient",
"who",
"had",
"developed",
"tracheal",
"stenosis.",
"2.",
"Case",
"Report",
"An",
"11-year-old",
"girl",
"with",
"hypoxic-ischemic",
"encephalopathy",
"had",
"gradually",
"developed",
"scoliosis,",
"and",
"she",
"had",
"experienced",
"several",
"episodes",
"of",
"mild",
"wheezing",
"associated",
"with",
"myotonia.",
"Her",
"SpO2",
"levels",
"had",
"decreased",
"to",
"20–30%",
"during",
"episodes",
"of",
"severe",
"myotonia.",
"She",
"was",
"referred",
"to",
"a",
"medical",
"center",
"after",
"the",
"abrupt",
"onset",
"of",
"wheezing",
"and",
"respiratory",
"distress.",
"Chest",
"X-ray",
"revealed",
"scoliosis",
"(Figure",
"1),",
"and",
"laryngoscopy",
"showed",
"neither",
"supraglottic",
"stenosis",
"nor",
"edema.",
"Chest",
"computed",
"tomography",
"(CT)",
"revealed",
"tracheal",
"stenosis",
"caused",
"by",
"com-",
"pression",
"by",
"the",
"innominate",
"artery",
"(Figure",
"2).",
"Bronchoscopy",
"demonstrated",
"narrowing",
"of",
"the",
"trachea",
"by",
"external",
"compres-",
"sion",
"of",
"its",
"anterior",
"wall",
"as",
"well",
"as",
"tracheomalacia",
"(Figure",
"3)",
"involving",
"the",
"middle",
"trachea",
"to",
"the",
"tracheal",
"bifurcation.",
"An",
"uncuffed",
"endotracheal",
"tube",
"was",
"inserted",
"distally",
"to",
"the",
"stenosis,",
"and",
"this",
"resulted",
"in",
"a",
"prompt",
"improvement",
"in",
"her",
"respiratory",
"condition.",
"However,",
"she",
"was",
"thought",
"to",
"require",
"long-term",
"tracheal",
"intubation",
"because",
"of",
"the",
"tracheal",
"stenosis",
"and",
"tracheomalacia.",
"Furthermore,",
"she",
"was",
"considered",
"at",
"increased",
"risk",
"of",
"developing",
"tracheal",
"damage",
"and",
"subsequent",
"formation",
"of",
"TIF",
"from",
"tracheal",
"intubation."
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] | [
"Sensors",
"2011,",
"11,",
"6685-6696;",
"doi:10.3390/s110706685",
"OPEN",
"ACCESS",
"sensors",
"ISSN",
"1424-8220",
"www.mdpi.com/journal/sensors",
"Article",
"Label",
"Free",
"Inhibitor",
"Screening",
"of",
"Hepatitis",
"C",
"Virus",
"(HCV)",
"NS5B",
"Viral",
"Protein",
"Using",
"RNA",
"Oligonucleotide",
"Changhyun",
"Roh",
"1,*,",
"Sang",
"Eun",
"Kim",
"2",
"and",
"Sung-Kee",
"Jo",
"1",
"1",
"Radiation",
"Research",
"Division",
"for",
"Biotechnology,",
"Advanced",
"Radiation",
"Technology",
"Institute",
"(ARTI),",
"Korea",
"Atomic",
"Energy",
"Research",
"Institute",
"(KAERI),",
"1266",
"Shinjeong-dong,",
"Jeongeup-si,",
"Jeollabuk-do",
"580-185,",
"Korea;",
"E-Mail:",
"skjo@kaeri.re.kr",
"2",
"Department",
"of",
"Nuclear",
"Medicine,",
"Seoul",
"National",
"University",
"College",
"of",
"Medicine,",
"Seoul",
"National",
"University",
"Bundang",
"Hospital,",
"Seongnam",
"463-707,",
"Korea;",
"E-Mail:",
"kse@snu.ac.kr",
"*",
"Author",
"to",
"whom",
"correspondence",
"should",
"be",
"addressed;",
"E-Mail:",
"chroh@kaeri.re.kr;",
"Tel.:",
"+82-63-570-3227;",
"Fax:",
"+82-63-570-3229.",
"Received:",
"11",
"May",
"2011;",
"in",
"revised",
"form:",
"22",
"June",
"2011",
"/",
"Accepted:",
"27",
"June",
"2011",
"/",
"Published:",
"27",
"June",
"2011",
"Abstract:",
"Globally,",
"over",
"170",
"million",
"people",
"(ca.",
"3%",
"of",
"the",
"World’s",
"population)",
"are",
"infected",
"with",
"the",
"hepatitis",
"C",
"virus",
"(HCV),",
"which",
"can",
"cause",
"serious",
"liver",
"diseases",
"such",
"as",
"chronic",
"hepatitis,",
"evolving",
"into",
"subsequent",
"health",
"problems.",
"Driven",
"by",
"the",
"need",
"to",
"detect",
"the",
"presence",
"of",
"HCV,",
"as",
"an",
"essential",
"factor",
"in",
"diagnostic",
"medicine,",
"the",
"monitoring",
"of",
"viral",
"protein",
"has",
"been",
"of",
"great",
"interest",
"in",
"developing",
"simple",
"and",
"reliable",
"HCV",
"detection",
"methods.",
"Despite",
"considerable",
"advances",
"in",
"viral",
"protein",
"detection",
"as",
"an",
"HCV",
"disease",
"marker,",
"the",
"current",
"enzyme",
"linked",
"immunosorbent",
"assay",
"(ELISA)",
"based",
"detection",
"methods",
"using",
"antibody",
"treatment",
"have",
"several",
"drawbacks.",
"To",
"overcome",
"this",
"bottleneck,",
"an",
"RNA",
"aptamer",
"become",
"to",
"be",
"emerged",
"as",
"an",
"antibody",
"substitute",
"in",
"the",
"application",
"of",
"biosensor",
"for",
"detection",
"of",
"viral",
"protein.",
"In",
"this",
"study,",
"we",
"demonstrated",
"a",
"streptavidin-biotin",
"conjugation",
"method,",
"namely,",
"the",
"RNA",
"aptamer",
"sensor",
"system",
"that",
"can",
"quantify",
"viral",
"protein",
"with",
"detection",
"level",
"of",
"700",
"pg",
"mL−1",
"using",
"a",
"biotinylated",
"RNA",
"oligonucleotide",
"on",
"an",
"Octet",
"optical",
"biosensor.",
"Also,",
"we",
"showed",
"this",
"method",
"can",
"be",
"used",
"to",
"screen",
"inhibitors",
"of",
"viral",
"protein",
"rapidly",
"and",
"simply",
"on",
"a",
"biotinylated",
"RNA",
"oligonucleotide",
"biosensor.",
"Among",
"the",
"inhibitors",
"screened,",
"(−)-Epigallocatechin",
"gallate",
"showed",
"high",
"binding",
"inhibition",
"effect",
"on",
"HCV",
"NS5B",
"viral",
"protein.",
"The",
"proposed",
"method",
"can",
"be",
"considered",
"a",
"real-time",
"monitoring",
"method",
"for",
"inhibitor",
"screening",
"of",
"HCV",
"viral",
"protein",
"and",
"is",
"expected",
"to",
"be",
"applicable",
"to",
"other",
"types",
"of",
"diseases."
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] | [
"BMC",
"Medical",
"Education",
"BioMed",
"Central",
"1BR2M0e0Cs1eM,aedriccahl",
"Eadrutciactiloen",
":6",
"Introducing",
"evidence",
"based",
"medicine",
"to",
"the",
"journal",
"club,",
"using",
"a",
"structured",
"pre",
"and",
"post",
"test:",
"a",
"cohort",
"study",
"J",
"Steven",
"Cramer*1",
"and",
"Martin",
"C",
"Mahoney2",
"Address:",
"1Department",
"of",
"Family",
"Medicine,",
"School",
"of",
"Medicine",
"and",
"Biomedical",
"Sciences,",
"State",
"University",
"of",
"New",
"York",
"at",
"Buffalo,",
"Buffalo,",
"New",
"York,",
"USA",
"and",
"2Department",
"of",
"Family",
"Medicine,",
"School",
"of",
"Medicine",
"and",
"Biomedical",
"Sciences,",
"State",
"University",
"of",
"New",
"York",
"at",
"Buffalo,",
"Buffalo,",
"New",
"York,",
"USA",
"E-mail:",
"J",
"Steven",
"Cramer*",
"-",
"CramerJS@email.msn.com;",
"Martin",
"C",
"Mahoney",
"-",
"MMahone@acsu.buffalo.edu",
"*Corresponding",
"author",
"Published:",
"6",
"November",
"2001",
"BMC",
"Medical",
"Education",
"2001,",
"1:6",
"This",
"article",
"is",
"available",
"from:",
"http://www.biomedcentral.com/1472-6920/1/6",
"Received:",
"28",
"August",
"2001",
"Accepted:",
"6",
"November",
"2001",
"©",
"2001",
"Cramer",
"and",
"Mahoney;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"Verbatim",
"copying",
"and",
"redistribution",
"of",
"this",
"article",
"are",
"permitted",
"in",
"any",
"medium",
"for",
"any",
"non-commercial",
"purpose,",
"provided",
"this",
"notice",
"is",
"preserved",
"along",
"with",
"the",
"article's",
"original",
"URL.",
"For",
"commercial",
"use,",
"contact",
"info@biomedcentral.com",
"Abstract",
"Background:",
"Journal",
"Club",
"at",
"a",
"University-based",
"residency",
"program",
"was",
"restructured",
"to",
"introduce,",
"reinforce",
"and",
"evaluate",
"residents",
"understanding",
"of",
"the",
"concepts",
"of",
"Evidence",
"Based",
"Medicine.",
"Methods:",
"Over",
"the",
"course",
"of",
"a",
"year",
"structured",
"pre",
"and",
"post-tests",
"were",
"developed",
"for",
"use",
"during",
"each",
"Journal",
"Club.",
"Questions",
"were",
"derived",
"from",
"the",
"articles",
"being",
"reviewed.",
"Performance",
"with",
"the",
"key",
"concepts",
"of",
"Evidence",
"Based",
"Medicine",
"was",
"assessed.",
"Study",
"subjects",
"were",
"35",
"PGY2",
"and",
"PGY3",
"residents",
"in",
"a",
"University",
"based",
"Family",
"Practice",
"Program.",
"Results:",
"Performance",
"on",
"the",
"pre-test",
"demonstrated",
"a",
"significant",
"improvement",
"from",
"a",
"median",
"of",
"54.5",
"%",
"to",
"78.9",
"%",
"over",
"the",
"course",
"of",
"the",
"year",
"(F",
"89.17,",
"p",
"<",
".001).",
"The",
"post-test",
"results",
"also",
"exhibited",
"a",
"significant",
"increase",
"from",
"63.6",
"%",
"to",
"81.6%",
"(F",
"85.84,",
"p",
"<",
".001).",
"Conclusions:",
"Following",
"organizational",
"revision,",
"the",
"introduction",
"of",
"a",
"pre-test/post-test",
"instrument",
"supported",
"achievement",
"of",
"the",
"learning",
"objectives",
"with",
"a",
"better",
"understanding",
"and",
"utilization",
"of",
"the",
"concepts",
"of",
"Evidence",
"Based",
"Medicine.",
"Background",
"The",
"Residency",
"Review",
"Committee",
"guidelines",
"for",
"Family",
"Medicine",
"require",
"teaching",
"the",
"skills",
"necessary",
"for",
"the",
"critical",
"appraisal",
"of",
"the",
"medical",
"literature.",
"Most",
"residen-",
"cy",
"training",
"programs",
"accomplish",
"this",
"in",
"the",
"setting",
"of",
"a",
"monthly",
"journal",
"club.",
"At",
"our",
"program,",
"faculty",
"involved",
"with",
"organizing",
"these",
"sessions",
"noted",
"an",
"ongoing",
"frustra-",
"tion",
"with",
"the",
"attendance,",
"preparation,",
"participation",
"and",
"focus",
"of",
"the",
"residents.",
"utility",
"of",
"the",
"Journal",
"Club.",
"This",
"opportunity",
"to",
"reorgan-",
"ize",
"also",
"allowed",
"reexamination",
"of",
"the",
"goals",
"and",
"objec-",
"tives",
"for",
"the",
"Journal",
"Club",
"in",
"line",
"with",
"those",
"suggested",
"by",
"others",
"[1].",
"A",
"formal",
"curriculum",
"review",
"with",
"new",
"goals",
"and",
"objectives",
"was",
"put",
"in",
"place,",
"acknowledged",
"by",
"renam-",
"ing",
"the",
"sessions",
"as",
"\"Evidence",
"Based",
"Medicine",
"/Journal",
"Club\".",
"Paramount",
"was",
"a",
"focus",
"on",
"critical",
"appraisal",
"and",
"clinical",
"epidemiology",
"from",
"the",
"Evidence-based",
"perspec-",
"tive.",
"Within",
"the",
"framework",
"of",
"a",
"needs",
"assessment,",
"residents",
"were",
"surveyed",
"to",
"identify",
"issues",
"directly",
"related",
"to",
"the",
"A",
"syllabus",
"of",
"material",
"on",
"the",
"approach",
"to",
"Evidence-",
"based",
"Medicine",
"was",
"chosen",
"to",
"provide",
"the",
"skills",
"neces-"
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] | [
"Mostafa",
"and",
"AL-Ayadhi",
"Journal",
"of",
"Neuroinflammation",
"2011,",
"8:71",
"http://www.jneuroinflammation.com/content/8/1/71",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"JOURNAL",
"OF",
"NEUROINFLAMMATION",
"Open",
"Access",
"A",
"lack",
"of",
"association",
"between",
"hyperserotonemia",
"and",
"the",
"increased",
"frequency",
"of",
"serum",
"anti-myelin",
"basic",
"protein",
"auto-antibodies",
"in",
"autistic",
"children",
"Gehan",
"Ahmed",
"Mostafa1,2*",
"and",
"Laila",
"Yousef",
"AL-Ayadhi1",
"Abstract",
"Background:",
"One",
"of",
"the",
"most",
"consistent",
"biological",
"findings",
"in",
"autism",
"is",
"the",
"elevated",
"blood",
"serotonin",
"levels.",
"Immune",
"abnormalities,",
"including",
"autoimmunity",
"with",
"production",
"of",
"brain",
"specific",
"auto-antibodies,",
"are",
"also",
"commonly",
"observed",
"in",
"this",
"disorder.",
"Hyperserotonemia",
"may",
"be",
"one",
"of",
"the",
"contributing",
"factors",
"to",
"autoimmunity",
"in",
"some",
"patients",
"with",
"autism",
"through",
"the",
"reduction",
"of",
"T-helper",
"(Th)",
"1-type",
"cytokines.",
"We",
"are",
"the",
"first",
"to",
"investigate",
"the",
"possible",
"role",
"of",
"hyperserotonemia",
"in",
"the",
"induction",
"of",
"autoimmunity,",
"as",
"indicated",
"by",
"serum",
"anti-myelin-basic",
"protein",
"(anti-MBP)",
"auto-antibodies,",
"in",
"autism.",
"Methods:",
"Serum",
"levels",
"of",
"serotonin",
"and",
"anti-MBP",
"auto-antibodies",
"were",
"measured,",
"by",
"ELISA,",
"in",
"50",
"autistic",
"patients,",
"aged",
"between",
"5",
"and",
"12",
"years,",
"and",
"30",
"healthy-matched",
"children.",
"Results:",
"Autistic",
"children",
"had",
"significantly",
"higher",
"serum",
"levels",
"of",
"serotonin",
"and",
"anti-MBP",
"auto-antibodies",
"than",
"healthy",
"children",
"(P",
"<",
"0.001",
"and",
"P",
"<",
"0.001,",
"respectively).",
"Increased",
"serum",
"levels",
"of",
"serotonin",
"and",
"anti-MBP",
"auto-",
"antibodies",
"were",
"found",
"in",
"92%",
"and",
"80%,",
"respectively",
"of",
"autistic",
"patients.",
"Patients",
"with",
"severe",
"autism",
"had",
"significantly",
"higher",
"serum",
"serotonin",
"levels",
"than",
"children",
"with",
"mild",
"to",
"moderate",
"autism",
"(P",
"<",
"0.001).",
"Serum",
"serotonin",
"levels",
"had",
"no",
"significant",
"correlations",
"with",
"serum",
"levels",
"of",
"anti-MBP",
"auto-antibodies",
"in",
"autistic",
"patients",
"(P",
"=",
"0.39).",
"Conclusions:",
"Hyperserotonemia",
"may",
"not",
"be",
"one",
"of",
"the",
"contributing",
"factors",
"to",
"the",
"increased",
"frequency",
"of",
"serum",
"anti-MBP",
"auto-antibodies",
"in",
"some",
"autistic",
"children.",
"These",
"data",
"should",
"be",
"treated",
"with",
"caution",
"until",
"further",
"investigations",
"are",
"performed.",
"However,",
"inclusion",
"of",
"serum",
"serotonin",
"levels",
"as",
"a",
"correlate",
"may",
"be",
"useful",
"in",
"other",
"future",
"immune",
"studies",
"in",
"autism",
"to",
"help",
"unravel",
"the",
"long-standing",
"mystery",
"of",
"hyperserotonemia",
"and",
"its",
"possible",
"role",
"in",
"the",
"pathophysiology",
"of",
"this",
"disorder.",
"Keywords:",
"Anti-myelin-basic",
"protein",
"antibodies,",
"autism,",
"autoimmunity,",
"hyperserotonemia,",
"serotonin",
"1.",
"Introduction",
"Autoimmunity",
"to",
"CNS",
"may",
"have",
"a",
"pathogenic",
"role",
"in",
"autism",
"[1].",
"This",
"may",
"be",
"indicated",
"by",
"the",
"presence",
"of",
"brain-specific",
"auto-antibodies",
"in",
"some",
"autistic",
"children",
"[2-8].",
"There",
"is",
"also",
"an",
"increase",
"in",
"the",
"frequency",
"of",
"auto-",
"immune",
"disorders",
"among",
"autistic",
"families",
"[9-15].",
"Serotonin",
"is",
"formed",
"by",
"hydroxylation",
"and",
"decarboxy-",
"lation",
"of",
"tryptophan.",
"Serotonin",
"is",
"known",
"to",
"play",
"a",
"role",
"*",
"Correspondence:",
"hafezg@softhome.net",
"1Autism",
"Research",
"and",
"Treatment",
"Center,",
"AL-Amodi",
"Autism",
"Research",
"Chair,",
"Department",
"of",
"Physiology,",
"Faculty",
"of",
"Medicine,",
"King",
"Saud",
"University,",
"Riyadh,",
"Saudi",
"Arabia",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"in",
"brain",
"development",
"prior",
"to",
"the",
"time",
"it",
"assumes",
"its",
"role",
"as",
"a",
"neurotransmitter.",
"Disruption",
"of",
"serotonergic",
"development",
"can",
"leave",
"permanent",
"alterations",
"in",
"brain",
"function",
"and",
"behavior.",
"This",
"may",
"be",
"the",
"case",
"in",
"autism",
"[16,17].",
"It",
"was",
"suggested",
"that",
"autism,",
"without",
"a",
"discern-",
"ible",
"cause,",
"may",
"be",
"a",
"genetic",
"disorder",
"of",
"serotonin",
"meta-",
"bolism.",
"The",
"interest",
"in",
"assessing",
"serotonergic",
"function",
"in",
"autism",
"stems",
"from",
"its",
"role",
"in",
"perception",
"and",
"filtering",
"of",
"sensory",
"signals,",
"social",
"attachment",
"and",
"facilitation",
"of",
"formation",
"of",
"synapses",
"which",
"is",
"crucial",
"to",
"acquire",
"learn-",
"ing",
"and",
"memory",
"[18].",
"Blood",
"serotonin",
"might",
"serve",
"as",
"analogue",
"marker",
"for",
"serotonergic",
"function",
"[19].",
"©",
"2011",
"Mostafa",
"and",
"AL-Ayadhi;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
] | [
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"Lausanne,",
"Switzerland",
"Correspondence:Aubin",
"Balmer",
"Privat-Docent,",
"Maître",
"d’enseignement",
"et",
"de",
"Recherche,",
"Hôpital",
"Ophtalmique",
"Jules",
"Gonin,",
"15,Avenue",
"de",
"France,",
"1004",
"Lausanne,",
"Switzerland",
"Tel",
"+41",
"27",
"323",
"22",
"12",
"Fax",
"+41",
"27",
"323",
"22",
"18",
"Email",
"aubin.balmer@bluewin.ch",
"Abstract:",
"Leukocoria",
"in",
"infants",
"is",
"always",
"a",
"danger",
"signal",
"as",
"retinoblastoma,",
"a",
"malignant",
"retinal",
"tumor,",
"is",
"responsible",
"for",
"half",
"of",
"the",
"cases",
"in",
"this",
"age",
"group.",
"More",
"common",
"signs",
"should",
"also",
"be",
"considered",
"suspicious",
"until",
"proved",
"otherwise,",
"such",
"as",
"strabismus,",
"the",
"second",
"most",
"frequent",
"sign",
"of",
"retinoblastoma.",
"Less",
"frequent",
"manifestations",
"are",
"inflammatory",
"conditions",
"resistant",
"to",
"treatment,",
"hypopyon,",
"orbital",
"cellulitis,",
"hyphema",
"or",
"heterochromia.",
"Other",
"causal",
"pathologies,",
"including",
"persistent",
"hyperplastic",
"primary",
"vitreous",
"(PHPV),",
"Coats’",
"disease,",
"ocular",
"toxocariasis",
"or",
"retinopathy",
"of",
"prematurity,",
"may",
"also",
"manifest",
"the",
"same",
"warning",
"signs",
"and",
"require",
"special-",
"ized",
"differential",
"diagnosis.",
"Members",
"of",
"the",
"immediate",
"family",
"circle",
"are",
"most",
"likely",
"to",
"notice",
"the",
"first",
"signs,",
"the",
"general",
"practitioner,",
"pediatrician",
"or",
"general",
"ophthalmologist",
"the",
"first",
"to",
"be",
"consulted.",
"On",
"their",
"attitude",
"will",
"depend",
"the",
"final",
"outcome",
"of",
"this",
"vision",
"and",
"life-threatening",
"disease.",
"Early",
"diagnosis",
"is",
"vital.",
"Keywords:",
"leukocoria,",
"strabismus,",
"retinoblastoma,",
"Coats’",
"disease,",
"persistent",
"hyperplastic",
"primary",
"vitreous",
"(PHPV)",
"Introduction",
"Retinoblastoma",
"represents",
"the",
"greatest",
"challenge",
"in",
"the",
"field",
"of",
"ophthalmology.",
"Affecting",
"very",
"young",
"infants,",
"in",
"most",
"cases",
"perfectly",
"healthy",
"in",
"all",
"other",
"respects,",
"this",
"highly",
"malignant",
"cancer",
"of",
"the",
"retina",
"threatens",
"those",
"individuals",
"with",
"the",
"longest",
"potential",
"lifespan.",
"Survivors",
"may",
"be",
"severely",
"handicapped",
"by",
"lesions",
"of",
"the",
"posterior",
"pole",
"affecting",
"central",
"visual",
"function.",
"These",
"children",
"can",
"be",
"cured,",
"however,",
"at",
"low",
"cost",
"and",
"with",
"minimal",
"suffering,",
"provided",
"that",
"treatment",
"is",
"given",
"in",
"the",
"early",
"stages",
"of",
"disease.",
"At",
"later",
"stages",
"treatment",
"is",
"costly,",
"burdensome,",
"and",
"with",
"no",
"certain",
"outcome.",
"Retinoblastoma",
"is",
"fortunately",
"a",
"rare",
"disease,",
"but",
"other",
"intraocular",
"lesions",
"may",
"mimic",
"the",
"initial",
"signs",
"or",
"clinical",
"features",
"and",
"are",
"sometimes",
"called",
"“pseudo-retinoblastomas”",
"(Dollfus",
"and",
"Auvert",
"1953).",
"Retinoblastoma",
"does,",
"however,",
"represent",
"80%",
"of",
"primary",
"ocular",
"tumors",
"in",
"children",
"under",
"15",
"years",
"of",
"age",
"(Mahoney",
"et",
"al",
"1990)",
"17%",
"of",
"all",
"neonatal",
"cancers",
"(Halperin",
"2000)",
"and",
"1%",
"of",
"all",
"deaths",
"due",
"to",
"cancer",
"(Miller",
"1969).",
"All",
"ages",
"considered,",
"it",
"is",
"the",
"third",
"most",
"frequent",
"cancer",
"of",
"the",
"eye",
"and",
"ocular",
"adnexa",
"(20%)",
"and",
"represents",
"3%",
"of",
"all",
"pediatric",
"cancers",
"(Scat",
"et",
"al",
"1996).",
"Thus",
"the",
"importance",
"of",
"keeping",
"in",
"mind",
"the",
"possibility",
"of",
"retinoblastoma",
"when",
"confronted",
"with",
"suspicious",
"signs",
"such",
"as",
"a",
"white",
"pupil",
"or",
"leukocoria",
"(Figure1a),",
"the",
"most",
"common",
"first",
"manifestation,",
"strabismus",
"or",
"any",
"other",
"unexplained",
"signs.",
"In",
"this",
"article,",
"other",
"conditions",
"to",
"take",
"into",
"consideration",
"in",
"the",
"differential",
"diagnosis",
"of",
"leukocoria",
"or",
"other",
"signs",
"associated",
"with",
"retinoblastoma",
"will",
"be",
"reviewed.",
"Clinical",
"Ophthalmology",
"2007:1(4)",
"431–439",
"©",
"2007",
"Dove",
"Medical",
"Press",
"Limited.",
"All",
"rights",
"reserved",
"431"
] | [
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] | [
"Psychopharmacology",
"(2011)",
"215:321–332",
"DOI",
"10.1007/s00213-010-2149-4",
"ORIGINAL",
"INVESTIGATION",
"Residual",
"effects",
"of",
"esmirtazapine",
"on",
"actual",
"driving",
"performance:",
"overall",
"findings",
"and",
"an",
"exploratory",
"analysis",
"into",
"the",
"role",
"of",
"CYP2D6",
"phenotype",
"Johannes",
"G.",
"Ramaekers",
"&",
"Silke",
"Conen",
"&",
"Pieter",
"Jan",
"de",
"Kam",
"&",
"Sabine",
"Braat",
"&",
"Pierre",
"Peeters",
"&",
"Eef",
"L.",
"Theunissen",
"&",
"Neely",
"Ivgy-may",
"Received:",
"25",
"October",
"2010",
"/",
"Accepted:",
"8",
"December",
"2010",
"/",
"Published",
"online:",
"19",
"January",
"2011",
"#",
"The",
"Author(s)",
"2011.",
"This",
"article",
"is",
"published",
"with",
"open",
"access",
"at",
"Springerlink.com",
"Abstract",
"Introduction",
"Esmirtazapine",
"is",
"evaluated",
"as",
"a",
"novel",
"drug",
"for",
"treatment",
"of",
"insomnia.",
"Purpose",
"The",
"present",
"study",
"was",
"designed",
"to",
"assess",
"residual",
"effects",
"of",
"single",
"and",
"repeated",
"doses",
"of",
"esmirtazapine",
"1.5",
"and",
"4.5",
"mg",
"on",
"actual",
"driving",
"in",
"32",
"healthy",
"volunteers",
"in",
"a",
"double-",
"blind,",
"placebo-controlled",
"study.",
"Treatment",
"with",
"single",
"doses",
"of",
"zopiclone",
"7.5",
"mg",
"was",
"included",
"as",
"active",
"control.",
"Methods",
"Treatments",
"were",
"administered",
"in",
"the",
"evening.",
"Driv-",
"ing",
"performance",
"was",
"assessed",
"in",
"the",
"morning,",
"11",
"h",
"after",
"drug",
"intake,",
"in",
"a",
"standardized",
"on-the-road",
"highway",
"driving",
"test.",
"The",
"primary",
"study",
"parameter",
"was",
"standard",
"deviation",
"of",
"lateral",
"position",
"(SDLP),",
"a",
"measure",
"of",
"“weaving”.",
"All",
"subjects",
"were",
"subjected",
"to",
"CYP2D6",
"phenotyping",
"in",
"order",
"to",
"distinguish",
"poor",
"metabolizers",
"from",
"extensive",
"metabolizers",
"of",
"esmirtazapine.",
"Results",
"Overall,",
"esmirtazapine",
"1.5",
"mg",
"did",
"not",
"produce",
"any",
"clinically",
"relevant",
"change",
"in",
"SDLP",
"after",
"single",
"and",
"repeated",
"dosing.",
"Driving",
"impairment,",
"i.e.,",
"a",
"rise",
"in",
"SDLP,",
"did",
"occur",
"after",
"a",
"single-dose",
"administration",
"of",
"esmirtazapine",
"4.5",
"mg",
"but",
"was",
"resolved",
"after",
"repeated",
"doses.",
"Acute",
"driving",
"impairment",
"was",
"more",
"pronounced",
"after",
"both",
"doses",
"of",
"esmirtazapine",
"in",
"a",
"This",
"trial",
"has",
"been",
"registered",
"at",
"ClinicalTrials.gov",
"as",
"NCT00798395",
"http://",
"www.clinicaltrials.gov/ct2/show/NCT00798395?term=21105&rank=1",
"J.",
"G.",
"Ramaekers",
"(*)",
":",
"S.",
"Conen",
":",
"E.",
"L.",
"Theunissen",
"Department",
"of",
"Neuropsychology",
"and",
"Psychopharmacology,",
"Faculty",
"of",
"Psychology",
"and",
"Neuroscience,",
"Maastricht",
"University,",
"Maastricht,",
"The",
"Netherlands",
"e-mail:",
"j.ramaekers@maastrichtuniversity.nl",
"P.",
"J.",
"de",
"Kam",
":",
"S.",
"Braat",
":",
"P.",
"Peeters",
"MSD,",
"Oss,",
"The",
"Netherlands",
"N.",
"Ivgy-may",
"Merck",
"&",
"Co.,",
"Summit,",
"NJ,",
"USA",
"select",
"group",
"of",
"poor",
"metabolizers",
"(N",
"=",
"7).",
"A",
"single-dose",
"zopiclone",
"7.5",
"mg",
"also",
"increased",
"SDLP",
"as",
"expected.",
"Conclusion",
"It",
"is",
"concluded",
"that",
"single",
"and",
"repeated",
"doses",
"of",
"1.5",
"mg",
"esmirtazapine",
"are",
"generally",
"not",
"associated",
"with",
"residual",
"impairment.",
"Single-dose",
"administration",
"of",
"4.5",
"mg",
"esmirtazapine",
"was",
"associated",
"with",
"residual",
"impairment",
"that",
"generally",
"resolved",
"after",
"repeated",
"administration.",
"Explorato-",
"ry",
"analysis",
"in",
"a",
"small",
"group",
"of",
"poor",
"CYP",
"2D6",
"metabolizers",
"suggested",
"that",
"these",
"subjects",
"are",
"more",
"sensitive",
"to",
"the",
"impairing",
"effects",
"of",
"esmirtazapine",
"on",
"car",
"driving.",
"Keywords",
"Hypnotics",
".",
"H1",
"antagonism",
".",
"Driving",
".",
"Cognition",
".",
"CYP2D6",
"phenotype",
"Introduction",
"Esmirtazapine",
"maleate",
"(Org",
"50081)",
"is",
"the",
"maleate",
"salt",
"of",
"the",
"S(+)-enantiomer",
"of",
"the",
"racemic",
"drug",
"mirtazapine.",
"Racemic",
"mirtazapine",
"is",
"marketed",
"for",
"the",
"treatment",
"of",
"major",
"depressive",
"disorder.",
"Mirtazapine",
"is",
"a",
"close",
"analog",
"of",
"its",
"predecessor",
"mianserin",
"that",
"also",
"has",
"been",
"marketed",
"for",
"major",
"depressive",
"disorder.",
"Esmirtazapine",
"and",
"mirtazapine",
"bind",
"to",
"presynaptic",
"α2",
"receptors",
"as",
"well",
"as",
"to",
"postsynaptic",
"5HT2",
"and",
"H1",
"receptors",
"where",
"they",
"act",
"as",
"antagonists",
"of",
"the",
"endogeneous",
"ligands",
"(de",
"Boer",
"and",
"Ruigt",
"1995b;",
"Pinder",
"and",
"van",
"Delft",
"1983);",
"however,",
"compared",
"with",
"mirtazapine",
"and",
"R-mirtazapine,",
"esmirtazapine",
"has",
"higher",
"affinity",
"to",
"5-HT2",
"receptors",
"and",
"low",
"affinity",
"to",
"the",
"5-HT3",
"receptors",
"and",
"to",
"the",
"muscarinic",
"receptors",
"(de",
"Boer",
"et",
"al.",
"1988;",
"Kooyman",
"et",
"al.",
"1994).",
"Esmirtazapine",
"is",
"under",
"development",
"for",
"the",
"treat-",
"ment",
"of",
"primary",
"insomnia",
"and",
"hot",
"flushes.",
"Antidepressants",
"such",
"as",
"mirtazapine",
"and",
"mianserin",
"are",
"well",
"known",
"for",
"their",
"sedative",
"properties",
"(Biswas",
"et",
"al."
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] | [
"Roebke",
"et",
"al.",
"Retrovirology",
"2010,",
"7:69",
"http://www.retrovirology.com/content/7/1/69",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"Open",
"Access",
"An",
"N-terminally",
"truncated",
"envelope",
"protein",
"encoded",
"by",
"a",
"human",
"endogenous",
"retrovirus",
"W",
"locus",
"on",
"chromosome",
"Xq22.3",
"Christina",
"Roebke1†,",
"Silke",
"Wahl1†,",
"Georg",
"Laufer1,",
"Christine",
"Stadelmann2,",
"Marlies",
"Sauter1,",
"Nikolaus",
"Mueller-Lantzsch1,",
"Jens",
"Mayer3,",
"Klemens",
"Ruprecht1,4*",
"Abstract",
"Background:",
"We",
"previously",
"showed",
"that",
"the",
"envelope",
"(env)",
"sequence",
"of",
"a",
"human",
"endogenous",
"retrovirus",
"(HERV)-",
"W",
"locus",
"on",
"chromosome",
"Xq22.3",
"is",
"transcribed",
"in",
"human",
"peripheral",
"blood",
"mononuclear",
"cells.",
"The",
"env",
"open",
"reading",
"frame",
"(ORF)",
"of",
"this",
"locus",
"is",
"interrupted",
"by",
"a",
"premature",
"stop",
"at",
"codon",
"39,",
"but",
"otherwise",
"harbors",
"a",
"long",
"ORF",
"for",
"an",
"N-terminally",
"truncated",
"475",
"amino",
"acid",
"Env",
"protein,",
"starting",
"at",
"an",
"in-frame",
"ATG",
"at",
"codon",
"68.",
"We",
"set",
"out",
"to",
"characterize",
"the",
"protein",
"encoded",
"by",
"that",
"ORF.",
"Results:",
"Transient",
"expression",
"of",
"the",
"475",
"amino",
"acid",
"Xq22.3",
"HERV-W",
"env",
"ORF",
"produced",
"an",
"N-terminally",
"truncated",
"HERV-W",
"Env",
"protein,",
"as",
"detected",
"by",
"the",
"monoclonal",
"anti-HERV-W",
"Env",
"antibodies",
"6A2B2",
"and",
"13H5A5.",
"Remarkably,",
"reversion",
"of",
"the",
"stop",
"at",
"codon",
"39",
"in",
"Xq22.3",
"HERV-W",
"env",
"reconstituted",
"a",
"full-length",
"HERV-W",
"Xq22.3",
"Env",
"protein.",
"Similar",
"to",
"the",
"full-length",
"HERV-W",
"Env",
"protein",
"Syncytin-1,",
"reconstituted",
"full-length",
"Xq22.3",
"HERV-W",
"Env",
"is",
"glycosylated,",
"forms",
"oligomers,",
"and",
"is",
"expressed",
"at",
"the",
"cell",
"surface.",
"In",
"contrast,",
"Xq22.3",
"HERV-W",
"Env",
"is",
"unglycosylated,",
"does",
"not",
"form",
"oligomers,",
"and",
"is",
"located",
"intracellularly,",
"probably",
"due",
"to",
"lack",
"of",
"a",
"signal",
"peptide.",
"Finally,",
"we",
"reconfirm",
"by",
"immunohistochemistry",
"that",
"monoclonal",
"antibody",
"6A2B2",
"detects",
"an",
"antigen",
"expressed",
"in",
"placenta",
"and",
"multiple",
"sclerosis",
"brain",
"lesions.",
"Conclusions:",
"A",
"partially",
"defective",
"HERV-W",
"env",
"gene",
"located",
"on",
"chromosome",
"Xq22.3,",
"which",
"we",
"propose",
"to",
"designate",
"ERVWE2,",
"has",
"retained",
"coding",
"capacity",
"and",
"can",
"produce",
"ex",
"vivo",
"an",
"N-terminally",
"truncated",
"Env",
"protein,",
"named",
"N-Trenv.",
"Detection",
"of",
"an",
"antigen",
"by",
"6A2B2",
"in",
"placenta",
"and",
"multiple",
"sclerosis",
"lesions",
"opens",
"the",
"possibility",
"that",
"N-Trenv",
"could",
"be",
"expressed",
"in",
"vivo.",
"More",
"generally,",
"our",
"findings",
"are",
"compatible",
"with",
"the",
"idea",
"that",
"defective",
"HERV",
"elements",
"may",
"be",
"capable",
"of",
"producing",
"incomplete",
"HERV",
"proteins",
"that,",
"speculatively,",
"may",
"exert",
"functions",
"in",
"human",
"physiology",
"or",
"pathology.",
"Background",
"Multiple",
"sclerosis",
"(MS)",
"is",
"a",
"chronic",
"inflammatory",
"demyelinating",
"disease",
"of",
"the",
"central",
"nervous",
"system",
"affecting",
"primarily",
"young",
"adults.",
"While",
"its",
"precise",
"aetiol-",
"ogy",
"is",
"unknown,",
"MS",
"is",
"thought",
"to",
"be",
"a",
"multifactorial",
"disorder",
"resulting",
"from",
"the",
"interaction",
"of",
"environmental",
"and",
"genetic",
"factors",
"[1].",
"A",
"multiple",
"sclerosis-associated",
"retrovirus",
"(MSRV)",
"has",
"previously",
"been",
"suggested",
"by",
"cDNA",
"clones",
"that",
"were",
"generated",
"from",
"particle-",
"*",
"Correspondence:",
"klemens.ruprecht@charite.de",
"†",
"Contributed",
"equally",
"1Institut",
"für",
"Virologie,",
"Gebäude",
"47,",
"Universitätsklinikum",
"des",
"Saarlandes,",
"66421",
"Homburg,",
"Germany",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"associated",
"RNA",
"from",
"plasma",
"or",
"supernatants",
"of",
"cul-",
"tured",
"cells",
"from",
"patients",
"with",
"MS",
"[2-4].",
"Subsequent",
"investigations",
"revealed",
"MSRV-related",
"sequences",
"in",
"the",
"human",
"genome,",
"the",
"human",
"endogenous",
"retrovirus",
"family",
"type",
"W",
"(HERV-W)",
"[5].",
"HERVs",
"are",
"considered",
"remnants",
"of",
"ancestral",
"germ",
"line",
"infections",
"by",
"once",
"active",
"retroviruses",
"and",
"contribute",
"approximately",
"8%",
"of",
"the",
"human",
"genome",
"(for",
"review",
"see",
"[6,7]).",
"Like",
"their",
"exogenous",
"counterparts,",
"HERVs",
"typi-",
"cally",
"consist",
"of",
"an",
"internal",
"region",
"containing",
"gag,",
"pro,",
"pol,",
"and",
"env",
"genes,",
"flanked",
"by",
"two",
"long",
"terminal",
"repeats",
"(LTR).",
"The",
"number",
"and",
"phylogenetic",
"relationships",
"among",
"HERV-W",
"sequences",
"in",
"the",
"human",
"genome",
"have",
"been",
"addressed",
"before",
"[8,9].",
"HERV-W",
"is",
"a",
"multicopy",
"©",
"2010",
"Roebke",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
] | [
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] | [
"Keikhaei",
"and",
"Soltani",
"Shirazi",
"Journal",
"of",
"Medical",
"Case",
"Reports",
"2011,",
"5:274",
"http://www.jmedicalcasereports.com/content/5/1/274",
"C",
"A",
"S",
"E",
"R",
"E",
"P",
"O",
"R",
"T",
"JOURNAL",
"OF",
"MEDICAL",
"CASE",
"REPORTS",
"Open",
"Access",
"Spontaneous",
"iliopsoas",
"muscle",
"hematoma",
"in",
"a",
"patient",
"with",
"von",
"Willebrand",
"disease:",
"a",
"case",
"report",
"Bijan",
"Keikhaei1*",
"and",
"Ahmad",
"Soltani",
"Shirazi2",
"Abstract",
"Introduction:",
"Iliopsoas",
"hemorrhage",
"is",
"a",
"serious",
"complication",
"of",
"bleeding",
"disorders",
"that",
"occurs",
"most",
"commonly",
"in",
"patients",
"with",
"hemophilia",
"and",
"less",
"commonly",
"in",
"patients",
"with",
"von",
"Willebrand",
"disease.",
"It",
"causes",
"severe",
"pain,",
"muscle",
"dysfunction",
"and",
"occasionally",
"femoral",
"nerve",
"palsy.",
"We",
"describe",
"the",
"case",
"of",
"a",
"patient",
"with",
"von",
"Willebrand",
"disease",
"type",
"3",
"with",
"a",
"large",
"iliopsoas",
"hematoma",
"who",
"was",
"treated",
"with",
"a",
"von",
"Willebrand",
"factor",
"concentrate",
"(Humate-P).",
"Case",
"presentation:",
"A",
"20-year-old",
"Iranian",
"man",
"was",
"referred",
"to",
"our",
"emergency",
"ward",
"because",
"of",
"the",
"gradual",
"onset",
"of",
"right",
"flank",
"pain.",
"He",
"was",
"known",
"to",
"have",
"been",
"diagnosed",
"with",
"von",
"Willebrand",
"disease",
"type",
"3",
"at",
"age",
"two",
"years",
"old.",
"Magnetic",
"resonance",
"imaging",
"showed",
"a",
"mass",
"in",
"the",
"right",
"iliopsoas",
"muscle.",
"The",
"diagnosis",
"of",
"iliopsoas",
"hemorrhage",
"and",
"partial",
"femoral",
"nerve",
"palsy",
"was",
"established,",
"and",
"he",
"responded",
"to",
"medical",
"treatment.",
"Conclusion:",
"We",
"report",
"a",
"case",
"of",
"von",
"Willebrand",
"disease",
"type",
"3",
"with",
"spontaneous",
"iliopsoas",
"hematoma",
"associated",
"with",
"femoral",
"nerve",
"palsy",
"that",
"was",
"well",
"managed",
"with",
"Humate-P",
"treatment.",
"Introduction",
"Von",
"Willebrand",
"disease",
"(vWD)",
"is",
"a",
"hereditary",
"bleeding",
"disorder",
"caused",
"by",
"a",
"quantitative",
"or",
"qualitative",
"defect",
"of",
"von",
"Willebrand",
"factor.",
"The",
"prevalence",
"of",
"this",
"disease",
"is",
"estimated",
"to",
"be",
"1%",
"to",
"2%",
"of",
"the",
"general",
"population.",
"Von",
"Willebrand",
"factor",
"is",
"a",
"coagulation",
"factor",
"for",
"initial",
"stages",
"of",
"blood",
"clotting",
"and",
"is",
"also",
"a",
"carrier",
"for",
"factor",
"VIII.",
"Patients",
"with",
"vWD",
"develop",
"coagulation",
"platelet",
"plugs",
"and",
"red",
"coagulation",
"clots",
"are",
"unable",
"to",
"form.",
"vWD",
"consists",
"of",
"a",
"broad",
"variation",
"of",
"clinical",
"manifesta-",
"tions,",
"with",
"one",
"extreme",
"being",
"a",
"minimal",
"bleeding",
"ten-",
"dency",
"and",
"the",
"other",
"being",
"a",
"severe",
"presentation",
"such",
"as",
"severe",
"hemophilia",
"A.",
"Luckily,",
"most",
"of",
"these",
"patients",
"present",
"with",
"mild",
"to",
"moderate",
"clinical",
"symptoms.",
"The",
"severe",
"type",
"of",
"the",
"vWD,",
"type",
"3,",
"occurs",
"in",
"less",
"than",
"5%",
"of",
"patients.",
"The",
"inheritance",
"pattern",
"of",
"this",
"type",
"is",
"usually",
"autosomal",
"recessive.",
"Patients",
"with",
"vWD",
"usually",
"show",
"clinical",
"features",
"such",
"as",
"recurrent",
"nosebleeds,",
"easy",
"bruising,",
"bleeding",
"post-tooth",
"extraction,",
"post-",
"*",
"Correspondence:",
"keikhaeib@yahoo.com",
"1Department",
"of",
"Thalassemia",
"&",
"Hemoglobinopathy",
"Research",
"Center,",
"Ahvaz",
"Jundishapur",
"University",
"of",
"Medical",
"Science,",
"Shafa",
"Hospital",
"(Golestan",
"Area),",
"Ahvaz",
"61357-33119,",
"Iran",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"tonsillectomy",
"or",
"other",
"surgical",
"bleeding,",
"and",
"excessive",
"menstrual",
"bleeding.",
"Musculoskeletal",
"hemorrhage",
"occurs",
"commonly",
"in",
"vWD",
"type",
"3-like",
"hemophilia",
"A.",
"Iliopsoas",
"hemorrhage",
"is",
"a",
"potentially",
"serious",
"complication",
"because",
"a",
"delay",
"in",
"beginning",
"treatment",
"may",
"result",
"in",
"permanent",
"femoral",
"nerve",
"palsy",
"[1].",
"The",
"present",
"case",
"report",
"describes",
"a",
"man",
"with",
"vWD",
"type",
"3",
"who",
"had",
"a",
"spontaneous",
"iliopsoas",
"hematoma",
"that",
"responded",
"well",
"to",
"Humate-P",
"treatment",
"(CSL",
"Behring,",
"King",
"of",
"Prussia,",
"PA,",
"USA)",
"[2].",
"Case",
"presentation",
"A",
"20-year-old",
"Iranian",
"man",
"came",
"to",
"our",
"hospital",
"because",
"of",
"the",
"gradual",
"onset",
"of",
"right",
"flank",
"pain.",
"He",
"was",
"known",
"to",
"have",
"had",
"vWD",
"type",
"3",
"since",
"he",
"was",
"two",
"years",
"old.",
"His",
"laboratory",
"findings",
"were",
"as",
"follows:",
"B-positive",
"blood",
"type,",
"partial",
"thromboplastin",
"time",
"56",
"seconds,",
"bleeding",
"time",
"more",
"than",
"12",
"minutes,",
"hemoglobin",
"10",
"g/dL,",
"mean",
"corpus-",
"cular",
"volume",
"75",
"fL,",
"mean",
"corpuscular",
"hemoglobin",
"24",
"pg/",
"red",
"blood",
"cell,",
"factor",
"VIIIc",
"activity",
"3%,",
"vWF",
"antigen",
"level",
"was",
"undetectable,",
"and",
"vWF",
"ristocetin",
"cofactor",
"activity",
"was",
"undetectable.",
"He",
"had",
"experienced",
"some",
"occasional",
"hemar-",
"throsis,",
"but",
"he",
"had",
"been",
"well",
"for",
"two",
"months",
"before",
"he",
"presented",
"to",
"our",
"hospital.",
"He",
"had",
"no",
"history",
"of",
"trauma.",
"©",
"2011",
"Keikhaei",
"and",
"Shirazi;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Human",
"Reproduction",
"Update,",
"Vol.14,",
"No.4",
"pp.",
"379–390,",
"2008",
"Advance",
"Access",
"publication",
"June",
"4,",
"2008",
"Cytogenetic",
"determinants",
"of",
"male",
"fertility",
"doi:10.1093/humupd/dmn017",
"R.H.",
"Martin1",
"1E-mail:",
"rhmartin@ucalgary.ca",
"Department",
"of",
"Medical",
"Genetics,",
"University",
"of",
"Calgary,",
"Room",
"287,",
"Heritage",
"Medical",
"Research",
"Building,",
"3330",
"Hospital",
"Drive",
"NW,",
"Calgary,",
"Alberta,",
"Canada",
"T2N",
"4N1",
"BACKGROUND:",
"Cytogenetic",
"abnormalities",
"have",
"been",
"known",
"to",
"be",
"important",
"causes",
"of",
"male",
"infertility",
"for",
"decades.",
"METHODS:",
"Research",
"publications",
"from",
"1978",
"to",
"2008,",
"from",
"PubMed,",
"have",
"been",
"reviewed.",
"RESULTS:",
"These",
"studies",
"have",
"greatly",
"improved",
"our",
"information",
"on",
"somatic",
"chromosomal",
"abnormalities",
"such",
"as",
"translocations,",
"inversions",
"and",
"sex",
"chromosomal",
"anomalies,",
"and",
"their",
"consequences",
"to",
"the",
"cytogenetic",
"make-up",
"of",
"human",
"sperm.",
"Also,",
"we",
"have",
"learned",
"that",
"infertile",
"men",
"with",
"a",
"normal",
"somatic",
"karyotype",
"have",
"an",
"increased",
"risk",
"of",
"chromosomally",
"abnormal",
"sperm",
"and",
"children.",
"New",
"techniques",
"such",
"as",
"single",
"sperm",
"typing",
"and",
"synaptonemal",
"complex",
"analysis",
"have",
"provided",
"valuable",
"insight",
"into",
"the",
"association",
"between",
"meiotic",
"recombination",
"and",
"the",
"production",
"of",
"aneuploid",
"sperm.",
"These",
"meiotic",
"studies",
"have",
"also",
"unveiled",
"errors",
"of",
"chromosome",
"pairing",
"and",
"synapsis,",
"which",
"are",
"more",
"common",
"in",
"infertile",
"men.",
"CONCLUSIONS:",
"These",
"studies",
"allow",
"us",
"to",
"provide",
"more",
"precise",
"information",
"to",
"infertile",
"patients,",
"and",
"further",
"our",
"basic",
"knowledge",
"in",
"the",
"causes",
"of",
"male",
"infertility.",
"Keywords:",
"male",
"infertility;",
"meiosis;",
"sperm",
"aneuploidy;",
"sperm",
"chromosome",
"abnormalities",
"Introduction",
"Infertility",
"is",
"a",
"significant",
"problem,",
"affecting",
"up",
"to",
"15%",
"of",
"couples",
"of",
"reproductive",
"age",
"(de",
"Kretser,",
"1997).",
"For",
"many",
"years,",
"it",
"was",
"assumed",
"that",
"most",
"reproductive",
"problems",
"could",
"be",
"attributed",
"to",
"the",
"female",
"partner",
"but",
"research",
"in",
"recent",
"years",
"has",
"demonstrated",
"that",
"30",
"–",
"50%",
"of",
"infertility",
"is",
"caused",
"by",
"a",
"male",
"factor",
"(Lipshultz",
"and",
"Howards,",
"1997).",
"Treatment",
"of",
"male-factor",
"infertility",
"by",
"in",
"vitro",
"fertilization",
"(IVF)",
"was",
"largely",
"unsuccessful.",
"However,",
"the",
"develop-",
"ment",
"of",
"intracytoplasmic",
"sperm",
"injection",
"(ICSI)",
"(Palermo",
"et",
"al.,",
"1992)",
"revolutionized",
"the",
"treatment",
"of",
"male",
"infertility,",
"providing",
"many",
"men",
"the",
"chance",
"to",
"father",
"their",
"own",
"children.",
"ICSI",
"also",
"greatly",
"stimulated",
"research",
"into",
"the",
"causes",
"of",
"male",
"infertility,",
"and",
"our",
"knowledge",
"has",
"increased",
"tremendously",
"in",
"the",
"past",
"decade.",
"The",
"development",
"of",
"new",
"techniques",
"has",
"provided",
"a",
"wealth",
"of",
"information",
"on",
"the",
"cytogenetics",
"of",
"human",
"sperm.",
"The",
"human",
"sperm",
"–",
"hamster",
"oocyte",
"fusion",
"system",
"allowed",
"the",
"first",
"analysis",
"of",
"human",
"sperm",
"chromosomes",
"(Rudak",
"et",
"al.,",
"1978;",
"Martin",
"et",
"al.,",
"1983;",
"Brandriff",
"et",
"al.,",
"1985;",
"Mikamo",
"et",
"al.,",
"1990;",
"Templado",
"et",
"al.,",
"1996).",
"This",
"technique",
"provides",
"precise",
"karyotypes",
"in",
"which",
"numerical",
"and",
"structural",
"abnormalities",
"can",
"be",
"assessed",
"for",
"each",
"chromosome",
"(Fig.",
"1).",
"Unfortunately,",
"the",
"technique",
"is",
"very",
"difficult",
"with",
"only",
"a",
"handful",
"of",
"laboratories",
"achieving",
"success;",
"also",
"the",
"data",
"yield,",
"though",
"of",
"great",
"significance,",
"is",
"low.",
"Fluorescence",
"in",
"situ",
"hybridization",
"(FISH)",
"analysis",
"with",
"chromosome-specific",
"DNA",
"probes",
"was",
"developed",
"in",
"the",
"1990s,",
"providing",
"a",
"faster,",
"cheaper,",
"easier",
"alternative",
"for",
"detecting",
"aneu-",
"ploidy",
"in",
"human",
"sperm",
"(Martin",
"et",
"al.,",
"1993;",
"Robbins",
"et",
"al.,",
"1993;",
"Wyrobek",
"et",
"al.,",
"1994;",
"Martin",
"et",
"al.,",
"1996).",
"Also,",
"sperm",
"hampered",
"by",
"abnormalities",
"in",
"motility",
"or",
"other",
"aspects",
"of",
"fertiliza-",
"tion",
"can",
"be",
"assessed",
"using",
"FISH",
"analysis",
"(Downie",
"et",
"al.,",
"1997;",
"Egozcue",
"et",
"al.,",
"1997;",
"Robbins",
"et",
"al.,",
"1997;",
"Martin",
"et",
"al.,",
"1999a;",
"Hristova",
"et",
"al.,",
"2002).",
"This",
"is",
"a",
"simple",
"technique",
"that",
"has",
"been",
"embraced",
"by",
"many",
"laboratories,",
"but",
"it",
"must",
"be",
"remembered",
"that",
"it",
"is",
"indirect:",
"fluorescent",
"signals,",
"rather",
"than",
"chromosomes,",
"are",
"counted",
"(Fig.",
"2).",
"Single",
"sperm",
"polymerase",
"chain",
"reaction",
"(PCR)",
"or",
"single",
"sperm",
"typing",
"is",
"a",
"difficult,",
"time-consuming",
"technique",
"but",
"it",
"can",
"be",
"used",
"in",
"a",
"very",
"powerful",
"manner",
"for",
"specific",
"studies",
"on",
"recombination",
"in",
"delimited",
"areas",
"of",
"the",
"genome",
"(Shi",
"et",
"al.,",
"2001,",
"2002;",
"Tiemann-",
"Boege",
"et",
"al.,",
"2006).",
"The",
"latest",
"development",
"to",
"shed",
"light",
"on",
"the",
"causes",
"of",
"chromo-",
"somal",
"abnormalities",
"and",
"infertility",
"is",
"meiotic",
"analysis",
"of",
"the",
"synaptonemal",
"complex",
"(SC).",
"Various",
"important",
"meiotic",
"structures",
"#",
"The",
"Author",
"2008.",
"Published",
"by",
"Oxford",
"University",
"Press",
"on",
"behalf",
"of",
"the",
"European",
"Society",
"of",
"Human",
"Reproduction",
"and",
"Embryology.",
"All",
"rights",
"reserved.",
"For",
"Permissions,",
"please",
"email:",
"journals.permissions@oxfordjournals.org",
"The",
"online",
"version",
"of",
"this",
"article",
"has",
"been",
"published",
"under",
"an",
"open",
"access",
"model.",
"Users",
"are",
"entitled",
"to",
"use,",
"reproduce,",
"disseminate,",
"or",
"display",
"the",
"open",
"access",
"version",
"of",
"this",
"article",
"for",
"non-commercial",
"purposes",
"provided",
"that:",
"the",
"original",
"authorship",
"is",
"properly",
"and",
"fully",
"attributed;",
"the",
"Journal",
"and",
"Oxford",
"University",
"Press",
"are",
"attributed",
"as",
"the",
"original",
"place",
"of",
"publication",
"with",
"the",
"correct",
"citation",
"details",
"given;",
"if",
"an",
"article",
"is",
"subsequently",
"reproduced",
"or",
"disseminated",
"not",
"in",
"its",
"entirety",
"but",
"only",
"in",
"part",
"or",
"as",
"a",
"derivative",
"work",
"this",
"must",
"be",
"clearly",
"indicated.",
"For",
"commercial",
"re-use,",
"please",
"contact",
"journals.permissions@oxfordjournals.org",
"379"
] | [
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] | [
"Westrom",
"et",
"al.",
"Trials",
"2010,",
"11:24",
"http://www.trialsjournal.com/content/11/1/24",
"S",
"T",
"U",
"D",
"Y",
"P",
"R",
"O",
"T",
"O",
"C",
"O",
"L",
"TRIALS",
"Open",
"Access",
"Individualized",
"chiropractic",
"and",
"integrative",
"care",
"for",
"low",
"back",
"pain:",
"the",
"design",
"of",
"a",
"randomized",
"clinical",
"trial",
"using",
"a",
"mixed-methods",
"approach",
"Kristine",
"K",
"Westrom*,",
"Michele",
"J",
"Maiers,",
"Roni",
"L",
"Evans,",
"Gert",
"Bronfort",
"Abstract",
"Background:",
"Low",
"back",
"pain",
"(LBP)",
"is",
"a",
"prevalent",
"and",
"costly",
"condition",
"in",
"the",
"United",
"States.",
"Evidence",
"suggests",
"there",
"is",
"no",
"one",
"treatment",
"which",
"is",
"best",
"for",
"all",
"patients,",
"but",
"instead",
"several",
"viable",
"treatment",
"options.",
"Additionally,",
"multidisciplinary",
"management",
"of",
"LBP",
"may",
"be",
"more",
"effective",
"than",
"monodisciplinary",
"care.",
"An",
"integrative",
"model",
"that",
"includes",
"both",
"complementary",
"and",
"alternative",
"medicine",
"(CAM)",
"and",
"conventional",
"therapies,",
"while",
"also",
"incorporating",
"patient",
"choice,",
"has",
"yet",
"to",
"be",
"tested",
"for",
"chronic",
"LBP.",
"The",
"primary",
"aim",
"of",
"this",
"study",
"is",
"to",
"determine",
"the",
"relative",
"clinical",
"effectiveness",
"of",
"1)",
"monodisciplinary",
"chiropractic",
"care",
"and",
"2)",
"multidisciplinary",
"integrative",
"care",
"in",
"200",
"adults",
"with",
"non-acute",
"LBP,",
"in",
"both",
"the",
"short-term",
"(after",
"12",
"weeks)",
"and",
"long-term",
"(after",
"52",
"weeks).",
"The",
"primary",
"outcome",
"measure",
"is",
"patient-rated",
"back",
"pain.",
"Secondary",
"aims",
"compare",
"the",
"treatment",
"approaches",
"in",
"terms",
"of",
"frequency",
"of",
"symptoms,",
"low",
"back",
"disability,",
"fear",
"avoidance,",
"self-effi-",
"cacy,",
"general",
"health",
"status,",
"improvement,",
"satisfaction,",
"work",
"loss,",
"medication",
"use,",
"lumbar",
"dynamic",
"motion,",
"and",
"torso",
"muscle",
"endurance.",
"Patients’",
"and",
"providers’",
"perceptions",
"of",
"treatment",
"will",
"be",
"described",
"using",
"qualitative",
"meth-",
"ods,",
"and",
"cost-effectiveness",
"and",
"cost",
"utility",
"will",
"be",
"assessed.",
"Methods",
"and",
"Design:",
"This",
"paper",
"describes",
"the",
"design",
"of",
"a",
"randomized",
"clinical",
"trial",
"(RCT),",
"with",
"cost-effectiveness",
"and",
"qualitative",
"studies",
"conducted",
"alongside",
"the",
"RCT.",
"Two",
"hundred",
"participants",
"ages",
"18",
"and",
"older",
"are",
"being",
"recruited",
"and",
"randomized",
"to",
"one",
"of",
"two",
"12-week",
"treatment",
"interventions.",
"Patient-rated",
"outcome",
"measures",
"are",
"collected",
"via",
"self-report",
"questionnaires",
"at",
"baseline,",
"and",
"at",
"4,",
"12,",
"26,",
"and",
"52",
"weeks",
"post-randomization.",
"Objective",
"outcome",
"measures",
"are",
"assessed",
"at",
"baseline",
"and",
"12",
"weeks",
"by",
"examiners",
"blinded",
"to",
"treatment",
"assignment.",
"Health",
"care",
"cost",
"data",
"is",
"collected",
"by",
"self-report",
"questionnaires",
"and",
"treatment",
"records",
"during",
"the",
"intervention",
"phase",
"and",
"by",
"monthly",
"phone",
"interviews",
"thereafter.",
"Qualitative",
"interviews,",
"using",
"a",
"semi-structured",
"format,",
"are",
"conducted",
"with",
"patients",
"at",
"the",
"end",
"of",
"the",
"12-week",
"treatment",
"period",
"and",
"also",
"with",
"providers",
"at",
"the",
"end",
"of",
"the",
"trial.",
"Discussion:",
"This",
"mixed-methods",
"randomized",
"clinical",
"trial",
"assesses",
"clinical",
"effectiveness,",
"cost-effectiveness,",
"and",
"patients’",
"and",
"providers’",
"perceptions",
"of",
"care,",
"in",
"treating",
"non-acute",
"LBP",
"through",
"evidence-based",
"individualized",
"care",
"delivered",
"by",
"monodisciplinary",
"or",
"multidisciplinary",
"care",
"teams.",
"Trial",
"registration:",
"ClinicalTrials.gov",
"NCT00567333",
"Background",
"It",
"is",
"well",
"recognized",
"that",
"low",
"back",
"pain",
"(LBP)",
"is",
"one",
"of",
"the",
"most",
"prevalent",
"and",
"costly",
"problems",
"facing",
"the",
"US",
"health-care",
"system",
"[1-3].",
"Approximately",
"80%",
"of",
"indivi-",
"duals",
"will",
"experience",
"non-specific",
"LBP",
"in",
"their",
"lifetime[4]",
"and",
"75%",
"will",
"experience",
"lingering",
"problems",
"one",
"year",
"*",
"Correspondence:",
"kwestrom@nwhealth.edu",
"Northwestern",
"Health",
"Sciences",
"University,",
"Wolfe-Harris",
"Center",
"for",
"Clinical",
"Studies,",
"2501",
"West",
"84th",
"Street,",
"Bloomington,",
"MN",
"55431,",
"USA",
"after",
"onset[5].",
"In",
"the",
"United",
"Kingdom,",
"the",
"incidence",
"of",
"chronic",
"low",
"back",
"disability",
"rose",
"exponentially",
"for",
"two",
"decades",
"through",
"1994,[6]",
"and",
"for",
"some",
"patients",
"the",
"asso-",
"ciated",
"psychological",
"distress",
"and",
"illness",
"behaviors",
"become",
"as",
"disabling",
"as",
"the",
"LBP",
"itself[7].",
"In",
"the",
"United",
"States,",
"the",
"costs",
"attributable",
"to",
"LBP",
"continue",
"to",
"soar",
"and",
"are",
"estimated",
"to",
"exceed",
"$100",
"billion",
"dollars",
"annually[8].",
"At",
"present,",
"more",
"than",
"500",
"randomized",
"controlled",
"trials",
"have",
"been",
"published",
"evaluating",
"conservative",
"and",
"alternative",
"treatments",
"for",
"LBP.",
"From",
"the",
"results",
"of",
"these",
"©",
"2010",
"Westrom",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"ORIGINAL",
"RESEARCH",
"ARTICLE",
"published:",
"20",
"February",
"2012",
"doi:",
"10.3389/fpsyg.2012.00039",
"Effects",
"of",
"speech",
"rate",
"and",
"practice",
"on",
"the",
"allocation",
"of",
"visual",
"attention",
"in",
"multiple",
"object",
"naming",
"Antje",
"S.",
"Meyer",
"1*,",
"Linda",
"Wheeldon2,",
"Femke",
"van",
"der",
"Meulen2",
"and",
"Agnieszka",
"Konopka3",
"1",
"Max",
"Planck",
"Institute",
"for",
"Psycholinguistics",
"and",
"Donders",
"Institute",
"for",
"Brain,",
"Cognition",
"and",
"Behavior,",
"Radboud",
"University,",
"Nijmegen,",
"Netherlands",
"2",
"School",
"of",
"Psychology,",
"University",
"of",
"Birmingham,",
"Birmingham,",
"UK",
"3",
"Max",
"Planck",
"Institute",
"for",
"Psycholinguistics,",
"Nijmegen,",
"Netherlands",
"Edited",
"by:",
"Andriy",
"Myachykov,",
"University",
"of",
"Glasgow,",
"UK",
"Reviewed",
"by:",
"Robert",
"J.",
"Hartsuiker,",
"University",
"of",
"Ghent,",
"Belgium",
"Zenzi",
"M.",
"Griffin,",
"University",
"of",
"Texas,",
"USA",
"*Correspondence:",
"Antje",
"S.",
"Meyer",
",",
"Max",
"Planck",
"Institute",
"for",
"Psycholinguistics",
"and",
"Donders",
"Institute",
"for",
"Brain,",
"Cognition",
"and",
"Behavior,",
"Radboud",
"University,",
"Postbus",
"310,",
"6500",
"AH",
"Nijmegen,",
"Netherlands.",
"e-mail:",
"antje.meyer@mpi.nl",
"Earlier",
"studies",
"had",
"shown",
"that",
"speakers",
"naming",
"several",
"objects",
"typically",
"look",
"at",
"each",
"object",
"until",
"they",
"have",
"retrieved",
"the",
"phonological",
"form",
"of",
"its",
"name",
"and",
"therefore",
"look",
"longer",
"at",
"objects",
"with",
"long",
"names",
"than",
"at",
"objects",
"with",
"shorter",
"names.",
"We",
"examined",
"whether",
"this",
"tight",
"eye-to-speech",
"coordination",
"was",
"maintained",
"at",
"different",
"speech",
"rates",
"and",
"after",
"increas-",
"ing",
"amounts",
"of",
"practice.",
"Participants",
"named",
"the",
"same",
"set",
"of",
"objects",
"with",
"monosyllabic",
"or",
"disyllabic",
"names",
"on",
"up",
"to",
"20",
"successive",
"trials.",
"In",
"Experiment",
"1,",
"they",
"spoke",
"as",
"fast",
"as",
"they",
"could,",
"whereas",
"in",
"Experiment",
"2",
"they",
"had",
"to",
"maintain",
"a",
"fixed",
"moderate",
"or",
"faster",
"speech",
"rate.",
"In",
"both",
"experiments,",
"the",
"durations",
"of",
"the",
"gazes",
"to",
"the",
"objects",
"decreased",
"with",
"increasing",
"speech",
"rate,",
"indicating",
"that",
"at",
"higher",
"speech",
"rates,",
"the",
"speakers",
"spent",
"less",
"time",
"planning",
"the",
"object",
"names.",
"The",
"eye–speech",
"lag",
"(the",
"time",
"interval",
"between",
"the",
"shift",
"of",
"gaze",
"away",
"from",
"an",
"object",
"and",
"the",
"onset",
"of",
"its",
"name)",
"was",
"independent",
"of",
"the",
"speech",
"rate",
"but",
"became",
"shorter",
"with",
"increasing",
"practice.",
"Consistent",
"word",
"length",
"effects",
"on",
"the",
"durations",
"of",
"the",
"gazes",
"to",
"the",
"objects",
"and",
"the",
"eye-speech",
"lags",
"were",
"only",
"found",
"in",
"Experiment",
"2.",
"The",
"results",
"indicate",
"that",
"shifts",
"of",
"eye",
"gaze",
"are",
"often",
"linked",
"to",
"the",
"completion",
"of",
"phonological",
"encoding,",
"but",
"that",
"speakers",
"can",
"deviate",
"from",
"this",
"default",
"coordination",
"of",
"eye",
"gaze",
"and",
"speech,",
"for",
"instance",
"when",
"the",
"descriptive",
"task",
"is",
"easy",
"and",
"they",
"aim",
"to",
"speak",
"fast.",
"Keywords:",
"utterance",
"planning,",
"speech",
"rate,",
"practice,",
"eye",
"movements,",
"visual",
"attention",
"INTRODUCTION",
"We",
"can",
"talk",
"in",
"different",
"ways.",
"We",
"can,",
"for",
"instance,",
"use",
"a",
"special",
"reg-",
"ister,",
"child",
"directed",
"speech,",
"to",
"talk",
"to",
"a",
"child,",
"and",
"we",
"tend",
"to",
"deliver",
"speeches,",
"and",
"formal",
"lectures",
"in",
"a",
"style",
"that",
"is",
"different",
"from",
"casual",
"dinner",
"table",
"conversations.",
"The",
"psychological",
"processes",
"underly-",
"ing",
"the",
"implementation",
"of",
"different",
"speech",
"styles",
"have",
"rarely",
"been",
"studied.",
"The",
"present",
"paper",
"concerns",
"one",
"important",
"feature",
"distin-",
"guishing",
"different",
"speech",
"styles,",
"i.e.,",
"speech",
"rate.",
"It",
"is",
"evident",
"that",
"speakers",
"can",
"control",
"their",
"speech",
"rate,",
"yet",
"little",
"is",
"known",
"about",
"how",
"they",
"do",
"this.",
"To",
"begin",
"to",
"explore",
"this",
"issue",
"we",
"used",
"a",
"simple",
"speech",
"produc-",
"tion",
"task:",
"speakers",
"named",
"sets",
"of",
"pictures",
"in",
"sequences",
"of",
"nouns",
"(e.g.,",
"“kite,",
"doll,",
"tap,",
"sock,",
"whale,",
"globe”).",
"Each",
"set",
"was",
"shown",
"on",
"several",
"successive",
"trials.",
"In",
"the",
"first",
"experiment,",
"the",
"speakers",
"were",
"asked",
"to",
"name",
"the",
"pictures",
"as",
"fast",
"as",
"they",
"could.",
"In",
"the",
"second",
"experiment,",
"they",
"had",
"to",
"maintain",
"a",
"fixed",
"moderate",
"or",
"faster",
"speech",
"rate,",
"which",
"allowed",
"us",
"to",
"separate",
"the",
"effects",
"of",
"speech",
"rate",
"and",
"practice.",
"Throughout",
"the",
"experiments,",
"the",
"speakers’",
"eye",
"move-",
"ments",
"were",
"recorded",
"along",
"with",
"their",
"spoken",
"utterances.",
"In",
"the",
"next",
"sections,",
"we",
"motivate",
"this",
"approach,",
"discuss",
"related",
"studies,",
"and",
"explain",
"the",
"predictions",
"for",
"the",
"experiments.",
"SPEECH-TO-GAZE",
"ALIGNMENT",
"IN",
"DESCRIPTIVE",
"UTTERANCES",
"In",
"many",
"language",
"production",
"studies",
"participants",
"have",
"been",
"asked",
"to",
"name",
"or",
"describe",
"pictures",
"of",
"one",
"or",
"more",
"objects.",
"Though",
"prob-",
"ably",
"not",
"the",
"most",
"common",
"way",
"of",
"using",
"language,",
"picture",
"naming",
"is",
"popular",
"in",
"language",
"production",
"research",
"because",
"it",
"offers",
"good",
"control",
"of",
"the",
"content",
"of",
"the",
"speakers’",
"utterances",
"and",
"captures",
"a",
"central",
"component",
"of",
"speech",
"planning,",
"namely",
"the",
"retrieval",
"of",
"words",
"from",
"the",
"mental",
"lexicon.",
"In",
"some",
"picture",
"naming",
"studies,",
"the",
"speakers’",
"eye",
"movements",
"were",
"recorded",
"along",
"with",
"their",
"speech.",
"This",
"is",
"useful",
"because",
"a",
"person’s",
"eye",
"gaze",
"reveals",
"where",
"their",
"visual",
"attention",
"is",
"focused,",
"that",
"is,",
"which",
"part",
"of",
"the",
"environment",
"they",
"are",
"processing",
"with",
"priority",
"(e.g.,",
"Deubel",
"and",
"Schneider,",
"1996;",
"Irwin,",
"2004;",
"Eimer",
"et",
"al.,",
"2007).",
"In",
"picture",
"naming,",
"visual",
"attention,",
"and",
"eye",
"gaze",
"are",
"largely",
"controlled",
"endogenously",
"(i.e.,",
"governed",
"by",
"the",
"speaker’s",
"goals",
"and",
"intentions),",
"rather",
"than",
"exogenously",
"(i.e.,",
"by",
"environ-",
"mental",
"stimuli).",
"That",
"is,",
"speakers",
"actively",
"direct",
"their",
"gaze",
"to",
"the",
"objects",
"they",
"wish",
"to",
"focus",
"on.",
"Therefore,",
"eye",
"movements",
"provide",
"not",
"only",
"information",
"about",
"the",
"speaker’s",
"visual",
"processing,",
"but",
"also,",
"albeit",
"more",
"indirectly,",
"about",
"the",
"executive",
"control",
"processes",
"engaged",
"in",
"the",
"task",
"(for",
"discussions",
"of",
"executive",
"control",
"processes",
"see",
"Baddeley,",
"1986;",
"Posner",
"and",
"Petersen,",
"1990;",
"Miyake",
"et",
"al.,",
"2000).",
"The",
"eye",
"movement",
"studies",
"of",
"language",
"production",
"have",
"yielded",
"a",
"number",
"of",
"key",
"findings.",
"First,",
"when",
"speakers",
"name",
"sets",
"of",
"objects",
"they",
"typically",
"look",
"at",
"each",
"of",
"the",
"objects",
"in",
"the",
"order",
"of",
"mention,",
"just",
"before",
"naming",
"it",
"(e.g.,",
"Meyer",
"et",
"al.,",
"1998;",
"Griffin,",
"2001).",
"When",
"speakers",
"describe",
"cartoons",
"of",
"events",
"or",
"actions,",
"rather",
"than",
"nam-",
"ing",
"individual",
"objects,",
"there",
"can",
"be",
"a",
"brief",
"apprehension",
"phase",
"during",
"which",
"speakers",
"gain",
"some",
"understanding",
"of",
"the",
"gist",
"of",
"the",
"scene",
"and",
"during",
"which",
"their",
"eye",
"movements",
"are",
"not",
"related",
"in",
"any",
"obvious",
"way",
"to",
"the",
"structure",
"of",
"the",
"upcoming",
"utterances,",
"but",
"following",
"this,",
"there",
"is",
"again",
"a",
"tight",
"coupling",
"between",
"eye",
"gaze",
"and",
"www.frontiersin.org",
"February",
"2012",
"|",
"Volume",
"3",
"|",
"Article",
"39",
"|",
"1"
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"Invasion",
"of",
"Wolbachia",
"into",
"Anopheles",
"and",
"Other",
"Insect",
"Germlines",
"in",
"an",
"Ex",
"vivo",
"Organ",
"Culture",
"System",
"Grant",
"L.",
"Hughes1.,",
"Andrew",
"D.",
"Pike2.,",
"Ping",
"Xue2,",
"Jason",
"L.",
"Rasgon",
"1",
"*",
"1",
"The",
"Department",
"of",
"Entomology,",
"Center",
"for",
"Infectious",
"Disease",
"Dynamics",
"and",
"Huck",
"Institutes",
"of",
"the",
"Life",
"Sciences,",
"Pennsylvania",
"State",
"University,",
"University",
"Park,",
"Pennsylvania,",
"United",
"States",
"of",
"America,",
"2",
"The",
"W.",
"Harry",
"Feinstone",
"Department",
"of",
"Molecular",
"Microbiology",
"and",
"Immunology,",
"Bloomberg",
"School",
"of",
"Public",
"Health,",
"Johns",
"Hopkins",
"University,",
"Baltimore,",
"Maryland,",
"United",
"States",
"of",
"America",
"Abstract",
"The",
"common",
"bacterial",
"endosymbiont",
"Wolbachia",
"manipulates",
"its",
"host’s",
"reproduction",
"to",
"promote",
"its",
"own",
"maternal",
"transmission,",
"and",
"can",
"interfere",
"with",
"pathogen",
"development",
"in",
"many",
"insects",
"making",
"it",
"an",
"attractive",
"agent",
"for",
"the",
"control",
"of",
"arthropod-borne",
"disease.",
"However,",
"many",
"important",
"species,",
"including",
"Anopheles",
"mosquitoes,",
"are",
"uninfected.",
"Wolbachia",
"can",
"be",
"artificially",
"transferred",
"between",
"insects",
"in",
"the",
"laboratory",
"but",
"this",
"can",
"be",
"a",
"laborious",
"and",
"sometimes",
"fruitless",
"process.",
"We",
"used",
"a",
"simple",
"ex",
"vivo",
"culturing",
"technique",
"to",
"assess",
"the",
"suitability",
"of",
"Wolbachia-host",
"germline",
"associations.",
"Wolbachia",
"infects",
"the",
"dissected",
"germline",
"tissue",
"of",
"multiple",
"insect",
"species",
"when",
"the",
"host",
"tissue",
"and",
"bacteria",
"are",
"cultured",
"together.",
"Ovary",
"and",
"testis",
"infection",
"occurs",
"in",
"a",
"density-dependent",
"manner.",
"Wolbachia",
"strains",
"are",
"more",
"capable",
"of",
"invading",
"the",
"germline",
"of",
"their",
"native",
"or",
"closely",
"related",
"rather",
"than",
"divergent",
"hosts.",
"The",
"ability",
"of",
"Wolbachia",
"to",
"associate",
"with",
"the",
"germline",
"of",
"novel",
"hosts",
"is",
"crucial",
"for",
"the",
"development",
"of",
"stably-transinfected",
"insect",
"lines.",
"Rapid",
"assessment",
"of",
"the",
"suitability",
"of",
"a",
"strain-host",
"combination",
"prior",
"to",
"transinfection",
"may",
"dictate",
"use",
"of",
"a",
"particular",
"Wolbachia",
"strain.",
"Furthermore,",
"the",
"cultured",
"germline",
"tissues",
"of",
"two",
"major",
"Anopheline",
"vectors",
"of",
"Plasmodium",
"parasites",
"are",
"susceptible",
"to",
"Wolbachia",
"infection.",
"This",
"finding",
"further",
"enhances",
"the",
"prospect",
"of",
"using",
"Wolbachia",
"for",
"the",
"biological",
"control",
"of",
"malaria.",
"Citation:",
"Hughes",
"GL,",
"Pike",
"AD,",
"Xue",
"P,",
"Rasgon",
"JL",
"(2012)",
"Invasion",
"of",
"Wolbachia",
"into",
"Anopheles",
"and",
"Other",
"Insect",
"Germlines",
"in",
"an",
"Ex",
"vivo",
"Organ",
"Culture",
"System.",
"PLoS",
"ONE",
"7(4):",
"e36277.",
"doi:10.1371/journal.pone.0036277",
"Editor:",
"Luciano",
"A.",
"Moreira,",
"Centro",
"de",
"Pesquisas",
"Rene´",
"Rachou,",
"Brazil",
"Received",
"November",
"28,",
"2011;",
"Accepted",
"April",
"1,",
"2012;",
"Published",
"April",
"30,",
"2012",
"Copyright:",
"2012",
"Hughes",
"et",
"al.",
"This",
"is",
"an",
"open-access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"author",
"and",
"source",
"are",
"credited.",
"Funding:",
"This",
"research",
"was",
"supported",
"by",
"United",
"States",
"National",
"Institutes",
"of",
"Health",
"grant",
"R21AI070178",
"to",
"JLR.",
"GLH",
"was",
"supported",
"by",
"the",
"Johns",
"Hopkins",
"School",
"of",
"Public",
"Health",
"(JHSPH)",
"Jane",
"Welsh",
"Russell",
"Scholarship",
"and",
"a",
"Johns",
"Hopkins",
"Malaria",
"Research",
"Institute",
"(JHMRI)",
"postdoctoral",
"fellowship.",
"The",
"funders",
"had",
"no",
"role",
"in",
"study",
"design,",
"data",
"collection",
"and",
"analysis,",
"decision",
"to",
"publish,",
"or",
"preparation",
"of",
"the",
"manuscript.",
"Competing",
"Interests:",
"The",
"authors",
"have",
"declared",
"that",
"no",
"competing",
"interests",
"exist.",
"*",
"E-mail:",
"jlr54@psu.edu",
".",
"These",
"authors",
"contributed",
"equally",
"to",
"this",
"work.",
"Introduction",
"Wolbachia",
"are",
"intracellular",
"a-proteobacteria",
"that",
"infect",
"approx-",
"imately",
"two-thirds",
"of",
"insect",
"species",
"along",
"with",
"numerous",
"other",
"arthropods",
"[1,2].",
"Generally",
"classified",
"as",
"reproductive",
"parasites,",
"Wolbachia",
"are",
"able",
"to",
"manipulate",
"their",
"hosts",
"reproduction",
"in",
"various",
"ways",
"[3].",
"These",
"reproductive",
"manipulations",
"exploit",
"the",
"maternal",
"transmission",
"route",
"of",
"the",
"bacteria",
"to",
"the",
"progeny",
"of",
"the",
"host,",
"facilitating",
"the",
"spread",
"of",
"Wolbachia",
"into",
"the",
"host",
"population.",
"In",
"addition",
"to",
"maternal",
"transmission,",
"the",
"incongruence",
"between",
"the",
"phylogenies",
"of",
"Wolbachia",
"and",
"their",
"hosts",
"suggests",
"horizontal",
"transmission",
"has",
"occurred",
"repeatedly",
"over",
"evolutionary",
"time,",
"which",
"has",
"extended",
"the",
"host",
"range",
"of",
"the",
"bacteria",
"[4,5,6].",
"The",
"ability",
"of",
"Wolbachia",
"to",
"invade",
"new",
"species",
"has",
"been",
"reproduced",
"in",
"the",
"laboratory,",
"with",
"artificial",
"transfers",
"into",
"novel",
"insect",
"species.",
"Despite",
"transinfection",
"of",
"Wolbachia",
"into",
"many",
"new",
"insect",
"species,",
"it",
"is",
"uncertain",
"why",
"some",
"species",
"are",
"capable",
"of",
"infection",
"yet",
"others",
"are",
"seemingly",
"not.",
"For",
"either",
"horizontal",
"transmission",
"or",
"transinfection",
"to",
"occur,",
"Wolbachia",
"must",
"establish",
"in",
"the",
"female",
"germline",
"to",
"allow",
"the",
"bacteria",
"to",
"be",
"transmitted",
"to",
"the",
"next",
"generation.",
"When",
"artificially",
"transferred",
"into",
"a",
"new",
"host,",
"Wolbachia",
"are",
"usually",
"microinjected",
"into",
"the",
"preblastoderm",
"embryo,",
"a",
"scenario",
"that",
"is",
"unlikely",
"to",
"occur",
"in",
"nature.",
"However,",
"in",
"experiments",
"that",
"more",
"closely",
"mimic",
"potential",
"natural",
"routes",
"of",
"horizontal",
"transfer,",
"Wolbachia",
"has",
"been",
"shifted",
"between",
"insects",
"by",
"adult",
"injection,",
"hemolymph",
"transfer",
"and",
"co-rearing",
"[7,8,9].",
"When",
"injected",
"into",
"uninfected",
"Drosophila,",
"Wolbachia",
"migrate",
"across",
"numerous",
"tissues",
"to",
"establish",
"in",
"the",
"stem",
"cell",
"niche",
"of",
"the",
"ovary",
"[7].",
"Hemolymph",
"transfer",
"between",
"infected",
"and",
"uninfected",
"pillbugs",
"(Armadillidium",
"vulgare,",
"Porcellionides",
"pruinosus",
"and",
"Chaetophiliscia",
"elongate)",
"resulted",
"in",
"stable",
"intraspecific",
"transfer",
"of",
"Wolbachia",
"and",
"manipulation",
"of",
"host",
"reproductive",
"[8].",
"The",
"capacity",
"for",
"Wolbachia",
"to",
"spread",
"though",
"host",
"populations",
"and",
"interfere",
"with",
"pathogen",
"development",
"in",
"insects",
"makes",
"them",
"attractive",
"agents",
"for",
"the",
"control",
"of",
"vector-borne",
"diseases.",
"Currently,",
"Wolbachia",
"is",
"being",
"investigated",
"to",
"control",
"malaria,",
"a",
"devastating",
"disease",
"transmitted",
"by",
"Anopheles",
"mosquitoes.",
"Wolbachia",
"is",
"capable",
"of",
"infecting",
"Anopheles",
"cells",
"in",
"vitro",
"and",
"Anopheles",
"somatic",
"tissues",
"in",
"vivo,",
"and",
"influences",
"the",
"expression",
"of",
"numerous",
"host",
"genes",
"[10,11,12].",
"After",
"injection",
"into",
"adult",
"Anopheles",
"mosquitoes,",
"Wolbachia",
"influences",
"Plasmodium",
"levels,",
"with",
"wAlbB",
"and",
"wMelPop",
"reducing",
"P.",
"falciparum",
"intensity",
"[10].",
"Interestingly,",
"somatic",
"infection",
"of",
"An.",
"gambiae",
"with",
"the",
"wAlbB",
"strains",
"enhances",
"oocyst",
"density",
"of",
"P.",
"berghei,",
"the",
"model",
"murine",
"malaria",
"species",
"[13].",
"However,",
"all",
"Anopheles",
"mosquitoes",
"lack",
"Wolbachia",
"infection",
"in",
"the",
"wild",
"and",
"despite",
"numerous",
"attempts",
"seem",
"impervious",
"to",
"stable",
"transinfection",
"in",
"the",
"lab",
"[14,15].",
"To",
"increase",
"the",
"probability",
"of",
"infecting",
"Anopheles",
"mosquitoes,",
"a",
"variety",
"of",
"combinations",
"of",
"PLoS",
"ONE",
"|",
"www.plosone.org",
"1",
"April",
"2012",
"|",
"Volume",
"7",
"|",
"Issue",
"4",
"|",
"e36277"
] | [
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] | [
"Jaspan",
"et",
"al.",
"BMC",
"Pediatrics",
"2011,",
"11:104",
"http://www.biomedcentral.com/1471-2431/11/104",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"A",
"R",
"T",
"I",
"C",
"L",
"E",
"Open",
"Access",
"Utility",
"of",
"clinical",
"parameters",
"to",
"identify",
"HIV",
"infection",
"in",
"infants",
"below",
"ten",
"weeks",
"of",
"age",
"in",
"South",
"Africa:",
"a",
"prospective",
"cohort",
"study",
"Heather",
"B",
"Jaspan1,2,3,9*,",
"Landon",
"Myer4,",
"Shabir",
"A",
"Madhi5,",
"Avy",
"Violari6,",
"Diana",
"M",
"Gibb7,",
"Wendy",
"S",
"Stevens8,",
"Els",
"Dobbels1",
"and",
"Mark",
"F",
"Cotton1",
"Abstract",
"Background:",
"As",
"HIV-infected",
"infants",
"have",
"high",
"mortality,",
"the",
"World",
"Health",
"Organization",
"now",
"recommends",
"initiating",
"antiretroviral",
"therapy",
"as",
"early",
"as",
"possible",
"in",
"the",
"first",
"year",
"of",
"life.",
"However,",
"in",
"many",
"settings,",
"laboratory",
"diagnosis",
"of",
"HIV",
"in",
"infants",
"is",
"not",
"readily",
"available.",
"We",
"aimed",
"to",
"develop",
"a",
"clinical",
"algorithm",
"for",
"HIV",
"presumptive",
"diagnosis",
"in",
"infants",
"<",
"10",
"weeks",
"old",
"using",
"screening",
"data",
"from",
"the",
"Children",
"with",
"HIV",
"Early",
"Antiretroviral",
"therapy",
"(CHER)",
"study",
"in",
"South",
"Africa.",
"HIV-infected",
"and",
"HIV-uninfected",
"exposed",
"infants",
"<",
"10",
"weeks",
"of",
"age",
"were",
"identified",
"through",
"Vertical",
"Transmission",
"Prevention",
"programs.",
"Clinical",
"and",
"laboratory",
"data",
"were",
"systematically",
"recorded,",
"groups",
"were",
"compared",
"using",
"Kruskal-Wallis,",
"analysis",
"of",
"variance",
"(ANOVA),",
"and",
"Fisher’s",
"exact",
"tests.",
"Receiver",
"Operating",
"Characteristic",
"(ROC)",
"curves",
"were",
"compiled",
"using",
"combinations",
"of",
"clinical",
"findings.",
"Results:",
"417",
"HIV-infected",
"and",
"125",
"HIV-exposed,",
"uninfected",
"infants,",
"median",
"age",
"46",
"days",
"(IQR",
"38-55),",
"were",
"included.",
"The",
"median",
"CD4",
"percentage",
"in",
"HIV-infected",
"infants",
"was",
"34",
"(IQR",
"28-41)%.",
"HIV-infected",
"infants",
"had",
"lower",
"weight-",
"for-age,",
"more",
"lymphadenopathy,",
"oral",
"thrush,",
"and",
"hepatomegaly",
"than",
"exposed",
"uninfected",
"infants",
"(Adjusted",
"Odds",
"Ratio",
"0.51,",
"8.8,",
"5.6",
"and",
"23.5",
"respectively;",
"p",
"<",
"0.001",
"for",
"all).",
"Sensitivity",
"of",
"individual",
"signs",
"was",
"low",
"(<",
"20%)",
"but",
"specificity",
"high",
"(98-100%).",
"If",
"any",
"one",
"of",
"oral",
"thrush,",
"hepatomegaly,",
"splenomegaly,",
"lymphadenopathy,",
"diaper",
"dermatitis,",
"weight",
"<",
"50th",
"centile",
"are",
"present,",
"sensitivity",
"for",
"HIV",
"infection",
"amongst",
"HIV-exposed",
"infants",
"was",
"86%.",
"These",
"algorithms",
"performed",
"similarly",
"when",
"used",
"to",
"predict",
"severe",
"immune",
"suppression.",
"Conclusions:",
"A",
"combination",
"of",
"physical",
"findings",
"is",
"helpful",
"in",
"identifying",
"infants",
"most",
"likely",
"to",
"be",
"HIV-infected.",
"This",
"may",
"inform",
"management",
"algorithms",
"and",
"provide",
"guidance",
"for",
"focused",
"laboratory",
"testing",
"in",
"some",
"settings,",
"and",
"should",
"be",
"further",
"validated",
"in",
"these",
"settings",
"and",
"elsewhere.",
"Background",
"Identifying",
"HIV",
"infection",
"in",
"early",
"infancy",
"is",
"an",
"impor-",
"tant",
"challenge",
"to",
"effective",
"paediatric",
"HIV",
"care",
"and",
"treat-",
"ment.",
"HIV-infected",
"infants",
"have",
"a",
"high",
"mortality,",
"particularly",
"in",
"heavily",
"disease-burdened",
"settings",
"[1-6].",
"The",
"Children",
"with",
"HIV",
"Early",
"Antiretroviral",
"Therapy",
"(CHER)",
"trial",
"[4]",
"recently",
"showed",
"that",
"early",
"antiretroviral",
"therapy",
"(ART),",
"commenced",
"at",
"a",
"median",
"of",
"7",
"weeks",
"of",
"age",
"was",
"associated",
"with",
"a",
"75%",
"reduction",
"in",
"mortality",
"*",
"Correspondence:",
"heather.jaspan@sbri.org",
"1Children’s",
"Infectious",
"Diseases",
"Clinical",
"Research",
"Unit,",
"Department",
"of",
"Paediatrics",
"and",
"Child",
"Health",
"and",
"Centre",
"for",
"Infectious",
"Diseases,",
"Faculty",
"of",
"Health",
"Sciences,",
"Stellenbosch",
"University,",
"Tygerberg,",
"South",
"Africa",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"versus",
"the",
"prevailing",
"standard",
"of",
"care",
"at",
"the",
"time",
"(the",
"WHO",
"2006",
"guidelines)",
"[7].",
"Importantly,",
"most",
"deaths",
"occurred",
"in",
"the",
"first",
"few",
"months",
"of",
"life",
"and",
"none",
"of",
"the",
"infants",
"had",
"a",
"CD4",
"<",
"25%",
"or",
"advanced",
"HIV",
"disease",
"according",
"to",
"Centers",
"for",
"Diseases",
"Control",
"criteria",
"[4].",
"Diagnostic",
"HIV-1",
"DNA",
"PCR",
"is",
"recommended",
"at",
"6",
"weeks",
"of",
"age",
"in",
"HIV-exposed",
"infants",
"going",
"through",
"Ver-",
"tical",
"Transmission",
"Prevention",
"(VTP)",
"programs",
"[8].",
"Although",
"qualitative",
"HIV-1",
"PCR",
"testing",
"is",
"becoming",
"more",
"available,",
"turn-around",
"time",
"for",
"results",
"and",
"subse-",
"quent",
"initiation",
"of",
"ART",
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] | [
"Kim",
"et",
"al.",
"Journal",
"of",
"Hematology",
"&",
"Oncology",
"2012,",
"5:49",
"http://www.jhoonline.org/content/5/1/49",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"JOURNAL",
"OF",
"HEMATOLOGY",
"&",
"ONCOLOGY",
"Open",
"Access",
"Prognostic",
"factors",
"in",
"primary",
"diffuse",
"large",
"B-cell",
"lymphoma",
"of",
"adrenal",
"gland",
"treated",
"with",
"rituximab-CHOP",
"chemotherapy",
"from",
"the",
"Consortium",
"for",
"Improving",
"Survival",
"of",
"Lymphoma",
"(CISL)",
"Yu",
"Ri",
"Kim1,",
"Jin",
"Seok",
"Kim1,15*,",
"Yoo",
"Hong",
"Min1,",
"Dok",
"HyunYoon2,",
"Ho-Jin",
"Shin3,",
"Yeung-Chul",
"Mun4,",
"Yong",
"Park5,",
"Young",
"Rok",
"Do6,",
"Seong",
"Hyun",
"Jeong7,",
"Joon",
"Seong",
"Park7,",
"Sung",
"Yong",
"Oh8,",
"Suee",
"Lee8,",
"Eun",
"Kyung",
"Park9,",
"Joung-Soon",
"Jang9,",
"Won-Sik",
"Lee10,",
"Hwe-Won",
"Lee11,",
"HyeonSeok",
"Eom11,",
"Jae-sook",
"Ahn12,",
"Jae-Heon",
"Jeong13,",
"Sun",
"Kyung",
"Baek13,",
"Seok",
"Jin",
"Kim14,",
"Won",
"Seog",
"Kim14",
"and",
"Cheolwon",
"Suh2",
"Abstract",
"Background:",
"The",
"objective",
"of",
"this",
"study",
"was",
"to",
"identify",
"prognostic",
"factors",
"for",
"survival",
"in",
"patients",
"with",
"primary",
"diffuse",
"large",
"B-cell",
"lymphoma",
"(DLBCL)",
"of",
"the",
"adrenal",
"gland.",
"Methods:",
"Thirty",
"one",
"patients",
"diagnosed",
"with",
"primary",
"adrenal",
"DLBCL",
"from",
"14",
"Korean",
"institutions",
"and",
"treated",
"with",
"R-CHOP",
"(rituximab,",
"cyclophosphamide,",
"doxorubicin,",
"vincristine",
"and",
"prednisone)",
"were",
"analyzed.",
"Results:",
"Complete",
"remission",
"(CR)",
"and",
"overall",
"response",
"rate",
"after",
"R-CHOP",
"chemotherapy",
"were",
"54.8%",
"and",
"87.0%.",
"The",
"2-year",
"estimates",
"of",
"overall",
"survival",
"(OS)",
"and",
"progression-free",
"survival",
"(PFS)",
"were",
"68.3%",
"and",
"51.1%.",
"In",
"patients",
"achieving",
"CR,",
"significant",
"prolongations",
"of",
"OS",
"(P",
"=",
"0.029)",
"and",
"PFS",
"(P",
"=",
"0.005)",
"were",
"observed.",
"Ann",
"Arbor",
"stage",
"had",
"no",
"influence",
"on",
"OS.",
"There",
"was",
"no",
"significant",
"difference",
"in",
"OS",
"between",
"patients",
"with",
"unilateral",
"involvement",
"of",
"adrenal",
"gland",
"and",
"those",
"with",
"bilateral",
"involvement.",
"When",
"staging",
"was",
"modified",
"to",
"include",
"bilateral",
"adrenal",
"involvement",
"as",
"one",
"extranodal",
"site,",
"early",
"stage",
"(I",
"or",
"II)",
"significantly",
"correlated",
"with",
"longer",
"OS",
"(P",
"=",
"0.021)",
"and",
"PFS",
"(P",
"<0.001).",
"Conclusions:",
"Contrary",
"to",
"prior",
"reports,",
"our",
"data",
"suggests",
"that",
"outcomes",
"of",
"primary",
"adrenal",
"DLBCL",
"are",
"encouraging",
"using",
"a",
"regimen",
"of",
"R-CHOP,",
"and",
"that",
"achieving",
"CR",
"after",
"R-CHOP",
"is",
"predictive",
"of",
"survival.",
"Likewise,",
"our",
"modified",
"staging",
"system",
"may",
"have",
"prognostic",
"value.",
"Keywords:",
"Primary",
"adrenal",
"lymphoma,",
"Diffuse",
"large",
"B-cell",
"lymphoma,",
"Prognostic",
"factor,",
"R-CHOP",
"Background",
"Primary",
"extranodal",
"non-Hodgkin’s",
"lymphoma",
"(NHL)",
"is",
"characterized",
"by",
"disease",
"confined",
"wholly",
"or",
"chiefly",
"to",
"an",
"extranodal",
"site",
"[1].",
"The",
"adrenal",
"gland",
"is",
"an",
"extremely",
"rare",
"site",
"of",
"primary",
"extranodal",
"NHL,",
"accounting",
"for",
"less",
"than",
"1%",
"of",
"all",
"NHL",
"and",
"only",
"3%",
"of",
"primary",
"extranodal",
"*",
"Correspondence:",
"hemakim@yuhs.ac",
"1Department",
"of",
"Internal",
"Medicine,",
"Yonsei",
"University",
"College",
"of",
"Medicine,",
"Seoul,",
"Korea",
"15Department",
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"Medicine,",
"Division",
"of",
"Hematology,",
"Yonsei",
"University",
"College",
"of",
"Medicine,",
"50",
"Yonsei-ro,",
"Seodaemun-gu,",
"Seoul",
"120-752,",
"Korea",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"lymphomas",
"[2,3].",
"While",
"bilateral",
"involvement",
"of",
"adrenal",
"gland,",
"predominantly",
"male",
"and",
"elderly,",
"and",
"frequent",
"as-",
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"with",
"adrenal",
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"are",
"commonly",
"re-",
"ported",
"clinical",
"features",
"of",
"primary",
"adrenal",
"NHL,",
"diffuse",
"large",
"B-cell",
"lymphoma",
"(DLBCL)",
"is",
"the",
"most",
"common",
"histologic",
"subtype,",
"with",
"a",
"non-germinal",
"center",
"B-cell",
"(non-GCB)",
"phenotype",
"[4-7].",
"To",
"date,",
"only",
"about",
"120",
"publications",
"(case",
"reports",
"or",
"patient",
"series)",
"appear",
"in",
"the",
"literature,",
"each",
"limited",
"in",
"scope.",
"Conclusions",
"have",
"thus",
"been",
"drawn",
"from",
"clinical",
"data",
"and",
"treatment",
"outcomes",
"©",
"2012",
"Kim",
"et",
"al.;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Ionic",
"Components",
"of",
"Electric",
"Current",
"at",
"Rat",
"Corneal",
"Wounds",
"Ana",
"Carolina",
"Vieira1,2.,",
"Brian",
"Reid3*.,",
"Lin",
"Cao",
"3",
",",
"Mark",
"J.",
"Mannis1,",
"Ivan",
"R.",
"Schwab",
"1",
",",
"Min",
"Zhao1,3",
"1",
"Department",
"of",
"Ophthalmology,",
"University",
"of",
"California",
"Davis,",
"Davis,",
"California,",
"United",
"States",
"of",
"America,",
"2",
"Department",
"of",
"Ophthalmology,",
"Federal",
"University",
"of",
"Sao",
"Paulo,",
"Sao",
"Paulo,",
"Brazil,",
"3",
"Department",
"of",
"Dermatology,",
"University",
"of",
"California",
"Davis,",
"Davis,",
"California,",
"United",
"States",
"of",
"America",
"Abstract",
"Background:",
"Endogenous",
"electric",
"fields",
"and",
"currents",
"occur",
"naturally",
"at",
"wounds",
"and",
"are",
"a",
"strong",
"signal",
"guiding",
"cell",
"migration",
"into",
"the",
"wound",
"to",
"promote",
"healing.",
"Many",
"cells",
"involved",
"in",
"wound",
"healing",
"respond",
"to",
"small",
"physiological",
"electric",
"fields",
"in",
"vitro.",
"It",
"has",
"long",
"been",
"assumed",
"that",
"wound",
"electric",
"fields",
"are",
"produced",
"by",
"passive",
"ion",
"leakage",
"from",
"damaged",
"tissue.",
"Could",
"these",
"fields",
"be",
"actively",
"maintained",
"and",
"regulated",
"as",
"an",
"active",
"wound",
"response?",
"What",
"are",
"the",
"molecular,",
"ionic",
"and",
"cellular",
"mechanisms",
"underlying",
"the",
"wound",
"electric",
"currents?",
"Methodology/Principal",
"Findings:",
"Using",
"rat",
"cornea",
"wounds",
"as",
"a",
"model,",
"we",
"measured",
"the",
"dynamic",
"timecourses",
"of",
"individual",
"ion",
"fluxes",
"with",
"ion-selective",
"probes.",
"We",
"also",
"examined",
"chloride",
"channel",
"expression",
"before",
"and",
"after",
"wounding.",
"After",
"wounding,",
"Ca2+",
"efflux",
"increased",
"steadily",
"whereas",
"K+",
"showed",
"an",
"initial",
"large",
"efflux",
"which",
"rapidly",
"decreased.",
"Surprisingly,",
"Na+",
"flux",
"at",
"wounds",
"was",
"inward.",
"A",
"most",
"significant",
"observation",
"was",
"a",
"persistent",
"large",
"influx",
"of",
"Cl2,",
"which",
"had",
"a",
"time",
"course",
"similar",
"to",
"the",
"net",
"wound",
"electric",
"currents",
"we",
"have",
"measured",
"previously.",
"Fixation",
"of",
"the",
"tissues",
"abolished",
"ion",
"fluxes.",
"Pharmacological",
"agents",
"which",
"stimulate",
"ion",
"transport",
"significantly",
"increased",
"flux",
"of",
"Cl2,",
"Na+",
"and",
"K+.",
"Injury",
"to",
"the",
"cornea",
"caused",
"significant",
"changes",
"in",
"distribution",
"and",
"expression",
"of",
"Cl2",
"channel",
"CLC2.",
"Conclusions/Significance:",
"These",
"data",
"suggest",
"that",
"the",
"outward",
"electric",
"currents",
"occurring",
"naturally",
"at",
"corneal",
"wounds",
"are",
"carried",
"mainly",
"by",
"a",
"large",
"influx",
"of",
"chloride",
"ions,",
"and",
"in",
"part",
"by",
"effluxes",
"of",
"calcium",
"and",
"potassium",
"ions.",
"Ca2+",
"and",
"Cl2",
"fluxes",
"appear",
"to",
"be",
"mainly",
"actively",
"regulated,",
"while",
"K+",
"flux",
"appears",
"to",
"be",
"largely",
"due",
"to",
"leakage.",
"The",
"dynamic",
"changes",
"of",
"electric",
"currents",
"and",
"specific",
"ion",
"fluxes",
"after",
"wounding",
"suggest",
"that",
"electrical",
"signaling",
"is",
"an",
"active",
"response",
"to",
"injury",
"and",
"offers",
"potential",
"novel",
"approaches",
"to",
"modulate",
"wound",
"healing,",
"for",
"example",
"eye-drops",
"targeting",
"ion",
"transport",
"to",
"aid",
"in",
"the",
"challenging",
"management",
"of",
"non-healing",
"corneal",
"ulcers.",
"Citation:",
"Vieira",
"AC,",
"Reid",
"B,",
"Cao",
"L,",
"Mannis",
"MJ,",
"Schwab",
"IR,",
"et",
"al.",
"(2011)",
"Ionic",
"Components",
"of",
"Electric",
"Current",
"at",
"Rat",
"Corneal",
"Wounds.",
"PLoS",
"ONE",
"6(2):",
"e17411.",
"doi:10.1371/journal.pone.0017411",
"Editor:",
"Che",
"Connon,",
"University",
"of",
"Reading,",
"United",
"Kingdom",
"Received",
"November",
"9,",
"2010;",
"Accepted",
"January",
"31,",
"2011;",
"Published",
"February",
"25,",
"2011",
"Copyright:",
"2011",
"Vieira",
"et",
"al.",
"This",
"is",
"an",
"open-access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"author",
"and",
"source",
"are",
"credited.",
"Funding:",
"This",
"work",
"was",
"supported",
"by",
"the",
"National",
"Institutes",
"of",
"Health",
"National",
"Eye",
"Institute",
"grant",
"1R01EY019101",
"(to",
"MZ",
"and",
"BR).",
"The",
"authors",
"thank",
"the",
"Wellcome",
"Trust",
"for",
"continuous",
"support",
"(068012).",
"This",
"work",
"was",
"also",
"supported",
"in",
"part",
"by",
"Research",
"to",
"Prevent",
"Blindness,",
"Inc.,",
"an",
"NSFC",
"grant",
"(30628026),",
"and",
"UC",
"Davis",
"Dermatology",
"Department",
"developmental",
"fund.",
"MZ",
"is",
"also",
"supported",
"by",
"grants",
"from",
"the",
"California",
"Institute",
"of",
"Regenerative",
"Medicine",
"RB1-01417,",
"NSF",
"MCB-",
"0951199.",
"The",
"funders",
"had",
"no",
"role",
"in",
"study",
"design,",
"data",
"collection/analysis,",
"decision",
"to",
"publish,",
"or",
"preparation",
"of",
"the",
"manuscript.",
"Competing",
"Interests:",
"The",
"authors",
"have",
"declared",
"that",
"no",
"competing",
"interests",
"exist.",
"*",
"E-mail:",
"brireid@ucdavis.edu",
".",
"These",
"authors",
"contributed",
"equally",
"to",
"this",
"work.",
"Introduction",
"At",
"human",
"skin",
"wounds,",
"naturally",
"occurring",
"electric",
"fields",
"and",
"currents",
"were",
"detected",
"many",
"years",
"ago",
"[1–4].",
"Modern",
"techniques",
"have",
"confirmed",
"and",
"significantly",
"extended",
"our",
"understanding",
"of",
"these",
"endogenous",
"electric",
"fields.",
"Electric",
"currents",
"of",
",10–100",
"mA/",
"cm2",
"and",
"fields",
"of",
",40–177",
"mV/mm",
"at",
"wounds",
"in",
"humans",
"and",
"various",
"animals",
"have",
"been",
"measured",
"in",
"recent",
"years",
"with",
"vibrating",
"probes,",
"micro-glass",
"electrodes,",
"micro-needle",
"arrays,",
"and",
"bioelec-",
"tric",
"imagers",
"[5–9].",
"Endogenously",
"induced",
"electric",
"fields",
"at",
"wounds",
"have",
"emerged",
"as",
"an",
"important",
"signal",
"that",
"plays",
"a",
"critical",
"role",
"in",
"wound",
"healing",
"[10–13].",
"Chemotaxis,",
"haptotaxis",
"(response",
"to",
"surface-bound",
"molecules),",
"contact",
"guidance,",
"free",
"edges",
"and",
"other",
"factors",
"at",
"wounds",
"are",
"directional",
"cues",
"for",
"cell",
"migration",
"and",
"wound",
"healing.",
"Recently,",
"we",
"demonstrated",
"that",
"electric",
"signals",
"in",
"cell",
"migration",
"during",
"wound",
"healing",
"are",
"far",
"more",
"important",
"than",
"previously",
"thought",
"since",
"they",
"override",
"other",
"directional",
"cues",
"[6,10,14].",
"Applied",
"electric",
"fields",
"have",
"been",
"shown",
"to",
"stimulate",
"division,",
"migration",
"and",
"differentiation",
"of",
"many",
"types",
"of",
"cells:",
"corneal",
"epithelial",
"cells",
"[15–18],",
"neuronal",
"cells",
"[19–21],",
"fibroblasts",
"[22]",
"and",
"skin",
"epithelial",
"cells",
"[23–24]",
"in",
"a",
"process",
"called",
"galvanotaxis",
"or",
"electrotaxis.",
"The",
"mechanisms",
"of",
"how",
"the",
"electric",
"currents",
"are",
"generated",
"and",
"maintained",
"however",
"remain",
"very",
"poorly",
"understood",
"and",
"largely",
"unstudied.",
"It",
"is",
"generally",
"assumed",
"that",
"the",
"wound",
"electric",
"currents",
"are",
"caused",
"by",
"a",
"short-circuit",
"of",
"the",
"trans-epithelial",
"potential",
"difference",
"(TEPD)",
"at",
"the",
"wound",
"site.",
"In",
"another",
"words,",
"a",
"passive",
"leakage",
"of",
"ions",
"and",
"other",
"charged",
"molecules.",
"The",
"TEPD",
"is",
"a",
"common",
"feature",
"of",
"most",
"epithelia,",
"including",
"skin",
"and",
"corneal",
"epithelia.",
"In",
"the",
"cornea,",
"ions",
"are",
"constantly",
"being",
"transported",
"across",
"the",
"corneal",
"epithelium,",
"which",
"generates",
"and",
"maintains",
"the",
"TEPD",
"with",
"the",
"outer",
"side",
"negative",
"[25].",
"Sodium",
"ions",
"are",
"actively",
"transported",
"from",
"the",
"tears",
"to",
"the",
"aqueous",
"humor",
"while",
"chloride",
"PLoS",
"ONE",
"|",
"www.plosone.org",
"1",
"February",
"2011",
"|",
"Volume",
"6",
"|",
"Issue",
"2",
"|",
"e17411"
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] | [
"Original",
"Article",
"Elmer",
"Press",
"J",
"Clin",
"Med",
"Res",
"•",
"2010;2(3):117-120",
"Latent",
"Toxoplasmosis",
"in",
"Patients",
"With",
"Different",
"Malignancy:",
"A",
"Hospital",
"Based",
"Study",
"Amal",
"Nimira,",
"c,",
"Amizah",
"Othmanb,",
"Soon",
"Eeb,",
"Zohdy",
"Musab,",
"Iffah",
"Abd",
"Majidb,",
"Zalikha",
"Kamarudinb,",
"Chee",
"Xianb,",
"Noor",
"Hayati",
"Isab",
"Abstract",
"Background:",
"Seroprevalence",
"of",
"toxoplasmosis",
"in",
"different",
"popula-",
"tions",
"may",
"vary",
"according",
"to",
"different",
"environments,",
"social",
"customs",
"and",
"habits.",
"This",
"study",
"was",
"designed",
"to",
"measure",
"the",
"seroprevalence",
"of",
"toxoplasmosis",
"among",
"patients",
"with",
"different",
"malignancies",
"and",
"to",
"ascertain",
"the",
"association",
"between",
"common",
"risk",
"factors",
"and",
"disease",
"transmission.",
"Methods:",
"This",
"Cross-sectional",
"study",
"was",
"from",
"January",
"to",
"April",
"of",
"2009.",
"Four",
"Oncology",
"wards",
"in",
"Hospital",
"Universiti",
"Kebangsaan",
"Ma-",
"laysia",
"(HUKM)",
"were",
"selected",
"as",
"the",
"site",
"for",
"undertaking",
"the",
"present",
"study.",
"The",
"survey",
"involved",
"129",
"patients",
"with",
"different",
"malignan-",
"cies.",
"Information",
"was",
"gathered",
"by",
"using",
"study",
"subject",
"information",
"sheet",
"and",
"a",
"standardized",
"structured",
"questionnaire.",
"Toxoplasma",
"was",
"screened",
"by",
"a",
"standerd",
"ELISA",
"commercial",
"kit",
"in",
"accordance",
"with",
"the",
"manufacturer’s",
"instructions",
"and",
"performed",
"at",
"the",
"Department",
"of",
"Microbiology,",
"HUKM",
"Kuala",
"Lumpur.",
"A",
"result",
"of",
">",
"51",
"IU/ml",
"of",
"anti-Toxoplasma",
"(IgG)",
"antibody",
"was",
"regarded",
"as",
"positive,",
"indicat-",
"ing",
"latent",
"or",
"pre-existing",
"Toxoplasma",
"infection.",
"A",
"result",
"of",
">",
"51",
"IU/",
"ml",
"of",
"anti-Toxoplasma",
"(IgM)",
"antibody",
"was",
"regarded",
"as",
"positive,",
"indicating",
"recently",
"acquired",
"Toxoplasma",
"infection.",
"Results:",
"Total",
"number",
"of",
"seropositive",
"patients",
"was",
"54",
"(67.6%),",
"the",
"mean",
"age",
"was",
"51",
"years",
"(range15",
"-",
"88",
"years).",
"Toxoplasma",
"IgG",
"positivity",
"was",
"highest",
"among",
"Malaysian",
"(32%).",
"Male",
"to",
"female",
"ra-",
"tio",
"was",
"almost",
"equal.",
"There",
"was",
"a",
"statistically",
"significant",
"difference",
"in",
"seropositivity",
"between",
"patients",
"living",
"in",
"rural",
"areas",
"compared",
"to",
"those",
"living",
"in",
"urban",
"areas,",
"positive",
"history",
"of",
"consumption",
"of",
"undercooked",
"meat",
"and/or",
"blood",
"transfusion",
"(p",
"<",
"0.05).",
"Manuscript",
"accepted",
"for",
"publication",
"May",
"26,",
"2010",
"aDepartment",
"of",
"Pathology,",
"Cyberjaya",
"University",
"College",
"of",
"Medical",
"Sciences,",
"Malaysia",
"bDepartment",
"of",
"Parasitology,",
"Universiti",
"Kebangsaan",
"Malaysia,",
"Malaysia",
"cCorresponding",
"author,",
"Email:",
"aralmadi@yahoo.com",
"doi:10.4021/jocmr2010.06.375w",
"Conclusions:",
"These",
"findings",
"give",
"some",
"support",
"to",
"Toxoplasma",
"screening",
"program",
"and",
"health",
"education,",
"including",
"promotion",
"of",
"a",
"healthy",
"lifestyle",
"exclusively",
"in",
"seronegative",
"patients",
"in",
"order",
"to",
"prevent",
"seroconversion",
"and",
"the",
"incidence",
"of",
"clinically",
"evident",
"op-",
"portunistic",
"infection.",
"Keywords:",
"Toxoplasma",
"gondii;",
"Risk",
"factors;",
"Immunocompro-",
"mised;",
"seroconversion;",
"Seroprevalence",
"Introduction",
"Toxoplasma",
"gondii",
"(T.",
"gondii)",
"is",
"a",
"protozoan",
"parasite",
"that",
"is",
"endemic",
"worldwide",
"and",
"is",
"a",
"major",
"opportunistic",
"pathogen",
"in",
"immunocompromised",
"hosts.",
"Infection",
"is",
"mainly",
"acquired",
"by",
"ingestion",
"of",
"food,",
"water",
"or",
"soil",
"that",
"is",
"contaminated",
"with",
"oocysts",
"shed",
"by",
"cats,",
"or",
"by",
"eating",
"undercooked",
"or",
"raw",
"meat",
"containing",
"tissue",
"cysts",
"[1].",
"Primary",
"infection",
"is",
"usually",
"subclinical,",
"but",
"in",
"severely",
"immunocompromised",
"patients",
"it",
"may",
"be",
"life-threatening.",
"Most",
"primary",
"infections",
"subsequently",
"phase",
"into",
"chronic",
"in-",
"fections",
"in",
"which",
"the",
"parasite",
"persist",
"in",
"tissue",
"cysts,",
"mainly",
"in",
"the",
"brain,",
"retina,",
"skeletal",
"and",
"cardiac",
"muscles",
"[2].",
"These",
"chronic",
"infections",
"probably",
"persist",
"indefinitely",
"throughout",
"the",
"life",
"and",
"may",
"remain",
"undiagnosed",
"until",
"or",
"unless",
"it",
"is",
"re-",
"activated",
"as",
"a",
"result",
"of",
"severe",
"immune",
"suppression",
"[3].",
"For",
"the",
"diagnosis",
"of",
"T.",
"gondii",
"infection,",
"detection",
"of",
"the",
"organism",
"itself",
"is",
"confirmative",
"but",
"very",
"difficult.",
"Thus,",
"most",
"clinical",
"laboratories",
"use",
"serological",
"tests",
"to",
"detect",
"antibodies",
"against",
"T.",
"gondii",
"such",
"as",
"the",
"latex",
"agglutination",
"(LA)",
"test,",
"ELISA",
"and",
"indirect",
"fluorescent",
"antibody",
"test",
"because",
"of",
"its",
"high",
"specificity",
"and",
"sensitivity",
"[4].",
"Seroprevalence",
"in",
"different",
"populations",
"may",
"vary",
"ac-",
"cording",
"to",
"different",
"environments,",
"social",
"customs",
"and",
"habits",
"[5,",
"6].",
"Analysis",
"of",
"worldwide",
"reports",
"indicated",
"that",
"about",
"38.5%",
"humans,",
"32.9%",
"cats",
"and",
"24.2%",
"goats",
"were",
"seroposi-",
"tive",
"for",
"toxoplasmosis",
"[7].",
"This",
"study",
"was",
"designed",
"to",
"measure",
"the",
"seroprevalence",
"of",
"toxoplasmosis",
"among",
"patients",
"with",
"different",
"malignancies",
"and",
"to",
"ascertain",
"the",
"association",
"between",
"common",
"risk",
"factors",
"Articles",
"©",
"The",
"authors",
"|",
"Journal",
"compilation",
"©",
"J",
"Clin",
"Med",
"Res",
"and",
"Elmer",
"Press™",
"|",
"www.jocmr.org",
"117"
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] | [
"Ophir",
"et",
"al.",
"BMC",
"Genomics",
"2010,",
"11:269",
"http://www.biomedcentral.com/1471-2164/11/269",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"A",
"R",
"T",
"I",
"C",
"L",
"E",
"Open",
"Access",
"RHesiegarchh",
"-atrthicleroughput",
"marker",
"discovery",
"in",
"melon",
"using",
"a",
"self-designed",
"oligo",
"microarray",
"Ron",
"Ophir1,",
"Ravit",
"Eshed1,",
"Rotem",
"Harel-Beja2,",
"Galil",
"Tzuri2,",
"Vitaly",
"Portnoy2,",
"Yoseph",
"Burger2,",
"Shai",
"Uliel1,",
"Nurit",
"Katzir2",
"and",
"Amir",
"Sherman*1",
"Abstract",
"Background:",
"Genetic",
"maps",
"constitute",
"the",
"basis",
"of",
"breeding",
"programs",
"for",
"many",
"agricultural",
"organisms.",
"The",
"creation",
"of",
"these",
"maps",
"is",
"dependent",
"on",
"marker",
"discovery.",
"Melon,",
"among",
"other",
"crops,",
"is",
"still",
"lagging",
"in",
"genomic",
"resources,",
"limiting",
"the",
"ability",
"to",
"discover",
"new",
"markers",
"in",
"a",
"high-throughput",
"fashion.",
"One",
"of",
"the",
"methods",
"used",
"to",
"search",
"for",
"molecular",
"markers",
"is",
"DNA",
"hybridization",
"to",
"microarrays.",
"Microarray",
"hybridization",
"of",
"DNA",
"from",
"different",
"accessions",
"can",
"reveal",
"differences",
"between",
"them--single-feature",
"polymorphisms",
"(SFPs).",
"These",
"SFPs",
"can",
"be",
"used",
"as",
"markers",
"for",
"breeding",
"purposes,",
"or",
"they",
"can",
"be",
"converted",
"to",
"conventional",
"markers",
"by",
"sequencing.",
"This",
"method",
"has",
"been",
"utilized",
"in",
"a",
"few",
"different",
"plants",
"to",
"discover",
"genetic",
"variation,",
"using",
"Affymetrix",
"arrays",
"that",
"exist",
"for",
"only",
"a",
"few",
"organisms.",
"We",
"applied",
"this",
"approach",
"with",
"some",
"modifications",
"for",
"marker",
"discovery",
"in",
"melon.",
"Results:",
"Using",
"a",
"custom-designed",
"oligonucleotide",
"microarray",
"based",
"on",
"a",
"partial",
"EST",
"collection",
"of",
"melon,",
"we",
"discovered",
"6184",
"putative",
"SFPs",
"between",
"the",
"parents",
"of",
"our",
"mapping",
"population.",
"Validation",
"by",
"sequencing",
"of",
"245",
"SFPs",
"from",
"the",
"two",
"parents",
"showed",
"a",
"sensitivity",
"of",
"around",
"79%.",
"Most",
"SFPs",
"(81%)",
"contained",
"single-nucleotide",
"polymorphisms.",
"Testing",
"the",
"SFPs",
"on",
"another",
"mapping",
"population",
"of",
"melon",
"confirmed",
"that",
"many",
"of",
"them",
"are",
"conserved.",
"Conclusion:",
"Thousands",
"of",
"new",
"SFPs",
"that",
"can",
"be",
"used",
"for",
"genetic",
"mapping",
"and",
"molecular-assisted",
"breeding",
"in",
"melon",
"were",
"discovered",
"using",
"a",
"custom-designed",
"oligo",
"microarray.",
"A",
"portion",
"of",
"these",
"SFPs",
"are",
"conserved",
"and",
"can",
"be",
"used",
"in",
"different",
"breeding",
"populations.",
"Although",
"improvement",
"of",
"the",
"discovery",
"rate",
"is",
"still",
"needed,",
"this",
"approach",
"is",
"applicable",
"to",
"many",
"agricultural",
"systems",
"with",
"limited",
"genomic",
"resources.",
"Background",
"Genetic",
"maps",
"based",
"on",
"molecular",
"markers",
"are",
"a",
"key",
"step",
"in",
"marker-assisted",
"selection",
"(MAS)",
"for",
"plant",
"breeding",
"and",
"for",
"gene",
"identification",
"based",
"on",
"positional",
"informa-",
"tion",
"[1].",
"Discovery",
"of",
"novel",
"genetic",
"variation,",
"enhanced",
"selection",
"techniques",
"and",
"the",
"identification",
"of",
"genotypes",
"with",
"new",
"or",
"improved",
"traits",
"can",
"lead",
"to",
"superior",
"strains",
"of",
"interest.",
"The",
"density",
"of",
"the",
"markers",
"on",
"a",
"genetic",
"map",
"defines",
"the",
"map's",
"resolution",
"and",
"the",
"ability",
"to",
"introduce",
"these",
"traits",
"using",
"molecular",
"means.",
"New",
"high-through-",
"put",
"technologies",
"for",
"the",
"discovery",
"of",
"genetic",
"markers",
"and",
"linkage",
"analysis",
"can",
"enhance",
"plant",
"breeding",
"efforts",
"[2].",
"In",
"the",
"last",
"few",
"years,",
"genomic",
"tools",
"have",
"begun",
"to",
"replace",
"the",
"traditional",
"methods",
"of",
"molecular",
"marker",
"dis-",
"*",
"Correspondence:",
"asherman@agri.gov.il",
"1",
"Genomic",
"Unit,",
"Plant",
"Sciences",
"Institute,",
"Volcani",
"Center,",
"Agricultural",
"Research",
"Organization,",
"PO",
"Box",
"6,",
"Bet",
"Dagan",
"50250,",
"Israel",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"covery.",
"Use",
"of",
"computational",
"tools",
"to",
"search",
"sequence",
"information",
"for",
"molecular",
"markers",
"[3,4],",
"or",
"genomic",
"technologies",
"such",
"as",
"whole-genome",
"scanning",
"(WGS),",
"have",
"enabled",
"the",
"discovery",
"of",
"thousands",
"of",
"markers",
"in",
"a",
"single",
"experiment",
"[3].",
"These",
"markers",
"can",
"be",
"mapped",
"to",
"create",
"high-density",
"genetic",
"maps",
"or",
"used",
"directly",
"for",
"MAS",
"[3-5].",
"However,",
"use",
"of",
"these",
"types",
"of",
"technologies",
"for",
"plant",
"breeding",
"is",
"still",
"restricted,",
"as",
"many",
"agricultural",
"systems",
"have",
"a",
"limited",
"amount",
"of",
"genomic",
"resources.",
"Furthermore,",
"plant",
"species",
"contain",
"wide",
"genetic",
"variation",
"that",
"cannot",
"be",
"explored",
"by",
"sequencing",
"only",
"one",
"or",
"two",
"plants",
"from",
"each",
"species.",
"One",
"of",
"the",
"technologies",
"that",
"has",
"been",
"used",
"for",
"identifi-",
"cation",
"of",
"genetic",
"variation",
"is",
"single-feature",
"polymor-",
"phism",
"(SFP)",
"[3-5].",
"This",
"approach",
"is",
"based",
"on",
"the",
"concept",
"that",
"target",
"DNA",
"that",
"perfectly",
"matches",
"its",
"probes",
"binds",
"with",
"greater",
"affinity",
"than",
"one",
"with",
"a",
"mismatch.",
"Thus,",
"nat-",
"ural",
"imperfections",
"can",
"be",
"detected",
"as",
"a",
"difference",
"in",
"sig-",
"©",
"2010",
"Ophir",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"BioMed",
"Central",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"metal-organic",
"compounds",
"Acta",
"Crystallographica",
"Section",
"E",
"Structure",
"Reports",
"Online",
"ISSN",
"1600-5368",
"(2-{[2-(2-Aminoethylamino)ethylimino]-",
"4",
"methyl}phenolato-j",
"O,N0,N0",
"0,N000)-",
"copper(II)",
"perchlorate",
"Moussa",
"Dieng,a",
"Aliou",
"Hamady",
"Barry,b",
"Mohamed",
"Gaye,a*",
"Abdou",
"Salam",
"Sall,a",
"Paulo",
"Pe´",
"rez-Louridoc",
"and",
"Laura",
"Valencia-Matarranzc",
"aDe´partement",
"de",
"Chimie,",
"Faculte´",
"des",
"Sciences",
"et",
"Techniques,",
"Universite´",
"Cheikh",
"Anta",
"Diop,",
"Dakar,",
"Senegal,",
"bDe´partement",
"de",
"Chimie,",
"Faculte´",
"des",
"Sciences,",
"Universite´",
"de",
"Nouakchott,",
"Nouakchott,",
"Mauritania,",
"and",
"cDepartamento",
"de",
"Qu´ımica",
"Inorga´nica,",
"Facultade",
"de",
"Qu´ımica,",
"Universidad",
"de",
"Vigo,",
"36310",
"Vigo,",
"Pontevedra,",
"Spain",
"Correspondence",
"e-mail:",
"mlgayeastou@yahoo.fr",
"Received",
"13",
"April",
"2011;",
"accepted",
"26",
"May",
"2011",
"Key",
"indicators:",
"single-crystal",
"X-ray",
"study;",
"T",
"=",
"293",
"K;",
"mean",
"(C–C)",
"=",
"0.008",
"A˚;",
"R",
"factor",
"=",
"0.037;",
"wR",
"factor",
"=",
"0.131;",
"data-to-parameter",
"ratio",
"=",
"12.4.",
"The",
"asymmetric",
"unit",
"of",
"the",
"title",
"complex,",
"[Cu(C11H16N3O)]-",
"ClO4,",
"consists",
"of",
"two",
"CuII",
"ions",
"coordinated",
"by",
"Schiff",
"base",
"ligands",
"and",
"two",
"perchlorate",
"anions.",
"The",
"Schiff",
"base",
"molecules",
"are",
"linked",
"to",
"the",
"CuII",
"atoms",
"via",
"three",
"N",
"atoms",
"and",
"one",
"O",
"atom,",
"resulting",
"in",
"a",
"square-planar",
"geometry.",
"Intermolecular",
"hydrogen",
"bonds",
"involving",
"the",
"NH",
"groups",
"as",
"donors",
"and",
"O",
"atoms",
"of",
"the",
"perchlorate",
"anions",
"as",
"acceptors",
"are",
"observed.",
"Related",
"literature",
"For",
"related",
"structures,",
"see:",
"Ambrosi",
"et",
"al.",
"(2003);",
"Jiang",
"et",
"al.",
"(2009).",
"b",
"=",
"12.615",
"(3)",
"A˚",
"c",
"=",
"13.390",
"(3)",
"A˚",
"=",
"108.240",
"(4)",
"=",
"105.568",
"(4)",
"=",
"108.154",
"(4)",
"V",
"=",
"1445.2",
"(6)",
"A˚",
"3",
"Data",
"collection",
"Enraf–Nonius",
"CAD-4",
"diffractometer",
"9604",
"measured",
"reflections",
"4979",
"independent",
"reflections",
"4043",
"reflections",
"with",
"I",
">",
"2",
"(I)",
"Refinement",
"R[F",
"2",
">",
"2",
"(F",
"2)]",
"=",
"0.037",
"wR(F",
"2)",
"=",
"0.131",
"S",
"=",
"1.04",
"4979",
"reflections",
"403",
"parameters",
"6",
"restraints",
"Table",
"1",
"Selected",
"bond",
"lengths",
"(A˚",
").",
"Cu1—O2",
"Cu1—N6",
"Cu1—N5",
"Cu1—N4",
"Table",
"2",
"Hydrogen-bond",
"geometry",
"(A˚",
",",
").",
"D—H",
"A",
"N1—H1",
"O3Pi",
"N1—H1",
"O3P",
"N2—H2",
"O9Pii",
"N2—H3",
"O2",
"N4—H4",
"O8P",
"N4—H5",
"O1",
"N5—H6",
"O6Piii",
"N5—H6",
"O4P",
"Symmetry",
"codes:",
"(i)",
"x",
"þ",
"1;",
"y",
"þ",
"2;",
"z",
"þ",
"1.",
"D—H",
"0.85",
"(2)",
"0.85",
"(2)",
"0.85",
"(2)",
"0.86",
"(2)",
"0.86",
"(2)",
"0.86",
"(2)",
"0.84",
"(2)",
"0.84",
"(2)",
"Z",
"=",
"4",
"Mo",
"K",
"radiation",
"=",
"1.72",
"mm",
"1",
"T",
"=",
"293",
"K",
"0.14",
"0.12",
"0.10",
"mm",
"Rint",
"=",
"0.024",
"2",
"standard",
"reflections",
"every",
"167",
"reflections",
"intensity",
"decay:",
"none",
"H",
"atoms",
"treated",
"by",
"a",
"mixture",
"of",
"independent",
"and",
"constrained",
"refinement",
"max",
"=",
"0.53",
"e",
"A˚",
"3",
"min",
"=",
"0.52",
"e",
"A˚",
"3",
"1.891",
"(3)",
"1.933",
"(4)",
"2.005",
"(4)",
"2.006",
"(4)",
"Cu2—O1",
"Cu2—N3",
"Cu2—N2",
"Cu2—N1",
"H",
"A",
"2.52",
"(3)",
"2.54",
"(3)",
"2.30",
"(3)",
"2.12",
"(2)",
"2.46",
"(3)",
"2.24",
"(2)",
"2.47",
"(4)",
"2.51",
"(3)",
"D",
"A",
"3.188",
"(5)",
"3.208",
"(5)",
"3.069",
"(6)",
"2.955",
"(5)",
"3.223",
"(7)",
"3.084",
"(5)",
"3.081",
"(5)",
"3.195",
"(5)",
"x",
"þ",
"2;",
"y",
"þ",
"2;",
"z",
"þ",
"1;",
"(ii)",
"x",
"þ",
"1;",
"y",
"þ",
"1;",
"z;",
"(iii)",
"1.895",
"(3)",
"1.930",
"(3)",
"2.010",
"(4)",
"2.012",
"(3)",
"D—H",
"A",
"136",
"(4)",
"136",
"(4)",
"151",
"(4)",
"162",
"(4)",
"148",
"(3)",
"168",
"(4)",
"131",
"(4)",
"139",
"(4)",
"Experimental",
"Crystal",
"data",
"[Cu(C11H16N3O)]ClO4",
"Mr",
"=",
"369.26",
"m830",
"Dieng",
"et",
"al.",
"Triclinic,",
"P1",
"a",
"=",
"10.371",
"(3)",
"A˚",
"Data",
"collection:",
"CAD-4",
"EXPRESS",
"(Enraf–Nonius,",
"1994);",
"cell",
"refinement:",
"CAD-4",
"EXPRESS;",
"data",
"reduction:",
"MolEN",
"(Fair,",
"1990);",
"program(s)",
"used",
"to",
"solve",
"structure:",
"SHELXS97",
"(Sheldrick,",
"2008);",
"program(s)",
"used",
"to",
"refine",
"structure:",
"SHELXL97",
"(Sheldrick,",
"2008);",
"molecular",
"graphics:",
"ORTEP-3",
"for",
"Windows",
"(Farrugia,",
"1997);",
"soft-",
"ware",
"used",
"to",
"prepare",
"material",
"for",
"publication:",
"SHELXL97.",
"The",
"authors",
"thank",
"the",
"Agence",
"Universitaire",
"de",
"la",
"Franco-",
"phonie",
"for",
"financial",
"support",
"(AUF-PSCI",
"No.",
"6314PS804).",
"Supplementary",
"data",
"and",
"figures",
"for",
"this",
"paper",
"are",
"available",
"from",
"the",
"IUCr",
"electronic",
"archives",
"(Reference:",
"AA2008).",
"References",
"Ambrosi,",
"G.,",
"Formica,",
"M.,",
"Fusi,",
"V.,",
"Giorgi,",
"L.,",
"Guerri,",
"A.,",
"Micheloni,",
"M.,",
"Pontellini,",
"R.",
"&",
"Rossi,",
"P.",
"(2003).",
"Polyhedron,",
"22,",
"1135–1146.",
"doi:10.1107/S1600536811020095",
"Acta",
"Cryst.",
"(2011).",
"E67,",
"m830–m831"
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738,
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550,
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657,
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712,
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[
550,
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707,
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725,
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728,
623,
777,
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550,
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562,
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574,
652
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[
577,
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610,
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612,
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625,
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635,
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683,
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550,
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594,
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652,
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[
714,
652,
778,
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[
550,
667,
589,
681
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[
592,
667,
641,
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[
644,
667,
663,
681
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[
667,
667,
685,
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[
689,
667,
731,
681
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[
734,
667,
777,
681
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[
550,
682,
588,
696
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[
591,
682,
608,
696
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[
611,
682,
644,
696
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[
647,
682,
666,
696
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[
669,
682,
710,
696
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[
713,
682,
754,
696
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[
757,
682,
777,
696
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550,
696,
572,
710
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575,
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613,
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617,
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639,
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643,
696,
675,
710
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679,
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692,
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695,
696,
738,
710
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[
742,
696,
777,
710
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[
550,
711,
599,
725
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[
602,
711,
624,
725
],
[
628,
711,
644,
725
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[
647,
711,
674,
725
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[
677,
711,
734,
725
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738,
711,
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725
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[
550,
725,
570,
739
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[
572,
725,
604,
739
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[
607,
725,
619,
739
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[
622,
725,
659,
739
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[
661,
725,
690,
739
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[
692,
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[
746,
725,
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[
550,
740,
577,
754
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[
580,
740,
599,
754
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[
603,
740,
623,
754
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[
626,
740,
649,
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[
653,
740,
676,
754
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680,
740,
725,
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729,
740,
763,
754
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[
767,
740,
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[
550,
755,
575,
769
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579,
755,
609,
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[
613,
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654,
769
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[
657,
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679,
755,
702,
769
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[
706,
755,
749,
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752,
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765,
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695,
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744,
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549,
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586,
791,
653,
803
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657,
791,
666,
803
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669,
791,
680,
803
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683,
791,
721,
803
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724,
791,
777,
803
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549,
804,
558,
816
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561,
804,
610,
816
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614,
804,
659,
816
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662,
804,
700,
816
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704,
804,
713,
816
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717,
804,
777,
816
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549,
816,
566,
828
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570,
816,
640,
828
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644,
816,
691,
828
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696,
816,
721,
828
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725,
816,
777,
828
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549,
829,
599,
841
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601,
829,
615,
841
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617,
829,
660,
841
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662,
829,
688,
841
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[
691,
829,
727,
841
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728,
829,
777,
841
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[
549,
841,
616,
853
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[
620,
841,
639,
853
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[
642,
841,
709,
853
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[
713,
841,
747,
853
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750,
841,
777,
853
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549,
854,
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866
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557,
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] | [
"Research",
"Low-Level",
"Environmental",
"Cadmium",
"Exposure",
"Is",
"Associated",
"with",
"DNA",
"Hypomethylation",
"in",
"Argentinean",
"Women",
"Mohammad",
"Bakhtiar",
"Hossain,1,2",
"Marie",
"Vahter,3",
"Gabriela",
"Concha,4",
"and",
"Karin",
"Broberg",
"1",
"1Department",
"of",
"Laboratory",
"Medicine,",
"Division",
"of",
"Occupational",
"and",
"Environmental",
"Medicine,",
"Lund",
"University,",
"Lund,",
"Sweden;",
"2International",
"Centre",
"for",
"Diarrhoeal",
"Disease",
"Research,",
"Bangladesh,",
"Dhaka,",
"Bangladesh;",
"3Institute",
"of",
"Environmental",
"Medicine,",
"Karolinska",
"Institutet,",
"Stockholm,",
"Sweden;",
"4Risk",
"and",
"Benefit",
"Assessment",
"Department,",
"National",
"Food",
"Agency,",
"Uppsala,",
"Sweden",
"Background",
":",
"Cadmium,",
"a",
"common",
"food",
"pollutant,",
"alters",
"DNA",
"methylation",
"in",
"vitro.",
"Epigenetic",
"effects",
"might",
"therefore",
"partly",
"explain",
"cadmium’s",
"toxicity,",
"including",
"its",
"carcinogenicity;",
"however,",
"human",
"data",
"on",
"epigenetic",
"effects",
"are",
"lacking.",
"o",
"Bjectiv",
":",
"We",
"evaluated",
"the",
"effects",
"of",
"dietary",
"cadmium",
"exposure",
"on",
"DNA",
"methylation,",
"consider",
"ing",
"other",
"environmental",
"exposures,",
"genetic",
"predisposition,",
"and",
"gene",
"expression.",
"Methods",
":",
"Concentrations",
"of",
"cadmium,",
"arsenic,",
"selenium,",
"and",
"zinc",
"in",
"blood",
"and",
"urine",
"of",
"non",
"smoking",
"women",
"(n",
"=",
"202)",
"from",
"the",
"northern",
"Argentinean",
"Andes",
"were",
"measured",
"by",
"inductively",
"coupled",
"mass",
"spectrometry.",
"Methylation",
"in",
"CpG",
"islands",
"of",
"LINE-1",
"(long",
"interspersed",
"nuclear",
"element1;",
"a",
"proxy",
"for",
"global",
"DNA",
"methylation)",
"and",
"promoter",
"regions",
"of",
"p16",
"[cyclindependent",
"kinase",
"inhibitor",
"2A",
"(CDKN2A)]",
"and",
"MLH1",
"(mutL",
"homolog",
"1)",
"in",
"peripheral",
"blood",
"were",
"measured",
"by",
"bisulfite",
"polymerase",
"chain",
"reaction",
"pyrosequencing.",
"Genotyping",
"(n",
"=",
"172)",
"for",
"the",
"DNA",
"(cytosine",
"5)methyltransferase",
"1",
"gene",
"(",
"DNMT1",
"rs10854076",
"and",
"rs2228611)",
"and",
"DNA",
"(cytosine5)methyl",
"transferase",
"3",
"beta",
"gene",
"(DNMT3B",
"rs2424913",
"and",
"rs2424932)",
"was",
"performed",
"with",
"Sequenom",
"iPLEX",
"GOLD",
"SNP",
"genotyping;",
"and",
"gene",
"expression",
"(n",
"=",
"90),",
"with",
"DirectHyb",
"HumanHT12",
"(version",
"3.0).",
"r",
"esult",
":",
"Cadmium",
"exposure",
"was",
"low:",
"median",
"concentrations",
"in",
"blood",
"and",
"urine",
"were",
"0.36",
"and",
"0.23",
"µg/L,",
"respectively.",
"Urinary",
"cadmium",
"(natural",
"log",
"transformed)",
"was",
"inversely",
"associated",
"with",
"LINE-1",
"methylation",
"(β",
"=",
"–0.50,",
"p",
"=",
"0.0070;",
"β",
"=",
"–0.44,",
"p",
"=",
"0.026,",
"adjusted",
"for",
"age",
"and",
"coca",
"chew",
"ing)",
"but",
"not",
"with",
"p16",
"or",
"MLH1",
"methylation.",
"Both",
"DNMT1",
"rs10854076",
"and",
"DNMT1",
"rs2228611",
"polymorphisms",
"modified",
"associations",
"between",
"urinary",
"cadmium",
"and",
"LINE-1",
"(pvalues",
"for",
"interaction",
"in",
"adjusted",
"models",
"were",
"0.045",
"and",
"0.064,",
"respectively).",
"The",
"rare",
"genotypes",
"demonstrated",
"stronger",
"hypomethylation",
"with",
"increasing",
"urinary",
"cadmium",
"concentrations.",
"Cadmium",
"was",
"inversely",
"associated",
"with",
"DNMT3B",
"(rS",
"=",
"–0.28,",
"p",
"=",
"0.0086)",
"but",
"not",
"with",
"DNMT1",
"expression",
"(rS",
"=",
"–0.075,",
"p",
"=",
"0.48).",
"c",
"onclusi",
":",
"Environmental",
"cadmium",
"exposure",
"was",
"associated",
"with",
"DNA",
"hypomethylation",
"in",
"peripheral",
"blood,",
"and",
"DNMT1",
"genotypes",
"modified",
"this",
"association.",
"The",
"role",
"of",
"epigenetic",
"modifica",
"tions",
"in",
"cadmiumassociated",
"diseases",
"needs",
"clarification.",
"k",
"ey",
"w",
"ords",
":",
"cadmium,",
"DNMT1,",
"DNMT3B,",
"epigenetic,",
"genotype,",
"LINE-1,",
"MLH1,",
"p16,",
"pyro",
"sequencing.",
"Environ",
"Health",
"Perspect",
"120:879–884",
"(2012).",
"http://dx.doi.org/10.1289/ehp.1104600",
"[Online",
"1",
"March",
"2012]",
"Cadmium",
"is",
"a",
"widespread",
"environmental",
"pollutant",
"associated",
"with",
"adverse",
"health",
"effects,",
"including",
"cancer,",
"kidney",
"damage,",
"low",
"bone-mineral",
"density,",
"bone",
"fractures,",
"and",
"probably",
"impaired",
"early-life",
"development",
"(Engström",
"A",
"et",
"al.",
"2011;",
"Järup",
"and",
"Åkesson",
"2009;",
"Kippler",
"et",
"al.",
"2011).",
"The",
"general",
"popu-",
"lation",
"is",
"exposed",
"to",
"cadmium",
"mainly",
"through",
"the",
"diet,",
"in",
"particular,",
"through",
"cereals",
"and",
"vegetables,",
"and",
"through",
"smoking.",
"Potential",
"mechanisms",
"of",
"cadmium",
"toxicity",
"described",
"so",
"far",
"include",
"interactions",
"with",
"sulfhydryl",
"groups",
"and",
"endocrine",
"disruption,",
"as",
"well",
"as",
"oxidative",
"stress",
"(Hartwig",
"2010;",
"Johnson",
"et",
"al.",
"2003;",
"Monroe",
"and",
"Halvorsen",
"2006;",
"Xu",
"et",
"al.",
"2011;",
"Yu",
"et",
"al.",
"2010).",
"DNA",
"methylation",
"is",
"essential",
"for",
"embryo-",
"genesis",
"and",
"for",
"maintaining",
"cell-lineage–",
"specific",
"gene",
"expression",
"throughout",
"life.",
"Dysregulation",
"of",
"epigenetic",
"processes,",
"such",
"as",
"DNA",
"methylation,",
"may",
"lead",
"to",
"impaired",
"child-",
"hood",
"development",
"or",
"chronic",
"diseases",
"later",
"in",
"life,",
"including",
"cancer",
"(Faulk",
"and",
"Dolinoy",
"2011;",
"Feinberg",
"2007;",
"Robins",
"et",
"al.",
"2011).",
"In",
"carcinogenesis,",
"global",
"DNA",
"methylation",
"is",
"generally",
"decreased,",
"whereas",
"specific",
"regions",
"of",
"DNA",
"that",
"contain",
"tumor",
"suppressor",
"genes",
"often",
"show",
"hypermethylation",
"(Chalitchagorn",
"et",
"al.",
"2004;",
"Deng",
"et",
"al.",
"2006;",
"Gaudet",
"et",
"al.",
"2003;",
"Robertson",
"and",
"Jones",
"2000).",
"In",
"vitro",
"studies",
"have",
"indicated",
"that",
"cadmium",
"may",
"interfere",
"with",
"epigenetic",
"processes:",
"Both",
"gene-",
"specific",
"DNA",
"hypermethylation",
"with",
"gene",
"silencing",
"of",
"p16INK4a",
"[CDKN2A",
"(cyclin-",
"dependent",
"kinase",
"inhibitor",
"2A)],",
"RASSF1",
"[Ras",
"association",
"(RalGDS/AF-6)",
"domain",
"family",
"member",
"1],",
"and",
"MT1",
"(metallothionein",
"1)",
"genes,",
"and",
"global",
"DNA",
"hypomethylation",
"have",
"been",
"reported",
"(Benbrahim-Tallaa",
"et",
"al.",
"2007;",
"Huang",
"et",
"al.",
"2008;",
"Jiang",
"et",
"al.",
"2008;",
"Martinez-Zamudio",
"and",
"Ha",
"2011;",
"Takiguchi",
"et",
"al.",
"2003).",
"However,",
"there",
"are",
"no",
"reports",
"on",
"the",
"epigenetic",
"effects",
"of",
"cadmium",
"exposure",
"in",
"humans.",
"The",
"aim",
"of",
"this",
"study",
"was",
"to",
"evaluate",
"whether",
"environmental",
"cadmium",
"exposure,",
"mainly",
"through",
"the",
"normal",
"diet,",
"may",
"affect",
"DNA",
"methylation,",
"both",
"of",
"repetitive",
"genetic",
"Environmental",
"Health",
"Perspectives",
"•",
"volume",
"120",
"|",
"number",
"6",
"|",
"June",
"2012",
"elements",
"(as",
"a",
"proxy",
"for",
"global",
"methylation)",
"and",
"of",
"specific",
"genes.",
"Materials",
"and",
"Methods",
"Participants.",
"We",
"studied",
"202",
"women",
"living",
"in",
"the",
"Andean",
"plateau",
"(3,800",
"m",
"above",
"sea",
"level)",
"in",
"northern",
"Argentina,",
"an",
"area",
"that",
"has",
"minimal",
"industrial",
"or",
"vehicle-derived",
"pollu-",
"tion.",
"Most",
"of",
"the",
"study",
"participants",
"(161)",
"were",
"from",
"the",
"village",
"of",
"San",
"Antonio",
"de",
"los",
"Cobres,",
"which",
"has",
"about",
"5,000",
"inhabitants.",
"The",
"41",
"remaining",
"participants",
"were",
"from",
"small",
"surrounding",
"villages.",
"The",
"study",
"area",
"is",
"known",
"to",
"have",
"elevated",
"concentrations",
"of",
"arsenic",
"(Vahter",
"et",
"al.",
"1995),",
"but",
"not",
"cadmium",
"(Concha",
"et",
"al.",
"2010),",
"in",
"the",
"drinking",
"water.",
"The",
"study",
"individuals",
"were",
"recruited",
"with",
"the",
"assistance",
"of",
"local",
"medical",
"personnel,",
"except",
"in",
"the",
"small",
"mining",
"village",
"of",
"Tolar",
"Grande,",
"where",
"we",
"went",
"from",
"house",
"to",
"house",
"to",
"explain",
"the",
"study",
"and",
"invited",
"the",
"adults",
"to",
"participate.",
"We",
"included",
"only",
"women",
"because",
"men",
"were",
"often",
"away",
"from",
"home",
"for",
"longer",
"periods",
"for",
"work",
"and",
"were",
"therefore",
"likely",
"to",
"be",
"exposed",
"to",
"a",
"different",
"variety",
"of",
"environmental",
"hazards.",
"Furthermore,",
"women",
"may",
"be",
"more",
"susceptible",
"to",
"cadmium",
"exposure",
"than",
"are",
"men",
"because",
"of",
"their",
"increased",
"gastrointestinal",
"cadmium",
"absorption",
"when",
"iron",
"stores",
"are",
"low",
"(Berglund",
"et",
"al.",
"1994),",
"as",
"is",
"common",
"in",
"women",
"of",
"child-",
"bearing",
"age.",
"Only",
"four",
"study",
"participants",
"smoked",
"cigarettes,",
"and",
"one",
"reported",
"drinking",
"alcohol,",
"but",
"almost",
"half",
"(46.5%)",
"reported",
"that",
"they",
"chewed",
"coca",
"leaves.",
"As",
"reported",
"before,",
"interviews",
"with",
"the",
"study",
"participants",
"revealed",
"that",
"almost",
"all",
"women",
"drank",
"exclusively",
"public",
"water",
"and",
"that",
"their",
"diets",
"consisted",
"mainly",
"of",
"corn,",
"beans,",
"chicken,",
"and",
"pork",
"(Broberg",
"et",
"al.",
"2011).",
"Only",
"three",
"women",
"reported",
"taking",
"Address",
"correspondence",
"to",
"K.",
"Broberg,",
"Department",
"of",
"Laboratory",
"Medicine,",
"Division",
"of",
"Occupational",
"and",
"Environmental",
"Medicine,",
"Lund",
"University,",
"Klinikgatan",
"21,",
"SE-22185",
"Lund,",
"Sweden.",
"Telephone:",
"46046173819.",
"Fax:",
"46046143207.",
"E-mail:",
"karin.",
"broberg_palmgren@med.lu.se",
"Supplemental",
"Material",
"is",
"available",
"online",
"(http://",
"dx.doi.org/10.1289/ehp.1104600).",
"We",
"thank",
"the",
"Department",
"of",
"Oncology,",
"Lund",
"University,",
"for",
"technical",
"assistance.",
"This",
"research",
"was",
"supported",
"by",
"the",
"Swedish",
"Council",
"for",
"Working",
"Life",
"and",
"Social",
"Research,",
"Karolinska",
"Institutet,",
"and",
"Kungliga",
"fysiografiska",
"sällskapet,",
"European",
"Union",
"(FP6;",
"“PHIME”",
"FOOD-CT-2006-",
"016253).",
"The",
"authors",
"declare",
"they",
"have",
"no",
"actual",
"or",
"potential",
"competing",
"financial",
"interests.",
"Received",
"10",
"October",
"2011;",
"accepted",
"1",
"March",
"2012.",
"879"
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] | [
"Hindawi",
"Publishing",
"Corporation",
"Case",
"Reports",
"in",
"Medicine",
"Volume",
"2012,",
"Article",
"ID",
"529246,",
"2",
"pages",
"doi:10.1155/2012/529246",
"Case",
"Report",
"Unusual",
"Cause",
"of",
"Intestinal",
"Obstruction:",
"Left",
"Paraduodenal",
"Hernia",
"Sami",
"Akbulut",
"Department",
"of",
"Surgery,",
"Diyarbakir",
"Education",
"and",
"Research",
"Hospital,",
"21400",
"Diyarbakir,",
"Turkey",
"Correspondence",
"should",
"be",
"addressed",
"to",
"Sami",
"Akbulut,",
"akbulutsami@gmail.com",
"Received",
"13",
"November",
"2011;",
"Accepted",
"2",
"January",
"2012",
"Academic",
"Editor:",
"Michail",
"Varras",
"Copyright",
"©",
"2012",
"Sami",
"Akbulut.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Internal",
"intestinal",
"hernia",
"has",
"been",
"defined",
"as",
"bulging",
"of",
"the",
"intestines",
"through",
"a",
"normal",
"or",
"an",
"abnormal",
"peritoneal",
"or",
"mesenteric",
"opening.",
"Paraduodenal",
"hernias",
"comprise",
"30%–53%",
"of",
"all",
"internal",
"intestinal",
"herniations",
"and",
"account",
"for",
"0.2%–0.9%",
"of",
"all",
"bowel",
"obstructions.",
"In",
"this",
"paper,",
"we",
"aimed",
"to",
"present",
"a",
"male",
"patient",
"of",
"42",
"years",
"of",
"age",
"who",
"developed",
"intestinal",
"obstruction",
"due",
"to",
"left",
"paraduodenal",
"hernias.",
"Left",
"paraduodenal",
"hernia",
"should",
"be",
"taken",
"into",
"consideration",
"in",
"the",
"differential",
"diagnosis",
"in",
"patients",
"of",
"relatively",
"younger",
"ages",
"with",
"no",
"prior",
"abdominal",
"surgery",
"who",
"frequently",
"have",
"bowel",
"obstruction",
"episodes.",
"1.",
"Introduction",
"Internal",
"intestinal",
"hernia",
"has",
"been",
"defined",
"as",
"bulging",
"of",
"the",
"intestines",
"through",
"a",
"normal",
"or",
"an",
"abnormal",
"peritoneal",
"or",
"mesenteric",
"opening.",
"This",
"clinical",
"entity",
"can",
"occur",
"for",
"con-",
"genital",
"or",
"acquired",
"reasons",
"and",
"accounts",
"for",
"around",
"1%–",
"5.8%",
"of",
"all",
"intestinal",
"obstructions",
"[1–3].",
"Although",
"the",
"intestinal",
"herniations",
"are",
"divided",
"into",
"distinct",
"subgroups",
"based",
"on",
"the",
"localizations,",
"it",
"is",
"the",
"paraduedonal",
"hernias",
"which",
"are",
"responsible",
"in",
"nearly",
"half",
"of",
"the",
"patients.",
"Also",
"known",
"as",
"Treitz’s",
"hernia,",
"the",
"paraduedonal",
"herniations",
"even-",
"tuate",
"from",
"abnormal",
"rotation",
"of",
"intestine.",
"Paraduedonal",
"hernias",
"comprise",
"30%–53%",
"of",
"all",
"intestinal",
"herniations",
"and",
"account",
"for",
"0.2%–0.9%",
"of",
"all",
"bowel",
"obstructions",
"[1–4].",
"In",
"this",
"study,",
"we",
"aimed",
"to",
"present",
"a",
"male",
"patient",
"of",
"42",
"years",
"of",
"age",
"who",
"developed",
"intestinal",
"obstruction",
"due",
"to",
"left",
"para-",
"duedonal",
"hernias.",
"2.",
"Case",
"Presentation",
"A",
"42-year-old",
"male",
"patient",
"was",
"admitted",
"to",
"our",
"emergency",
"department",
"with",
"the",
"complaints",
"of",
"nausea,",
"vomiting,",
"and",
"abdominal",
"pain",
"that",
"had",
"lasted",
"for",
"3",
"days",
"and",
"had",
"shown",
"progressive",
"worsening.",
"The",
"patient",
"especially",
"expressed",
"that",
"the",
"pain",
"had",
"intensified",
"around",
"the",
"umbilical",
"region",
"and",
"that",
"he",
"had",
"been",
"unable",
"to",
"pass",
"stool",
"or",
"gas.",
"The",
"patient’s",
"history",
"revealed",
"no",
"systemic",
"disease",
"or",
"prior",
"operation.",
"As",
"for",
"the",
"vital",
"signs",
"of",
"the",
"patient,",
"the",
"blood",
"pressure,",
"the",
"pulse",
"rate,",
"and",
"the",
"body",
"temperature",
"were",
"measured",
"to",
"be",
"130/85",
"mmHg,",
"83",
"beats/min",
"and",
"37.3◦C,",
"respectively.",
"Marked",
"abdominal",
"distension",
"and",
"rebound",
"tenderness",
"were",
"detected",
"in",
"the",
"physical",
"examination",
"performed,",
"whereas",
"no",
"abdominal",
"guarding",
"was",
"observed.",
"In",
"standing",
"abdominal",
"direct",
"X-ray,",
"widespread",
"air-fluid",
"levels",
"were",
"observed.",
"While",
"no",
"pathological",
"finding",
"was",
"detected",
"other",
"than",
"mild",
"uremia",
"in",
"the",
"blood",
"chemistry,",
"leukocyte",
"counts",
"was",
"reported",
"to",
"be",
"16.450/mm3.",
"We",
"were",
"not",
"able",
"to",
"obtain",
"ultrasonographic",
"or",
"contrast-enhanced",
"abdominal",
"CT",
"evaluation",
"because",
"of",
"the",
"fact",
"that",
"the",
"patient",
"was",
"admitted",
"to",
"our",
"emergency",
"depart-",
"ment",
"at",
"11.00",
"pm.",
"Given",
"the",
"physical",
"examination",
"findings,",
"plain",
"X-ray",
"imaging",
"and",
"the",
"absence",
"of",
"any",
"prior",
"surgery",
"in",
"the",
"case",
"history,",
"the",
"patient",
"was",
"taken",
"into",
"surgery",
"consid-",
"ering",
"that",
"widespread",
"peritonitis",
"was",
"likely",
"to",
"exist",
"due",
"to",
"a",
"possible",
"congenital",
"brid",
"or",
"a",
"perforated",
"appendicitis",
"with",
"delayed",
"diagnosis.",
"We",
"observed,",
"in",
"the",
"surgical",
"exploration",
"via",
"midline",
"incision,",
"that",
"all",
"of",
"the",
"small",
"intestinal",
"segments",
"except",
"a",
"distal",
"ileal",
"portion",
"of",
"50–60",
"cm",
"length",
"was",
"stuck",
"in",
"the",
"sac",
"of",
"a",
"left",
"paraduedonal",
"hernia.",
"The",
"inferior",
"mesenteric",
"vein",
"constituted",
"the",
"anterior",
"portion",
"of",
"the",
"hernial",
"sac",
"from",
"the",
"orifice",
"(Figure",
"1).",
"After",
"reducing",
"the",
"intestinal",
"segments",
"in",
"the",
"hernial",
"sac",
"into",
"the",
"abdominal",
"cavity,",
"IMV",
"was",
"released",
"alongside",
"its",
"length.",
"Then",
"followed",
"sealing",
"off"
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"Weekes,a,c",
"Tiffany",
"Wooten,a,f",
"Qingping",
"Xu,a,b",
"Keith",
"O.",
"Hodgson,a,g",
"John",
"Wooley,a,e",
"Ashley",
"M.",
"Deacon,a,b",
"Adam",
"Godzik,a,c,e",
"Scott",
"A.",
"Lesleya,d,f",
"and",
"Ian",
"A.",
"Wilsona,d*",
"aJoint",
"Center",
"for",
"Structural",
"Genomics,",
"http://www.jcsg.org,",
"USA,",
"bStanford",
"Synchrotron",
"Radiation",
"Lightsource,",
"SLAC",
"National",
"Accelerator",
"Laboratory,",
"Menlo",
"Park,",
"California,",
"USA,",
"cProgram",
"on",
"Bioinformatics",
"and",
"Systems",
"Biology,",
"Burnham",
"Institute",
"for",
"Medical",
"Research,",
"La",
"Jolla,",
"California,",
"USA,",
"dDepartment",
"of",
"Molecular",
"Biology,",
"The",
"Scripps",
"Research",
"Institute,",
"La",
"Jolla,",
"California,",
"USA,",
"eCenter",
"for",
"Research",
"in",
"Biological",
"Systems,",
"University",
"of",
"California,",
"San",
"Diego,",
"La",
"Jolla,",
"California,",
"USA,",
"fProtein",
"Sciences",
"Department,",
"Genomics",
"Institute",
"of",
"the",
"Novartis",
"Research",
"Foundation,",
"San",
"Diego,",
"California,",
"USA,",
"and",
"gPhoton",
"Science,",
"SLAC",
"National",
"Accelerator",
"Laboratory,",
"Menlo",
"Park,",
"California,",
"USA",
"Correspondence",
"e-mail:",
"wilson@scripps.edu",
"Received",
"16",
"April",
"2009",
"Accepted",
"13",
"May",
"2009",
"PDB",
"Reference:",
"KPN03535,",
"3flz,",
"r3f1zsf.",
"The",
"structure",
"of",
"KPN03535",
"(gi|152972051),",
"a",
"novel",
"putative",
"lipoprotein",
"from",
"Klebsiella",
"pneumoniae,",
"reveals",
"an",
"OB-fold",
"KPN03535",
"(gi|152972051)",
"is",
"a",
"putative",
"lipoprotein",
"of",
"unknown",
"function",
"that",
"is",
"secreted",
"by",
"Klebsiella",
"pneumoniae",
"MGH",
"78578.",
"The",
"crystal",
"structure",
"reveals",
"that",
"despite",
"a",
"lack",
"of",
"any",
"detectable",
"sequence",
"similarity",
"to",
"known",
"structures,",
"it",
"is",
"a",
"novel",
"variant",
"of",
"the",
"OB-fold",
"and",
"structurally",
"similar",
"to",
"the",
"bacterial",
"Cpx-",
"pathway",
"protein",
"NlpE,",
"single-stranded",
"DNA-binding",
"(SSB)",
"proteins",
"and",
"toxins.",
"K.",
"pneumoniae",
"MGH",
"78578",
"forms",
"part",
"of",
"the",
"normal",
"human",
"skin,",
"mouth",
"and",
"gut",
"flora",
"and",
"is",
"an",
"opportunistic",
"pathogen",
"that",
"is",
"linked",
"to",
"about",
"8%",
"of",
"all",
"hospital-acquired",
"infections",
"in",
"the",
"USA.",
"This",
"structure",
"provides",
"the",
"foundation",
"for",
"further",
"investigations",
"into",
"this",
"divergent",
"member",
"of",
"the",
"OB-fold",
"family.",
"1.",
"Introduction",
"KPN03535",
"(gi|152972051)",
"is",
"an",
"orphan",
"protein",
"that",
"is",
"exclusively",
"found",
"in",
"Klebsiella",
"pneumoniae",
"MGH",
"78578",
"(an",
"opportunistic",
"human",
"pathogen",
"belonging",
"to",
"enterbacteriales",
"of",
"gammaproteo-",
"bacteria;",
"Galperin",
"et",
"al.,",
"2007;",
"Gill",
"et",
"al.,",
"2006;",
"Frank",
"&",
"Pace,",
"2008;",
"Ley",
"et",
"al.,",
"2008)",
"and",
"K.",
"pneumoniae",
"342",
"(three-residue",
"substitution).",
"It",
"consists",
"of",
"132",
"residues",
"with",
"a",
"calculated",
"pI",
"of",
"9.40",
"and",
"a",
"predicted",
"signal",
"peptide.",
"The",
"N-terminus",
"of",
"KPN03535",
"has",
"a",
"lipoprotein",
"signature,",
"indicated",
"by",
"the",
"presence",
"of",
"an",
"LSGC",
"motif",
"(von",
"Heijne,",
"1989),",
"as",
"well",
"as",
"predictions",
"from",
"LipoP",
"1.0",
"(Juncker",
"et",
"al.,",
"2003).",
"It",
"is",
"a",
"singleton",
"protein",
"that",
"has",
"not",
"been",
"assigned",
"to",
"any",
"Pfam",
"family,",
"but",
"sequence-based",
"fold-prediction",
"methods",
"(Ginalski",
"et",
"al.,",
"2003)",
"suggest",
"similarity",
"to",
"members",
"of",
"the",
"PF01336",
"family",
"(OB-fold",
"nucleic",
"acid-binding",
"domain).",
"We",
"determined",
"the",
"crystal",
"structure",
"of",
"KPN03535",
"in",
"order",
"to",
"explore",
"this",
"extremely",
"divergent",
"member",
"of",
"the",
"commonly",
"occurring",
"OB-fold.",
"Structural",
"comparisons",
"show",
"similarities",
"to",
"the",
"OB-fold-containing",
"Cpx-pathway",
"protein",
"NlpE,",
"single-stranded",
"DNA-binding",
"(SSB)",
"proteins,",
"bacterial",
"OB-fold",
"(BOF)",
"and",
"toxin",
"proteins,",
"which",
"enable",
"inferences",
"about",
"function",
"that",
"may",
"now",
"be",
"tested",
"biochemically.",
"This",
"structure",
"should",
"serve",
"as",
"a",
"basis",
"for",
"understanding",
"structure–function",
"relationships",
"in",
"any",
"newly",
"discovered",
"proteins",
"with",
"a",
"similar",
"sequence,",
"such",
"as",
"those",
"identified",
"by",
"whole",
"microbial",
"genome",
"sequencing",
"and",
"metagenomic",
"surveys",
"of",
"the",
"human",
"microbiome.",
"2.",
"Materials",
"and",
"methods",
"2.1.",
"KPN03535",
"expression,",
"purification",
"and",
"crystallization",
"Clones",
"were",
"generated",
"using",
"the",
"Polymerase",
"Incomplete",
"Primer",
"Extension",
"(PIPE;",
"Klock",
"et",
"al.,",
"2008)",
"cloning",
"method.",
"The",
"gene",
"encoding",
"KPN03535",
"(gi|152972051;",
"Swiss-Prot",
"A6TEE6)",
"was",
"amplified",
"by",
"polymerase",
"chain",
"reaction",
"(PCR)",
"from",
"K.",
"pneumoniae",
"MGH",
"78578",
"genomic",
"DNA",
"using",
"PfuTurbo",
"DNA",
"polymerase",
"(Stratagene)",
"and",
"I-PIPE",
"(Insert)",
"primers",
"(forward",
"primer,",
"50-ctgtac-",
"ttccagggcGCTTCTAAAGCCTTTTATTCCGCGGGAG-30;",
"reverse",
"primer,",
"50-aattaagtcgcgttaTTTAACCACCTTGGGATTCTGTAGC-",
"GTC-30;",
"target",
"sequence",
"in",
"upper",
"case)",
"that",
"included",
"sequences",
"for",
"the",
"predicted",
"50-",
"and",
"30-ends.",
"The",
"expression",
"vector,",
"pSpeedET,",
"which",
"encodes",
"an",
"amino-terminal",
"tobacco",
"etch",
"virus",
"(TEV)",
"protease-",
"cleavable",
"expression",
"and",
"purification",
"tag",
"(MGSDKIHHHHHHEN-",
"1254",
"doi:10.1107/S1744309109018168",
"Acta",
"Cryst.",
"(2010).",
"F66,",
"1254–1260"
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] | [
"Hindawi",
"Publishing",
"Corporation",
"International",
"Journal",
"of",
"Endocrinology",
"Volume",
"2012,",
"Article",
"ID",
"420370,",
"7",
"pages",
"doi:10.1155/2012/420370",
"Research",
"Article",
"Free",
"Triiodothyronine",
"and",
"Cholesterol",
"Levels",
"in",
"Euthyroid",
"Elderly",
"T2DM",
"Patients",
"F.",
"Strollo,1",
"I.",
"Carucci,1",
"M.",
"More`",
",1",
"G.",
"Marico,2",
"G.",
"Strollo,3",
"M.",
"A.",
"Masini,4",
"and",
"S.",
"Gentile2",
"1",
"Endocrine",
"Unit,",
"INRCA,",
"Via",
"Cassia",
"1167,",
"00189",
"Rome,",
"Italy",
"2",
"Department",
"of",
"Clinical",
"and",
"Experimental",
"Medicine,",
"Second",
"University",
"of",
"Naples,",
"Via",
"Pansini",
"5,",
"80131",
"Naples,",
"Italy",
"3",
"Endocrinology",
"and",
"Diabetes",
"Service,",
"FBF",
"St.",
"Peter’s",
"Hospital,",
"Via",
"Cassia",
"600,",
"001879",
"Rome,",
"Italy",
"4",
"DipTeRis,",
"University",
"of",
"Genoa,",
"Viale",
"Benedetto",
"XV",
"3,",
"16132",
"Genoa,",
"Italy",
"Correspondence",
"should",
"be",
"addressed",
"to",
"S.",
"Gentile,",
"sandro.gentile1@gmail.com",
"Received",
"30",
"March",
"2012;",
"Revised",
"5",
"July",
"2012;",
"Accepted",
"23",
"July",
"2012",
"Academic",
"Editor:",
"Bronwen",
"Martin",
"Copyright",
"©",
"2012",
"F.",
"Strollo",
"et",
"al.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Thyroid",
"function",
"regulates",
"lipid",
"metabolism.",
"Despite",
"the",
"fact",
"that",
"T2DM",
"is",
"more",
"prevalent",
"in",
"the",
"elderly,",
"often",
"associates",
"with",
"thyroid",
"dysfunction",
"and",
"increases",
"cardiovascular",
"risk",
"both",
"per",
"se",
"and",
"via",
"high",
"TC",
"and",
"LDL-C",
"levels,",
"the",
"association",
"of",
"the",
"latter",
"with",
"FT3",
"and",
"FT4",
"levels",
"has",
"not",
"yet",
"been",
"fully",
"investigated",
"in",
"T2DM.",
"While",
"trying",
"to",
"fill",
"this",
"gap",
"in",
"296",
"elderly",
"outpatients",
"with",
"T2DM,",
"we",
"found",
"that",
"TC",
"and",
"LDL-C",
"correlated",
"negatively",
"with",
"FT4",
"and",
"positively",
"with",
"FT3.",
"When",
"divided",
"according",
"to",
"treatment",
"by",
"oral",
"hypoglycaemic",
"agents",
"(OHA)",
"and",
"insulin",
"(IT),",
"they",
"reacted",
"differently",
"with",
"respect",
"to",
"investigated",
"associations:",
"in",
"the",
"OHA’s",
"TC",
"and",
"LDL-C",
"correlated",
"negatively",
"with",
"FT4",
"and",
"showed",
"no",
"association",
"with",
"FT3,",
"whereas,",
"in",
"the",
"IT’s",
"TC",
"and",
"LDL-",
"C",
"correlated",
"positively",
"with",
"FT3",
"and",
"negatively",
"with",
"FT4.",
"When",
"controlled",
"for",
"possible",
"confounding",
"factors,",
"these",
"associations",
"did",
"not",
"change",
"in",
"the",
"IT’s",
"but",
"were",
"missing",
"in",
"the",
"OHA’s.",
"Recent",
"literature",
"reports",
"upon",
"complex",
"hypothalamic",
"and",
"peripheral",
"interactions",
"between",
"T2DM",
"and",
"thyroid,",
"and",
"suggests",
"T3",
"to",
"enhance",
"cholesterol",
"synthesis",
"and",
"to",
"have",
"a",
"role",
"in",
"insulin",
"resistance",
"states.",
"Further",
"investigations",
"are",
"needed",
"to",
"understand",
"the",
"intimate",
"mechanisms",
"of",
"lipid",
"metabolism",
"in",
"T2DM",
"with",
"respect",
"to",
"thyroid",
"function.",
"1.",
"Introduction",
"Thyroid",
"function",
"affects",
"both",
"lipid",
"profiles",
"and",
"metabolic",
"parameters",
"[1].",
"Thyroxine",
"(T4)",
"and",
"triiodothyronine",
"(T3),",
"the",
"two",
"main",
"thyroid",
"hormones,",
"are",
"secreted",
"after",
"thyroglob-",
"ulin",
"macropinocytosis",
"and",
"hydrolysis",
"under",
"the",
"stimulation",
"of",
"pituitary",
"thyrotropin",
"(TSH)",
"and",
"are",
"present",
"in",
"the",
"blood",
"mainly",
"in",
"noncovalent",
"interactions",
"with",
"thyroxine-binding",
"globulin,",
"prealbumin,",
"and",
"albumin.",
"Only",
"0.4%",
"T3",
"and",
"0.04%",
"T4",
"dynamically",
"escape",
"binding",
"and,",
"since",
"free",
"to",
"interact",
"directly",
"with",
"peripheral",
"organs",
"and",
"tissues,",
"are",
"called",
"free",
"T3",
"(FT3)",
"and",
"free",
"T4",
"(FT4)",
"and",
"are",
"the",
"only",
"fractions",
"believed",
"to",
"be",
"metabolically",
"active",
"[2].",
"FT4",
"levels",
"are",
"about",
"100",
"times",
"higher",
"than",
"those",
"of",
"FT3,",
"which",
"is",
"considered",
"to",
"be",
"the",
"most",
"active",
"form",
"of",
"thyroid",
"hormone",
"and",
"into",
"which",
"FT4",
"is",
"converted",
"within",
"the",
"peripheral",
"tissue",
"[3].",
"Inside",
"a",
"variety",
"of",
"cells,",
"both",
"interact",
"with",
"different",
"affinity",
"with",
"α1,",
"α2,",
"β1,",
"and",
"β2",
"nuclear",
"receptors",
"in",
"regulating",
"the",
"expression",
"of",
"target",
"genes",
"through",
"the",
"so-called",
"thyroid",
"response",
"elements",
"(TRE’s),",
"thus",
"exerting",
"the",
"typical",
"physiological",
"functions",
"which",
"characterize",
"them.",
"These",
"are",
"mostly",
"represented",
"by",
"enhanced",
"calorigenesis,",
"increased",
"stroke",
"volume",
"and",
"heart",
"rate,",
"enhanced",
"sensitivity",
"to",
"catecholamines,",
"bone",
"turnover,",
"gluconeogenesis,",
"glycogenolysis,",
"and",
"lipolysis.",
"The",
"latter",
"is",
"mainly",
"due",
"to",
"enhanced",
"lipoprotein-lipase",
"activity",
"and",
"increased",
"hepatic",
"low-density",
"lipoprotein",
"(LDL)",
"receptor",
"concentrations",
"[4].",
"Besides",
"genomic",
"effects,",
"widespread",
"rapid",
"onset",
"nongenomic",
"effects",
"of",
"FT3",
"and",
"FT4",
"have",
"been",
"reported",
"involving",
"membrane-signalling",
"pathways",
"[5],",
"the",
"real",
"extent",
"of",
"which",
"has",
"not",
"been",
"well",
"defined",
"yet",
"[6]."
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] | [
"Inchingolo",
"et",
"al.",
"Head",
"&",
"Face",
"Medicine",
"2010,",
"6:13",
"http://www.head-face-med.com/content/6/1/13",
"H",
"Y",
"P",
"O",
"T",
"H",
"E",
"S",
"I",
"S",
"HEAD",
"&",
"FACE",
"MEDICINE",
"Open",
"Access",
"HAyphotyhepsisothetical",
"correlation",
"between",
"hyaluronic",
"acid",
"gel",
"and",
"development",
"of",
"cutaneous",
"metaplastic",
"synovial",
"cyst",
"Francesco",
"Inchingolo*1,",
"Marco",
"Tatullo2,",
"Fabio",
"M",
"Abenavoli3,",
"Massimo",
"Marrelli4,",
"Alessio",
"D",
"Inchingolo5,",
"Andrea",
"Servili6,",
"Angelo",
"M",
"Inchingolo7",
"and",
"Gianna",
"Dipalma8",
"Abstract",
"Thousands",
"of",
"patients",
"receive",
"hyaluronic",
"acid",
"filler",
"injections,",
"and",
"the",
"effects",
"are",
"generally",
"considered",
"acceptable.",
"The",
"acid",
"rarely",
"causes",
"cutaneous",
"reactions,",
"which",
"are",
"only",
"occasionally",
"reported",
"in",
"the",
"literature.",
"The",
"aim",
"of",
"the",
"present",
"work",
"is",
"to",
"analyze",
"a",
"clinical",
"case",
"that",
"has",
"never",
"been",
"reported",
"in",
"the",
"literature",
"to",
"our",
"knowledge.",
"This",
"case",
"is",
"of",
"a",
"26-year-old",
"woman",
"who",
"presented",
"with",
"a",
"cyst",
"in",
"the",
"infrazygomatic",
"region",
"that",
"was",
"injected",
"with",
"non-animal",
"stabilized",
"hyaluronic",
"acid",
"at",
"another",
"centre",
"a",
"few",
"months",
"ago.",
"Consequently,",
"we",
"made",
"an",
"external",
"incision",
"to",
"remove",
"the",
"neoplasm:",
"histological",
"examination",
"of",
"the",
"capsule",
"revealed",
"it",
"to",
"be",
"a",
"cutaneous",
"metaplastic",
"synovial",
"cyst.",
"Introduction",
"Thousands",
"of",
"patients",
"receive",
"hyaluronic",
"acid",
"filler",
"injec-",
"tions,",
"the",
"effects",
"of",
"which",
"are",
"generally",
"considered",
"acceptable.",
"However,",
"in",
"all",
"cases,",
"the",
"product",
"is",
"regarded",
"as",
"resorbable,",
"and",
"the",
"risk",
"of",
"either",
"local",
"or",
"systemic",
"toxic",
"reactions",
"is",
"reduced",
"[1,2].",
"Hyaluronic",
"acid",
"should",
"be",
"administered",
"with",
"caution,",
"like",
"any",
"type",
"of",
"commonly",
"employed",
"dermal",
"fillers,",
"but",
"the",
"injection",
"technique",
"can",
"be",
"easily",
"performed",
"after",
"a",
"brief",
"learning",
"course.",
"The",
"acid",
"rarely",
"causes",
"cutaneous",
"reactions,",
"which",
"are",
"reported",
"only",
"occasionally",
"in",
"the",
"lit-",
"erature.",
"Case",
"Report",
"The",
"aim",
"of",
"the",
"present",
"work",
"is",
"to",
"analyze",
"a",
"clinical",
"case",
"that",
"has",
"never",
"been",
"reported",
"in",
"the",
"literature",
"to",
"our",
"knowledge.",
"This",
"case",
"is",
"of",
"a",
"26-year-old",
"woman",
"who",
"pre-",
"sented",
"with",
"a",
"cyst",
"in",
"the",
"infrazygomatic",
"region",
"(FIG.",
"1)",
"that",
"was",
"injected",
"with",
"non-animal",
"stabilized",
"hyaluronic",
"acid",
"(NASHA)",
"at",
"another",
"centre",
"a",
"few",
"months",
"ago.",
"The",
"patient",
"did",
"not",
"have",
"a",
"medical",
"history",
"of",
"cystic",
"forma-",
"tions",
"in",
"that",
"specific",
"region",
"before",
"NASHA",
"injection.",
"However,",
"the",
"cyst",
"tended",
"to",
"increase",
"in",
"volume",
"without",
"*",
"Correspondence:",
"f.inchingolo@doc.uniba.it",
"1",
"Department",
"of",
"Dental",
"Sciences",
"and",
"Surgery,",
"General",
"Hospital,",
"Bari,",
"Italy",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"any",
"painful",
"sensation",
"or",
"appearance",
"of",
"other",
"symptoms.",
"We",
"performed",
"an",
"MRI",
"that",
"revealed",
"the",
"presence",
"of",
"a",
"cyst",
"that",
"strongly",
"adhered",
"to",
"the",
"bone",
"surface.",
"Conse-",
"quently,",
"we",
"made",
"an",
"external",
"incision",
"to",
"remove",
"the",
"neo-",
"plasm.",
"In",
"the",
"subcutis,",
"we",
"identified",
"a",
"cyst",
"that",
"we",
"removed",
"with",
"some",
"difficulty",
"because",
"it",
"tenaciously",
"adhered",
"to",
"the",
"underlying",
"bone",
"surface.",
"After",
"opening",
"the",
"cyst,",
"we",
"observed",
"a",
"thick",
"gelatinous",
"fluid",
"similar",
"to",
"hyaluronic",
"acid",
"(FIG.",
"2),",
"and",
"histological",
"examination",
"of",
"the",
"capsule",
"revealed",
"the",
"cyst",
"to",
"be",
"a",
"cuta-",
"neous",
"metaplastic",
"synovial",
"cyst",
"(FIG.",
"3).",
"Cutaneous",
"metaplastic",
"synovial",
"cyst",
"is",
"a",
"rare",
"cystic",
"tumor",
"that",
"typically",
"presents",
"as",
"a",
"solitary",
"tender",
"subcuta-",
"neous",
"nodule.",
"Histological",
"examination",
"revealed",
"a",
"cystic",
"structure",
"with",
"villous-like",
"projections",
"and",
"a",
"lining",
"that",
"resembled",
"hyperplastic",
"synovium.",
"Discussion",
"Injection-site",
"reactions",
"result",
"from",
"acute",
"inflammatory",
"reactions",
"in",
"response",
"to",
"tissue",
"damage",
"after",
"drug",
"injec-",
"tion.",
"They",
"are",
"generally",
"short-term",
"and",
"symptoms",
"typi-",
"cally",
"include",
"swelling,",
"pain,",
"tenderness,",
"and",
"bruising;",
"these",
"symptoms",
"can",
"be",
"observed",
"in",
"most",
"patients",
"treated",
"with",
"injectable",
"hyaluronic",
"acid",
"derivatives",
"[3].",
"Besides,",
"the",
"overall",
"incidence",
"of",
"long-term",
"adverse",
"reactions",
"sec-",
"©",
"2010",
"Inchingolo",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
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] | [
"CLINICS",
"2011;66(S1):25-32",
"10.1590/S1807-59322011001300004",
"Future",
"developments",
"in",
"brain-machine",
"interface",
"research",
"Mikhail",
"A.",
"Lebedev,I",
"Andrew",
"J.",
"Tate,I,II",
"Timothy",
"L.",
"Hanson,I,II",
"Zheng",
"Li,I,II",
"Joseph",
"E.",
"O’Doherty,I,II",
"Jesse",
"A.",
"Winans,I",
"Peter",
"J.",
"Ifft,I",
"Katie",
"Z.",
"Zhuang,I",
"Nathan",
"A.",
"Fitzsimmons,I",
"David",
"A.",
"Schwarz,I",
"Andrew",
"M.",
"Fuller,I",
"Je",
"Hi",
"An,I",
"Miguel",
"A.",
"L.",
"NicolelisI,III",
"I",
"Neurobiology,Duke",
"University,",
"Durham,",
"NC,",
"USA.",
"II",
"Duke",
"University",
"Center",
"for",
"Neuroengineering,",
"Duke",
"University,",
"Durham,",
"NC,",
"USA.",
"III",
"Edmond",
"and",
"Lily",
"Safra",
"International",
"Institute",
"of",
"Neuroscience",
"of",
"Natal",
"Neuroprosthetic",
"devices",
"based",
"on",
"brain-machine",
"interface",
"technology",
"hold",
"promise",
"for",
"the",
"restoration",
"of",
"body",
"mobility",
"in",
"patients",
"suffering",
"from",
"devastating",
"motor",
"deficits",
"caused",
"by",
"brain",
"injury,",
"neurologic",
"diseases",
"and",
"limb",
"loss.",
"During",
"the",
"last",
"decade,",
"considerable",
"progress",
"has",
"been",
"achieved",
"in",
"this",
"multidisciplinary",
"research,",
"mainly",
"in",
"the",
"brain-machine",
"interface",
"that",
"enacts",
"upper-limb",
"functionality.",
"However,",
"a",
"considerable",
"number",
"of",
"problems",
"need",
"to",
"be",
"resolved",
"before",
"fully",
"functional",
"limb",
"neuroprostheses",
"can",
"be",
"built.",
"To",
"move",
"towards",
"developing",
"neuroprosthetic",
"devices",
"for",
"humans,",
"brain-machine",
"interface",
"research",
"has",
"to",
"address",
"a",
"number",
"of",
"issues",
"related",
"to",
"improving",
"the",
"quality",
"of",
"neuronal",
"recordings,",
"achieving",
"stable,",
"long-term",
"performance,",
"and",
"extending",
"the",
"brain-machine",
"interface",
"approach",
"to",
"a",
"broad",
"range",
"of",
"motor",
"and",
"sensory",
"functions.",
"Here,",
"we",
"review",
"the",
"future",
"steps",
"that",
"are",
"part",
"of",
"the",
"strategic",
"plan",
"of",
"the",
"Duke",
"University",
"Center",
"for",
"Neuroengineering,",
"and",
"its",
"partners,",
"the",
"Brazilian",
"National",
"Institute",
"of",
"Brain-Machine",
"Interfaces",
"and",
"the",
"E´cole",
"Polytechnique",
"F",
"e´de´",
"rale",
"de",
"Lausanne",
"(EPFL)",
"Center",
"for",
"Neuroprosthetics,",
"to",
"bring",
"this",
"new",
"technology",
"to",
"clinical",
"fruition.",
"KEYWORDS:",
"Brain-machine",
"interface;",
"Neuroprosthetic;",
"Primate;",
"Bipedal",
"locomotion;",
"Intracortical",
"microstimulation;",
"Sensory",
"substitution.",
"Lebedev",
"MA,",
"Tate",
"AJ,",
"Hanson",
"TL,",
"Li",
"Z,",
"O’Doherty",
"JE,",
"Winans",
"JA,",
"Ifft",
"PJ,",
"Zhuang",
"KZ,",
"Fitzsimmons",
"NA,",
"Schwarz",
"DA,",
"Fuller",
"AM,",
"An",
"JH,",
"Nicolelis",
"MAL.",
"Future",
"developments",
"in",
"brain-machine",
"interface",
"research.",
"Clinics.",
"2011;66(S1):25-32.",
"Received",
"for",
"publication",
"on",
"January",
"28,",
"2011;",
"Accepted",
"for",
"publicaiton",
"on",
"January",
"30,",
"2011",
"E-mail:",
"nicoleli@neuro.duke.edu",
"Tel.:",
"919",
"684",
"4580",
"INTRODUCTION",
"Millions",
"of",
"people",
"worldwide",
"suffer",
"from",
"sensorimotor",
"deficits",
"caused",
"by",
"neurologic",
"injuries,",
"diseases",
"or",
"limb",
"loss.",
"According",
"to",
"recent",
"data",
"reported",
"in",
"Medical",
"News",
"Today,",
"five",
"million",
"people",
"in",
"the",
"USA",
"alone",
"currently",
"suffer",
"from",
"some",
"type",
"of",
"severe",
"body",
"paralysis.1",
"Currently,",
"there",
"is",
"no",
"cure",
"for",
"such",
"devastating",
"cases",
"of",
"paralysis,",
"for",
"example",
"complete",
"spinal",
"cord",
"injury",
"(SCI).2",
"Meanwhile,",
"treatment",
"is",
"only",
"partially",
"effective",
"in",
"less",
"severe",
"cases.3",
"Neural",
"prosthetic",
"devices",
"based",
"on",
"brain-machine",
"interfaces",
"(BMIs)",
"hold",
"promise",
"to",
"restore",
"both",
"partial",
"and",
"full",
"body",
"mobility",
"in",
"paralyzed",
"patients.4–10",
"BMIs",
"bypass",
"the",
"site",
"of",
"the",
"neural",
"lesion",
"and",
"connect",
"the",
"remaining",
"healthy",
"motor",
"areas",
"of",
"the",
"brain,",
"particularly",
"the",
"motor",
"cortex,",
"directly",
"to",
"assistive",
"and",
"prosthetic",
"devices",
"that",
"can",
"take",
"the",
"shape",
"of,",
"for",
"example,",
"robotic",
"limbs",
"or",
"a",
"full",
"body",
"exoskeleton.",
"The",
"main",
"idea",
"behind",
"BMIs",
"is",
"to",
"employ",
"the",
"activity",
"of",
"healthy",
"motor",
"brain",
"areas,",
"which",
"in",
"many",
"cases",
"of",
"paralysis",
"remain",
"capable",
"of",
"generating",
"motor",
"commands",
"despite",
"being",
"disconnected",
"from",
"the",
"body",
"effectors,11",
"to",
"control",
"artificial",
"tools",
"that",
"restore",
"the",
"patient’s",
"mobility.",
"Copyright",
"2011",
"CLINICS",
"–",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://",
"creativecommons.org/licenses/by-nc/3.0/)",
"which",
"permits",
"unrestricted",
"non-",
"commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"25",
"During",
"the",
"last",
"decade,",
"the",
"field",
"of",
"BMIs",
"has",
"experienced",
"an",
"explosive",
"development.7,9",
"Hence,",
"it",
"has",
"generated",
"high",
"expectations",
"among",
"neuroscientists,",
"physicians",
"and",
"patients",
"alike,",
"regarding",
"its",
"potential",
"clinical",
"applications.",
"A",
"number",
"of",
"BMI",
"systems",
"have",
"been",
"studied",
"in",
"rodents12",
"and",
"nonhuman",
"primates.13–17",
"BMI",
"technology",
"also",
"entered",
"human",
"clinical",
"research",
"where",
"both",
"non-invasive",
"EEG-",
"based",
"systems5,18,19",
"and",
"invasive",
"BMIs",
"based",
"on",
"brain",
"implants20–22",
"have",
"been",
"tested.",
"Notwithstanding",
"the",
"success",
"of",
"these",
"pioneering",
"experiments,",
"a",
"number",
"of",
"issues",
"need",
"to",
"be",
"resolved",
"before",
"a",
"fully",
"functional",
"practical",
"neuropros-",
"thetic",
"for",
"long-term",
"use",
"can",
"be",
"built.7",
"These",
"include:",
"implant",
"biocompatibility",
"issues;23",
"increasing",
"the",
"number",
"of",
"neural",
"channels",
"of",
"the",
"recording",
"system;",
"improving",
"BMI",
"decoding",
"algorithms;",
"building",
"fully",
"implantable",
"systems;",
"sensorizing",
"neuroprosthetic",
"limbs;",
"and",
"extending",
"the",
"BMI",
"approach",
"to",
"a",
"broader",
"range",
"of",
"motor",
"control",
"tasks,",
"especially",
"tasks",
"that",
"require",
"lower",
"limb",
"control:",
"bipedal",
"walking24",
"and",
"upright",
"posture",
"control.25",
"The",
"Duke",
"University",
"Center",
"for",
"Neuroengineering",
"(DUCN)",
"has",
"been",
"at",
"the",
"forefront",
"of",
"BMI",
"research",
"on",
"cortical",
"prosthetic",
"devices",
"for",
"motor",
"rehabilitation",
"since",
"this",
"field",
"emerged",
"about",
"12",
"years",
"ago.",
"At",
"the",
"DUCN,",
"we",
"have",
"developed",
"pioneering",
"BMI",
"systems",
"that",
"enact",
"a",
"wide",
"range",
"of",
"motor",
"functions,",
"from",
"arm",
"reaching",
"and",
"grasping",
"13,17,26",
"to",
"bipedal",
"locomotion24,27",
"in",
"a",
"variety",
"of",
"artificial",
"actuators.",
"DUCN",
"researchers",
"were",
"also",
"the",
"first",
"to",
"incorporate",
"artificial",
"somatic",
"sensation",
"in",
"BMIs.28,29",
"Here,",
"we",
"review",
"the",
"most",
"recent",
"findings",
"of",
"the",
"BMI",
"initiative",
"at",
"the",
"DUCN",
"and",
"discuss"
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] | [
"Hindawi",
"Publishing",
"Corporation",
"Clinical",
"and",
"Developmental",
"Immunology",
"Volume",
"2011,",
"Article",
"ID",
"439752,",
"7",
"pages",
"doi:10.1155/2011/439752",
"Review",
"Article",
"The",
"Confluence",
"of",
"Stereotactic",
"Ablative",
"Radiotherapy",
"and",
"Tumor",
"Immunology",
"Steven",
"Eric",
"Finkelstein,1",
"Robert",
"Timmerman,2",
"William",
"H.",
"McBride,3",
"Do¨rthe",
"Schaue,3",
"Sarah",
"E.",
"Hoffe,4",
"Constantine",
"A.",
"Mantz,1",
"and",
"George",
"D.",
"Wilson5",
"1",
"21st",
"Century",
"Oncology",
"Translational",
"Research",
"Consortium,",
"Scottsdale,",
"AZ",
"85251,",
"USA",
"2",
"Department",
"of",
"Radiation",
"Oncology",
"and",
"Neurologic",
"Surgery,",
"University",
"of",
"Texas",
"Southwestern",
"Medical",
"Center,",
"Dallas,",
"TX",
"75391,",
"USA",
"3",
"Department",
"of",
"Radiation",
"Oncology,",
"David",
"Geffen",
"School",
"of",
"Medicine",
"at",
"UCLA,",
"Los",
"Angeles,",
"CA",
"90095,",
"USA",
"4",
"Department",
"of",
"Radiation",
"Oncology,",
"Moffitt",
"International,",
"Tampa,",
"FL",
"33612,",
"USA",
"5",
"Division",
"of",
"Radiation",
"Biology,",
"William",
"Beaumont",
"Hospital,",
"Royal",
"Oak,",
"MI",
"48073,",
"USA",
"Correspondence",
"should",
"be",
"addressed",
"to",
"Steven",
"Eric",
"Finkelstein,",
"sfinkels@rtsx.com",
"Received",
"25",
"August",
"2011;",
"Accepted",
"5",
"September",
"2011",
"Academic",
"Editor:",
"Luca",
"Gattinoni",
"Copyright",
"©",
"2011",
"Steven",
"Eric",
"Finkelstein",
"et",
"al.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Stereotactic",
"radiation",
"approaches",
"are",
"gaining",
"more",
"popularity",
"for",
"the",
"treatment",
"of",
"intracranial",
"as",
"well",
"as",
"extracranial",
"tumors",
"in",
"organs",
"such",
"as",
"the",
"liver",
"and",
"lung.",
"Technology,",
"rather",
"than",
"biology,",
"is",
"driving",
"the",
"rapid",
"adoption",
"of",
"stereotactic",
"body",
"radiation",
"therapy",
"(SBRT),",
"also",
"known",
"as",
"stereotactic",
"ablative",
"radiotherapy",
"(SABR),",
"in",
"the",
"clinic",
"due",
"to",
"advances",
"in",
"precise",
"positioning",
"and",
"targeting.",
"Dramatic",
"improvements",
"in",
"tumor",
"control",
"have",
"been",
"demonstrated;",
"however,",
"our",
"knowledge",
"of",
"normal",
"tissue",
"biology",
"response",
"mechanisms",
"to",
"large",
"fraction",
"sizes",
"is",
"lacking.",
"Herein,",
"we",
"will",
"discuss",
"how",
"SABR",
"can",
"induce",
"cellular",
"expression",
"of",
"MHC",
"I,",
"adhesion",
"molecules,",
"costimulatory",
"molecules,",
"heat",
"shock",
"proteins,",
"inflammatory",
"mediators,",
"immunomodulatory",
"cytokines,",
"and",
"death",
"receptors",
"to",
"enhance",
"antitumor",
"immune",
"responses.",
"1.",
"Introduction",
"Stereotactic",
"radiosurgery",
"(SRS)",
"was",
"originally",
"developed",
"for",
"the",
"treatment",
"of",
"intracranial",
"tumors",
"and",
"has",
"demonstrated",
"clinical",
"effectiveness",
"in",
"treating",
"a",
"variety",
"of",
"benign",
"and",
"malignant",
"conditions.",
"Its",
"extracranial",
"counterpart,",
"stereotac-",
"tic",
"body",
"radiation",
"therapy",
"(SBRT),",
"also",
"known",
"as",
"stereotactic",
"ablative",
"radiotherapy",
"(SABR),",
"has",
"more",
"recently",
"shown",
"efficacy",
"for",
"the",
"treatment",
"of",
"tumors",
"in",
"organs",
"such",
"as",
"the",
"liver",
"and",
"lung.",
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"potential",
"for",
"using",
"SABR",
"is",
"likely",
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"than",
"for",
"SRS",
"given",
"the",
"larger",
"volume",
"of",
"potential",
"indications",
"outside",
"the",
"central",
"nervous",
"system.",
"Technology,",
"rather",
"than",
"biology,",
"is",
"driving",
"the",
"rapid",
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"of",
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"in",
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"clinic",
"due",
"to",
"advances",
"in",
"precise",
"positioning,",
"motion",
"control,",
"dosimetry,",
"and",
"precise",
"targeting",
"with",
"image",
"guid-",
"ance.",
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"improvements",
"in",
"tumor",
"control",
"have",
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"in",
"several",
"studies",
"due",
"to",
"the",
"demonstration",
"that",
"very",
"potent",
"dose",
"can",
"be",
"delivered",
"by",
"use",
"of",
"the",
"mentioned",
"technology.",
"However,",
"our",
"knowledge",
"of",
"normal",
"tissue",
"biology",
"response",
"mechanisms",
"to",
"large",
"fraction",
"sizes",
"is",
"relatively",
"lacking",
"compared",
"to",
"conventional",
"fractionation.",
"2.",
"Radiobiologic",
"Considerations",
"A",
"fundamental",
"issue",
"in",
"SABR",
"is",
"whether",
"classical",
"radiobi-",
"ologic",
"modeling",
"with",
"the",
"linear-quadratic",
"(LQ)",
"model",
"is",
"a",
"valid",
"method",
"to",
"assess",
"the",
"biologically",
"effective",
"dose",
"at",
"the",
"high",
"doses",
"typically",
"encountered",
"in",
"radiosurgery.",
"This",
"point",
"was",
"debated",
"in",
"back-to-back",
"papers",
"in",
"seminars",
"in",
"radiation",
"oncology",
"[1,",
"2],",
"where",
"Brenner",
"argued",
"that",
"LQ",
"formalism",
"was",
"appropriate",
"whilst",
"Kirkpatrick",
"and",
"colleagues",
"suggested",
"it",
"was",
"inappropriate.",
"Brenner’s",
"argument",
"is",
"based",
"on",
"the",
"robustness",
"of",
"the",
"LQ",
"model",
"to",
"predict",
"fractionation",
"and",
"dose-rate",
"effects",
"in",
"experimental",
"models",
"in",
"vitro",
"and",
"in",
"vivo",
"at",
"doses",
"up",
"to",
"10",
"Gy.",
"This",
"conclusion",
"is",
"based",
"on",
"the",
"premise",
"that",
"cell",
"killing",
"is",
"the",
"dominant",
"process",
"mediating",
"the",
"radiotherapeutic",
"response",
"for",
"both",
"early",
"and",
"late",
"effects",
"including",
"vascular",
"effects.",
"Brenner",
"argued",
"that,",
"to",
"date,",
"there"
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] | [
"Reproductive",
"Health",
"Research",
"Religiosity",
"and",
"teen",
"birth",
"rate",
"in",
"the",
"United",
"States",
"Joseph",
"M",
"Strayhorn*1,2",
"and",
"Jillian",
"C",
"Strayhorn3",
"BioMed",
"Central",
"Open",
"Access",
"Address:",
"1Drexel",
"University",
"College",
"of",
"Medicine,",
"Department",
"of",
"Psychiatry,",
"2900",
"W.",
"Queen",
"Lane,",
"Philadelphia,",
"PA",
"19129,",
"2University",
"of",
"Pittsburgh",
"School",
"of",
"Medicine,",
"Department",
"of",
"Psychiatry,",
"3811",
"O'Hara",
"Street,",
"Pittsburgh,",
"PA",
"15213",
"and",
"3263",
"Seasons",
"Drive,",
"Wexford,",
"Pennsylvania",
"15090,",
"USA",
"Email:",
"Joseph",
"M",
"Strayhorn*",
"-",
"joestrayhorn@gmail.com;",
"Jillian",
"C",
"Strayhorn",
"-",
"jillianstrayhorn@gmail.com",
"*",
"Corresponding",
"author",
"Published:",
"17",
"September",
"2009",
"Reproductive",
"Health",
"2009,",
"6:14",
"doi:10.1186/1742-4755-6-14",
"Received:",
"28",
"April",
"2009",
"Accepted:",
"17",
"September",
"2009",
"This",
"article",
"is",
"available",
"from:",
"http://www.reproductive-health-journal.com/content/6/1/14",
"©",
"2009",
"Strayhorn",
"and",
"Strayhorn;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"The",
"children",
"of",
"teen",
"mothers",
"have",
"been",
"reported",
"to",
"have",
"higher",
"rates",
"of",
"several",
"unfavorable",
"mental",
"health",
"outcomes.",
"Past",
"research",
"suggests",
"several",
"possible",
"mechanisms",
"for",
"an",
"association",
"between",
"religiosity",
"and",
"teen",
"birth",
"rate",
"in",
"communities.",
"Methods:",
"The",
"present",
"study",
"compiled",
"publicly",
"accessible",
"data",
"on",
"birth",
"rates,",
"conservative",
"religious",
"beliefs,",
"income,",
"and",
"abortion",
"rates",
"in",
"the",
"U.S.,",
"aggregated",
"at",
"the",
"state",
"level.",
"Data",
"on",
"teen",
"birth",
"rates",
"and",
"abortion",
"originated",
"from",
"the",
"Center",
"for",
"Disease",
"Control;",
"on",
"income,",
"from",
"the",
"U.S.",
"Bureau",
"of",
"the",
"Census,",
"and",
"on",
"religious",
"beliefs,",
"from",
"the",
"U.S.",
"Religious",
"Landscape",
"Survey",
"carried",
"out",
"by",
"the",
"Pew",
"Forum",
"on",
"Religion",
"and",
"Public",
"Life.",
"We",
"computed",
"correlations",
"and",
"partial",
"correlations.",
"Results:",
"Increased",
"religiosity",
"in",
"residents",
"of",
"states",
"in",
"the",
"U.S.",
"strongly",
"predicted",
"a",
"higher",
"teen",
"birth",
"rate,",
"with",
"r",
"=",
"0.73",
"(p",
"<",
"0.0005).",
"Religiosity",
"correlated",
"negatively",
"with",
"median",
"household",
"income,",
"with",
"r",
"=",
"-0.66,",
"and",
"income",
"correlated",
"negatively",
"with",
"teen",
"birth",
"rate,",
"with",
"r",
"=",
"-0.63.",
"But",
"the",
"correlation",
"between",
"religiosity",
"and",
"teen",
"birth",
"rate",
"remained",
"highly",
"significant",
"when",
"income",
"was",
"controlled",
"for",
"via",
"partial",
"correlation:",
"the",
"partial",
"correlation",
"between",
"religiosity",
"and",
"teen",
"birth",
"rate,",
"controlling",
"for",
"income,",
"was",
"0.53",
"(p",
"<",
"0.0005).",
"Abortion",
"rate",
"correlated",
"negatively",
"with",
"religiosity,",
"with",
"r",
"=",
"-0.45,",
"p",
"=",
"0.002.",
"However,",
"the",
"partial",
"correlation",
"between",
"teen",
"birth",
"rate",
"and",
"religiosity",
"remained",
"high",
"and",
"significant",
"when",
"controlling",
"for",
"abortion",
"rate",
"(partial",
"correlation",
"=",
"0.68,",
"p",
"<",
"0.0005)",
"and",
"when",
"controlling",
"for",
"both",
"abortion",
"rate",
"and",
"income",
"(partial",
"correlation",
"=",
"0.54,",
"p",
"=",
"0.001).",
"Conclusion:",
"With",
"data",
"aggregated",
"at",
"the",
"state",
"level,",
"conservative",
"religious",
"beliefs",
"strongly",
"predict",
"U.S.",
"teen",
"birth",
"rates,",
"in",
"a",
"relationship",
"that",
"does",
"not",
"appear",
"to",
"be",
"the",
"result",
"of",
"confounding",
"by",
"income",
"or",
"abortion",
"rates.",
"One",
"possible",
"explanation",
"for",
"this",
"relationship",
"is",
"that",
"teens",
"in",
"more",
"religious",
"communities",
"may",
"be",
"less",
"likely",
"to",
"use",
"contraception.",
"Background",
"The",
"children",
"of",
"teen",
"mothers",
"in",
"the",
"U.S.,",
"on",
"the",
"average,",
"have",
"worse",
"outcomes",
"in",
"a",
"number",
"of",
"ways.",
"They",
"score",
"lower",
"in",
"school",
"achievement",
"tests,",
"have",
"a",
"greater",
"likeli-",
"hood",
"of",
"repeating",
"a",
"grade,",
"are",
"rated",
"more",
"unfavorably",
"by",
"teachers",
"while",
"in",
"high",
"school,",
"have",
"worse",
"physical",
"health,",
"are",
"more",
"likely",
"to",
"be",
"indicated",
"victims",
"of",
"abuse",
"and",
"neglect,",
"have",
"higher",
"durations",
"of",
"foster",
"care",
"placement,",
"Page",
"1",
"of",
"7",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"Comparison",
"of",
"CT-Guided",
"Sclerotherapy",
"with",
"Using",
"95%",
"Ethanol",
"and",
"20%",
"Hypertonic",
"Saline",
"for",
"Managing",
"Simple",
"Renal",
"Cyst",
"Hulusi",
"Egilmez,",
"MD1",
"Vedat",
"Gok,",
"MD1",
"Ibrahim",
"Oztoprak,",
"MD1",
"Mehmet",
"Atalar,",
"MD1",
"Ali",
"Cetin,",
"MD2",
"Mubeccel",
"Arslan,",
"MD1",
"Yener",
"Gultekin,",
"MD3",
"Orhan",
"Solak,",
"MD1",
"Index",
"terms",
":",
"Kidney,",
"cyst",
"Kidney,",
"interventional",
"procedures",
"Sclerotherapy",
"Alcohol",
"Kidney,",
"CT",
"Korean",
"J",
"Radiol",
"2007;8:512-519",
"Received",
"July",
"2,",
"2006;",
"accepted",
"after",
"revision",
"December",
"27,",
"2006.",
"Departments",
"of",
"1Radiology,",
"2Obstetrics",
"and",
"Gynecology,",
"and",
"3Urology,",
"Cumhuriyet",
"University",
"School",
"of",
"Medicine,",
"58140",
"Sivas,",
"Turkey",
"Address",
"reprint",
"requests",
"to:",
"Hulusi",
"Egilmez,",
"MD,",
"Department",
"of",
"Radiology,",
"Cumhuriyet",
"University",
"School",
"of",
"Medicine,",
"58140",
"Sivas,",
"Turkey.",
"Tel.",
"+346",
"2191300",
"Fax.",
"+346",
"2191284",
"e-mail:",
"hegilmez@cumhuriyet.edu.tr",
"512",
"Objective:",
"We",
"wanted",
"to",
"compare",
"the",
"efficacies",
"of",
"95%",
"ethanol",
"and",
"20%",
"hypertonic",
"saline",
"(HS)",
"sclerotherapies",
"that",
"were",
"performed",
"in",
"a",
"single",
"session",
"under",
"CT",
"guidance",
"for",
"the",
"management",
"of",
"simple",
"renal",
"cysts.",
"Materials",
"and",
"Methods:",
"A",
"prospective",
"series",
"of",
"74",
"consecutive",
"patients",
"(aver-",
"age",
"age:",
"57.6",
"8.1",
"years)",
"with",
"simple",
"renal",
"cysts",
"were",
"enrolled",
"in",
"this",
"study.",
"They",
"were",
"randomized",
"into",
"two",
"groups",
"and",
"95%",
"ethanol",
"or",
"20%",
"HS,",
"respective-",
"ly,",
"corresponding",
"to",
"25%",
"of",
"the",
"aspiration",
"volume,",
"was",
"injected.",
"Treatment",
"suc-",
"cess",
"was",
"determined",
"six",
"months",
"later",
"with",
"follow-up",
"clinical",
"evaluation",
"and",
"per-",
"forming",
"ultrasonography.",
"Results:",
"The",
"sclerotherapy",
"was",
"accepted",
"as",
"technically",
"successful",
"without",
"major",
"complications",
"in",
"all",
"except",
"two",
"patients",
"who",
"were",
"excluded",
"because",
"of",
"a",
"communication",
"between",
"the",
"simple",
"renal",
"cyst",
"and",
"the",
"pelvicalyceal",
"collecting",
"system.",
"Thirty-six",
"patients",
"in",
"the",
"ethanol",
"group",
"received",
"sclerotherapy",
"with",
"95%",
"ethanol",
"and",
"36",
"patients",
"in",
"the",
"HS",
"group",
"underwent",
"sclerotherapy",
"with",
"20%",
"HS.",
"The",
"complete",
"regression",
"ratio",
"of",
"the",
"ethanol",
"group",
"was",
"significantly",
"higher",
"(94%",
"versus",
"72%,",
"respectively)",
"than",
"that",
"of",
"the",
"HS",
"group.",
"There",
"was",
"one",
"patient",
"with",
"partial",
"regression",
"in",
"each",
"group.",
"The",
"failure",
"ratio",
"of",
"the",
"ethanol",
"group",
"was",
"signifi-",
"cantly",
"lower",
"(3%",
"versus",
"25%,",
"respectively)",
"than",
"that",
"of",
"the",
"HS",
"group.",
"Conclusion:",
"Ethanol",
"sclerotherapy",
"under",
"CT",
"guidance",
"is",
"a",
"successful",
"and",
"safe",
"procedure",
"and",
"it",
"can",
"be",
"used",
"for",
"the",
"treatment",
"of",
"simple",
"renal",
"cysts.",
"Sclerotherapy",
"with",
"95%",
"ethanol",
"is",
"more",
"effective",
"than",
"20%",
"HS",
"sclerotherapy.",
"Sclerotherapy",
"with",
"HS",
"may",
"be",
"an",
"option",
"for",
"patients",
"preferring",
"to",
"undergo",
"a",
"less",
"painful",
"treatment",
"procedure.",
"S",
"for",
"approximately",
"65",
"to",
"70%",
"of",
"all",
"of",
"them",
"(1).",
"They",
"often",
"occur",
"in",
"imple",
"renal",
"cysts",
"are",
"the",
"most",
"common",
"renal",
"masses,",
"and",
"they",
"account",
"patients",
"over",
"the",
"age",
"of",
"50",
"as",
"has",
"been",
"determined",
"with",
"performing",
"postmortem",
"examination",
"or",
"renal",
"ultrasonography",
"(US)",
"(2,",
"3).",
"Simple",
"renal",
"cysts",
"are",
"often",
"incidentally",
"discovered",
"on",
"US,",
"CT",
"or",
"urography",
"examinations",
"that",
"are",
"performed",
"for",
"urinary",
"tract",
"problems",
"or",
"other",
"abdominal",
"problems.",
"The",
"characteristic",
"appearance",
"of",
"simple",
"renal",
"cysts",
"on",
"US,",
"CT",
"and",
"magnetic",
"resonance",
"imaging",
"allows",
"the",
"radiologist",
"to",
"make",
"an",
"accurate",
"diagnosis.",
"US",
"is",
"commonly",
"used",
"to",
"exclude",
"the",
"possibility",
"of",
"benign",
"or",
"malignant",
"pathology",
"because",
"the",
"kidney",
"is",
"readily",
"accessible",
"for",
"US",
"examination",
"(4).",
"A",
"small",
"proportion",
"of",
"simple",
"renal",
"cysts",
"may",
"be",
"associated",
"with",
"symptoms,",
"of",
"which",
"pain",
"is",
"the",
"commonest.",
"Hematuria,",
"hypertension,",
"pelvicalyceal",
"obstruction",
"and",
"cyst",
"rupture",
"are",
"less",
"common",
"symptoms",
"(2).",
"When",
"cysts",
"are",
"very",
"large,",
"they",
"may",
"produce",
"the",
"mechanical",
"effects",
"of",
"a",
"space-occupying",
"lesion.",
"Percutaneous",
"or",
"surgical",
"interven-",
"Korean",
"J",
"Radiol",
"8(6),",
"December",
"2007"
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] | [
"BMC",
"Health",
"Services",
"Research",
"Research",
"article",
"Developing",
"evidence-based",
"clinical",
"practice",
"guidelines",
"in",
"hospitals",
"in",
"Australia,",
"Indonesia,",
"Malaysia,",
"the",
"Philippines",
"and",
"Thailand:",
"values,",
"requirements",
"and",
"barriers",
"Tari",
"J",
"Turner",
"BioMed",
"Central",
"Open",
"Access",
"Address:",
"Monash",
"Institute",
"of",
"Health",
"Services",
"Research,",
"Monash",
"University,",
"Monash",
"Medical",
"Centre,",
"Clayton,",
"Victoria,",
"Australia",
"Email:",
"Tari",
"J",
"Turner",
"-",
"tari.turner@med.monash.edu.au",
"Published:",
"15",
"December",
"2009",
"BMC",
"Health",
"Services",
"Research",
"2009,",
"9:235",
"doi:10.1186/1472-6963-9-235",
"This",
"article",
"is",
"available",
"from:",
"http://www.biomedcentral.com/1472-6963/9/235",
"Received:",
"19",
"May",
"2009",
"Accepted:",
"15",
"December",
"2009",
"©",
"2009",
"Turner;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"Evidence-based",
"clinical",
"practice",
"guidelines",
"support",
"clinical",
"decision-making",
"by",
"making",
"recommendations",
"to",
"guide",
"clinical",
"practice.",
"These",
"recommendations",
"are",
"developed",
"by",
"integrating",
"the",
"expertise",
"of",
"a",
"multidisciplinary",
"group",
"of",
"clinicians",
"with",
"the",
"perspectives",
"of",
"consumers",
"and",
"the",
"best",
"available",
"research",
"evidence.",
"However",
"studies",
"have",
"raised",
"concerns",
"about",
"the",
"quality",
"of",
"guideline",
"development,",
"and",
"particularly",
"the",
"link",
"between",
"research",
"and",
"recommendations.",
"The",
"reasons",
"why",
"guideline",
"developers",
"are",
"not",
"following",
"the",
"established",
"development",
"methods",
"are",
"not",
"clear.",
"We",
"aimed",
"to",
"explore",
"the",
"barriers",
"to",
"developing",
"evidence-based",
"guidelines",
"in",
"eleven",
"hospitals",
"in",
"Australia,",
"Indonesia,",
"Malaysia,",
"the",
"Philippines",
"and",
"Thailand,",
"so",
"as",
"to",
"better",
"understand",
"how",
"evidence-based",
"guideline",
"development",
"could",
"be",
"facilitated",
"in",
"these",
"settings.",
"The",
"research",
"aimed",
"to",
"identify",
"the",
"value",
"clinicians",
"place",
"on",
"guidelines,",
"what",
"clinicians",
"want",
"in",
"guidelines",
"developed",
"in",
"hospital",
"settings",
"and",
"what",
"factors",
"limit",
"rigorous",
"evidence-based",
"guideline",
"development",
"in",
"these",
"settings.",
"Methods:",
"Semi-structured,",
"face-to-face",
"interviews",
"were",
"undertaken",
"with",
"senior",
"and",
"junior",
"healthcare",
"providers",
"(nurses,",
"midwives,",
"doctors,",
"allied",
"health)",
"from",
"the",
"maternal",
"and",
"neonatal",
"services",
"of",
"the",
"eleven",
"participating",
"hospitals.",
"Interviews",
"were",
"audio-recorded,",
"transcribed",
"and",
"a",
"thematic",
"analysis",
"undertaken.",
"Results:",
"Ninety-three",
"individual,",
"25",
"pair",
"and",
"eleven",
"group",
"interviews",
"were",
"conducted.",
"Participants",
"were",
"clear",
"that",
"they",
"want",
"guidelines",
"that",
"are",
"based",
"on",
"evidence",
"and",
"updated",
"regularly.",
"They",
"were",
"also",
"clear",
"that",
"there",
"are",
"major",
"barriers",
"to",
"this.",
"Most",
"of",
"the",
"barriers",
"were",
"shared",
"across",
"countries,",
"and",
"included",
"lack",
"of",
"time,",
"lack",
"of",
"skills",
"in",
"finding,",
"appraising",
"and",
"interpreting",
"evidence,",
"lack",
"of",
"access",
"to",
"relevant",
"evidence",
"and",
"difficulty",
"arranging",
"meetings",
"and",
"achieving",
"consensus.",
"Barriers",
"that",
"were",
"primarily",
"identified",
"in",
"Australian",
"hospitals",
"include",
"cumbersome",
"organisational",
"processes",
"and",
"a",
"feeling",
"that",
"guidelines",
"are",
"being",
"developed",
"for",
"bureaucratic",
"ends.",
"Barriers",
"that",
"were",
"primarily",
"identified",
"in",
"South",
"East",
"Asian",
"hospitals",
"include",
"difficulty",
"accessing",
"evidence",
"due",
"to",
"limited",
"resources",
"available",
"for",
"computers,",
"internet",
"and",
"journal",
"subscriptions",
"and",
"limited",
"skills",
"in",
"computing",
"and",
"English.",
"Conclusions:",
"The",
"clinicians",
"in",
"these",
"eleven",
"very",
"different",
"hospitals",
"want",
"evidence-based",
"guidelines.",
"However",
"they",
"are",
"frustrated",
"by",
"guideline",
"development",
"processes",
"that",
"are",
"enormously",
"time,",
"skill",
"and",
"resource",
"intensive.",
"They",
"feel",
"strongly",
"that",
"\"there's",
"got",
"to",
"be",
"a",
"better",
"way\".",
"The",
"fact",
"that",
"the",
"great",
"majority",
"of",
"the",
"identified",
"barriers",
"were",
"shared",
"across",
"settings",
"may",
"provide",
"an",
"opportunity",
"to",
"develop",
"a",
"more",
"pragmatic",
"way",
"of",
"developing",
"guidelines",
"that",
"can",
"be",
"applied",
"in",
"many",
"contexts.",
"Page",
"1",
"of",
"7",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"Minireview",
"The",
"topless",
"plant",
"developmental",
"phenotype",
"explained!",
"Karen",
"S",
"Osmont",
"and",
"Christian",
"S",
"Hardtke",
"Address:",
"Department",
"of",
"Plant",
"Molecular",
"Biology,",
"University",
"of",
"Lausanne,",
"Biophore",
"Building,",
"CH-1015",
"Lausanne,",
"Switzerland.",
"Correspondence:",
"Christian",
"S",
"Hardtke.",
"Email:",
"christian.hardtke@unil.ch",
"Published:",
"30",
"April",
"2008",
"Genome",
"Biology",
"2008,",
"9:219",
"(doi:10.1186/gb-2008-9-4-219)",
"The",
"electronic",
"version",
"of",
"this",
"article",
"is",
"the",
"complete",
"one",
"and",
"can",
"be",
"found",
"online",
"at",
"http://genomebiology.com/2008/9/4/219",
"©",
"2008",
"BioMed",
"Central",
"Ltd",
"Abstract",
"The",
"molecular-genetic",
"cues",
"that",
"regulate",
"plant",
"embryo",
"pattern",
"formation",
"are",
"the",
"subject",
"of",
"intense",
"scrutiny",
"at",
"present.",
"Recent",
"work",
"in",
"Arabidopsis",
"implicates",
"the",
"TOPLESS",
"protein",
"in",
"auxin-",
"dependent",
"transcriptional",
"repression,",
"highlighting",
"once",
"again",
"the",
"crucial",
"role",
"of",
"auxin",
"signaling",
"during",
"embryogenesis.",
"Biologists",
"have",
"long",
"been",
"fascinated",
"by",
"the",
"question",
"of",
"how",
"body",
"patterns",
"are",
"specified",
"during",
"embryogenesis,",
"starting",
"from",
"an",
"undifferentiated",
"zygote.",
"In",
"animals,",
"embryogenesis",
"typically",
"lays",
"down",
"the",
"adult",
"body",
"plan,",
"whereas",
"in",
"higher",
"plants,",
"embryogenesis",
"produces",
"a",
"minimal",
"plant",
"-",
"the",
"seedling.",
"Consequently,",
"the",
"vast",
"majority",
"of",
"adult",
"organs",
"in",
"plants",
"are",
"only",
"initiated",
"during",
"post-embryonic",
"growth.",
"Nevertheless,",
"embryogenesis",
"is",
"of",
"pivotal",
"importance",
"for",
"adult",
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"Genome",
"Biology",
"2008,",
"9:219"
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] | [
"4168–4177",
"Nucleic",
"Acids",
"Research,",
"2012,",
"Vol.",
"40,",
"No.",
"9",
"doi:10.1093/nar/gkr1231",
"Published",
"online",
"5",
"January",
"2012",
"Visualization",
"of",
"a",
"DNA-PK/PARP1",
"complex",
"Laura",
"Spagnolo1,2,*,",
"Jody",
"Barbeau",
"3",
",",
"Nicola",
"J.",
"Curtin3,",
"Edward",
"P.",
"Morris4",
"and",
"Laurence",
"H.",
"Pearl1,5",
"1Cancer",
"Research",
"UK",
"DNA",
"Repair",
"Enzymes",
"Group,",
"The",
"Institute",
"of",
"Cancer",
"Research,",
"London",
"SW3",
"6JB,",
"2Institute",
"of",
"Structural",
"Molecular",
"Biology,",
"University",
"of",
"Edinburgh,",
"EH9",
"3JR,",
"3Northern",
"Institute",
"for",
"Cancer",
"Research,",
"Medical",
"School,",
"Newcastle",
"University,",
"Newcastle",
"upon",
"Tyne,",
"4Structural",
"Electron",
"Microscopy",
"Group,",
"Section",
"of",
"Structural",
"Biology,",
"The",
"Institute",
"of",
"Cancer",
"Research,",
"London",
"SW3",
"6JB",
"and",
"5School",
"of",
"Life",
"Sciences,",
"University",
"of",
"Sussex,",
"Brighton,",
"BN1",
"9RH,",
"UK",
"Received",
"June",
"16,",
"2011;",
"Revised",
"November",
"23,",
"2011;",
"Accepted",
"November",
"24,",
"2011",
"ABSTRACT",
"The",
"DNA-dependent",
"protein",
"kinase",
"(DNA-PK)",
"and",
"Poly(ADP-ribose)",
"polymerase-1",
"(PARP1)",
"are",
"critical",
"enzymes",
"that",
"reduce",
"genomic",
"damage",
"caused",
"by",
"DNA",
"lesions.",
"They",
"are",
"both",
"activated",
"by",
"DNA",
"strand",
"breaks",
"generated",
"by",
"physiological",
"and",
"envir-",
"onmental",
"factors,",
"and",
"they",
"have",
"been",
"shown",
"to",
"interact.",
"Here,",
"we",
"report",
"in",
"vivo",
"evidence",
"that",
"DNA-PK",
"and",
"PARP1",
"are",
"equally",
"necessary",
"for",
"rapid",
"repair.",
"We",
"purified",
"a",
"DNA-PK/PARP1",
"complex",
"loaded",
"on",
"DNA",
"and",
"performed",
"electron",
"microscopy",
"and",
"single",
"particle",
"analysis",
"on",
"its",
"tetra-",
"meric",
"and",
"dimer-of-tetramers",
"forms.",
"By",
"comparison",
"with",
"the",
"DNA-PK",
"holoenzyme",
"and",
"fitting",
"crystal-",
"lographic",
"structures,",
"we",
"see",
"that",
"the",
"PARP1",
"density",
"is",
"in",
"close",
"contact",
"with",
"the",
"Ku",
"subunit.",
"Crucially,",
"PARP1",
"binding",
"elicits",
"substantial",
"con-",
"formational",
"changes",
"in",
"the",
"DNA-PK",
"synaptic",
"dimer",
"assembly.",
"Taken",
"together,",
"our",
"data",
"support",
"a",
"func-",
"tional,",
"in-pathway",
"role",
"for",
"DNA-PK",
"and",
"PARP1",
"in",
"double-strand",
"break",
"(DSB)",
"repair.",
"We",
"also",
"propose",
"a",
"NHEJ",
"model",
"where",
"protein–protein",
"interactions",
"alter",
"substantially",
"the",
"architecture",
"of",
"DNA-PK",
"dimers",
"at",
"DSBs,",
"to",
"trigger",
"subsequent",
"interactions",
"or",
"enzymatic",
"reactions.",
"INTRODUCTION",
"DNA",
"double-strand",
"breaks",
"(DSBs)",
"are",
"the",
"most",
"cytotoxic",
"form",
"of",
"DNA",
"damage.",
"If",
"unrepaired",
"or",
"incorrectly",
"repaired,",
"they",
"can",
"lead",
"to",
"apoptosis",
"or",
"genome",
"instability.",
"Two",
"major",
"DSB",
"repair",
"pathways",
"exist:",
"homologous",
"recombination",
"(HR)",
"and",
"non-homologous",
"end",
"joining",
"(NHEJ)",
"(1).",
"In",
"the",
"presence",
"of",
"sister",
"chromatids",
"acting",
"as",
"templates",
"for",
"repair,",
"DSBs",
"can",
"be",
"repaired",
"by",
"HR.",
"In",
"NHEJ,",
"the",
"DNA",
"broken",
"ends",
"are",
"resected",
"and/or",
"pro-",
"cessed",
"and",
"the",
"DNA",
"backbones",
"ligated",
"to",
"restore",
"strand",
"continuity",
"without",
"the",
"need",
"for",
"a",
"template.",
"The",
"DNA-dependent",
"protein",
"kinase",
"(DNA-PK)",
"heterotrimeric",
"enzyme",
"is",
"the",
"early",
"player",
"in",
"mammalian",
"NHEJ",
"(2).",
"DNA-PK",
"is",
"formed",
"by",
"a",
"DSB",
"recognition",
"module,",
"called",
"Ku",
"(preassembled",
"as",
"a",
"heterodimer",
"of",
"the",
"Ku70",
"and",
"Ku80",
"proteins)",
"(3)",
"and",
"a",
"large",
"catalytic",
"subunit",
"(DNA-PKcs,",
"0.5",
"MDa)",
"(4,5).",
"After",
"recognizing",
"and",
"binding",
"to",
"a",
"DSB,",
"Ku",
"recruits",
"the",
"catalytic",
"subunit",
"via",
"the",
"C-terminal",
"domain",
"of",
"the",
"Ku80",
"subunit.",
"DNA-PKcs",
"is",
"a",
"serine/threonine",
"kinase",
"belonging",
"to",
"the",
"phosphatidylinositol-3-OH",
"kinase",
"(PI3K)-related",
"(PIKK)",
"family.",
"DNA-PK",
"assembles",
"on",
"DNA",
"as",
"a",
"bridging",
"complex,",
"where",
"two",
"heterotrimers",
"maintain",
"the",
"two",
"DNA",
"broken",
"ends",
"in",
"close",
"proximity,",
"providing",
"a",
"scaf-",
"folding",
"platform",
"to",
"recruit",
"further",
"NHEJ",
"enzymes",
"(6).",
"These",
"factors",
"include",
"Artemis",
"and",
"PNK,",
"which",
"are",
"required",
"to",
"process",
"the",
"broken",
"ends;",
"X",
"family",
"polymer-",
"ases,",
"which",
"promote",
"microhomology",
"and",
"cohesion",
"between",
"the",
"broken",
"ends;",
"DNA",
"ligase",
"IV-XRCC4,",
"which",
"closes",
"the",
"phospho-diester",
"backbone",
"on",
"both",
"strands,",
"and",
"the",
"XLF/Cernunnos",
"factor",
"(7).",
"Autophos-",
"phorylation",
"sites,",
"crucial",
"to",
"NHEJ",
"regulation,",
"have",
"been",
"identified",
"in",
"DNA-PKcs",
"at",
"two",
"main",
"clusters,",
"as",
"well",
"as",
"within",
"its",
"catalytic",
"domain",
"(7).",
"A",
"recent",
"electron",
"micros-",
"copy",
"study",
"visualized",
"a",
"substantial",
"remodeling",
"of",
"DNA-PK",
"on",
"autophosphorylation",
"(8).",
"PARP",
"enzymes",
"use",
"nicotinamide",
"as",
"a",
"substrate",
"to",
"polymerize",
"ADP-ribose",
"moieties",
"onto",
"target",
"proteins,",
"a",
"process",
"called",
"poly-ADP-ribosylation",
"(or",
"PARylation)",
"(9).",
"The",
"best-studied",
"PARP",
"enzyme",
"is",
"PARP1,",
"which",
"has",
"a",
"key",
"role",
"in",
"DNA",
"repair",
"and",
"in",
"particular",
"single-",
"strand",
"break",
"repair/base",
"excision",
"repair",
"(10).",
"PARP1",
"detects",
"and",
"binds",
"single",
"strand",
"DNA",
"breaks",
"and",
"then",
"poly-ADP-ribosylates",
"itself",
"(auto-PARylation)",
"and",
"other",
"*To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"Tel.",
"+44",
"0",
"131",
"650",
"7066;",
"Fax",
"+44",
"0",
"131",
"650",
"8650;",
"Email:",
"laura.spagnolo@ed.ac.uk",
"The",
"Author(s)",
"2012.",
"Published",
"by",
"Oxford",
"University",
"Press.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://creativecommons.org/licenses/",
"by-nc/3.0),",
"which",
"permits",
"unrestricted",
"non-commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Hindawi",
"Publishing",
"Corporation",
"Journal",
"of",
"Transplantation",
"Volume",
"2012,",
"Article",
"ID",
"201754,",
"7",
"pages",
"doi:10.1155/2012/201754",
"Research",
"Article",
"Antibody-Mediated",
"Rejection:",
"Pathogenesis,",
"Prevention,",
"Treatment,",
"and",
"Outcomes",
"Olivia",
"R.",
"Blume,1",
"Sarah",
"E.",
"Yost,2",
"and",
"Bruce",
"Kaplan3",
"1",
"Abdominal",
"Transplantation,",
"University",
"of",
"Arizona",
"Medical",
"Center,",
"Tucson,",
"AZ,",
"USA",
"2",
"Abdominal",
"Transplantation,",
"Department",
"of",
"Pharmacy,",
"University",
"of",
"Arizona",
"Medical",
"Center,",
"Tucson,",
"AZ,",
"USA",
"3",
"University",
"of",
"Arizona",
"College",
"of",
"Medicine,",
"1501",
"North",
"Campbell",
"Avenue,",
"Tucson,",
"AZ",
"85724,",
"USA",
"Correspondence",
"should",
"be",
"addressed",
"to",
"Olivia",
"R.",
"Blume,",
"olivia.blume@uahealth.com",
"Received",
"19",
"October",
"2011;",
"Revised",
"4",
"November",
"2011;",
"Accepted",
"28",
"December",
"2011",
"Academic",
"Editor:",
"Banu",
"Sis",
"Copyright",
"©",
"2012",
"Olivia",
"R.",
"Blume",
"et",
"al.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Antibody-mediated",
"rejection",
"(AMR)",
"is",
"a",
"major",
"cause",
"of",
"late",
"kidney",
"transplant",
"failure.",
"It",
"is",
"important",
"to",
"have",
"an",
"understanding",
"of",
"human-leukocyte",
"antigen",
"(HLA)",
"typing",
"including",
"well-designed",
"studies",
"to",
"determine",
"anti-MHC-class-I-related",
"chain",
"A",
"(MICA)",
"and",
"antibody",
"rejection",
"pathogenesis.",
"This",
"can",
"allow",
"for",
"more",
"specific",
"diagnosis",
"and",
"treatment",
"which",
"may",
"improve",
"long-term",
"graft",
"function.",
"HLA-specific",
"antibody",
"detection",
"prior",
"to",
"transplantation",
"allows",
"one",
"to",
"help",
"determine",
"the",
"risk",
"for",
"AMR",
"while",
"detection",
"of",
"DSA",
"along",
"with",
"a",
"biopsy",
"confirms",
"it.",
"It",
"is",
"now",
"appreciated",
"that",
"biopsy",
"for",
"AMR",
"does",
"not",
"have",
"to",
"include",
"diffuse",
"C4d,",
"but",
"does",
"require",
"a",
"closer",
"look",
"at",
"peritubular",
"capillary",
"microvasculature.",
"Although",
"plasmapheresis",
"(PP)",
"is",
"effective",
"in",
"removing",
"alloantibodies",
"(DSAs)",
"from",
"the",
"circulation,",
"rebound",
"synthesis",
"of",
"alloantibodies",
"can",
"occur.",
"Splenectomy",
"is",
"used",
"in",
"desensitization",
"protocols",
"for",
"ABO",
"incompatible",
"transplants",
"as",
"well",
"as",
"being",
"found",
"to",
"treat",
"AMR",
"refractory",
"to",
"conventional",
"treatment.",
"Also",
"used",
"are",
"agents",
"targeted",
"for",
"plasma",
"cells,",
"B",
"cells,",
"and",
"the",
"complement",
"cascade",
"which",
"are",
"bortezomib",
"rituximab",
"and",
"eculizumab,",
"respectively.",
"1.",
"Understanding",
"HLA",
"There",
"are",
"20",
"class",
"I",
"genes",
"and",
"in",
"transplantation",
"HLA-A,",
"B,",
"and",
"C",
"are",
"the",
"classic",
"genes",
"referenced",
"to",
"when",
"typing",
"the",
"recipient",
"[1].",
"Class",
"I",
"major",
"histocompatibility",
"complex",
"(MHC)",
"molecule",
"processing",
"and",
"loading",
"of",
"peptides",
"occurs",
"in",
"all",
"nucleated",
"cells,",
"where",
"class",
"II",
"MHC",
"molecule",
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"primarily",
"B",
"cells,",
"macrophages,",
"and",
"dendritic",
"cells",
"by",
"method",
"of",
"endocytosis",
"and",
"phagocytosis.",
"Class",
"II",
"MHC",
"molecule",
"nomenclature",
"is",
"designated",
"by",
"class",
"(D),",
"family",
"(M,",
"O,",
"P,",
"Q,",
"R),",
"and",
"chain",
"(A",
"or",
"B).",
"Late",
"antibody-mediated",
"rejection",
"(AMR)",
"is",
"a",
"major",
"cause",
"of",
"late",
"kidney",
"transplant",
"failure",
"and",
"several",
"developments",
"in",
"understanding",
"of",
"patho-",
"genesis",
"allow",
"for",
"improvement",
"of",
"diagnosis,",
"treatment,",
"and",
"prevention.",
"This",
"review",
"will",
"concentrate",
"on",
"reviewing",
"the",
"pathogenesis,",
"diagnosis,",
"and",
"treatment",
"of",
"AMR.",
"2.",
"Pathogenesis",
"of",
"HLA",
"Antibodies",
"Not",
"only",
"can",
"antibodies",
"form",
"against",
"HLA",
"molecules,",
"but",
"to",
"endothelial-cell",
"antigens",
"and",
"across",
"ABO",
"blood",
"group",
"[2].",
"Sensitization",
"prior",
"to",
"transplant",
"can",
"occur",
"by",
"pregnancy",
"or",
"blood",
"transfusions.",
"Previous",
"transplantation",
"can",
"also",
"sensitize",
"patients",
"against",
"HLA",
"molecules.",
"Blood",
"transfusions",
"can",
"induce",
"humoral",
"immunity",
"by",
"formation",
"of",
"HLA",
"alloan-",
"tibodies",
"and",
"are",
"more",
"likely",
"to",
"occur",
"in",
"individuals",
"who",
"have",
"been",
"previously",
"pregnant.",
"Our",
"understanding",
"of",
"how",
"blood",
"transfusions",
"cause",
"sensitization",
"is",
"incomplete,",
"but",
"it",
"is",
"not",
"inevitable",
"and",
"can",
"be",
"attenuated",
"by",
"immunosuppression.",
"In",
"a",
"study",
"performed",
"by",
"Eikmans",
"et",
"al.",
"it",
"was",
"found",
"two",
"weeks",
"after",
"blood",
"transfusion",
"in",
"both",
"nonsensitized",
"and",
"sensitized",
"recipients,",
"increased",
"numbers",
"of",
"IFN-γ-producing",
"cells",
"were",
"produced",
"stimulating",
"CD4+",
"and",
"NK",
"cells",
"[3].",
"With",
"de",
"novo",
"HLA",
"production,",
"antibody",
"rejection",
"can",
"occur",
"within",
"weeks",
"of",
"the",
"transplant.",
"Endothelium",
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"peritubular",
"and",
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"capillaries",
"display",
"MHC",
"molecules",
"which",
"are",
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"target",
"for",
"antibody",
"production.",
"Once",
"the",
"endothelium",
"is",
"damaged",
"by",
"antibody,",
"von",
"Willebrand",
"factor",
"and",
"P-",
"selectin",
"are",
"released",
"as",
"an",
"inflammatory",
"response.",
"Leukocytes",
"adhere",
"to",
"glomeruli",
"or",
"to",
"dilated",
"peritubular",
"capillaries",
"via",
"cytokines",
"(IL-1",
"α,",
"IL-8,",
"and",
"chemokine",
"ligand",
"2)",
"allowing"
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] | [
"Interleukin-13",
"Induces",
"Tissue",
"Fibrosis",
"by",
"Selectively",
"Stimulating",
"and",
"Activating",
"Transforming",
"Growth",
"Factor",
"1",
"Chun",
"Geun",
"Lee,1",
"Robert",
"J.",
"Homer,2,",
"3",
"Zhou",
"Zhu,1",
"Sophie",
"Lanone,1",
"Xiaoman",
"Wang,1",
"Victor",
"Koteliansky,4",
"J.",
"Michael",
"Shipley,5",
"Philip",
"Gotwals,4",
"Paul",
"Noble,1",
"Qingsheng",
"Chen,1",
"Robert",
"M.",
"Senior,5",
"and",
"Jack",
"A.",
"Elias1",
"1Yale",
"University",
"School",
"of",
"Medicine,",
"Section",
"of",
"Pulmonary",
"and",
"Critical",
"Care",
"Medicine,",
"Department",
"of",
"Internal",
"Medicine",
"and",
"the",
"2Department",
"of",
"Pathology,",
"New",
"Haven,",
"CT",
"06520",
"3Pathology",
"and",
"Laboratory",
"Medicine",
"Service,VA-CT",
"Health",
"Care",
"System,West",
"Haven,",
"CT",
"06516",
"4Biogen,",
"Inc.,",
"Cambridge,",
"MA",
"02142",
"5Washington",
"University",
"School",
"of",
"Medicine,",
"Section",
"of",
"Pulmonary",
"and",
"Critical",
"Care",
"Medicine,",
"Barnes-Jewish",
"Hospital,",
"St.",
"Louis,",
"MO",
"63110",
"Abstract",
"Interleukin",
"(IL)-13",
"is",
"a",
"key",
"mediator",
"of",
"tissue",
"fibrosis",
"caused",
"by",
"T",
"helper",
"cell",
"type",
"2",
"inflamma-",
"tion.",
"We",
"hypothesized",
"that",
"the",
"fibrogenic",
"effects",
"of",
"IL-13",
"are",
"mediated",
"by",
"transforming",
"growth",
"factor",
"(TGF)-",
".",
"To",
"test",
"this",
"hypothesis",
"we",
"compared",
"the",
"regulation",
"of",
"TGF-",
"in",
"lungs",
"from",
"wild-type",
"mice",
"and",
"CC10-IL-13",
"mice",
"in",
"which",
"IL-13",
"overexpression",
"causes",
"pul-",
"monary",
"fibrosis.",
"IL-13",
"selectively",
"stimulated",
"TGF-",
"1",
"production",
"in",
"transgenic",
"animals",
"and",
"macrophages",
"were",
"the",
"major",
"site",
"of",
"TGF-",
"1",
"production",
"and",
"deposition",
"in",
"these",
"tissues.",
"IL-13",
"also",
"activated",
"TGF-",
"1",
"in",
"vivo.",
"This",
"activation",
"was",
"associated",
"with",
"decreased",
"levels",
"of",
"mRNA",
"encoding",
"latent",
"TGF-",
"–binding",
"protein-1",
"and",
"increased",
"mRNA",
"encoding",
"urinary",
"plasmino-",
"gen",
"activator,",
"matrix",
"metalloproteinase",
"(MMP)-9,",
"and",
"CD44.",
"TGF-",
"1",
"activation",
"was",
"abro-",
"gated",
"by",
"the",
"plasmin/serine",
"protease",
"antagonist",
"aprotinin.",
"It",
"was",
"also",
"decreased",
"in",
"progeny",
"of",
"crosses",
"of",
"CC10-IL-13",
"mice",
"and",
"MMP-9",
"null",
"mice",
"but",
"was",
"not",
"altered",
"in",
"crosses",
"with",
"CD44",
"null",
"animals.",
"IL-13–induced",
"fibrosis",
"was",
"also",
"significantly",
"ameliorated",
"by",
"treatment",
"with",
"the",
"TGF-",
"antagonist",
"soluble",
"TGF",
"R-Fc",
"(sTGF",
"R-Fc).",
"These",
"studies",
"demonstrate",
"that",
"IL-13",
"is",
"a",
"potent",
"stimulator",
"and",
"activator",
"of",
"TGF-",
"1",
"in",
"vivo.",
"They",
"also",
"demonstrate",
"that",
"this",
"activation",
"is",
"mediated",
"by",
"a",
"plasmin/serine",
"protease-",
"and",
"MMP-9–dependent",
"and",
"CD44-independent",
"mechanism(s)",
"and",
"that",
"the",
"fibrogenic",
"effects",
"of",
"IL-13",
"are",
"mediated,",
"in",
"great",
"extent,",
"by",
"this",
"TGF-",
"pathway.",
"Key",
"words:",
"lung",
"•",
"plasmin",
"•",
"matrix",
"metalloproteinase-9",
"•",
"CD44",
"•",
"asthma",
"Introduction",
"Tissue",
"fibrosis",
"is",
"a",
"well-documented",
"consequence",
"of",
"Th2",
"cytokine-dominated",
"inflammatory",
"responses.",
"This",
"is",
"nicely",
"illustrated",
"in",
"asthma",
"where",
"Th2-dominated",
"inflammation",
"is",
"the",
"cornerstone",
"of",
"the",
"disorder",
"(1,",
"2)",
"and",
"airway",
"remodel-",
"ing",
"with",
"subepithelial",
"fibrosis",
"are",
"believed",
"to",
"be",
"adverse",
"consequences",
"of",
"this",
"inflammatory",
"response",
"(for",
"a",
"review,",
"see",
"reference",
"3).",
"Th2",
"inflammation",
"also",
"plays",
"a",
"central",
"role",
"in",
"the",
"pathogenesis",
"of",
"a",
"variety",
"of",
"other",
"fibrotic",
"disorders",
"including",
"progressive",
"systemic",
"sclerosis",
"(4–6),",
"idiopathic",
"Address",
"correspondence",
"to",
"Jack",
"A.",
"Elias,",
"Yale",
"University",
"School",
"of",
"Med-",
"icine,",
"Section",
"of",
"Pulmonary",
"and",
"Critical",
"Care",
"Medicine,",
"Dept.",
"of",
"Inter-",
"nal",
"Medicine,",
"333",
"Cedar",
"St.",
"-",
"105",
"LCI,",
"New",
"Haven,",
"CT",
"06520-8057.",
"Phone:",
"203-785-4163;",
"Fax:",
"203-785-3826;",
"E-mail:",
"jack.elias@yale.edu",
"pulmonary",
"fibrosis",
"(IPF*;",
"references",
"5–8),",
"radiation-",
"induced",
"pulmonary",
"fibrosis",
"(9),",
"chronic",
"lung",
"allograft",
"re-",
"jection",
"(10),",
"bleomycin",
"lung",
"(11),",
"and",
"hepatic",
"fibrosis",
"(12–",
"15).",
"In",
"vitro",
"polarized",
"Th2",
"cells",
"also",
"induce",
"tissue",
"fibrosis",
"when",
"passively",
"transferred",
"and",
"activated",
"in",
"vivo",
"(16).",
"In",
"contrast,",
"Th1",
"cytokine-dominated",
"responses",
"eventuate",
"in",
"tissue",
"fibrosis",
"less",
"frequently",
"and",
"IFN-",
",",
"the",
"prototypic",
"Th1",
"cytokine,",
"has",
"a",
"variety",
"of",
"antifibrotic",
"effector",
"proper-",
"*Abbreviations",
"used",
"in",
"this",
"paper:",
"BAL,",
"bronchoalveolar",
"lavage;",
"IPF,",
"idio-",
"pathic",
"pulmonary",
"fibrosis;",
"ISH,",
"in",
"situ",
"hybridization;",
"LAP,",
"latency-associ-",
"ated",
"peptide;",
"LTBP,",
"latent",
"TGF-",
"–binding",
"protein;",
"MMP,",
"matrix",
"me-",
"talloproteinase;",
"PAI,",
"plasminogen",
"activator",
"inhibitor;",
"RT,",
"reverse",
"transcription;",
"s,",
"soluble;",
"uPA,",
"urokinase",
"type",
"plasminogen",
"activator;",
"WT,",
"wild-type.",
"809",
"J.",
"Exp.",
"Med.",
"",
"The",
"Rockefeller",
"University",
"Press",
"•",
"0022-1007/2001/09/809/13",
"$5.00",
"Volume",
"194,",
"Number",
"6,",
"September",
"17,",
"2001",
"809–821",
"http://www.jem.org/cgi/content/full/194/6/809"
] | [
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] | [
"Published",
"online",
"25",
"October",
"2008",
"Nucleic",
"Acids",
"Research,",
"2009,",
"Vol.",
"37,",
"Database",
"issue",
"D369–D373",
"doi:10.1093/nar/gkn759",
"RsiteDB:",
"a",
"database",
"of",
"protein",
"binding",
"pockets",
"that",
"interact",
"with",
"RNA",
"nucleotide",
"bases",
"Alexandra",
"Shulman-Peleg1,*,",
"Ruth",
"Nussinov2,3",
"and",
"Haim",
"J.",
"Wolfson1",
"1School",
"of",
"Computer",
"Science,",
"Raymond",
"and",
"Beverly",
"Sackler",
"Faculty",
"of",
"Exact",
"Sciences,",
"Tel",
"Aviv",
"University,",
"2Sackler",
"Institute",
"of",
"Molecular",
"Medicine,",
"Sackler",
"Faculty",
"of",
"Medicine,",
"Tel",
"Aviv",
"University,",
"Tel",
"Aviv",
"69978,",
"Israel",
"and",
"3Basic",
"Research",
"Program,",
"SAIC-Frederick,",
"Inc.,",
"Laboratory",
"of",
"Experimental",
"and",
"Computational",
"Biology",
"NCI-Frederick",
"Bldg",
"469,",
"Rm",
"151,",
"Frederick,",
"MD",
"21702,",
"USA",
"Received",
"August",
"11,",
"2008;",
"Revised",
"September",
"30,",
"2008;",
"Accepted",
"October",
"6,",
"2008",
"ABSTRACT",
"We",
"present",
"a",
"new",
"database",
"and",
"an",
"on-line",
"search",
"engine,",
"which",
"store",
"and",
"query",
"the",
"protein",
"binding",
"pockets",
"that",
"interact",
"with",
"single-stranded",
"RNA",
"nucleotide",
"bases.",
"The",
"database",
"consists",
"of",
"a",
"clas-",
"sification",
"of",
"binding",
"sites",
"derived",
"from",
"protein–RNA",
"complexes.",
"Each",
"binding",
"site",
"is",
"assigned",
"to",
"a",
"clus-",
"ter",
"of",
"similar",
"binding",
"sites",
"in",
"other",
"protein–RNA",
"complexes.",
"Cluster",
"members",
"share",
"similar",
"spatial",
"arrangements",
"of",
"physico–chemical",
"properties,",
"thus",
"can",
"reveal",
"novel",
"similarity",
"between",
"proteins",
"and",
"RNAs",
"with",
"different",
"sequences",
"and",
"folds.",
"The",
"clusters",
"provide",
"3D",
"consensus",
"binding",
"patterns",
"important",
"for",
"protein–nucleotide",
"recognition.",
"The",
"database",
"search",
"engine",
"allows",
"two",
"types",
"of",
"useful",
"queries:",
"first,",
"given",
"a",
"PDB",
"code",
"of",
"a",
"protein–RNA",
"complex,",
"RsiteDB",
"can",
"detail",
"and",
"classify",
"the",
"proper-",
"ties",
"of",
"the",
"protein",
"binding",
"pockets",
"accommodat-",
"ing",
"extruded",
"RNA",
"nucleotides",
"not",
"involved",
"in",
"local",
"RNA",
"base",
"pairing.",
"Second,",
"given",
"an",
"unbound",
"pro-",
"tein",
"structure,",
"RsiteDB",
"can",
"perform",
"an",
"on-line",
"structural",
"search",
"against",
"the",
"constructed",
"database",
"of",
"3D",
"consensus",
"binding",
"patterns.",
"Regions",
"similar",
"to",
"known",
"patterns",
"are",
"predicted",
"to",
"serve",
"as",
"binding",
"sites.",
"Alignment",
"of",
"the",
"query",
"to",
"these",
"patterns",
"with",
"their",
"corresponding",
"RNA",
"nucleotides",
"allows",
"making",
"unique",
"predictions",
"of",
"the",
"protein–RNA",
"interactions",
"at",
"the",
"atomic",
"level",
"of",
"detail.",
"This",
"database",
"is",
"acces-",
"sable",
"at",
"http://bioinfo3d.cs.tau.ac.il/RsiteDB.",
"INTRODUCTION",
"Understanding",
"and",
"predicting",
"protein–RNA",
"interactions",
"at",
"the",
"atomic",
"level",
"is",
"crucial",
"for",
"our",
"ability",
"to",
"interfere",
"with",
"such",
"processes",
"as",
"gene",
"expression",
"and",
"regulation.",
"Several",
"works",
"have",
"classified",
"protein–RNA",
"interactions",
"based",
"on",
"the",
"sequences",
"and",
"folds",
"of",
"the",
"corresponding",
"protein",
"(1–3)",
"or",
"RNA",
"molecules",
"(4–6).",
"However,",
"these",
"do",
"not",
"always",
"capture",
"the",
"similarity",
"in",
"the",
"local",
"regions",
"which",
"are",
"responsible",
"for",
"protein–RNA",
"recognition.",
"These",
"regions",
"are",
"important",
"since",
"even",
"proteins",
"of",
"the",
"same",
"family",
"can",
"form",
"different",
"interactions",
"with",
"RNA",
"nucleotides",
"(7,8).",
"By",
"analyzing",
"the",
"amino",
"acid",
"composi-",
"tion",
"in",
"RNA",
"binding",
"sites,",
"several",
"successful",
"methods",
"for",
"prediction",
"of",
"RNA",
"binding",
"regions",
"were",
"developed",
"(9–12).",
"However,",
"there",
"are",
"only",
"few",
"methods",
"(5)",
"that",
"distinguish",
"between",
"two",
"main",
"interaction",
"types",
"formed",
"across",
"protein–RNA",
"interfaces:",
"(i)",
"interactions",
"with",
"the",
"back-",
"bone",
"of",
"double-stranded",
"RNA",
"molecules;",
"(ii)",
"interactions",
"with",
"single-stranded",
"RNA",
"bases",
"that",
"are",
"buried",
"in",
"the",
"protein",
"binding",
"pockets",
"(14).",
"Here,",
"we",
"focus",
"on",
"the",
"classification",
"and",
"prediction",
"of",
"protein",
"interactions",
"formed",
"with",
"single-stranded",
"nucleo-",
"tide",
"bases.",
"Sequences",
"of",
"such",
"nucleotides,",
"which",
"are",
"not",
"involved",
"in",
"local",
"base",
"pairs",
"and",
"are",
"extruded",
"from",
"the",
"surrounding",
"double-stranded",
"helix",
"were",
"also",
"termed",
"extruded",
"helical",
"single",
"strands",
"and",
"described",
"as",
"Structural",
"Classification",
"of",
"RNA",
"(SCOR)",
"motifs",
"(6,15).",
"As",
"estimated",
"by",
"the",
"recent",
"study",
"of",
"Ellis",
"and",
"Jones",
"(16),",
"the",
"flexibility",
"in",
"the",
"protein",
"binding",
"sites",
"is",
"not",
"significant",
"and",
"should",
"allow",
"structural",
"prediction",
"of",
"protein–RNA",
"interaction.",
"In",
"our",
"recent",
"work",
"(17),",
"we",
"investigated",
"the",
"protein",
"binding",
"pockets",
"that",
"accommodate",
"extruded",
"nucleotides.",
"We",
"observed",
"that",
"most",
"of",
"the",
"protein",
"inter-",
"acting",
"nucleotides",
"are",
"part",
"of",
"a",
"consecutive",
"fragment",
"of",
"at",
"least",
"two",
"nucleotides,",
"whose",
"rings",
"have",
"significant",
"inter-",
"actions",
"with",
"the",
"protein.",
"Many",
"such",
"pairs",
"were",
"observed",
"to",
"share",
"the",
"same",
"protein",
"binding",
"cavity",
"and",
">30%",
"of",
"these",
"pairs",
"are",
"p-stacked.",
"We",
"showed",
"that",
"the",
"classifica-",
"tion",
"of",
"the",
"nucleotide",
"and",
"dinucleotide",
"binding",
"sites",
"reveals",
"similarities",
"in",
"patterns",
"important",
"in",
"protein–",
"RNA",
"recognition.",
"We",
"further",
"showed",
"that",
"searching",
"for",
"*To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"Tel:",
"+972-3-640",
"8268",
"or",
"640",
"5375;",
"Fax:",
"+972-3-640",
"5728",
"or",
"640",
"6476;",
"Email:",
"shulmana@post.tau.ac.il",
"Correspondence",
"may",
"also",
"be",
"addressed",
"to",
"Haim",
"J.",
"Wolfson.",
"Email:",
"wolfson@post.tau.ac.il",
"2008",
"The",
"Author(s)",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://creativecommons.org/licenses/",
"by-nc/2.0/uk/)",
"which",
"permits",
"unrestricted",
"non-commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
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"the",
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] | [
"www.kjurology.org",
"DOI:10.4111/kju.2010.51.7.501",
"Case",
"Report",
"Mesenteric",
"Fibromatosis",
"Causing",
"Ureteral",
"Stenosis",
"Jae",
"Young",
"Choi,",
"Kyung",
"Mo",
"Kang,",
"Bum",
"Soo",
"Kim,",
"Tae-Hwan",
"Kim",
"Department",
"of",
"Urology,",
"School",
"of",
"Medicine,",
"Kyungpook",
"National",
"University,",
"Daegu,",
"Korea",
"Mesenteric",
"fibromatosis",
"is",
"a",
"rare",
"benign",
"disease",
"characterized",
"by",
"proliferating",
"fibrous",
"tissue",
"in",
"the",
"bowel",
"mesentery.",
"We",
"report",
"a",
"case",
"of",
"aggressive",
"mesenteric",
"fibromatosis",
"with",
"ureteral",
"stenosis",
"arising",
"in",
"a",
"46-year-old",
"woman",
"who",
"suffered",
"from",
"intermittent",
"right",
"abdominal",
"pain.",
"Computed",
"tomography",
"revealed",
"a",
"right",
"retroperitoneal",
"mass",
"with",
"right",
"ureteral",
"stenosis",
"at",
"the",
"level",
"of",
"the",
"right",
"common",
"iliac",
"vessel.",
"The",
"mass",
"was",
"excised",
"with",
"resection",
"of",
"the",
"affected",
"segment",
"of",
"the",
"ileum,",
"ascending",
"colon,",
"and",
"ureter,",
"and",
"end-to-end",
"ureter",
"anastomosis",
"was",
"performed.",
"Pathological",
"examination",
"con-",
"firmed",
"mesenteric",
"fibromatosis.",
"Key",
"Words:",
"Aggressive",
"fibromatosis;",
"Retroperitoneal",
"neoplasms",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://creativecommons.org/licenses/by-nc/3.0)",
"which",
"permits",
"unrestricted",
"non-commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Article",
"History:",
"received",
"18",
"February,",
"2010",
"accepted",
"18",
"March,",
"2010",
"Corresponding",
"Author:",
"Tae-Hwan",
"Kim",
"Department",
"of",
"Urology,",
"School",
"of",
"Medicine,",
"Kyungpook",
"National",
"University,",
"200,",
"Dongduk-ro,",
"Jung-gu,",
"Daegu",
"700-721,",
"Korea",
"TEL:",
"+82-53-420-5841",
"FAX:",
"+82-53-421-9618",
"E-mail:",
"peak@urology.or.kr",
"Mesenteric",
"fibromatosis",
"(MF)",
"is",
"a",
"rare,",
"benign,",
"intra-ab-",
"dominal",
"tumor.",
"MF",
"is",
"characterized",
"by",
"proliferating",
"fi-",
"brous",
"tissue",
"in",
"the",
"bowel",
"mesentery.",
"Although",
"MF",
"occa-",
"sionally",
"invades",
"the",
"bowel",
"or",
"adjacent",
"tissues",
"with",
"ag-",
"gressive",
"myofibroblastic",
"proliferation,",
"MF",
"lacks",
"the",
"ca-",
"pacity",
"of",
"malignant",
"tumorigenesis",
"with",
"distant",
"metastasis",
"[1].",
"MF",
"is",
"frequently",
"associated",
"with",
"Gardner’s",
"syndrome,",
"previous",
"trauma,",
"prolonged",
"estrogen",
"intake,",
"and",
"preg-",
"nancy,",
"but",
"MF",
"can",
"occur",
"as",
"a",
"primary",
"condition",
"in",
"the",
"ab-",
"sence",
"of",
"predisposing",
"factors",
"[2].",
"MF-induced",
"ureteral",
"stenosis",
"is",
"a",
"very",
"rare",
"urological",
"problem.",
"We",
"present",
"a",
"case",
"of",
"primary",
"MF",
"causing",
"ureteral",
"stenosis",
"with",
"a",
"review",
"of",
"the",
"relevant",
"literature.",
"CASE",
"REPORT",
"A",
"46-year-old",
"woman",
"presented",
"with",
"intermittent",
"right",
"flank",
"pain",
"she",
"had",
"experienced",
"for",
"a",
"year.",
"The",
"patient",
"had",
"previously",
"been",
"healthy",
"and",
"had",
"no",
"history",
"of",
"disease.",
"Physical",
"examination",
"revealed",
"no",
"significant",
"findings",
"such",
"as",
"tenderness",
"at",
"the",
"costovertebral",
"angle",
"area,",
"a",
"pal-",
"pable",
"mass,",
"or",
"peripheral",
"lymphadenopathy.",
"Urinalysis,",
"a",
"complete",
"blood",
"count,",
"and",
"routine",
"blood",
"biochemistry",
"tests",
"showed",
"no",
"abnormal",
"findings.",
"Plain",
"abdominal",
"radio-",
"graphs",
"were",
"normal.",
"There",
"were",
"no",
"abnormal",
"findings",
"in",
"urine",
"cytology",
"or",
"cystoscopic",
"examination.",
"Computed",
"to-",
"mography",
"(CT)",
"showed",
"a",
"2.7x1.5",
"cm",
"diffuse,",
"noncalcified,",
"moderately",
"infiltrating",
"mass",
"with",
"ill-defined",
"lobulated",
"Korean",
"Journal",
"of",
"Urology",
"Ⓒ",
"The",
"Korean",
"Urological",
"Association,",
"2010",
"walls",
"located",
"at",
"the",
"right",
"common",
"iliac",
"vessel",
"level",
"(Fig.",
"1).",
"The",
"mass",
"was",
"located",
"in",
"the",
"right",
"ureter",
"anteriorly,",
"and",
"mild",
"focal",
"enhancement,",
"wall",
"thickening,",
"and",
"luminal",
"nar-",
"rowing",
"were",
"found",
"in",
"the",
"ureter",
"(Fig.",
"1).",
"The",
"mass",
"looked",
"as",
"if",
"it",
"compressed",
"the",
"right",
"ureter,",
"resulting",
"in",
"moderate",
"hydroureteronephrosis",
"above",
"the",
"affected",
"level",
"(Fig.",
"1).",
"Retroperitoneal",
"lymphadenopathy",
"was",
"not",
"observed.",
" In",
"a",
"ureterorenoscopic",
"examination,",
"there",
"was",
"no",
"in-",
"trinsic",
"obstructive",
"lesion",
"such",
"as",
"a",
"ureteral",
"tumor",
"causing",
"ipsilateral",
"hydronephrosis.",
"A",
"laparoscopic",
"exploration",
"was",
"undertaken",
"to",
"debulk",
"the",
"tumor",
"due",
"to",
"the",
"patient’s",
"increasing",
"symptoms.",
"At",
"the",
"time",
"of",
"surgery,",
"due",
"to",
"ex-",
"tensive",
"adhesion",
"of",
"the",
"ileocecal",
"valve",
"area",
"and",
"mass,",
"the",
"laparoscopic",
"exploration",
"was",
"converted",
"to",
"open",
"surgery",
"to",
"safely",
"perform",
"the",
"tumor",
"resection.",
"We",
"could",
"not",
"rule",
"out",
"the",
"possibility",
"of",
"a",
"malignant",
"tumor",
"before",
"final",
"histo-",
"pathological",
"confirmation",
"of",
"the",
"affected",
"lesion.",
"The",
"pa-",
"tient",
"underwent",
"extensive",
"debulking",
"of",
"the",
"mass",
"including",
"bowel",
"segmentectomy",
"with",
"anastomosis",
"and",
"excision",
"of",
"the",
"affected",
"ureter.",
"Then,",
"end-to-end",
"ureter",
"anastomosis",
"was",
"performed,",
"and",
"a",
"ureteral",
"stent",
"was",
"deployed",
"in",
"the",
"right",
"urinary",
"tract",
"for",
"decompression.",
"A",
"white",
"wedge",
"of",
"tissue",
"was",
"obtained",
"for",
"pathological",
"evaluation.",
" The",
"specimen",
"except",
"of",
"resected",
"bowel",
"segment",
"was",
"a",
"5.5x3x3",
"cm",
"firm,",
"poorly",
"circumscribed",
"mass.",
"Upon",
"section-",
"ing,",
"the",
"cut",
"surface",
"of",
"the",
"mass",
"revealed",
"a",
"white,",
"whorled",
"fibrous",
"and",
"trabecular",
"appearance",
"and",
"ill-defined",
"margins",
"with",
"the",
"surrounding",
"fat",
"tissue",
"(Fig.",
"2).",
"Microscopically,",
"501",
"Korean",
"J",
"Urol",
"2010;51:501-504"
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] | [
"Hindawi",
"Publishing",
"Corporation",
"Mediators",
"of",
"Inflammation",
"Volume",
"2008,",
"Article",
"ID",
"129873,",
"6",
"pages",
"doi:10.1155/2008/129873",
"Review",
"Article",
"Proinflammatory",
"Role",
"of",
"Vascular",
"Endothelial",
"Growth",
"Factor",
"in",
"the",
"Pathogenesis",
"of",
"Rheumatoid",
"Arthritis:",
"Prospects",
"for",
"Therapeutic",
"Intervention",
"Seung-Ah",
"Yoo,",
"Seung-Ki",
"Kwok,",
"and",
"Wan-Uk",
"Kim",
"Division",
"of",
"Rheumatology,",
"Department",
"of",
"Internal",
"Medicine,",
"School",
"of",
"Medicine,",
"Catholic",
"University",
"of",
"Korea,",
"Seoul",
"137040,",
"South",
"Korea",
"Correspondence",
"should",
"be",
"addressed",
"to",
"Wan-Uk",
"Kim,",
"wan725@catholic.ac.kr",
"Received",
"18",
"July",
"2008;",
"Accepted",
"1",
"December",
"2008",
"Recommended",
"by",
"Yvette",
"Mandi",
"Recent",
"experimental",
"and",
"clinical",
"studies",
"have",
"placed",
"new",
"emphasis",
"on",
"the",
"role",
"of",
"angiogenesis",
"in",
"chronic",
"inflammatory",
"disease.",
"Vascular",
"endothelial",
"growth",
"factor",
"(VEGF)",
"and",
"its",
"receptors",
"are",
"the",
"best",
"characterized",
"system",
"in",
"the",
"regulation",
"of",
"rheumatoid",
"arthritis",
"(RA)",
"by",
"angiogenesis.",
"Furthermore,",
"in",
"addition",
"to",
"its",
"angiogenic",
"role,",
"VEGF",
"can",
"act",
"as",
"a",
"direct",
"proinflammatory",
"mediator",
"during",
"the",
"pathogenesis",
"of",
"RA,",
"and",
"protect",
"rheumatoid",
"synoviocytes",
"from",
"apoptosis,",
"which",
"contributes",
"to",
"synovial",
"hyperplasia.",
"Therefore,",
"the",
"developments",
"of",
"synovial",
"inflammation,",
"hyperplasia,",
"and",
"angiogenesis",
"in",
"the",
"joints",
"of",
"RA",
"patients",
"seem",
"to",
"be",
"regulated",
"by",
"a",
"common",
"cue,",
"namely,",
"VEGF.",
"Agents",
"that",
"target",
"VEGF,",
"such",
"as",
"anti-VEGF",
"antibody",
"and",
"aptamer,",
"have",
"yielded",
"promising",
"clinical",
"data",
"in",
"patients",
"with",
"cancer",
"or",
"macular",
"degeneration,",
"and",
"in",
"RA",
"patients,",
"pharmacologic",
"modulations",
"targeting",
"VEGF",
"or",
"its",
"receptor",
"may",
"offer",
"new",
"therapeutic",
"approaches.",
"In",
"this",
"review,",
"the",
"authors",
"integrate",
"current",
"knowledge",
"of",
"VEGF",
"signaling",
"and",
"information",
"on",
"VEGF",
"antagonists",
"gleaned",
"experimentally",
"and",
"place",
"emphasis",
"on",
"the",
"use",
"of",
"synthetic",
"anti-VEGF",
"hexapeptide",
"to",
"prevent",
"VEGF",
"interacting",
"with",
"its",
"receptor.",
"Copyright",
"©",
"2008",
"Seung-Ah",
"Yoo",
"et",
"al.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"1.",
"INTRODUCTION",
"The",
"pathology",
"of",
"rheumatoid",
"arthritis",
"(RA)",
"is",
"characterized",
"by",
"the",
"proliferation",
"of",
"synovial",
"cells",
"and",
"angiogenesis,",
"pannus",
"formation.",
"Multiple",
"cell",
"types,",
"including",
"lympho-",
"cytes,",
"dendritic",
"cells,",
"macrophages,",
"and",
"synovial",
"fibroblasts,",
"contribute",
"to",
"the",
"chronic",
"inflammatory",
"responses",
"of",
"RA,",
"and",
"comprise",
"a",
"major",
"portion",
"of",
"the",
"invasive",
"pannus",
"[1].",
"In",
"addition,",
"angiogenesis,",
"the",
"process",
"of",
"new",
"blood",
"vessel",
"formation,",
"is",
"highly",
"active",
"in",
"RA,",
"particularly",
"during",
"the",
"earliest",
"stages",
"of",
"the",
"disease",
"[2,",
"3].",
"Newly",
"formed",
"vessels",
"can",
"maintain",
"the",
"chronic",
"inflammatory",
"state",
"by",
"transporting",
"inflammatory",
"cells",
"to",
"sites",
"of",
"synovitis,",
"and",
"supply",
"nutrients",
"and",
"oxygen",
"to",
"the",
"pannus",
"[2,",
"3].",
"Angiogenesis",
"is",
"strictly",
"regulated",
"by",
"many",
"inducers",
"and",
"inhibitors,",
"and",
"a",
"number",
"of",
"proangiogenic",
"factors",
"have",
"been",
"suggested",
"to",
"be",
"involved",
"in",
"neovascularization",
"in",
"RA",
"joints.",
"These",
"include",
"acidic",
"and",
"basic",
"fibroblast",
"growth",
"factors,",
"transforming",
"growth",
"factor",
"(TGF)-β,",
"angiopoietin,",
"and",
"placenta",
"growth",
"factor",
"(PIGF)",
"in",
"addition",
"to",
"vascular",
"endothelial",
"growth",
"factor",
"(VEGF)",
"[2–4].",
"The",
"final",
"goal",
"of",
"RA",
"treatment",
"is",
"complete",
"disease",
"remission,",
"and",
"not",
"symptomatic",
"relief.",
"At",
"one",
"end",
"of",
"the",
"spectrum",
"of",
"RA",
"treatment",
"outcomes",
"lie",
"a",
"large",
"group",
"of",
"patients",
"who",
"do",
"not",
"respond",
"to",
"single",
"disease-modifying",
"antirheumatic",
"drugs",
"(DMARDs)",
"[5].",
"Recent",
"clinical",
"trials",
"have",
"suggested",
"that",
"several",
"biologic",
"agents,",
"such",
"as",
"TNF-α",
"blockers,",
"rituximab,",
"abatacept,",
"and",
"anakinra,",
"are",
"effective",
"at",
"retarding",
"joint",
"destruction",
"and",
"at",
"alleviating",
"RA",
"activity",
"[5,",
"6].",
"However,",
"these",
"biologic",
"agents",
"may",
"have",
"serious",
"side",
"effects,",
"such",
"as",
"predispositions",
"to",
"tuberculosis,",
"lymphoma,",
"progressive",
"multifocal",
"leukoencephalopathy,",
"and",
"high",
"cost,",
"which",
"limit",
"their",
"use",
"[7].",
"It",
"is",
"also",
"a",
"concern",
"that",
"abrupt",
"stoppages",
"or",
"reductions",
"in",
"these",
"treatments",
"may",
"result",
"in",
"a",
"relapse",
"of",
"disease",
"activity.",
"Moreover,",
"the",
"pathology",
"of",
"RA",
"suggests",
"that",
"it",
"is",
"unlikely",
"that",
"a",
"single",
"biologic",
"agent",
"that",
"targets",
"a",
"specific",
"subset",
"of",
"immune",
"cells",
"is",
"capable",
"of",
"effecting",
"cure."
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] | [
"BMC",
"Cancer",
"Research",
"article",
"Effects",
"of",
"polymorphisms",
"in",
"ERCC1,",
"ASE-1",
"and",
"RAI",
"on",
"the",
"risk",
"of",
"colorectal",
"carcinomas",
"and",
"adenomas:",
"a",
"case",
"control",
"study",
"Camilla",
"F",
"Skjelbred†1,2,",
"Mona",
"Sæbø†2,",
"Bjørn",
"A",
"Nexø3,",
"Håkan",
"Wallin4,",
"Inger-",
"Lise",
"Hansteen1,",
"Ulla",
"Vogel4",
"and",
"Elin",
"H",
"Kure*2,5",
"BioMed",
"Central",
"Open",
"Access",
"Address:",
"1Department",
"of",
"Laboratory",
"Medicine,",
"Section",
"of",
"Medical",
"Genetics,",
"Telemark",
"Hospital,",
"N-3710",
"Skien,",
"Norway,",
"2Telemark",
"University",
"College,",
"Faculty",
"of",
"Arts",
"and",
"Sciences,",
"Department",
"of",
"Environmental",
"and",
"Health",
"Studies,",
"Hallvard",
"Eikas",
"plass,",
"N-3800",
"Bø",
"i",
"Telemark,",
"Norway,",
"3Institute",
"of",
"Human",
"Genetics,",
"University",
"of",
"Aarhus,",
"Aarhus,",
"Denmark,",
"4National",
"Institute",
"of",
"Occupational",
"Health,",
"Copenhagen,",
"Denmark",
"and",
"5Department",
"of",
"Pathology,",
"Ullevaal",
"University",
"Hospital,",
"Oslo,",
"Norway",
"Email:",
"Camilla",
"F",
"Skjelbred",
"-",
"camilla-furu.skjelbred@sthf.no;",
"Mona",
"Sæbø",
"-",
"mona.sabo@hit.no;",
"Bjørn",
"A",
"Nexø",
"-",
"nexo@humgen.au.dk;",
"Håkan",
"Wallin",
"-",
"hwa@ami.dk;",
"Inger-Lise",
"Hansteen",
"-",
"inger-lise.hansteen@sthf.no;",
"Ulla",
"Vogel",
"-",
"ubv@ami.dk;",
"Elin",
"H",
"Kure*",
"-",
"elin.kure@hit.no",
"*",
"Corresponding",
"author",
"†Equal",
"contributors",
"Published:",
"03",
"July",
"2006",
"BMC",
"Cancer",
"2006,",
"6:175",
"doi:10.1186/1471-2407-6-175",
"This",
"article",
"is",
"available",
"from:",
"http://www.biomedcentral.com/1471-2407/6/175",
"Received:",
"24",
"March",
"2006",
"Accepted:",
"03",
"July",
"2006",
"©",
"2006",
"Skjelbred",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"The",
"risk",
"of",
"sporadic",
"colorectal",
"cancer",
"is",
"mainly",
"associated",
"with",
"lifestyle",
"factors",
"and",
"may",
"be",
"modulated",
"by",
"several",
"genetic",
"factors",
"of",
"low",
"penetrance.",
"Genetic",
"variants",
"represented",
"by",
"single",
"nucleotide",
"polymorphisms",
"in",
"genes",
"encoding",
"key",
"players",
"in",
"the",
"adenoma",
"carcinoma",
"sequence",
"may",
"contribute",
"to",
"variation",
"in",
"susceptibility",
"to",
"colorectal",
"cancer.",
"In",
"this",
"study,",
"we",
"aimed",
"to",
"evaluate",
"whether",
"the",
"recently",
"identified",
"haplotype",
"encompassing",
"genes",
"of",
"DNA",
"repair",
"and",
"apoptosis,",
"is",
"associated",
"with",
"increased",
"risk",
"of",
"colorectal",
"adenomas",
"and",
"carcinomas.",
"Methods:",
"We",
"used",
"a",
"case-control",
"study",
"design",
"(156",
"carcinomas,",
"981",
"adenomas",
"and",
"399",
"controls)",
"to",
"test",
"the",
"association",
"between",
"polymorphisms",
"in",
"the",
"chromosomal",
"region",
"19q13.2-3,",
"encompassing",
"the",
"genes",
"ERCC1,",
"ASE-1",
"and",
"RAI,",
"and",
"risk",
"of",
"colorectal",
"adenomas",
"and",
"carcinomas",
"in",
"a",
"Norwegian",
"cohort.",
"Odds",
"ratio",
"(OR)",
"and",
"95%",
"confidence",
"interval",
"(CI)",
"were",
"estimated",
"by",
"binary",
"logistic",
"regression",
"model",
"adjusting",
"for",
"age",
"and",
"gender.",
"Results:",
"The",
"ASE-1",
"polymorphism",
"was",
"associated",
"with",
"an",
"increased",
"risk",
"of",
"adenomas,",
"OR",
"of",
"1.39",
"(95%",
"CI",
"1.06–1.81),",
"which",
"upon",
"stratification",
"was",
"apparent",
"among",
"women",
"only,",
"OR",
"of",
"1.66",
"(95%",
"CI",
"1.15–2.39).",
"The",
"RAI",
"polymorphism",
"showed",
"a",
"trend",
"towards",
"risk",
"reduction",
"for",
"both",
"adenomas",
"(OR",
"of",
"0.70,",
"95%",
"CI",
"0.49–1.01)",
"and",
"carcinomas",
"(OR",
"of",
"0.49,",
"95%",
"CI",
"0.21–1.13)",
"among",
"women,",
"although",
"not",
"significant.",
"Women",
"who",
"were",
"homozygous",
"carriers",
"of",
"the",
"high",
"risk",
"haplotype",
"had",
"an",
"increased",
"risk",
"of",
"colorectal",
"cancer,",
"OR",
"of",
"2.19",
"(95%",
"CI",
"0.95–5.04)",
"compared",
"to",
"all",
"non-carriers",
"although",
"the",
"estimate",
"was",
"not",
"statistically",
"significant.",
"Conclusion:",
"We",
"found",
"no",
"evidence",
"that",
"the",
"studied",
"polymorphisms",
"were",
"associated",
"with",
"risk",
"of",
"adenomas",
"or",
"colorectal",
"cancer",
"among",
"men,",
"but",
"we",
"found",
"weak",
"indications",
"that",
"the",
"chromosomal",
"region",
"may",
"influence",
"risk",
"of",
"colorectal",
"cancer",
"and",
"adenoma",
"development",
"in",
"women.",
"Page",
"1",
"of",
"6",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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663,
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722,
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526,
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614,
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694,
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594,
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635,
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648,
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650,
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662,
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663,
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693,
1195
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163,
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202,
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205,
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230,
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233,
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276,
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279,
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290,
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293,
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323,
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325,
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368,
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371,
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398,
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155,
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165,
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452,
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] | [
"Copyedited",
"by:",
"TRJ",
"MANUSCRIPT",
"CATEGORY:",
"APPLICATIONS",
"NOTE",
"BIOINFORMATICS",
"APPLICATIONS",
"NOTE",
"Vol.",
"28",
"no.",
"15",
"2012,",
"pages",
"2064–2066",
"doi:10.1093/bioinformatics/bts309",
"Phylogenetics",
"Advance",
"Access",
"publication",
"May",
"24,",
"2012",
"RAxML-Light:",
"a",
"tool",
"for",
"computing",
"terabyte",
"phylogenies",
"A.",
"Stamatakis1,∗,",
"A.J.",
"Aberer1,",
"C.",
"Goll1,",
"S.A.",
"Smith",
"2",
",",
"S.A.",
"Berger1",
"and",
"F.",
"Izquierdo-Carrasco1",
"1The",
"Exelixis",
"Lab,",
"Scientific",
"Computing",
"Group,",
"Heidelberg",
"Institute",
"for",
"Theoretical",
"Studies,",
"Schloss-Wolfsbrunnenweg",
"35,",
"D-68159",
"Heidelberg,",
"Germany",
"and",
"2Blackrim",
"Lab,",
"Department",
"of",
"Ecology",
"and",
"Evolutionary",
"Biology,",
"University",
"of",
"Michigan,",
"2071A",
"Kraus",
"Natural",
"Science",
"Building,",
"830",
"North",
"University",
"Ann",
"Arbor,",
"MI",
"48109-1048,",
"USA",
"Associate",
"Editor:",
"Jonathan",
"Wren",
"ABSTRACT",
"Motivation:",
"Due",
"to",
"advances",
"in",
"molecular",
"sequencing",
"and",
"the",
"increasingly",
"rapid",
"collection",
"of",
"molecular",
"data,",
"the",
"field",
"of",
"phyloinformatics",
"is",
"transforming",
"into",
"a",
"computational",
"science.",
"Therefore,",
"new",
"tools",
"are",
"required",
"that",
"can",
"be",
"deployed",
"in",
"supercomputing",
"environments",
"and",
"that",
"scale",
"to",
"hundreds",
"or",
"thousands",
"of",
"cores.",
"Results:",
"We",
"describe",
"RAxML-Light,",
"a",
"tool",
"for",
"large-scale",
"phylogenetic",
"inference",
"on",
"supercomputers",
"under",
"maximum",
"likelihood.",
"It",
"implements",
"a",
"light-weight",
"checkpointing",
"mechanism,",
"deploys",
"128-bit",
"(SSE3)",
"and",
"256-bit",
"(AVX)",
"vector",
"intrinsics,",
"offers",
"two",
"orthogonal",
"memory",
"saving",
"techniques",
"and",
"provides",
"a",
"fine-grain",
"production-level",
"message",
"passing",
"interface",
"parallelization",
"of",
"the",
"likelihood",
"function.",
"To",
"demonstrate",
"scalability",
"and",
"robustness",
"of",
"the",
"code,",
"we",
"inferred",
"a",
"phylogeny",
"on",
"a",
"simulated",
"DNA",
"alignment",
"(1481",
"taxa,",
"20",
"000",
"000",
"bp)",
"using",
"672",
"cores.",
"This",
"dataset",
"requires",
"one",
"terabyte",
"of",
"RAM",
"to",
"compute",
"the",
"likelihood",
"score",
"on",
"a",
"single",
"tree.",
"Code",
"Availability:",
"https://github.com/stamatak/RAxML-Light-1.0.5",
"Data",
"Availability:",
"http://www.exelixis-lab.org/onLineMaterial.tar.bz2",
"Contact:",
"alexandros.stamatakis@h-its.org",
"Supplementary",
"Information:",
"Supplementary",
"data",
"are",
"available",
"at",
"Bioinformatics",
"online.",
"Received",
"on",
"March",
"7,",
"2012;",
"revised",
"on",
"May",
"15,",
"2012;",
"accepted",
"on",
"May",
"18,",
"2012",
"1",
"INTRODUCTION",
"Phyloinformatics",
"is",
"facing",
"a",
"paradigm",
"shift",
"toward",
"becoming",
"a",
"‘real’",
"computational",
"science.",
"Molecular",
"sequencing",
"technologies",
"are",
"developing",
"at",
"a",
"rapid",
"pace,",
"generating",
"enormous",
"amounts",
"of",
"new",
"data.",
"Due",
"to",
"the",
"necessity",
"to",
"process",
"(and",
"store)",
"huge",
"amounts",
"of",
"data,",
"we",
"expect",
"the",
"field",
"to",
"undergo",
"an",
"analogous",
"transition",
"that",
"physics",
"or",
"computational",
"fluid",
"dynamics",
"underwent",
"20–30",
"years",
"ago.",
"Projects",
"such",
"as",
"the",
"1000",
"insect",
"transcriptome",
"sequencing",
"project",
"(www.1kite.org)",
"already",
"face",
"these",
"challenges.",
"Such",
"evolutionary",
"studies",
"require",
"software",
"that",
"scales",
"beyond",
"a",
"single",
"node,",
"that",
"can",
"be",
"checkpointed",
"and",
"restarted,",
"and",
"that",
"can",
"accommodate",
"the",
"memory",
"requirements",
"of",
"whole-genome",
"datasets",
"under",
"likelihood-based",
"models.",
"RAxML-Light",
"is",
"a",
"production-level",
"tool",
"for",
"phylogenetic",
"inference",
"on",
"supercomputers",
"that",
"implements",
"new",
"approaches",
"for",
"handling",
"load",
"imbalance,",
"checkpointing",
"and",
"reducing",
"the",
"RAM",
"∗To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"requirements",
"of",
"likelihood",
"computations.",
"Implementation",
"details",
"are",
"discussed",
"in",
"the",
"online",
"supplement.",
"2",
"FEATURES",
"We",
"briefly",
"discuss",
"the",
"features",
"that",
"distinguish",
"RAxML-Light",
"from",
"standard",
"RAxML,",
"other",
"likelihood-based",
"phylogeny",
"programs,",
"and",
"the",
"BEAGLE",
"library",
"(Ayres",
"et",
"al.,",
"2011).",
"One",
"important",
"feature",
"(in",
"contrast",
"to",
"BEAGLE,",
"MrBayes",
"(Ronquist",
"and",
"Huelsenbeck,",
"2003)",
"or",
"GARLI",
"(Zwickl,",
"2006))",
"is",
"that",
"RAxML-Light",
"implements",
"a",
"fine-",
"grain",
"message",
"passing",
"interface",
"(MPI)",
"parallelization",
"to",
"compute",
"the",
"likelihood",
"on",
"a",
"single",
"huge",
"dataset",
"and",
"a",
"single",
"tree",
"across",
"several",
"nodes.",
"We",
"introduced",
"the",
"proof-of-concept",
"implementation",
"in",
"(Ott",
"et",
"al.,",
"2007).",
"The",
"work",
"is",
"split",
"by",
"distributing",
"alignment",
"sites",
"or",
"entire",
"partitions",
"(depending",
"on",
"the",
"selected",
"command",
"line",
"options)",
"among",
"processors.",
"Another",
"essential",
"feature",
"is",
"the",
"light-weight",
"checkpointing",
"and",
"restart",
"capability,",
"that",
"is",
"required",
"on",
"typical",
"HPC",
"systems",
"that",
"have",
"queues",
"with",
"24-",
"or",
"48-h",
"run-time",
"limits.",
"Light",
"weight",
"means",
"that",
"only",
"those",
"data-structures",
"are",
"stored",
"in",
"a",
"checkpoint",
"which",
"are",
"really",
"required",
"to",
"restart",
"the",
"code.",
"The",
"design",
"goal",
"is",
"to",
"minimize",
"checkpoint",
"writing/reading",
"times",
"and",
"file",
"sizes.",
"To",
"the",
"best",
"of",
"our",
"knowledge,",
"RAxML-Light",
"comprises",
"the",
"only",
"fine-grain",
"parallelization",
"of",
"the",
"likelihood",
"function",
"that",
"also",
"incorporates",
"load",
"balance",
"mechanisms",
"as",
"described",
"in",
"(Stamatakis",
"and",
"Ott,",
"2009)",
"and",
"(Zhang",
"and",
"Stamatakis,",
"2012).",
"Load",
"imbalance",
"can",
"deteriorate",
"parallel",
"efficiency",
"in",
"partitioned",
"phylogenetic",
"analyzes.",
"RAxML-Light",
"also",
"contains",
"a",
"production-level",
"implementation",
"of",
"two",
"orthogonal",
"memory",
"saving",
"techniques",
"that",
"can",
"be",
"used",
"simultaneously",
"(described",
"in",
"Izquierdo-Carrasco",
"et",
"al.,",
"2011a,b).",
"These",
"techniques",
"allow",
"for",
"deploying",
"RAxML-Light",
"on",
"systems",
"that",
"do",
"not",
"have",
"enough",
"RAM",
"to",
"store",
"all",
"conditional",
"probability",
"vectors",
"required",
"for",
"likelihood",
"calculations.",
"Finally,",
"RAxML-Light",
"also",
"uses",
"256-bit",
"wide",
"AVX",
"vector",
"intrinsics",
"to",
"accelerate",
"likelihood",
"computations",
"on",
"Intel",
"Sandy-",
"Bridge",
"and",
"AMD",
"Bulldozer",
"CPUs",
"that",
"will",
"become",
"available",
"in",
"many",
"HPC",
"systems",
"over",
"the",
"next",
"2–3",
"years.",
"3",
"3.1",
"PERFORMANCE",
"AND",
"STRESS",
"TESTS",
"Parallel",
"scalability",
"We",
"measured",
"the",
"relative",
"speedup",
"of",
"the",
"MPI",
"version",
"of",
"RAxML-",
"Light",
"on",
"a",
"dataset",
"with",
"150",
"taxa",
"and",
"20",
"000",
"000",
"bp",
"(extracted",
"from",
"the",
"above",
"simulated",
"dataset)",
"on",
"an",
"AMD",
"Magny-Cours-based",
"cluster",
"©",
"The",
"Author(s)",
"2012.",
"Published",
"by",
"Oxford",
"University",
"Press.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://creativecommons.org/licenses/",
"by-nc/3.0),",
"which",
"permits",
"unrestricted",
"non-commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"[12:10",
"20/7/2012",
"Bioinformatics-bts309.tex]",
"Page:",
"2064",
"2064–2066"
] | [
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] | [
"Published",
"online",
"17",
"October",
"2008",
"Nucleic",
"Acids",
"Research,",
"2008,",
"Vol.",
"36,",
"No.",
"20",
"6571–6584",
"doi:10.1093/nar/gkn719",
"The",
"N-clasp",
"of",
"human",
"DNA",
"polymerase",
"i",
"promotes",
"blockage",
"or",
"error-free",
"bypass",
"of",
"adenine-",
"or",
"guanine-benzo[a]pyrenyl",
"lesions",
"Lei",
"Jia1,",
"Nicholas",
"E.",
"Geacintov2",
"and",
"Suse",
"Broyde1,2,*",
"1Department",
"of",
"Biology",
"and",
"2Department",
"of",
"Chemistry,",
"New",
"York",
"University,",
"100",
"Washington",
"Square",
"East,",
"New",
"York,",
"NY",
"10003,",
"USA",
"Received",
"August",
"22,",
"2008;",
"Revised",
"September",
"29,",
"2008;",
"Accepted",
"September",
"30,",
"2008",
"ABSTRACT",
"DNA",
"bypass",
"polymerases",
"are",
"utilized",
"to",
"transit",
"bulky",
"DNA",
"lesions",
"during",
"replication,",
"but",
"the",
"pro-",
"cess",
"frequently",
"causes",
"mutations.",
"The",
"structural",
"origins",
"of",
"mutagenic",
"versus",
"high",
"fidelity",
"replication",
"in",
"lesion",
"bypass",
"is",
"therefore",
"of",
"fundamental",
"interest.",
"As",
"model",
"systems,",
"we",
"investigated",
"the",
"molecular",
"basis",
"of",
"the",
"experimentally",
"observed",
"essentially",
"faithful",
"bypass",
"of",
"the",
"guanine",
"10S-(+)-trans-anti-",
"benzo[a]pyrene-N2-dG",
"adduct",
"by",
"the",
"Y-family",
"human",
"DNA",
"polymerase",
"i,",
"and",
"the",
"observed",
"block-",
"age",
"of",
"pol",
"i",
"produced",
"by",
"the",
"adenine",
"10S-(+)-trans-",
"anti-benzo[a]pyrene-N2-dA",
"adduct.",
"These",
"lesions",
"are",
"derived",
"from",
"the",
"most",
"tumorigenic",
"metabolite",
"of",
"the",
"ubiquitous",
"cancer-causing",
"pollutant,",
"ben-",
"zo[a]pyrene.",
"We",
"compare",
"our",
"results",
"for",
"the",
"dG",
"adduct",
"with",
"our",
"earlier",
"studies",
"for",
"the",
"pol",
"i",
"archaeal",
"homolog",
"Dpo4,",
"which",
"processes",
"the",
"same",
"lesion",
"in",
"an",
"error-prone",
"manner.",
"Molecular",
"modeling,",
"mole-",
"cular",
"mechanics",
"calculations",
"and",
"molecular",
"dynamics",
"simulations",
"were",
"utilized.",
"Our",
"results",
"show",
"that",
"the",
"pol",
"i",
"N-clasp",
"is",
"a",
"key",
"structural",
"fea-",
"ture",
"that",
"accounts",
"for",
"the",
"dA",
"adduct",
"blockage",
"and",
"the",
"near-error-free",
"bypass",
"of",
"the",
"dG",
"lesion.",
"Absence",
"of",
"the",
"N-clasp",
"in",
"Dpo4",
"explains",
"the",
"error-",
"prone",
"processing",
"of",
"the",
"same",
"lesion",
"by",
"this",
"enzyme.",
"Thus,",
"our",
"studies",
"elucidate",
"structure-function",
"rela-",
"tionships",
"in",
"the",
"fidelity",
"of",
"lesion",
"bypass.",
"INTRODUCTION",
"Bulky",
"lesions",
"normally",
"block",
"the",
"progress",
"of",
"processive",
"high",
"fidelity",
"DNA",
"polymerases",
"(1–5).",
"Subsequently,",
"the",
"replicative",
"polymerase",
"may",
"be",
"replaced",
"by",
"one",
"or",
"more",
"translesion",
"bypass",
"polymerases",
"(6–10).",
"The",
"error-free",
"bypass",
"of",
"DNA",
"lesions",
"during",
"translesion",
"synthesis",
"(TLS)",
"is",
"a",
"repair",
"pathway,",
"which",
"plays",
"an",
"important",
"role",
"in",
"coping",
"with",
"highly",
"blocking",
"lesions",
"in",
"all",
"three",
"domains",
"of",
"life",
"(6,10).",
"However,",
"translesion",
"synthesis",
"is",
"often",
"carried",
"out",
"by",
"low-fidelity",
"bypass",
"DNA",
"polymerases",
"(11–14).",
"In",
"error-prone",
"TLS,",
"the",
"mismatched",
"nucleotides",
"incorporated",
"opposite",
"the",
"lesion",
"introduce",
"mutations",
"into",
"the",
"genome",
"that",
"can",
"result",
"in",
"the",
"development",
"of",
"cancer",
"(15,16).",
"In",
"humans,",
"there",
"are",
"four",
"known",
"Y-family",
"bypass",
"DNA",
"polymerases,",
"pol",
"Z,",
"pol",
"i,",
"pol",
"k",
"and",
"Rev1",
"(7,17).",
"Pol",
"k",
"is",
"the",
"only",
"Y-family",
"polymerase",
"found",
"in",
"humans",
"which",
"has",
"homologs",
"in",
"both",
"bacteria",
"(DinB",
"or",
"Pol",
"IV",
"in",
"Escherichia",
"coli)",
"and",
"archaea",
"(Dbh",
"in",
"Sulfolobus",
"acidocaldarius",
"and",
"Dpo4",
"in",
"Sufolobus",
"solfataricus)",
"(18).",
"The",
"structural",
"features",
"of",
"low-fidelity",
"bypass",
"poly-",
"merases",
"that",
"allow",
"for",
"TLS",
"of",
"some",
"lesions",
"but",
"not",
"others,",
"while",
"high-fidelity",
"polymerases",
"are",
"stalled",
"by",
"the",
"same",
"lesions,",
"is",
"a",
"topic",
"of",
"significant",
"interest",
"(3,9,10).",
"The",
"structures",
"of",
"a",
"number",
"of",
"Y-family",
"polymerases",
"have",
"been",
"investigated",
"(10,19).",
"A",
"ternary",
"complex",
"crystal",
"structure",
"of",
"pol",
"k",
"lacking",
"its",
"C-terminal",
"domain",
"has",
"recently",
"been",
"determined",
"(20).",
"This",
"structure",
"contains",
"the",
"major",
"domains",
"of",
"pol",
"k",
"including",
"its",
"signature",
"N-terminal",
"domain,",
"namely,",
"the",
"‘N-clasp’,",
"an",
"unmodified",
"DNA",
"primer/template",
"complex,",
"and",
"an",
"incoming",
"dTTP",
"Watson–Crick",
"paired",
"with",
"the",
"templating",
"base",
"adenine",
"(20).",
"The",
"N-clasp",
"in",
"pol",
"k",
"is",
"at",
"present",
"unique,",
"as",
"it",
"has",
"not",
"yet",
"been",
"observed",
"in",
"any",
"other",
"Y-family",
"polymerase.",
"With",
"the",
"N-clasp",
"on",
"the",
"major",
"groove",
"side",
"(Figure",
"1)",
"of",
"the",
"nascent",
"duplex,",
"pol",
"k",
"completely",
"encircles",
"a",
"region",
"of",
"the",
"DNA",
"containing",
"the",
"template–primer",
"junction",
"at",
"its",
"active",
"site.",
"It",
"is",
"noteworthy",
"that",
"pol",
"k",
"lacking",
"the",
"N-clasp",
"(pol",
"k68–526)",
"is",
"severely",
"impaired",
"in",
"its",
"DNA",
"synthesis",
"activity",
"(20).",
"The",
"ability",
"of",
"pol",
"k",
"to",
"synthesize",
"DNA",
"both",
"in",
"the",
"absence",
"and",
"presence",
"of",
"lesions",
"has",
"received",
"considerable",
"attention.",
"In",
"the",
"case",
"of",
"unmodified",
"DNA",
"templates,",
"pol",
"k",
"synthesizes",
"DNA",
"with",
"low",
"fidelity",
"(21),",
"and",
"it",
"has",
"also",
"been",
"shown",
"that",
"it",
"is",
"promiscuous",
"in",
"extending",
"primer",
"strands",
"past",
"mispaired",
"primer–template",
"termini",
"(22).",
"The",
"processing",
"of",
"DNA",
"lesions",
"by",
"pol",
"k,",
"whether",
"error-free",
"or",
"error-prone,",
"has",
"been",
"shown",
"to",
"be",
"highly",
"lesion",
"*To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"Tel:",
"+1",
"212",
"998",
"8231;",
"Fax:",
"+1",
"212",
"995",
"4015;",
"Email:",
"broyde@nyu.edu",
"2008",
"The",
"Author(s)",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://creativecommons.org/licenses/",
"by-nc/2.0/uk/)",
"which",
"permits",
"unrestricted",
"non-commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
] | [
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] | [
"J",
"Orthopaed",
"Traumatol",
"(2012)",
"13:137–143",
"DOI",
"10.1007/s10195-012-0187-x",
"O",
"R",
"I",
"G",
"I",
"N",
"A",
"L",
"A",
"R",
"T",
"I",
"C",
"L",
"E",
"The",
"migration",
"pattern",
"of",
"the",
"Charnley",
"femoral",
"stem:",
"a",
"five-year",
"follow-up",
"RSA",
"study",
"in",
"a",
"well-functioning",
"patient",
"group",
"Kristin",
"Haugan",
"•",
"Otto",
"S.",
"Husby",
"•",
"Jomar",
"Klaksvik",
"•",
"Olav",
"A.",
"Foss",
"Received:",
"1",
"July",
"2011",
"/",
"Accepted:",
"10",
"March",
"2012",
"/",
"Published",
"online:",
"11",
"May",
"2012",
"The",
"Author(s)",
"2012.",
"This",
"article",
"is",
"published",
"with",
"open",
"access",
"at",
"Springerlink.com",
"Abstract",
"Background",
"Implant",
"stability",
"is",
"considered",
"vital",
"to",
"long-",
"time",
"implant",
"survival",
"in",
"total",
"hip",
"arthroplasty",
"(THA),",
"since",
"loose",
"implants",
"are",
"reported",
"to",
"be",
"a",
"major",
"cause",
"of",
"hip",
"revision.",
"There",
"is",
"an",
"association",
"between",
"early",
"implant",
"micromotion",
"and",
"increased",
"risk",
"of",
"revision.",
"More",
"implant-",
"specific",
"data",
"are",
"needed",
"to",
"establish",
"acceptable",
"levels",
"of",
"early",
"implant",
"movement.",
"Materials",
"and",
"methods",
"Thirty-five",
"patients",
"(36",
"hips)",
"undergoing",
"Charnley",
"THA",
"were",
"followed",
"with",
"repeated",
"clinical,",
"radiographic,",
"and",
"radiostereometric",
"analysis",
"(RSA)",
"over",
"5",
"years.",
"Twenty-three",
"patients",
"attended",
"5",
"years",
"postoperatively.",
"Results",
"The",
"patient",
"group",
"was",
"well",
"functioning",
"based",
"on",
"the",
"radiological",
"and",
"clinical",
"evaluations.",
"The",
"stems",
"con-",
"stantly",
"moved",
"up",
"to",
"5",
"years",
"postoperatively,",
"with",
"subsi-",
"dence,",
"retroversion,",
"and",
"varus",
"tilt,",
"based",
"on",
"the",
"RSA.",
"Conclusion",
"Continuous",
"movement",
"of",
"the",
"Charnley",
"stem",
"was",
"observed",
"up",
"to",
"5",
"years",
"postoperatively",
"in",
"a",
"well-",
"functioning",
"patient",
"group.",
"The",
"migration",
"data",
"presented",
"herein",
"could",
"be",
"useful",
"when",
"defining",
"acceptable",
"migration",
"limits",
"for",
"certain",
"types",
"of",
"cemented",
"femoral",
"stems.",
"Keywords",
"RSA",
"Migration",
"pattern",
"Charnley",
"THR",
"Five-year",
"follow-up",
"K.",
"Haugan",
"(&)",
"O.",
"S.",
"Husby",
"J.",
"Klaksvik",
"O.",
"A.",
"Foss",
"Orthopaedic",
"Research",
"Centre,",
"Trondheim",
"University",
"Hospital,",
"7006",
"Trondheim,",
"Norway",
"e-mail:",
"kristin.haugan@ntnu.no",
"O.",
"S.",
"Husby",
"Orthopaedic",
"Department,",
"Trondheim",
"University",
"Hospital,",
"7006",
"Trondheim,",
"Norway",
"Introduction",
"Implant",
"stability",
"influences",
"the",
"revision",
"rate",
"observed",
"in",
"total",
"hip",
"arthroplasty",
"(THA).",
"According",
"to",
"the",
"Swedish,",
"Australian",
"and",
"Norwegian",
"hip",
"registers,",
"aseptic",
"loosening",
"is",
"the",
"most",
"common",
"cause",
"of",
"revision",
"[1–3].",
"Revision",
"surgery",
"is",
"expensive",
"to",
"both",
"patients",
"and",
"the",
"community.",
"Major",
"efforts",
"have",
"been",
"made",
"to",
"reduce",
"these",
"numbers",
"from",
"the",
"earliest",
"days",
"of",
"THA.",
"Radiostereometric",
"analysis",
"(RSA)",
"has",
"become",
"a",
"gold",
"standard",
"when",
"measuring",
"implant",
"migrations",
"with",
"respect",
"to",
"the",
"cement",
"mantle",
"as",
"well",
"as",
"the",
"surrounding",
"bone",
"[4].",
"RSA",
"can",
"describe",
"early",
"implant",
"migration,",
"and",
"is",
"therefore",
"well",
"suited",
"and",
"recommended",
"when",
"introducing",
"new",
"implants",
"into",
"clinical",
"use",
"and",
"minimizing",
"the",
"number",
"of",
"enrolled",
"patients",
"[5].",
"The",
"main",
"rationale",
"for",
"monitoring",
"early",
"implant",
"migration",
"is",
"based",
"on",
"results",
"from",
"clinical",
"studies",
"reporting",
"an",
"association",
"between",
"early",
"subsidence",
"and",
"increased",
"risk",
"of",
"early",
"or",
"mid-term",
"hip",
"implant",
"revision.",
"Early",
"migration",
"[6],",
"continuous",
"migration",
"[7],",
"and",
"subsidence",
"in",
"combination",
"with",
"medial",
"and",
"posterior",
"migration",
"[6]",
"are",
"of",
"concern.",
"However,",
"when",
"defining",
"acceptable",
"limits",
"for",
"migration,",
"factors",
"such",
"as",
"measurement",
"procedures,",
"implant",
"design,",
"and",
"fixation",
"principles",
"should",
"be",
"taken",
"into",
"account.",
"The",
"level",
"of",
"early",
"implant",
"stability",
"is",
"mainly",
"determined",
"by",
"the",
"fixation",
"method",
"used.",
"In",
"cement",
"fixation",
"of",
"femoral",
"stems,",
"two",
"different",
"principles",
"apply",
"[8,",
"9].",
"In",
"a",
"composite",
"construction,",
"such",
"as",
"the",
"Charnley",
"stem,",
"there",
"should",
"be",
"perfect",
"bonding",
"between",
"stem",
"and",
"cement.",
"In",
"contrast,",
"there",
"is",
"the",
"construction",
"in",
"which",
"the",
"stem",
"is",
"not",
"intended",
"to",
"be",
"bonded",
"to",
"the",
"cement,",
"but",
"rather",
"to",
"act",
"as",
"a",
"‘‘loaded",
"taper’’",
"that",
"is",
"constrained",
"by",
"its",
"surrounding",
"cement",
"man-",
"tle,",
"such",
"as",
"the",
"Exeter",
"stem.",
"123"
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] | [
"Alshaker",
"and",
"Matalka",
"Cancer",
"Cell",
"International",
"2011,",
"11:33",
"http://www.cancerci.com/content/11/1/33",
"R",
"E",
"V",
"I",
"E",
"W",
"Open",
"Access",
"IFN-g,",
"IL-17",
"and",
"TGF-b",
"involvement",
"in",
"shaping",
"the",
"tumor",
"microenvironment:",
"The",
"significance",
"of",
"modulating",
"such",
"cytokines",
"in",
"treating",
"malignant",
"solid",
"tumors",
"Heba",
"A",
"Alshaker",
"and",
"Khalid",
"Z",
"Matalka*",
"Abstract",
"Multiple",
"innate",
"and",
"adaptive",
"immune",
"effector",
"cells",
"and",
"molecules",
"partake",
"in",
"the",
"recognition",
"and",
"destruction",
"of",
"cancer",
"cells",
"to",
"protect",
"against",
"growing",
"tumors,",
"a",
"concept",
"that",
"is",
"known",
"as",
"cancer",
"immunosurveillance.",
"Unfortunately,",
"cancer",
"cells",
"are",
"capable",
"of",
"avoiding",
"this",
"process",
"by",
"immunoselection",
"of",
"poorly",
"immunogenic",
"tumor",
"cells",
"variants",
"along",
"with",
"subversion",
"of",
"the",
"immune",
"system",
"and",
"thus",
"shaping",
"both",
"the",
"tumor",
"and",
"its",
"microenvironment.",
"Cytokines",
"represent",
"part",
"of",
"the",
"complex",
"pattern",
"of",
"the",
"immune",
"response",
"which",
"can",
"assist",
"the",
"development",
"of",
"cancer",
"as",
"well",
"as",
"to",
"eliminate",
"it.",
"Simultaneously,",
"a",
"large",
"number",
"of",
"cytokines",
"may",
"be",
"involved",
"in",
"the",
"complex",
"interactions",
"between",
"host",
"and",
"tumor",
"cells",
"where",
"this",
"dynamic",
"cross-talk,",
"between",
"tumors",
"and",
"the",
"immune",
"system,",
"can",
"either",
"regulate",
"tumor",
"growth",
"or",
"tumor",
"growth,",
"invasion",
"and",
"metastasis",
"take",
"place.",
"In",
"this",
"review,",
"we",
"are",
"stressing",
"on",
"the",
"interface",
"between",
"infiltrated",
"immune",
"cells",
"and",
"tumor",
"cells",
"with",
"the",
"emphasis",
"on",
"the",
"bidirectional",
"activities",
"of",
"specific",
"cytokines:",
"IFN-g,",
"TGF-b",
"and",
"IL-17",
"within",
"the",
"tumor",
"microenvironment",
"and",
"their",
"role",
"in",
"shaping",
"it.",
"In",
"addition,",
"the",
"significance",
"of",
"modulating",
"such",
"cytokines",
"in",
"favor",
"of",
"anti-tumor",
"response",
"is",
"discussed",
"and",
"merits",
"the",
"use",
"of",
"mixture",
"of",
"targeted",
"modulators",
"to",
"overcome",
"the",
"network",
"complexity",
"of",
"cytokines",
"in",
"the",
"tumor",
"microenvironment.",
"Keywords:",
"cytokines,",
"transcription",
"factors,",
"crosstalk,",
"tumor",
"microenvironment",
"1.",
"Introduction",
"The",
"failure",
"of",
"the",
"immune",
"system",
"to",
"recognize",
"and",
"era-",
"dicate",
"cancer",
"cells",
"may",
"partly",
"be",
"a",
"result",
"of",
"insufficient",
"immunological",
"activation.",
"It",
"is",
"now",
"increasingly",
"recog-",
"nized",
"that",
"the",
"microenvironment",
"plays",
"a",
"critical",
"role",
"in",
"the",
"progression",
"of",
"tumors",
"where",
"immune-resistant",
"tumor",
"variants",
"are",
"selected",
"initiating",
"the",
"process",
"of",
"can-",
"cer",
"immunoediting.",
"Tumor-derived",
"soluble",
"factors",
"can",
"impel",
"various",
"mechanisms",
"for",
"escape",
"from",
"immune",
"attack",
"in",
"the",
"tumor",
"microenvironment",
"[1,2].",
"The",
"tumor",
"microenvironment",
"is",
"a",
"pivotal",
"factor",
"in",
"the",
"course",
"of",
"carcinogenesis",
"and",
"is",
"largely",
"dependent",
"on",
"its",
"interac-",
"tions",
"with",
"microenvironmental",
"components",
"in",
"a",
"bidirec-",
"tional",
"way",
"and",
"consequently",
"tumor",
"progression",
"or",
"regression",
"[3,4].",
"*",
"Correspondence:",
"kzm@uop.edu.jo",
"Department",
"of",
"Pharmacology",
"and",
"Biomedical",
"Sciences,",
"Faculty",
"of",
"Pharmacy",
"and",
"Medical",
"Sciences,",
"Petra",
"University,",
"Amman,",
"Jordan",
"The",
"tumor",
"microenvironment",
"was",
"lately",
"recognized",
"as",
"the",
"product",
"of",
"a",
"developing",
"crosstalk",
"between",
"different",
"cells",
"types.",
"In",
"addition",
"to",
"tumor",
"cells,",
"the",
"tumor",
"microen-",
"vironment",
"is",
"comprised",
"of",
"immune",
"cells,",
"fibroblasts,",
"stro-",
"mal",
"cells",
"and",
"the",
"extracellular",
"matrix",
"[3].",
"Normal",
"cellular",
"microenvironment",
"can",
"inhibit",
"tumor",
"cell",
"proliferation",
"and",
"cancer",
"formation",
"[4].",
"Contrariwise,",
"as",
"tissue",
"becomes",
"can-",
"cerous",
"pathological",
"interactions",
"between",
"cancer",
"cells",
"and",
"host",
"immune",
"cells",
"in",
"the",
"tumor",
"microenvironment",
"and",
"lymphoid",
"organs",
"create",
"an",
"immunosuppressive",
"network",
"that",
"protects",
"the",
"tumor",
"from",
"immune",
"attack",
"leading",
"to",
"tumor",
"growth,",
"progression",
"as",
"well",
"as",
"invasion",
"and",
"metas-",
"tasis",
"which",
"is",
"basically",
"due",
"to",
"a",
"deranged",
"relationship",
"between",
"tumor",
"and",
"stromal",
"cells",
"[3-5].",
"In",
"this",
"review,",
"we",
"are",
"stressing",
"on",
"the",
"interface",
"between",
"infiltrated",
"immune",
"cells",
"and",
"tumor",
"cells",
"with",
"the",
"emphasis",
"on",
"the",
"bidirec-",
"tional",
"activities",
"of",
"cytokines",
"mainly",
"IFN-g,",
"TGF-b",
"and",
"IL-17",
"within",
"the",
"tumor",
"microenvironment",
"and",
"their",
"role",
"©",
"2011",
"Alshaker",
"and",
"Matalka;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Chappell",
"Arthritis",
"Research",
"&",
"Therapy",
"2010,",
"12:128",
"http://arthritis-research.com/content/12/3/128",
"E",
"D",
"I",
"T",
"O",
"R",
"I",
"A",
"L",
"Angiotensin-converting",
"enzyme",
"2",
"autoantibodies:",
"further",
"evidence",
"for",
"a",
"role",
"of",
"the",
"renin–",
"angiotensin",
"system",
"in",
"inflammation",
"Mark",
"C",
"Chappell*",
"See",
"related",
"research",
"by",
"Takahashi",
"et",
"al.,",
"http://arthritis-research.com/content/12/3/R85",
"Abstract",
"Traditionally",
"viewed",
"as",
"important",
"in",
"the",
"regulation",
"of",
"blood",
"pressure,",
"the",
"renin–angiotensin",
"system",
"–",
"and",
"specifically",
"the",
"angiotensin-converting",
"enzyme",
"(ACE)–",
"angiotensin",
"(Ang)",
"II–AT1",
"receptor",
"axis",
"–",
"may",
"play",
"a",
"prominent",
"role",
"to",
"promote",
"inflammation",
"and",
"fibrosis.",
"ACE2,",
"a",
"new",
"component",
"of",
"the",
"renin–angiotensin",
"system,",
"has",
"emerged",
"as",
"a",
"key",
"enzyme",
"that",
"selectively",
"degrades",
"Ang",
"II",
"and",
"generates",
"Ang-(1–7),",
"a",
"bioactive",
"peptide",
"with",
"anti-inflammatory",
"and",
"anti-fibrotic",
"actions.",
"Takahashi",
"and",
"colleagues",
"demonstrate",
"circulating",
"titers",
"of",
"inhibitory",
"autoantibodies",
"against",
"ACE2",
"in",
"patients",
"with",
"systemic",
"sclerosis.",
"The",
"current",
"study",
"reveals",
"a",
"potentially",
"novel",
"mechanism",
"to",
"attenuate",
"the",
"catalytic",
"activity",
"of",
"ACE2,",
"thereby",
"promoting",
"the",
"actions",
"of",
"Ang",
"II.",
"The",
"discovery",
"of",
"the",
"angiotensin-converting",
"enzyme",
"(ACE)",
"homolog",
"ACE2",
"[EC",
"3.4.15.1]",
"has",
"provoked",
"intensive",
"efforts",
"to",
"elucidate",
"the",
"role",
"of",
"this",
"enzyme",
"in",
"various",
"pathologies,",
"including",
"hypertension,",
"diabetes,",
"heart",
"failure,",
"viral",
"infection,",
"pulmonary",
"injury",
"and",
"liver",
"fibrosis.",
"The",
"biological",
"relevance",
"of",
"ACE2",
"reflects",
"its",
"critical",
"location",
"in",
"the",
"enzymatic",
"cascade",
"of",
"the",
"renin–",
"angiotensin",
"system",
"to",
"directly",
"govern",
"the",
"local",
"expression",
"of",
"angiotensin",
"(Ang)",
"II",
"and",
"Ang-(1–7),",
"two",
"bioactive",
"hormones",
"with",
"significant",
"and",
"opposing",
"actions.",
"In",
"the",
"present",
"issue",
"of",
"Arthritis",
"Research",
"&",
"Therapy,",
"Takahashi",
"and",
"colleagues",
"assessed",
"circulating",
"levels",
"of",
"ACE2",
"in",
"patients",
"with",
"connective",
"tissue",
"pathologies",
"including",
"pulmonary",
"hypertension",
"and",
"persistent",
"digital",
"*Correspondence:",
"mchappel@wfubmc.edu",
"Hypertension",
"and",
"Vascular",
"Disease",
"Center,",
"Wake",
"Forest",
"School",
"of",
"Medicine,",
"Medical",
"Center",
"Boulevard,",
"Winston-Salem,",
"NC",
"27015,",
"USA",
"©",
"2010",
"BioMed",
"Central",
"Ltd",
"©",
"2010",
"BioMed",
"Central",
"Ltd",
"ischemia",
"[1].",
"In",
"comparison",
"with",
"normal",
"controls,",
"patients",
"with",
"overt",
"vasculopathy",
"expressed",
"significantly",
"higher",
"amounts",
"of",
"ACE2",
"protein",
"in",
"the",
"circulation.",
"These",
"patients,",
"however,",
"exhibited",
"reduced",
"ACE2",
"activity",
"in",
"serum",
"and",
"circulating",
"autoantibodies",
"against",
"the",
"enzyme.",
"There",
"are",
"few",
"reports",
"on",
"the",
"circulating",
"levels",
"of",
"ACE2",
"in",
"humans",
"or",
"experimental",
"models,",
"possibly",
"reflecting",
"the",
"difficulty",
"of",
"obtaining",
"a",
"consistent",
"measurement",
"of",
"the",
"enzymatic",
"activity.",
"The",
"current",
"study",
"reveals",
"a",
"potentially",
"novel",
"mechanism",
"to",
"attenuate",
"the",
"catalytic",
"activity",
"of",
"ACE2,",
"thereby",
"promoting",
"the",
"inflammatory",
"actions",
"of",
"Ang",
"II.",
"ACE",
"and",
"ACE2",
"are",
"both",
"chloride-activated",
"metallo-",
"peptidases",
"that",
"are",
"predominantly",
"associated",
"with",
"the",
"cell",
"membrane",
"and",
"are",
"widely",
"distributed",
"in",
"various",
"tissues",
"and",
"vascular",
"beds.",
"In",
"contrast",
"to",
"ACE,",
"which",
"cleaves",
"two",
"amino",
"acid",
"residues",
"from",
"the",
"carboxyl",
"terminus",
"of",
"Ang",
"I",
"to",
"form",
"Ang",
"II,",
"ACE2",
"hydrolyzes",
"a",
"single",
"amino",
"acid",
"from",
"the",
"carboxyl",
"end",
"of",
"Ang",
"II",
"to",
"form",
"Ang-(1–7)",
"[2].",
"ACE",
"is",
"considered",
"the",
"primary",
"enzymatic",
"pathway",
"that",
"catalyzes",
"the",
"generation",
"of",
"Ang",
"II",
"in",
"the",
"circulation",
"and",
"tissues.",
"ACE",
"inhibitors,",
"which",
"have",
"become",
"standard",
"therapies",
"in",
"the",
"treatment",
"of",
"hyper-",
"tension",
"and",
"other",
"cardiovascular",
"disease,",
"have",
"little",
"or",
"no",
"inhibitory",
"activity",
"against",
"ACE2,",
"but",
"they",
"reduce",
"the",
"metabolism",
"of",
"Ang-(1–7)",
"[2].",
"Circulating",
"levels",
"of",
"ACE",
"activity",
"are",
"readily",
"measurable",
"in",
"humans",
"and",
"other",
"species",
"using",
"synthetic",
"substrates",
"or",
"assessing",
"the",
"direct",
"conversion",
"of",
"Ang",
"I",
"to",
"Ang",
"II.",
"In",
"comparison",
"with",
"serum",
"ACE,",
"Rice",
"and",
"colleagues",
"reported",
"that",
"the",
"circulating",
"levels",
"of",
"ACE2",
"were",
"100-fold",
"lower",
"and",
"that",
"<10%",
"(40",
"out",
"of",
"494)",
"of",
"their",
"patients",
"expressed",
"measurable",
"ACE2",
"activity",
"[3].",
"Nevertheless,",
"families",
"with",
"detectable",
"circulating",
"ACE2",
"exhibited",
"a",
"greater",
"incidence",
"of",
"cardiovascular",
"pathologies",
"although",
"the",
"overall",
"sample",
"population",
"was",
"low.",
"More",
"recent",
"studies",
"by",
"Epelman",
"and",
"colleagues",
"find",
"that",
"circulating",
"levels",
"of",
"ACE2",
"are",
"highly",
"associated",
"with",
"increasing",
"severity",
"of",
"progressive",
"heart",
"failure",
"[4].",
"However,",
"patients"
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718
],
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766,
704,
790,
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441,
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458,
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463,
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441,
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728,
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560,
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646,
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743,
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689,
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692,
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760,
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441,
838,
466,
852
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470,
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482,
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486,
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503,
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507,
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536,
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539,
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590,
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838,
768,
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772,
838,
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441,
854,
460,
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464,
854,
484,
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488,
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514,
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517,
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577,
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581,
854,
598,
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602,
854,
640,
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644,
854,
666,
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669,
854,
700,
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704,
854,
715,
868
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[
719,
854,
733,
868
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735,
854,
789,
868
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441,
871,
482,
885
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487,
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558,
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562,
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574,
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616,
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682,
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666,
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683,
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479,
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518,
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[
575,
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600,
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[
761,
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] | [
"RESEARCH",
"First",
"Isolation",
"of",
"West",
"Nile",
"virus",
"from",
"a",
"Patient",
"with",
"Encephalitis",
"in",
"the",
"United",
"States",
"Cinnia",
"Huang,*",
"Brett",
"Slater,*",
"Robert",
"Rudd,*",
"Nandakishore",
"Parchuri,†",
"Rene",
"Hull,*",
"Michelle",
"Dupuis,*",
"and",
"Alexander",
"Hindenburg†",
"West",
"Nile",
"virus",
"(WNV)",
"was",
"isolated",
"from",
"a",
"patient",
"who",
"developed",
"encephalitis",
"while",
"undergoing",
"treatment",
"with",
"CHOP",
"(cyclophosphamide,",
"hydroxydoxorubicin,",
"vincristine",
"[Oncovin],",
"predisone)",
"and",
"rituximab",
"for",
"a",
"non-Hodgkin",
"B-cell",
"lymphoma.",
"Both",
"standard",
"reverse",
"transcription–polymerase",
"chain",
"reaction",
"(RT-PCR)",
"and",
"Taqman",
"RT-PCR",
"established",
"the",
"diagnosis",
"of",
"WNV",
"infection",
"from",
"cerebrospinal",
"fluid",
"(CSF).",
"Several",
"whole",
"blood",
"samples",
"and",
"one",
"serum",
"sample",
"underwent",
"further",
"testing.",
"CSF",
"and",
"serum",
"samples",
"were",
"negative",
"for",
"WNV",
"antibody;",
"however,",
"all",
"samples",
"were",
"positive",
"by",
"both",
"RT-PCR",
"assays.",
"Infectious",
"virus",
"was",
"recovered",
"from",
"a",
"blood",
"sample,",
"and",
"its",
"identity",
"was",
"confirmed",
"by",
"using",
"a",
"WNV-specific",
"immunofluo-",
"rescence",
"assay.",
"The",
"complete",
"WNV",
"genomes",
"determined",
"from",
"CSF",
"and",
"from",
"the",
"virus",
"isolate",
"adapted",
"from",
"cell",
"culture",
"were",
"the",
"same.",
"The",
"results",
"represent",
"the",
"first",
"complete",
"WNV",
"genome",
"sequence",
"obtained",
"directly",
"from",
"human",
"CSF",
"and",
"the",
"first",
"time",
"that",
"infectious",
"WNV",
"has",
"been",
"recovered",
"from",
"a",
"patient",
"with",
"encephalitis",
"in",
"North",
"America.",
"W",
"member",
"of",
"the",
"Japanese",
"encephalitis",
"virus",
"serocomplex",
"est",
"Nile",
"virus",
"(WNV),",
"an",
"arthropod-borne",
"virus,",
"is",
"a",
"of",
"the",
"genus",
"Flavivirus,",
"family",
"Flaviviridae",
"(1),",
"discovered",
"in",
"Uganda",
"in",
"1937",
"(2).",
"Although",
"WNV",
"infections",
"are",
"usually",
"mild",
"or",
"asymptomatic,",
"in",
"some",
"instances,",
"a",
"severe",
"and",
"fatal",
"encephalitis",
"is",
"produced,",
"typically",
"in",
"the",
"elderly",
"(3).",
"This",
"virus",
"was",
"first",
"recognized",
"in",
"the",
"Western",
"Hemisphere",
"in",
"an",
"outbreak",
"in",
"New",
"York",
"in",
"1999",
"(4).",
"As",
"of",
"October",
"2,",
"2002,",
"a",
"total",
"of",
"2.671",
"cases",
"of",
"human",
"illness",
"in",
"the",
"United",
"States",
"have",
"been",
"reported",
"to",
"the",
"Centers",
"for",
"Disease",
"Control",
"and",
"Prevention",
"(CDC).",
"Although",
"WNV",
"has",
"been",
"recovered",
"from",
"mosquitoes,",
"birds,",
"and",
"horses,",
"no",
"isolations",
"from",
"humans",
"have",
"been",
"reported",
"in",
"the",
"Western",
"Hemisphere.",
"Thus,",
"all",
"prior",
"data",
"regarding",
"the",
"virus",
"responsible",
"for",
"human",
"illness",
"in",
"North",
"America",
"have",
"come",
"from",
"nucleic",
"acid",
"sequencing",
"of",
"the",
"viral",
"genome",
"in",
"either",
"cerebrospinal",
"fluid",
"(CSF)",
"or",
"brain",
"tissue.",
"We",
"describe",
"the",
"first",
"isolation",
"of",
"WNV",
"from",
"a",
"human",
"case-patient",
"associated",
"with",
"the",
"U.S.",
"outbreak.",
"Because",
"the",
"virus",
"was",
"also",
"directly",
"detected",
"by",
"reverse",
"transcription–polymerase",
"chain",
"reaction",
"(RT-PCR)",
"in",
"specimens",
"from",
"the",
"same",
"patient,",
"we",
"were",
"able",
"to",
"compare",
"the",
"entire",
"genomic",
"sequence",
"of",
"the",
"directly",
"detected",
"virus",
"with",
"that",
"of",
"the",
"cell-culture",
"isolate.",
"Case",
"Report",
"The",
"patient",
"was",
"a",
"70-year-old",
"woman,",
"who",
"has",
"been",
"diag-",
"nosed",
"with",
"intermediate-grade,",
"CD",
"20-positive,",
"B-cell",
"non-",
"Hodgkin",
"lymphoma,",
"involving",
"a",
"left",
"intraparotid",
"lymph",
"node.",
"Staging",
"workup",
"demonstrated",
"stage",
"1-A",
"disease.",
"Treatment",
"plans",
"for",
"the",
"patient",
"included",
"three",
"courses",
"of",
"CHOP",
"(cyclo-",
"*Wadsworth",
"Center,",
"New",
"York",
"State",
"Department",
"of",
"Health,",
"Albany,",
"New",
"York,",
"USA;",
"and",
"†Winthrop",
"University",
"Hospital,",
"Mineola,",
"New",
"York,",
"USA",
"phosphamide,",
"hydroxydoxorubicin,",
"vincristine",
"[Oncovin],",
"and",
"predisone)",
"chemotherapy",
"plus",
"rituximab",
"(chimeric",
"CD",
"20",
"monoclonal",
"antibody),",
"to",
"be",
"followed",
"by",
"involved",
"field",
"radia-",
"tion.",
"After",
"the",
"first",
"cycle",
"of",
"chemotherapy",
"in",
"July",
"2001,",
"neu-",
"tropenia",
"developed",
"and",
"the",
"patient",
"was",
"treated",
"with",
"granulocyte",
"colony",
"stimulating",
"factor",
"(GCSF)",
"following",
"both",
"the",
"second",
"and",
"third",
"cycles",
"of",
"chemotherapy.",
"The",
"third",
"cycle",
"of",
"chemotherapy",
"was",
"administered",
"on",
"September",
"11,",
"2001.",
"Four",
"days",
"later,",
"she",
"was",
"treated",
"with",
"oral",
"levofloxacin",
"for",
"low-",
"grade",
"fever.",
"On",
"day",
"7",
"after",
"chemotherapy,",
"she",
"was",
"admitted",
"to",
"the",
"hospital",
"with",
"fever,",
"cough,",
"chills,",
"rhinorrhea,",
"joint",
"aches,",
"decreased",
"appetite,",
"lethargy,",
"and",
"lightheadedness.",
"She",
"had",
"no",
"recollection",
"of",
"any",
"ill",
"contacts",
"or",
"insect",
"bites.",
"She",
"was",
"a",
"resi-",
"dent",
"of",
"southern",
"Nassau",
"County,",
"New",
"York,",
"and",
"did",
"not",
"have",
"a",
"history",
"of",
"travel.",
"Physical",
"examination",
"was",
"within",
"normal",
"lim-",
"its.",
"The",
"patient",
"was",
"neutropenic;",
"G-CSF",
"was",
"continued,",
"and",
"she",
"was",
"given",
"cefipime",
"and",
"gentamicin.",
"One",
"day",
"after",
"admis-",
"sion,",
"she",
"continued",
"to",
"have",
"fever",
"and",
"experienced",
"mild",
"head-",
"aches",
"that",
"responded",
"to",
"acetaminophen.",
"Urine",
"cultures",
"showed",
"penicillin-sensitive",
"enterococci,",
"and",
"blood",
"cultures",
"were",
"nega-",
"tive.",
"Two",
"days",
"after",
"admission,",
"the",
"patient",
"continued",
"to",
"have",
"fever,",
"headaches,",
"and",
"dizziness.",
"A",
"computed",
"tomography",
"(CT)",
"scan",
"of",
"the",
"brain",
"revealed",
"no",
"acute",
"cerebral",
"processes.",
"On",
"the",
"3rd",
"day",
"after",
"admission,",
"the",
"patient",
"was",
"noted",
"to",
"be",
"confused.",
"Further",
"deterioration",
"of",
"mental",
"status",
"was",
"noted,",
"with",
"incom-",
"prehensible",
"speech,",
"but",
"she",
"was",
"able",
"to",
"follow",
"commands.",
"Arterial",
"blood-gas",
"analysis",
"showed",
"an",
"acute",
"respiratory",
"acido-",
"sis",
"pattern,",
"and",
"the",
"patient",
"was",
"subsequently",
"intubated",
"and",
"transferred",
"to",
"the",
"intensive",
"care",
"unit.",
"The",
"patient",
"had",
"a",
"hypotensive",
"episode",
"secondary",
"to",
"atrial",
"flutter,",
"which",
"required",
"cardioversion",
"for",
"stabilization.",
"Ceftriaxone",
"and",
"ampicillin",
"were",
"added",
"to",
"the",
"antibiotic",
"coverage,",
"and",
"antifungal",
"treatment",
"was",
"also",
"initiated",
"with",
"lipid",
"complex",
"amphotericin",
"B.",
"After",
"Emerging",
"Infectious",
"Diseases",
"•",
"Vol.",
"8,",
"No.",
"12,",
"December",
"2002",
"1367"
] | [
16,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
6,
6,
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] | [
"Freeman",
"et",
"al.",
"Fibrogenesis",
"&",
"Tissue",
"Repair",
"2010,",
"3:17",
"http://www.fibrogenesis.com/content/3/1/17",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"Open",
"Access",
"Mast",
"cells",
"and",
"hypoxia",
"drive",
"tissue",
"metaplasia",
"and",
"heterotopic",
"ossification",
"in",
"idiopathic",
"arthrofibrosis",
"after",
"total",
"knee",
"arthroplasty",
"Theresa",
"A",
"Freeman1,",
"Javad",
"Parvizi2,",
"Craig",
"J",
"Dela",
"Valle3,",
"Marla",
"J",
"Steinbeck4*",
"Abstract",
"Background:",
"Idiopathic",
"arthrofibrosis",
"occurs",
"in",
"3-4%",
"of",
"patients",
"who",
"undergo",
"total",
"knee",
"arthroplasty",
"(TKA).",
"However,",
"little",
"is",
"known",
"about",
"the",
"cellular",
"or",
"molecular",
"changes",
"involved",
"in",
"the",
"onset",
"or",
"progression",
"of",
"this",
"condition.",
"To",
"classify",
"the",
"histomorphologic",
"changes",
"and",
"evaluate",
"potential",
"contributing",
"factors,",
"periarticular",
"tissues",
"from",
"the",
"knees",
"of",
"patients",
"with",
"arthrofibrosis",
"were",
"analyzed",
"for",
"fibroblast",
"and",
"mast",
"cell",
"proliferation,",
"heterotopic",
"ossification,",
"cellular",
"apoptosis,",
"hypoxia",
"and",
"oxidative",
"stress.",
"Results:",
"The",
"arthrofibrotic",
"tissue",
"was",
"composed",
"of",
"dense",
"fibroblastic",
"regions,",
"with",
"limited",
"vascularity",
"along",
"the",
"outer",
"edges.",
"Within",
"the",
"fibrotic",
"regions,",
"elevated",
"numbers",
"of",
"chymase/fibroblast",
"growth",
"factor",
"(FGF)-expressing",
"mast",
"cells",
"were",
"observed.",
"In",
"addition,",
"this",
"region",
"contained",
"fibrocartilage",
"and",
"associated",
"heterotopic",
"ossification,",
"which",
"quantitatively",
"correlated",
"with",
"decreased",
"range",
"of",
"motion",
"(stiffness).",
"Fibrotic,",
"fibrocartilage",
"and",
"ossified",
"regions",
"contained",
"few",
"terminal",
"dUTP",
"nick",
"end",
"labeling",
"(TUNEL)-positive",
"or",
"apoptotic",
"cells,",
"despite",
"positive",
"immunostaining",
"for",
"lactate",
"dehydrogenase",
"(LDH)5,",
"a",
"marker",
"of",
"hypoxia,",
"and",
"nitrotyrosine,",
"a",
"marker",
"for",
"protein",
"nitrosylation.",
"LDH5",
"and",
"nitrotyrosine",
"were",
"found",
"in",
"the",
"same",
"tissue",
"areas,",
"indicating",
"that",
"hypoxic",
"areas",
"within",
"the",
"tissue",
"were",
"associated",
"with",
"increased",
"production",
"of",
"reactive",
"oxygen",
"and",
"nitrogen",
"species.",
"Conclusions:",
"Taken",
"together,",
"we",
"suggest",
"that",
"hypoxia-associated",
"oxidative",
"stress",
"initiates",
"mast",
"cell",
"proliferation",
"and",
"FGF",
"secretion,",
"spurring",
"fibroblast",
"proliferation",
"and",
"tissue",
"fibrosis.",
"Fibroblasts",
"within",
"this",
"hypoxic",
"environment",
"undergo",
"metaplastic",
"transformation",
"to",
"fibrocartilage,",
"followed",
"by",
"heterotopic",
"ossification,",
"resulting",
"in",
"increased",
"joint",
"stiffness.",
"Thus,",
"hypoxia",
"and",
"associated",
"oxidative",
"stress",
"are",
"potential",
"therapeutic",
"targets",
"for",
"fibrosis",
"and",
"metaplastic",
"progression",
"of",
"idiopathic",
"arthrofibrosis",
"after",
"TKA.",
"Background",
"Limited",
"range",
"of",
"motion",
"is",
"a",
"disabling",
"complication",
"of",
"total",
"knee",
"arthroplasty",
"(TKA)",
"[1-8].",
"Idiopathic",
"arthrofi-",
"brosis,",
"clinically",
"defined",
"as",
"abnormal",
"tissue",
"scarring",
"within",
"the",
"joint,",
"represents",
"the",
"most",
"severe",
"form",
"of",
"stiff-",
"ness.",
"Even",
"with",
"surgical",
"intervention",
"or",
"revision",
"arthro-",
"plasty,",
"the",
"formation",
"of",
"dense",
"fibrous",
"tissue",
"and",
"tissue",
"contractions",
"can",
"recur,",
"leading",
"to",
"increased",
"severity",
"of",
"the",
"fibrotic",
"condition",
"and",
"eventual",
"disability,",
"with",
"all",
"the",
"negative",
"psychological",
"and",
"societal",
"implications",
"this",
"carries",
"[8].",
"Unfortunately,",
"there",
"is",
"no",
"clear",
"method",
"by",
"*",
"Correspondence:",
"mjs348@drexel.edu",
"4School",
"of",
"Biomedical",
"Engineering",
"and",
"College",
"of",
"Drexel",
"Medicine,",
"Drexel",
"University,",
"3120",
"Market",
"Street,",
"323",
"Bossone,",
"Philadelphia,",
"PA",
"19104,",
"USA",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"which",
"patients",
"who",
"are",
"at",
"risk",
"of",
"developing",
"arthrofibro-",
"sis",
"can",
"be",
"identified.",
"It",
"is",
"known",
"that",
"arthrofibrosis",
"develops",
"in",
"response",
"to",
"surgical",
"intervention",
"in",
"approximately",
"3-4%",
"of",
"patients",
"undergoing",
"TKA,",
"and",
"the",
"resulting",
"pain",
"and",
"loss",
"of",
"range",
"of",
"motion",
"leads",
"to",
"patient",
"disability.",
"Thus,",
"to",
"have",
"the",
"possibility",
"of",
"developing",
"a",
"diagnostic",
"test",
"to",
"pre-",
"screen",
"patients",
"undergoing",
"TKA",
"and/or",
"of",
"implement-",
"ing",
"postoperative",
"treatments",
"that",
"may",
"improve",
"the",
"functional",
"outcome,",
"it",
"is",
"important",
"to",
"understand",
"the",
"pathoetiology",
"behind",
"the",
"condition.",
"In",
"this",
"study,",
"we",
"aimed",
"to",
"identify",
"the",
"specific",
"factor(s)",
"responsible",
"for",
"initiating",
"tissue",
"fibrosis,",
"metaplasia",
"and",
"other",
"histologi-",
"cal",
"changes",
"that",
"occur",
"in",
"arthrofibrosis.",
"In",
"agreement",
"with",
"other",
"investigators,",
"we",
"have",
"pre-",
"viously",
"reported",
"the",
"presence",
"of",
"aggressive",
"fibroblast",
"©",
"2010",
"Freeman",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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824,
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839
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824,
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577,
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] | [
"Homeostasis",
"of",
"Peripheral",
"B",
"Cells",
"in",
"the",
"Absence",
"of",
"B",
"Cell",
"Influx",
"from",
"the",
"Bone",
"Marrow",
"Zhenyue",
"Hao",
"and",
"Klaus",
"Rajewsky",
"Department",
"of",
"Immunology,",
"Institute",
"for",
"Genetics,",
"University",
"of",
"Cologne,",
"D-50931",
"Cologne,",
"Germany",
"Abstract",
"To",
"study",
"homeostasis",
"of",
"peripheral",
"B",
"lymphocytes",
"in",
"the",
"absence",
"of",
"B",
"cell",
"influx",
"from",
"the",
"bone",
"marrow,",
"we",
"generated",
"a",
"mouse",
"mutant",
"in",
"which",
"the",
"recombination-activating",
"gene",
"(RAG)-2",
"can",
"be",
"inducibly",
"deleted.",
"When",
"RAG-2",
"was",
"deleted",
"at",
"the",
"age",
"of",
"8–10",
"wk,",
"splenic",
"naive",
"follicular",
"B",
"cells",
"were",
"gradually",
"lost",
"over",
"a",
"year",
"of",
"observation,",
"with",
"a",
"half-life",
"of",
"4.5",
"mo.",
"By",
"contrast,",
"the",
"pool",
"of",
"marginal",
"zone",
"B",
"cells",
"in",
"the",
"spleen",
"and",
"of",
"B-1",
"cells",
"in",
"the",
"perito-",
"neal",
"cavity",
"were",
"kept",
"at",
"normal",
"level.",
"In",
"lymph",
"nodes,",
"90%",
"of",
"the",
"B",
"cells",
"were",
"lost",
"within",
"4",
"mo,",
"and",
"B",
"cell",
"numbers",
"remained",
"constant",
"thereafter.",
"Mice",
"in",
"which",
"RAG-2",
"was",
"deleted",
"at",
"birth",
"maintained",
"a",
"small",
"population",
"of",
"activated",
"B",
"cells",
"with",
"an",
"increased",
"proportion",
"of",
"mar-",
"ginal",
"zone",
"B",
"cells.",
"Additionally,",
"an",
"increase",
"of",
"the",
"pool",
"of",
"IgM",
"secreting",
"cells",
"and",
"B-1a",
"cells",
"was",
"observed.",
"Key",
"words:",
"RAG-2",
"•",
"mouse",
"•",
"marginal",
"zone",
"B",
"cells",
"•",
"follicular",
"B",
"cells",
"•",
"half-life",
"Introduction",
"In",
"mouse",
"and",
"man,",
"B",
"cells",
"are",
"continuously",
"generated",
"from",
"B",
"cell",
"progenitors",
"over",
"lifetime,",
"with",
"the",
"fetal",
"liver",
"and,",
"from",
"around",
"birth",
"on,",
"the",
"bone",
"marrow",
"(BM)*",
"as",
"the",
"main",
"sites",
"where",
"this",
"process",
"takes",
"place.",
"The",
"immature",
"B",
"cells",
"generated",
"in",
"the",
"BM",
"emigrate",
"into",
"the",
"peripheral",
"immune",
"system",
"and",
"give",
"rise",
"to",
"a",
"heterogeneous",
"population",
"of",
"pe-",
"ripheral",
"B",
"cells",
"including",
"naive,",
"memory",
"and",
"plasma",
"cells",
"(1).",
"In",
"terms",
"of",
"their",
"anatomical",
"location",
"and",
"surface",
"mark-",
"ers,",
"the",
"B",
"cell",
"population",
"in",
"the",
"periphery",
"consists",
"of",
"recir-",
"culating",
"IgMlowIgDhighCD21intCD23high",
"cells",
"located",
"in",
"follicles",
"in",
"spleen",
"and",
"lymph",
"nodes,",
"and",
"IgMhigh",
"IgDlowCD21highCD23low",
"non-recirculating",
"cells",
"enriched",
"mainly",
"in",
"the",
"marginal",
"zone",
"(MZ)",
"of",
"the",
"spleen",
"(2,",
"3).",
"Fol-",
"licular",
"(FO)",
"B",
"cells",
"in",
"the",
"spleen",
"account",
"for",
"80–90%",
"and",
"MZ",
"B",
"cells",
"for",
"5–10%",
"of",
"the",
"splenic",
"B",
"cells",
"in",
"an",
"adult",
"mouse",
"(4).",
"Another",
"B",
"cell",
"subset,",
"consisting",
"of",
"the",
"so-called",
"B-1",
"cells,",
"has",
"self-renewing",
"capacity",
"and",
"predominates",
"in",
"the",
"peritoneal",
"and",
"pleural",
"cavities",
"(5).",
"Recent",
"data",
"on",
"the",
"function",
"of",
"MZ",
"B",
"cells",
"(6–8)",
"and",
"B-1",
"cells",
"(9,",
"10)",
"suggest",
"that",
"these",
"cells",
"provide",
"a",
"first",
"line",
"of",
"defense",
"against",
"anti-",
"Address",
"correspondence",
"to",
"Klaus",
"Rajewsky,",
"Department",
"of",
"Immu-",
"nology,",
"Institute",
"for",
"Genetics,",
"University",
"of",
"Cologne,",
"Weyertal",
"121,",
"D-50931",
"Cologne,",
"Germany.",
"Phone:",
"49-221-4702467;",
"Fax:",
"49-221-",
"4705185;",
"E-mail:",
"klaus.rajewsky@mac.genetik.uni-koeln.de",
"*Abbreviations",
"used",
"in",
"this",
"paper:",
"BM,",
"bone",
"marrow;",
"BrdU,",
"bromo",
"deoxyuridine;",
"ELISPOT,",
"enzyme-linked",
"immunospot;",
"ES,",
"embryonic",
"stem;",
"FO,",
"follicular;",
"HSA,",
"heat",
"shock",
"antigen;",
"MZ,",
"marginal",
"zone;",
"RAG,",
"recombination-activating",
"gene.",
"gens",
"in",
"the",
"blood,",
"and",
"in",
"the",
"peritoneal",
"and",
"pleural",
"cavities,",
"respectively.",
"FO",
"B",
"cells",
"are",
"involved",
"in",
"T",
"cell–dependent",
"antibody",
"responses,",
"in",
"which",
"memory",
"and",
"plasma",
"cells",
"are",
"generated",
"(7).",
"About",
"1–2",
"107",
"immature",
"B",
"cells",
"are",
"generated",
"daily",
"in",
"the",
"adult",
"murine",
"BM",
"(11).",
"Of",
"these,",
"only",
"3%",
"enter",
"the",
"pool",
"of",
"mature",
"B",
"cells",
"of",
"the",
"various",
"subsets",
"(12).",
"Periph-",
"eral",
"B",
"cell",
"pools",
"represent",
"dynamic,",
"yet",
"stable",
"compart-",
"ments",
"where",
"the",
"input",
"contributed",
"by",
"BM",
"immigrants",
"and",
"antigen",
"driven",
"cell",
"proliferation",
"is",
"balanced",
"by",
"apoptosis",
"and",
"terminal",
"differentiation",
"(13).",
"For",
"an",
"understanding",
"of",
"this",
"homeostatic",
"control",
"it",
"is",
"of",
"critical",
"importance",
"to",
"determine",
"the",
"life",
"spans",
"of",
"B",
"cells",
"of",
"various",
"subsets",
"under",
"physiological",
"conditions.",
"It",
"is",
"there-",
"fore",
"not",
"surprising",
"that",
"B",
"cell",
"life",
"spans",
"have",
"been",
"the",
"sub-",
"ject",
"of",
"many",
"investigations",
"in",
"the",
"past.",
"However,",
"while",
"it",
"is",
"generally",
"agreed",
"that",
"newly",
"generated",
"immature",
"B",
"cells",
"in",
"adult",
"mice",
"have",
"life",
"spans",
"of",
"3-4",
"d",
"(12,",
"14),",
"the",
"life",
"spans",
"of",
"mature",
"B",
"cells",
"are",
"still",
"controversial.",
"Experiments",
"based",
"on",
"(a)",
"adoptive",
"transfer",
"of",
"LPS-reactive",
"B",
"cells",
"into",
"LPS-",
"nonreactive",
"recipient",
"mice",
"(15);",
"(b)",
"the",
"ablation",
"of",
"cycling",
"B",
"cell",
"precursors",
"with",
"cytotoxic",
"drugs",
"which",
"selectively",
"kill",
"cycling",
"cells",
"(16,",
"17);",
"and",
"(c)",
"induction",
"of",
"BM",
"aplasia",
"using",
"a",
"radioactive",
"strontium",
"isotope,",
"89S",
"(18)",
"support",
"the",
"hy-",
"pothesis",
"that",
"most",
"mature",
"B",
"cells",
"have",
"a",
"life",
"span",
"of",
"just",
"a",
"few",
"days",
"(13).",
"In",
"contrast,",
"experiments",
"in",
"which",
"B",
"cell",
"de-",
"velopment",
"was",
"blocked",
"by",
"anti–IL-7",
"(19),",
"or",
"anti–IL-7",
"re-",
"ceptor",
"antibodies",
"(20)",
"or",
"cells",
"were",
"labeled",
"by",
"[3H]thymi-",
"1151",
"J.",
"Exp.",
"Med.",
"",
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] | [
"Sun",
"et",
"al.",
"Nanoscale",
"Research",
"Letters",
"2011,",
"6:556",
"http://www.nanoscalereslett.com/content/6/1/556",
"N",
"A",
"N",
"O",
"E",
"X",
"P",
"R",
"E",
"S",
"S",
"Open",
"Access",
"Improved",
"characteristics",
"of",
"near-band-edge",
"and",
"deep-level",
"emissions",
"from",
"ZnO",
"nanorod",
"arrays",
"by",
"atomic-layer-deposited",
"Al",
"O",
"and",
"ZnO",
"shell",
"layers",
"2",
"3",
"Wen-Cheng",
"Sun1,2,",
"Yu-Cheng",
"Yeh1,2,",
"Chung-Ting",
"Ko1,",
"Hau",
"He",
"Jr2*",
"and",
"Miin-Jang",
"Chen1*",
"Abstract",
"We",
"report",
"on",
"the",
"characteristics",
"of",
"near-band-edge",
"(NBE)",
"emission",
"and",
"deep-level",
"band",
"from",
"ZnO/Al2O3",
"and",
"ZnO/",
"ZnO",
"core-shell",
"nanorod",
"arrays",
"(NRAs).",
"Vertically",
"aligned",
"ZnO",
"NRAs",
"were",
"synthesized",
"by",
"an",
"aqueous",
"chemical",
"method,",
"and",
"the",
"Al2O3",
"and",
"ZnO",
"shell",
"layers",
"were",
"prepared",
"by",
"the",
"highly",
"conformal",
"atomic",
"layer",
"deposition",
"technique.",
"Photoluminescence",
"measurements",
"revealed",
"that",
"the",
"deep-level",
"band",
"was",
"suppressed",
"and",
"the",
"NBE",
"emission",
"was",
"significantly",
"enhanced",
"after",
"the",
"deposition",
"of",
"Al2O3",
"and",
"ZnO",
"shells,",
"which",
"are",
"attributed",
"to",
"the",
"decrease",
"in",
"oxygen",
"interstitials",
"at",
"the",
"surface",
"and",
"the",
"reduction",
"in",
"surface",
"band",
"bending",
"of",
"ZnO",
"core,",
"respectively.",
"The",
"shift",
"of",
"deep-level",
"emissions",
"from",
"the",
"ZnO/ZnO",
"core-shell",
"NRAs",
"was",
"observed",
"for",
"the",
"first",
"time.",
"Owing",
"to",
"the",
"presence",
"of",
"the",
"ZnO",
"shell",
"layer,",
"the",
"yellow",
"band",
"associated",
"with",
"the",
"oxygen",
"interstitials",
"inside",
"the",
"ZnO",
"core",
"would",
"be",
"prevailed",
"over",
"by",
"the",
"green",
"luminescence,",
"which",
"originates",
"from",
"the",
"recombination",
"of",
"the",
"electrons",
"in",
"the",
"conduction",
"band",
"with",
"the",
"holes",
"trapped",
"by",
"the",
"oxygen",
"vacancies",
"in",
"the",
"ZnO",
"shell.",
"PACS",
"68.65.Ac;",
"71.35.-y;",
"78.45.+h;",
"78.55.-m;",
"78.55.Et;",
"78.67.Hc;",
"81.16.Be;",
"85.60.Jb.",
"Introduction",
"Because",
"of",
"large",
"surface-to-volume",
"ratio",
"and",
"spatial",
"con-",
"finement",
"of",
"carriers,",
"researches",
"on",
"one-dimensional",
"(1D)",
"nanostructures",
"have",
"attracted",
"great",
"interest",
"[1-3],",
"and",
"remarkable",
"progress",
"has",
"been",
"achieved",
"in",
"various",
"electro-",
"nic,",
"photonic,",
"and",
"sensing",
"devices",
"[3-7].",
"Novel",
"synthetic",
"approaches",
"to",
"the",
"fabrication",
"of",
"high-quality",
"semiconduc-",
"tor",
"nanotubes",
"have",
"been",
"reviewed",
"by",
"Yan",
"et",
"al.",
"[8].",
"Zinc",
"oxide",
"(ZnO)",
"has",
"been",
"regarded",
"as",
"one",
"of",
"the",
"most",
"promis-",
"ing",
"materials",
"for",
"1D",
"nanostructures",
"due",
"to",
"its",
"distin-",
"guished",
"characteristics",
"such",
"as",
"direct",
"and",
"wide",
"band",
"gap",
"(approximately",
"3.37",
"eV),",
"large",
"excitonic",
"binding",
"energy",
"(up",
"to",
"60",
"meV),",
"and",
"high",
"piezoelectricity",
"[9-11].",
"The",
"synthesis",
"of",
"well-aligned",
"ZnO",
"nanorod",
"arrays",
"(NRAs)",
"is",
"crucially",
"important",
"for",
"the",
"practical",
"applications",
"such",
"as",
"field",
"emitters",
"[12],",
"nanogenerators",
"[13],",
"solar",
"cells",
"[14],",
"and",
"nanolasers",
"[15].",
"One",
"of",
"the",
"popular",
"techniques",
"for",
"fabricating",
"ZnO",
"NRAs",
"is",
"to",
"use",
"Au",
"as",
"catalyst",
"on",
"a",
"lattice-",
"*",
"Correspondence:",
"jhhe@cc.ee.ntu.edu.tw;",
"mjchen@ntu.edu.tw",
"1Department",
"of",
"Materials",
"Science",
"and",
"Engineering,",
"National",
"Taiwan",
"University,",
"Taipei",
"10617,",
"Taiwan",
"2Graduate",
"Institute",
"of",
"Photonics",
"and",
"Optoelectronics,",
"National",
"Taiwan",
"University,",
"Taipei",
"10617,",
"Taiwan",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"matched",
"substrate",
"[16].",
"Since",
"the",
"optical",
"properties",
"of",
"ZnO",
"NRAs",
"are",
"strongly",
"dependent",
"on",
"surface",
"conditions",
"[17-20]",
"and",
"natural",
"defect",
"states",
"[21-24],",
"a",
"large",
"variety",
"of",
"surface",
"modifications",
"on",
"ZnO",
"NRAs",
"have",
"been",
"carried",
"out",
"by",
"depositing",
"a",
"shell",
"layer.",
"For",
"instance,",
"the",
"enhance-",
"ment",
"of",
"photoluminescence",
"(PL)",
"has",
"been",
"observed",
"in",
"ZnO/Er2O3",
"and",
"ZnO/MgZnO",
"core-shell",
"NRAs",
"[25,26].",
"The",
"enhanced",
"surface-excitonic",
"emission",
"together",
"with",
"the",
"suppression",
"in",
"deep-level",
"emission",
"has",
"also",
"been",
"reported",
"in",
"ZnO/amorphous-Al2O3",
"core-shell",
"nanowires",
"[27].",
"Apart",
"from",
"the",
"enhancement",
"of",
"light",
"emission,",
"strong",
"photoconductivity",
"[28],",
"photocatalytic",
"activity",
"[29],",
"and",
"quantum",
"confinement",
"[30]",
"have",
"been",
"observed",
"in",
"var-",
"ious",
"1D",
"ZnO",
"nanostructures.",
"In",
"this",
"paper,",
"vertically",
"aligned",
"ZnO",
"NRAs",
"were",
"synthe-",
"sized",
"using",
"an",
"aqueous",
"chemical",
"method,",
"which",
"is",
"benefi-",
"cial",
"for",
"low",
"reaction",
"temperature,",
"low",
"cost,",
"catalyst-free",
"synthesis,",
"and",
"large-scale",
"production.",
"The",
"growth",
"of",
"ZnO",
"NRAs",
"was",
"assisted",
"by",
"a",
"ZnO",
"seed",
"layer",
"prepared",
"by",
"atomic",
"layer",
"deposition",
"(ALD).",
"The",
"self-limiting",
"and",
"layer-by-layer",
"growth",
"of",
"ALD",
"contribute",
"to",
"many",
"advan-",
"tages",
"such",
"as",
"easy",
"and",
"accurate",
"thickness",
"control,",
"confor-",
"mal",
"step",
"coverage,",
"high",
"uniformity",
"over",
"a",
"large",
"area,",
"low",
"defect",
"density,",
"good",
"reproducibility,",
"and",
"low",
"deposition",
"©",
"2011",
"Sun",
"et",
"al;",
"licensee",
"Springer.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"BMC",
"Public",
"Health",
"Research",
"article",
"The",
"health",
"of",
"people",
"classified",
"as",
"lesbian,",
"gay",
"and",
"bisexual",
"attending",
"family",
"practitioners",
"in",
"London:",
"a",
"controlled",
"study",
"Michael",
"King1",
"and",
"Irwin",
"Nazareth*2",
"BioMed",
"Central",
"Open",
"Access",
"Address:",
"1Professor",
"of",
"Primary",
"Care",
"Psychiatry,",
"Department",
"of",
"Mental",
"Health",
"Sciences,",
"Royal",
"Free",
"and",
"University",
"College",
"Medical",
"School,",
"University",
"College",
"London,",
"Royal",
"Free",
"Campus,",
"Rowland",
"Hill",
"Street,",
"London",
"NW3",
"2PF,",
"UK",
"and",
"2Professor",
"of",
"Primary",
"Care",
"&",
"Population",
"Sciences",
"&",
"Director",
"MRC",
"General",
"Practice",
"Research",
"Framework,",
"Department",
"of",
"Primary",
"Care",
"and",
"Population",
"Sciences,",
"Royal",
"Free",
"and",
"University",
"College",
"Medical",
"School,",
"University",
"College",
"London",
"(UCL),",
"Rowland",
"Hill",
"Street,",
"London",
"NW3",
"2PF,",
"UK",
"Email:",
"Michael",
"King",
"-",
"m.king@medsch.ucl.ac.uk;",
"Irwin",
"Nazareth*",
"-",
"i.nazareth@pcps.ucl.ac.uk",
"*",
"Corresponding",
"author",
"Published:",
"08",
"May",
"2006",
"BMC",
"Public",
"Health",
"2006,",
"6:127",
"doi:10.1186/1471-2458-6-127",
"This",
"article",
"is",
"available",
"from:",
"http://www.biomedcentral.com/1471-2458/6/127",
"Received:",
"24",
"October",
"2005",
"Accepted:",
"08",
"May",
"2006",
"©",
"2006",
"King",
"and",
"Nazareth;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"The",
"morbidity",
"of",
"gay,",
"lesbian",
"or",
"bisexual",
"people",
"attending",
"family",
"practice",
"has",
"not",
"been",
"previously",
"assessed.",
"We",
"compared",
"health",
"measures",
"of",
"family",
"practice",
"attendees",
"classified",
"as",
"lesbian,",
"gay",
"and",
"bisexual.",
"Methods:",
"We",
"conducted",
"a",
"cross-sectional,",
"controlled",
"study",
"conducted",
"in",
"13",
"London",
"family",
"practices",
"and",
"compared",
"the",
"responses",
"of",
"26",
"lesbian",
"and",
"85",
"bisexual",
"classified",
"women,",
"with",
"that",
"of",
"934",
"heterosexual",
"classified",
"women",
"and",
"38",
"gay",
"and",
"23",
"bisexual",
"classified",
"men",
"with",
"that",
"of",
"373",
"heterosexual",
"classified",
"men.",
"Our",
"outcomes",
"of",
"interest",
"were:",
"General",
"health",
"questionnaire;",
"CAGE",
"questionnaire;",
"short",
"form12;",
"smoking",
"status;",
"sexual",
"experiences",
"during",
"childhood;",
"number",
"of",
"sexual",
"partners",
"and",
"sexual",
"function",
"and",
"satisfaction.",
"Results:",
"In",
"comparison",
"to",
"people",
"classified",
"as",
"heterosexuals:",
"men",
"classified",
"as",
"gay",
"reported",
"higher",
"levels",
"of",
"psychological",
"symptoms",
"(OR",
"2.48,",
"CI",
"1.05–5.90);",
"women",
"classified",
"as",
"bisexual",
"were",
"more",
"likely",
"to",
"misuse",
"alcohol",
"(OR",
"2.73,",
"1.70–4.40);",
"women",
"classified",
"as",
"bisexual",
"(OR",
"2.53,",
"1.60–4.00)",
"and",
"lesbian",
"(OR",
"3.13,",
"1.41–6.97)",
"and",
"men",
"classified",
"as",
"bisexual",
"(OR",
"2.48,",
"1,04,",
"5.86)",
"were",
"more",
"likely",
"to",
"be",
"smokers",
"and",
"women",
"classified",
"as",
"bisexual",
"(OR",
"3.27,",
"1.97–5.43)",
"and",
"men",
"classified",
"as",
"gay",
"(OR",
"4.86,",
"2.28–10.34)",
"were",
"much",
"more",
"likely",
"to",
"report",
"childhood",
"sexual",
"experiences",
"in",
"childhood.",
"Psychological",
"distress",
"was",
"associated",
"with",
"reporting",
"sexual",
"experiences",
"in",
"childhood",
"in",
"men",
"classified",
"as",
"gay",
"and",
"bisexual",
"and",
"women",
"classified",
"as",
"heterosexual.",
"Men",
"classified",
"as",
"bisexual",
"(OR",
"5.00,",
"1.73–14.51)",
"and",
"women",
"classified",
"as",
"bisexual",
"(OR",
"2.88,",
"1.24-",
"6.56)",
"were",
"more",
"likely",
"than",
"heterosexuals",
"to",
"report",
"more",
"than",
"one",
"sexual",
"partner",
"in",
"the",
"preceding",
"four",
"weeks.",
"Lesbian,",
"gay",
"and",
"bisexual",
"classified",
"people",
"encountered",
"no",
"more",
"sexual",
"function",
"problems",
"than",
"heterosexuals",
"but",
"men",
"classified",
"as",
"bisexual",
"(OR",
"2.74,",
"1.12–6.70)",
"were",
"more",
"dissatisfied",
"with",
"their",
"sex",
"lives.",
"Conclusion:",
"Bisexual",
"and",
"lesbian",
"classified",
"people",
"attending",
"London",
"general",
"practices",
"were",
"more",
"likely",
"to",
"be",
"smokers",
"and",
"gay",
"classified",
"men",
"were",
"at",
"increased",
"risk",
"of",
"psychological",
"distress",
"in",
"comparison",
"to",
"heterosexual",
"classified",
"people.",
"Increased",
"awareness",
"of",
"the",
"sexuality",
"of",
"people",
"seen",
"in",
"primary",
"care",
"can",
"provide",
"opportunities",
"for",
"health",
"promotion.",
"Page",
"1",
"of",
"12",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"ORIGINAL",
"ARTICLE",
"The",
"Effects",
"of",
"a",
"10-Week",
"Water",
"Aerobic",
"Exercise",
"on",
"the",
"Resting",
"Blood",
"Pressure",
"in",
"Patients",
"with",
"Essential",
"Hypertension",
"Ali",
"Vasheghani",
"Farahani",
"1,2,",
"MD;",
"Mohammad-Ali",
"Mansournia*1,",
"MD,",
"MPH;",
"Hossein",
"Asheri1,",
"MD;",
"Akbar",
"Fotouhi3,",
"MD,",
"PhD;",
"Masud",
"Yunesian3,",
"MD,",
"PhD;",
"Mohsen",
"Jamali1,",
"MD;",
"Vahid",
"Ziaee1,",
"MD",
"Authors’",
"Affiliation:",
"1.",
"Sports",
"Medicine",
"Research",
"Center,",
"Tehran",
"University",
"of",
"Medical",
"Sciences,",
"Tehran,",
"IR",
"Iran",
"2.",
"Department",
"of",
"Cardiology,",
"Tehran",
"University",
"of",
"Medical",
"Sciences,",
"Tehran,",
"IR",
"Iran",
"3.",
"School",
"of",
"Public",
"Health,",
"Tehran",
"University",
"of",
"Medical",
"Sciences,",
"Tehran,",
"IR",
"Iran",
"*",
"Corresponding",
"Author;",
"Address:",
"Sports",
"Medicine",
"Research",
"Center,",
"No",
"7,",
"Al-e-Ahmad",
"Highway,",
"P.O.",
"Box",
"14395-578,",
"Tehran,",
"IR",
"Iran",
"E-mail:",
"mansournia_ma@yahoo.com",
"Received:",
"May",
"29,",
"2010",
"Accepted:",
"Jul",
"23,",
"2010",
"Key",
"Words:",
"Water",
"aerobic",
"exercise;",
"Swimming;",
"Essential",
"hypertension;",
"Blood",
"pressure",
"Abstract",
"Purpose:",
"To",
"investigate",
"the",
"effects",
"of",
"a",
"10-week",
"water",
"aerobic",
"exercise",
"on",
"the",
"resting",
"blood",
"pressure",
"in",
"patients",
"with",
"stage",
"1",
"or",
"2",
"hypertension",
"referring",
"to",
"Tehran",
"University",
"Clinics.",
"Methods:",
"Forty",
"men",
"with",
"stage",
"1",
"or",
"2",
"essential",
"hypertension",
"were",
"assigned",
"to",
"two",
"groups",
"of",
"intervention",
"[n=12;",
"aged",
"48.33",
"±",
"10.74",
"years",
"(mean",
"±",
"SD)]",
"and",
"control",
"[n=28;",
"aged",
"46.96",
"±",
"11.58",
"years",
"(mean",
"±",
"SD)].",
"Subjects",
"in",
"the",
"intervention",
"group",
"participated",
"in",
"a",
"supervised",
"10-week",
"water",
"aerobic",
"training",
"program",
"of",
"55",
"min",
"sessions,",
"3",
"days",
"per",
"week",
"on",
"alternate",
"days,",
"while",
"those",
"in",
"the",
"control",
"group",
"were",
"not",
"involved",
"in",
"any",
"regular",
"training",
"program",
"during",
"this",
"period.",
"Blood",
"pressure",
"of",
"the",
"participants",
"was",
"recorded",
"and",
"compared",
"at",
"the",
"beginning",
"and",
"at",
"the",
"end",
"of",
"the",
"study",
"(48",
"hours",
"after",
"the",
"last",
"training",
"session).",
"Results:",
"Exercise",
"lowered",
"systolic",
"blood",
"pressure",
"and",
"mean",
"arterial",
"pressure",
"by",
"11.71",
"(95%",
"confidence",
"interval:",
"5.07",
"to",
"18.35)",
"and",
"5.90",
"(95%",
"confidence",
"interval:",
"1.17",
"to",
"10.63)",
"mm",
"Hg",
"respectively.",
"The",
"lowering",
"effect",
"of",
"exercise",
"on",
"diastolic",
"blood",
"pressure",
"was",
"neither",
"statistically",
"significant",
"nor",
"clinically",
"important",
"(0.55",
"mm",
"Hg;",
"P.",
"value",
"=",
"0.8).",
"There",
"was",
"no",
"significant",
"effect",
"of",
"age,",
"baseline",
"body",
"mass",
"index",
"and",
"stage",
"of",
"hypertension",
"on",
"the",
"exercise-induced",
"changes",
"in",
"blood",
"pressure.",
"Conclusion:",
"A",
"10-week",
"course",
"of",
"water",
"aerobic",
"exercise",
"markedly",
"reduced",
"the",
"systolic",
"and",
"mean",
"arterial",
"blood",
"pressure",
"of",
"patients",
"with",
"essential",
"hypertension",
"and",
"is",
"especially",
"recommended",
"for",
"the",
"obese",
"and",
"the",
"elderly",
"who",
"have",
"orthopedic",
"problems",
"or",
"bronchospasm.",
"Asian",
"Journal",
"of",
"Sports",
"Medicine,",
"Vol",
"1",
"(No",
"3),",
"Sep",
"2010,",
"Pages:",
"159-167",
"159",
"INTRODUCTION",
"Hpressure",
"of",
">=",
"140",
"and/or",
"diastolic",
"blood",
"ypertension,",
"defined",
"as",
"resting",
"systolic",
"blood",
"pressure",
"of",
">=",
"90",
"mmHg,",
"remains",
"the",
"most",
"common",
"risk",
"factor",
"for",
"cardiovascular",
"morbidity",
"and",
"mortality.",
"Currently,",
"more",
"than",
"a",
"quarter",
"of",
"the",
"world",
"adult",
"population",
"suffer",
"from",
"hypertension",
"and",
"it",
"is",
"expected",
"that",
"this",
"number",
"will",
"increase",
"to",
"1.56",
"billion",
"(29%)",
"by",
"2025[1,2].",
"The",
"primary",
"goal",
"of",
"the",
"treatment",
"of",
"©",
"2010",
"by",
"Sports",
"Medicine",
"Research",
"Center,",
"Tehran",
"University",
"of",
"Medical",
"Sciences,",
"All",
"rights",
"reserved."
] | [
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"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"Confocal",
"laser",
"scanning",
"microscopy",
"has",
"revolutionized",
"cell",
"biology.",
"However,",
"the",
"technique",
"has",
"major",
"limitations",
"in",
"speed",
"and",
"sensitivity",
"due",
"to",
"the",
"fact",
"that",
"a",
"single",
"laser",
"beam",
"scans",
"the",
"sample,",
"allowing",
"only",
"a",
"few",
"microseconds",
"signal",
"collection",
"for",
"each",
"pixel.",
"This",
"limitation",
"has",
"been",
"overcome",
"by",
"the",
"introduction",
"of",
"parallel",
"beam",
"illumination",
"techniques",
"in",
"combination",
"with",
"cold",
"CCD",
"camera",
"based",
"image",
"capture.",
"Methods:",
"Using",
"the",
"combination",
"of",
"microlens",
"enhanced",
"Nipkow",
"spinning",
"disc",
"confocal",
"illumination",
"together",
"with",
"fully",
"automated",
"image",
"capture",
"and",
"large",
"scale",
"in",
"silico",
"image",
"processing",
"we",
"have",
"developed",
"a",
"system",
"allowing",
"the",
"acquisition,",
"presentation",
"and",
"analysis",
"of",
"maximum",
"resolution",
"confocal",
"panorama",
"images",
"of",
"several",
"Gigapixel",
"size.",
"We",
"call",
"the",
"method",
"Extended",
"Field",
"Laser",
"Confocal",
"Microscopy",
"(EFLCM).",
"Results:",
"We",
"show",
"using",
"the",
"EFLCM",
"technique",
"that",
"it",
"is",
"possible",
"to",
"create",
"a",
"continuous",
"confocal",
"multi-colour",
"mosaic",
"from",
"thousands",
"of",
"individually",
"captured",
"images.",
"EFLCM",
"can",
"digitize",
"and",
"analyze",
"histological",
"slides,",
"sections",
"of",
"entire",
"rodent",
"organ",
"and",
"full",
"size",
"embryos.",
"It",
"can",
"also",
"record",
"hundreds",
"of",
"thousands",
"cultured",
"cells",
"at",
"multiple",
"wavelength",
"in",
"single",
"event",
"or",
"time-lapse",
"fashion",
"on",
"fixed",
"slides,",
"in",
"live",
"cell",
"imaging",
"chambers",
"or",
"microtiter",
"plates.",
"Conclusion:",
"The",
"observer",
"independent",
"image",
"capture",
"of",
"EFLCM",
"allows",
"quantitative",
"measurements",
"of",
"fluorescence",
"intensities",
"and",
"morphological",
"parameters",
"on",
"a",
"large",
"number",
"of",
"cells.",
"EFLCM",
"therefore",
"bridges",
"the",
"gap",
"between",
"the",
"mainly",
"illustrative",
"fluorescence",
"microscopy",
"and",
"purely",
"quantitative",
"flow",
"cytometry.",
"EFLCM",
"can",
"also",
"be",
"used",
"as",
"high",
"content",
"analysis",
"(HCA)",
"instrument",
"for",
"automated",
"screening",
"processes.",
"Background",
"The",
"introduction",
"of",
"laser",
"scanning",
"confocal",
"fluorescence",
"microscopy",
"represented",
"a",
"major",
"breakthrough",
"in",
"biology.",
"The",
"elimination",
"of",
"the",
"disturbing",
"out",
"of",
"focus",
"light",
"allowed",
"the",
"visualization",
"of",
"delicate",
"sub-cellular",
"struc-",
"tures",
"that",
"were",
"hidden",
"in",
"the",
"blur",
"of",
"thick",
"samples",
"[1-4].",
"Although",
"the",
"technique",
"reveals",
"structures",
"with",
"unprece-",
"dented",
"sharpness,",
"it",
"also",
"suffers",
"from",
"limitations.",
"The",
"images",
"generate",
"by",
"scanning",
"a",
"sample",
"with",
"a",
"single",
"laser",
"beam,",
"where",
"the",
"in-focus",
"signal",
"passes",
"a",
"pinhole",
"and",
"is",
"Page",
"1",
"of",
"13",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"Histochem",
"Cell",
"Biol",
"(2008)",
"129:5–11",
"DOI",
"10.1007/s00418-007-0355-x",
"R",
"E",
"V",
"I",
"E",
"W",
"Physiological",
"importance",
"of",
"RNA",
"and",
"protein",
"mobility",
"in",
"the",
"cell",
"nucleus",
"Tom",
"Misteli",
"Accepted:",
"27",
"October",
"2007",
"/",
"Published",
"online:",
"10",
"November",
"2007",
"©",
"Springer-Verlag",
"2007",
"Abstract",
"TraYcking",
"of",
"proteins",
"and",
"RNAs",
"is",
"essential",
"for",
"cellular",
"function",
"and",
"homeostasis.",
"While",
"it",
"has",
"long",
"been",
"appreciated",
"that",
"proteins",
"and",
"RNAs",
"move",
"within",
"cells,",
"only",
"recently",
"has",
"it",
"become",
"possible",
"to",
"visualize",
"traYcking",
"events",
"in",
"vivo.",
"Analysis",
"of",
"protein",
"and",
"RNA",
"motion",
"within",
"the",
"cell",
"nucleus",
"have",
"been",
"particularly",
"intriguing",
"as",
"they",
"have",
"revealed",
"an",
"unanticipated",
"degree",
"of",
"dynamics",
"within",
"the",
"organelle.",
"These",
"methods",
"have",
"revealed",
"that",
"the",
"intra-",
"nuclear",
"traYcking",
"occurs",
"largely",
"by",
"energy-independent",
"mechanisms",
"and",
"is",
"driven",
"by",
"diVusion.",
"RNA",
"molecules",
"and",
"non-DNA",
"binding",
"proteins",
"undergo",
"constrained",
"diVusion,",
"largely",
"limited",
"by",
"the",
"spatial",
"constraint",
"imposed",
"by",
"chro-",
"matin,",
"and",
"chromatin",
"binding",
"proteins",
"move",
"by",
"a",
"stop-and-",
"go",
"mechanism",
"where",
"their",
"free",
"diVusion",
"is",
"interrupted",
"by",
"random",
"association",
"with",
"the",
"chromatin",
"Wber.",
"The",
"ability",
"and",
"mode",
"of",
"motion",
"of",
"proteins",
"and",
"RNAs",
"has",
"implications",
"for",
"how",
"they",
"Wnd",
"nuclear",
"targets",
"on",
"chromatin",
"and",
"in",
"nuclear",
"subcompartments",
"and",
"how",
"macromolecular",
"com-",
"plexes",
"are",
"assembled",
"in",
"vivo.",
"Most",
"importantly,",
"the",
"dynamic",
"nature",
"of",
"proteins",
"and",
"RNAs",
"is",
"emerging",
"as",
"a",
"means",
"to",
"control",
"physiological",
"cellular",
"responses",
"and",
"path-",
"ways.",
"Keywords",
"Nuclear",
"architecture",
"·",
"Dynamics",
"·",
"DiVusion",
"·",
"RNA",
"T.",
"Misteli",
"(&)",
"National",
"Cancer",
"Institute,",
"National",
"Institutes",
"of",
"Health,",
"41",
"Library",
"Drive,",
"Bethesda,",
"MD",
"20892,",
"USA",
"e-mail:",
"mistelit@mail.nih.gov",
"Introduction",
"It",
"is",
"an",
"irony",
"of",
"science",
"that",
"the",
"discovery",
"of",
"fundamental",
"principles",
"is",
"often",
"delayed.",
"A",
"case",
"in",
"point",
"is",
"the",
"cell",
"bio-",
"logical",
"investigation",
"of",
"the",
"cell",
"nucleus.",
"The",
"nucleus",
"is",
"arguably",
"the",
"functionally",
"most",
"prominent",
"cellular",
"orga-",
"nelle",
"as",
"it",
"houses",
"the",
"vast",
"majority",
"of",
"the",
"genetic",
"informa-",
"tion",
"and",
"is",
"the",
"exclusive",
"site",
"of",
"essential",
"processes",
"including",
"transcription,",
"RNA",
"processing,",
"replication",
"and",
"DNA",
"repair.",
"Yet,",
"our",
"understanding",
"of",
"how",
"the",
"nucleus",
"is",
"organized",
"and",
"how",
"nuclear",
"architecture",
"contributes",
"to",
"cel-",
"lular",
"function",
"is",
"only",
"now",
"emerging",
"and",
"still",
"lags",
"behind",
"that",
"of",
"most",
"other",
"cellular",
"compartments.",
"Fortunately,",
"pioneering",
"studies",
"over",
"the",
"past",
"decade",
"have",
"uncovered",
"several",
"of",
"the",
"fundamental",
"principles",
"which",
"determine",
"nuclear",
"architecture",
"and",
"function",
"(Lanctot",
"et",
"al.",
"2007;",
"Misteli",
"2001;",
"Spector",
"2003).",
"These",
"studies",
"have",
"revealed",
"the",
"presence",
"of",
"distinct",
"structural",
"elements,",
"particularly",
"lamin",
"proteins",
"and",
"possibly",
"short",
"actin",
"Wlaments,",
"within",
"the",
"nucleus",
"and",
"they",
"have",
"led",
"to",
"the",
"identiWcation",
"of",
"a",
"large",
"number",
"of",
"distinct",
"nuclear",
"subcompartments",
"in",
"which",
"speciWc",
"nuclear",
"functions,",
"such",
"as",
"the",
"synthesis",
"and",
"processing",
"of",
"ribosomal",
"RNA",
"in",
"the",
"nucleolus,",
"occur",
"(Burke",
"and",
"Stewart",
"2006;",
"Gruenbaum",
"et",
"al.",
"2005;",
"Hand-",
"werger",
"and",
"Gall",
"2006;",
"Hernandez-Verdun",
"2006;",
"Lamond",
"and",
"Sleeman",
"2003)",
"(Fig.",
"1a).",
"In",
"addition,",
"it",
"has",
"become",
"clear",
"that",
"the",
"genome",
"is",
"non-randomly",
"organized",
"within",
"the",
"spatial",
"conWnes",
"of",
"the",
"nucleus",
"with",
"speciWc",
"chromo-",
"somes",
"and",
"genes",
"preferentially",
"localizing",
"to",
"speciWc",
"sites",
"(Lanctot",
"et",
"al.",
"2007;",
"Meaburn",
"and",
"Misteli",
"2007)",
"(Fig.",
"1b,",
"c).",
"These",
"observations",
"paint",
"a",
"picture",
"of",
"a",
"highly",
"complex",
"and",
"heterogeneous",
"cell",
"nucleus.",
"They",
"also",
"indicate",
"that",
"some",
"properties",
"of",
"the",
"nucleus",
"are",
"counterintuitive.",
"For",
"example,",
"despite",
"the",
"requirement",
"to",
"accommodate",
"»2",
"m",
"of",
"DNA",
"within",
"the",
"cell",
"nucleus",
"of",
"a",
"diameter",
"of",
"typically",
"123"
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] | [
"Hindawi",
"Publishing",
"Corporation",
"Journal",
"of",
"Tropical",
"Medicine",
"Volume",
"2012,",
"Article",
"ID",
"132583,",
"8",
"pages",
"doi:10.1155/2012/132583",
"Clinical",
"Study",
"A",
"Single",
"Dose",
"of",
"Oral",
"BCG",
"Moreau",
"Fails",
"to",
"Boost",
"Systemic",
"IFN-γ",
"Responses",
"to",
"Tuberculin",
"in",
"Children",
"in",
"the",
"Rural",
"Tropics:",
"Evidence",
"for",
"a",
"Barrier",
"to",
"Mucosal",
"Immunization",
"Maritza",
"Vaca,1",
"Ana-Lucia",
"Moncayo,1",
"Catherine",
"A.",
"Cosgrove,2",
"Martha",
"E.",
"Chico,1,",
"3",
"Luiz",
"R.",
"Castello-Branco,4,",
"5",
"David",
"J.",
"Lewis,2",
"and",
"Philip",
"J.",
"Cooper1,",
"3,",
"6,",
"7",
"1",
"Centro",
"de",
"Investigacio´nes",
"FEPIS,",
"Esmeraldas",
"Quinind´e,",
"Ecuador",
"2",
"Vaccine",
"Centre,",
"St",
"George’s",
"University",
"of",
"London,",
"Cranmer",
"Terrace,",
"London",
"SW17",
"ORE,",
"UK",
"3",
"Laboratorio",
"de",
"Biologia",
"Molecular,",
"Hospital",
"de",
"Los",
"Valles,",
"Via",
"Interoceanica",
"Km",
"12.5,",
"Cumbaya´,",
"Quito,",
"Ecuador",
"4",
"Fundacao",
"Ataulpho",
"de",
"Paiva,",
"Avenida",
"Pedro",
"II,",
"226",
"Sao",
"Cristovao,",
"20941-000",
"Rio",
"de",
"Janeiro,",
"RJ,",
"Brazil",
"5",
"Department",
"of",
"Immunology,",
"Fundacao",
"Instituto",
"Oswaldo",
"Cruz,",
"4365",
"Avenida",
"Brasil,",
"21040-360",
"Rio",
"de",
"Janeiro,",
"RJ,",
"Brazil",
"6",
"Molecular",
"and",
"Biochemical",
"Parasitology,",
"Liverpool",
"School",
"of",
"Tropical",
"Medicine,",
"Pembroke",
"Place,",
"Liverpool",
"L3",
"5QA,",
"UK",
"7",
"Colegio",
"de",
"Ciencias",
"de",
"la",
"Salud,",
"Universidad",
"San",
"Francisco",
"de",
"Quito,",
"Via",
"Interoceanica",
"S/N",
"y",
"Avenida",
"Pampite,",
"Quito,",
"Ecuador",
"Correspondence",
"should",
"be",
"addressed",
"to",
"Philip",
"J.",
"Cooper,",
"p.j.cooper@liv.ac.uk",
"Received",
"16",
"May",
"2011;",
"Revised",
"9",
"September",
"2011;",
"Accepted",
"28",
"September",
"2011",
"Academic",
"Editor:",
"Ann-Mari",
"Svennerholm",
"Copyright",
"©",
"2012",
"Maritza",
"Vaca",
"et",
"al.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Immune",
"responses",
"to",
"oral",
"vaccines",
"are",
"impaired",
"in",
"populations",
"living",
"in",
"conditions",
"of",
"poverty",
"in",
"developing",
"countries,",
"and",
"there",
"is",
"evidence",
"that",
"concurrent",
"geohelminth",
"infections",
"may",
"contribute",
"to",
"this",
"effect.",
"We",
"vaccinated",
"48",
"children",
"living",
"in",
"rural",
"communities",
"in",
"Ecuador",
"with",
"a",
"single",
"oral",
"dose",
"of",
"100",
"mg",
"of",
"BCG",
"Moreau",
"RDJ",
"and",
"measured",
"the",
"frequencies",
"of",
"tuberculin-",
"stimulated",
"peripheral",
"blood",
"mononuclear",
"cells",
"expressing",
"IFN-γ",
"before",
"and",
"after",
"vaccination.",
"Vaccinated",
"children",
"had",
"active",
"ascariasis",
"(n",
"=",
"20)",
"or",
"had",
"been",
"infected",
"but",
"received",
"short-",
"(n",
"=",
"13)",
"or",
"long-term",
"(n",
"=",
"15)",
"repeated",
"treatments",
"with",
"albendazole",
"prior",
"to",
"vaccination",
"to",
"treat",
"ascariasis.",
"All",
"children",
"had",
"a",
"BCG",
"scar",
"from",
"neonatal",
"vaccination.",
"There",
"was",
"no",
"evidence",
"of",
"a",
"boosting",
"of",
"postvaccination",
"IFN-γ",
"responses",
"in",
"any",
"of",
"the",
"3",
"study",
"groups.",
"Our",
"data",
"provide",
"support",
"for",
"the",
"presence",
"of",
"a",
"barrier",
"to",
"oral",
"vaccination",
"among",
"children",
"from",
"the",
"rural",
"tropics",
"that",
"appeared",
"to",
"be",
"independent",
"of",
"concurrent",
"ascariasis.",
"1.",
"Introduction",
"The",
"use",
"of",
"oral",
"vaccines",
"in",
"children",
"and",
"adults",
"from",
"poor",
"populations,",
"particularly",
"in",
"the",
"tropics,",
"has",
"been",
"associated",
"with",
"reduced",
"efficacy",
"and",
"impaired",
"immune",
"responses.",
"Impaired",
"immune",
"responses",
"have",
"been",
"reported",
"for",
"both",
"live-attenuated",
"and",
"killed",
"vaccines",
"including",
"Sabin",
"oral",
"polio",
"vaccine",
"[1],",
"rotavirus",
"[2,",
"3],",
"cholera",
"[4],",
"Shigella",
"[2,",
"5],",
"and",
"a",
"killed",
"Vibrio",
"cholerae",
"O1",
"plus",
"B",
"subunit",
"vaccine",
"[6].",
"Such",
"effects",
"are",
"observed",
"at",
"doses",
"that",
"are",
"highly",
"immunogenic",
"in",
"subjects",
"from",
"North",
"America",
"or",
"Europe",
"and,",
"in",
"some",
"circumstances,",
"may",
"be",
"overcome",
"by",
"an",
"increase",
"in",
"the",
"size",
"of",
"vaccine",
"dose",
"or",
"the",
"number",
"of",
"doses",
"administered",
"[4,",
"7–9].",
"Barriers",
"to",
"effective",
"vaccination",
"with",
"oral",
"vaccines",
"in",
"poor",
"populations",
"living",
"in",
"the",
"tropics",
"include",
"nutritional",
"deficiencies",
"(e.g.,",
"vitamin",
"A",
"and",
"zinc),",
"chronic",
"diarrhoea,",
"pre-existing",
"mucosal",
"immunity",
"(e.g.,",
"intestinal",
"secretory",
"IgA),",
"the",
"presence",
"of",
"maternal",
"antibodies",
"in",
"breast",
"milk,",
"environmental",
"enteropathy",
"[3,",
"4],",
"and",
"coinfections",
"with",
"enteric",
"bacterial",
"infections,",
"and",
"protozoal",
"(e.g.,",
"Giardia",
"intestinalis)",
"and",
"geohelminth",
"parasites",
"[10].",
"The",
"geo-",
"helminth",
"parasites,",
"Ascaris",
"lumbricoides,",
"Trichuris",
"trichiura,",
"and",
"hookworm",
"have",
"a",
"worldwide",
"distribution",
"and",
"are",
"strongly",
"associated",
"with",
"poverty.",
"Geohelminths",
"infect",
"an",
"estimated",
"2",
"billion",
"humans",
"[11]",
"and",
"prevalence,",
"in",
"the",
"case",
"of",
"A.",
"lumbricoides,",
"is",
"highest",
"among",
"preschool",
"and",
"school",
"age",
"children.",
"Infections",
"are",
"chronic,",
"tend",
"to",
"be",
"acquired",
"during",
"the",
"second",
"year",
"of",
"life,",
"and",
"may",
"persist",
"into",
"adulthood",
"through",
"residence",
"in",
"an",
"environment",
"that",
"is",
"heavily",
"contaminated",
"with",
"human",
"faeces.",
"Geohelminth"
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701,
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723,
1034
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763,
1034
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1036,
465,
1050
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470,
1036,
530,
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536,
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561,
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615,
1050
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693,
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742,
1050
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533,
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703,
1067
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603,
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564,
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416,
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432,
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460,
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525,
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529,
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577,
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] | [
"Journal",
"of",
"Child",
"Psychology",
"and",
"Psychiatry",
"53:10",
"(2012),",
"pp",
"1082–1083",
"doi:10.1111/j.1469-7610.2012.02610.x",
"Commentary:",
"Unravelling",
"the",
"effects",
"of",
"additional",
"sex",
"chromosomes",
"on",
"cognition",
"and",
"communication",
"–",
"reflections",
"on",
"Lee",
"et",
"al.",
"(2012)",
"Dorothy",
"V.M.",
"Bishop",
"Department",
"of",
"Experimental",
"Psychology,",
"University",
"of",
"Oxford,",
"Oxford,",
"UK",
"Most",
"people",
"have",
"23",
"pairs",
"of",
"chromosomes;",
"one",
"set",
"from",
"the",
"mother",
"and",
"one",
"from",
"the",
"father.",
"However,",
"nondisjunction",
"errors",
"during",
"meiosis",
"can",
"lead",
"to",
"a",
"case",
"of",
"trisomy,",
"where",
"there",
"are",
"three",
"rather",
"than",
"two",
"chromosomes.",
"Although",
"such",
"events",
"are",
"not",
"uncommon,",
"they",
"are",
"usually",
"lethal,",
"and",
"account",
"for",
"a",
"high",
"proportion",
"of",
"spontaneous",
"abortions.",
"The",
"most",
"common",
"trisomy",
"compatible",
"with",
"survival",
"to",
"birth",
"involves",
"chromosome",
"21,",
"one",
"of",
"the",
"smallest",
"chromosomes.",
"This",
"is",
"associated",
"with",
"serious",
"developmental",
"abnormalities",
"affecting",
"a",
"range",
"of",
"organs",
"(Down",
"syndrome).",
"In",
"comparison,",
"the",
"effects",
"of",
"a",
"sex",
"chromosome",
"trisomy",
"are",
"relatively",
"mild.",
"Most",
"children",
"with",
"XXX,",
"XXY",
"or",
"XYY",
"constitutions",
"attend",
"regular",
"school",
"and,",
"apart",
"from",
"a",
"tendency",
"to",
"be",
"somewhat",
"taller",
"than",
"average,",
"appear",
"physically",
"normal.",
"The",
"reason",
"for",
"this",
"can",
"be",
"found",
"in",
"the",
"peculiar",
"nature",
"of",
"the",
"sex",
"chromosomes.",
"The",
"Y",
"chromosome",
"is",
"very",
"small",
"and",
"is",
"thought",
"to",
"contain",
"fewer",
"than",
"100",
"genes,",
"com-",
"pared",
"with",
"over",
"1000",
"on",
"the",
"X",
"chromosome.",
"All",
"else",
"being",
"equal,",
"females",
"should",
"have",
"considerably",
"more",
"gene",
"product",
"than",
"males.",
"However,",
"in",
"normal",
"XX",
"females,",
"most",
"of",
"one",
"X-chromosome",
"is",
"inactivated.",
"A",
"process",
"of",
"methylation",
"causes",
"the",
"DNA",
"to",
"be",
"packed",
"in",
"a",
"tight",
"ball,",
"preventing",
"gene",
"expression.",
"This",
"process",
"of",
"‘dosage",
"compensation’",
"has",
"the",
"effect",
"of",
"reducing",
"the",
"difference",
"between",
"males",
"and",
"females",
"in",
"amount",
"of",
"gene",
"product.",
"X-inactivation",
"is",
"not",
"complete;",
"there",
"are",
"regions",
"on",
"the",
"tips",
"of",
"the",
"sex",
"chromosomes",
"that",
"remain",
"active",
"and",
"behave",
"just",
"like",
"autosomes;",
"these",
"are",
"referred",
"to",
"as",
"the",
"pseudoautosomal",
"region.",
"In",
"addition,",
"there",
"are",
"areas",
"of",
"the",
"X-chromosome",
"outside",
"the",
"pseudoaut-",
"osomal",
"region",
"that",
"escape",
"inactivation,",
"where",
"both",
"copies",
"of",
"a",
"gene",
"are",
"expressed.",
"There",
"appears",
"to",
"be",
"quite",
"substantial",
"individual",
"variation",
"in",
"the",
"number",
"and",
"location",
"of",
"genes",
"that",
"escape",
"inactivation.",
"If",
"we",
"put",
"these",
"pieces",
"of",
"information",
"together,",
"we",
"start",
"to",
"see",
"why",
"the",
"impact",
"of",
"an",
"additional",
"sex",
"chromosome",
"is",
"relatively",
"mild.",
"For",
"boys",
"with",
"XYY",
"constitution,",
"the",
"additional",
"Y",
"chromosome",
"contains",
"relatively",
"few",
"genes.",
"For",
"girls",
"or",
"boys",
"with",
"an",
"extra",
"X,",
"only",
"one",
"X",
"chromosome",
"is",
"completely",
"activated,",
"and",
"so",
"a",
"minority",
"of",
"X-linked",
"genes",
"are",
"expressed",
"in",
"extra",
"dose.",
"The",
"author",
"has",
"declared",
"that",
"she",
"has",
"no",
"competing",
"or",
"poten-",
"tial",
"conflicts",
"of",
"interest.",
"Nevertheless,",
"there",
"are",
"cognitive",
"impacts",
"of",
"an",
"extra",
"sex",
"chromosome,",
"as",
"discussed",
"in",
"the",
"article",
"by",
"Lee",
"et",
"al.",
"(2012),",
"with",
"intriguing",
"differences",
"between",
"those",
"with",
"an",
"extra",
"X",
"or",
"Y.",
"There",
"is",
"surprisingly",
"little",
"research",
"on",
"sex",
"chromosome",
"trisomies:",
"The",
"expla-",
"nation",
"is",
"largely",
"due",
"to",
"the",
"mild",
"impact",
"of",
"the",
"tri-",
"somy,",
"which",
"means",
"that",
"many",
"people",
"who",
"have",
"a",
"sex",
"chromosome",
"trisomy",
"would",
"not",
"be",
"aware",
"of",
"their",
"status.",
"Most",
"of",
"the",
"information",
"we",
"have",
"about",
"prev-",
"alence",
"and",
"consequences",
"of",
"sex",
"chromosome",
"triso-",
"mies",
"comes",
"from",
"a",
"set",
"of",
"studies",
"carried",
"out",
"in",
"the",
"1960–1970s",
"in",
"which",
"newborn",
"babies",
"underwent",
"chromosome",
"screening.",
"Such",
"studies",
"are",
"unlikely",
"to",
"be",
"repeated",
"now",
"for",
"two",
"reasons.",
"First,",
"they",
"are",
"highly",
"labour-intensive:",
"given",
"that,",
"for",
"instance,",
"XXX",
"chromosome",
"constitution",
"is",
"found",
"in",
"around",
"1",
"in",
"1,000",
"girls,",
"this",
"means",
"we",
"would",
"have",
"to",
"screen",
"10,000",
"cases",
"to",
"get",
"a",
"sample",
"of",
"just",
"10",
"affected",
"cases.",
"Research",
"is",
"also",
"limited",
"by",
"ethical",
"concerns.",
"The",
"studies",
"done",
"in",
"the",
"1960s",
"proved",
"problematic",
"as",
"the",
"researchers",
"started",
"to",
"realise",
"that",
"telling",
"parents",
"that",
"their",
"newborn",
"child",
"had",
"a",
"sex",
"chromosome",
"tri-",
"somy",
"was",
"bound",
"to",
"cause",
"anxiety",
"and",
"distress,",
"especially",
"since",
"information",
"about",
"its",
"likely",
"impact",
"was",
"so",
"uncertain.",
"Findings",
"from",
"the",
"newborn",
"screening",
"studies",
"were",
"summarized",
"in",
"a",
"systematic",
"review",
"by",
"Leggett,",
"Jacobs,",
"Nation,",
"Scerif,",
"and",
"Bishop",
"(2010),",
"who",
"noted",
"a",
"reduction",
"in",
"IQ",
"in",
"XXX,",
"XXY",
"and",
"XYY",
"groups,",
"with",
"both",
"groups",
"of",
"males",
"showing",
"evidence",
"of",
"disproportionate",
"verbal",
"impairments.",
"Such",
"deficits",
"are",
"assumed",
"to",
"be",
"caused",
"by",
"the",
"excess",
"proteins",
"that",
"arise",
"from",
"supernumerary",
"X-",
"or",
"Y-",
"linked",
"genes",
"that",
"escape",
"inactivation.",
"The",
"report",
"by",
"Lee",
"et",
"al.",
"makes",
"a",
"unique",
"contribu-",
"tion",
"by",
"extending",
"the",
"study",
"of",
"the",
"impact",
"of",
"super-",
"numerary",
"sex",
"chromosomes",
"to",
"include",
"rare",
"cases",
"of",
"children",
"with",
"four",
"or",
"five",
"sex",
"chromosomes.",
"They",
"demonstrate",
"a",
"clear",
"‘dosage’",
"effect,",
"whereby",
"the",
"more",
"chromosomes,",
"the",
"greater",
"the",
"negative",
"impact",
"on",
"IQ",
"and",
"development.",
"Each",
"additional",
"X-",
"or",
"Y-",
"chromosome",
"was",
"associated",
"with",
"a",
"decrease",
"in",
"IQ",
"of",
"around",
"1",
"SD.",
"Intriguingly,",
"they",
"also",
"found",
"that",
"additional",
"X",
"chromosomes",
"had",
"a",
"greater",
"effect",
"on",
"structural",
"language",
"skills,",
"whereas",
"additional",
"Y",
"chromosomes",
"had",
"disproportionate",
"effect",
"on",
"prag-",
"matic",
"problems",
"and",
"autistic",
"features.",
"It",
"should",
"be",
"noted,",
"however,",
"that",
"those",
"with",
"extra",
"X",
"chromo-",
"somes",
"included",
"both",
"girls",
"and",
"boys,",
"whereas",
"the",
"extra-Y",
"chromosome",
"group",
"were",
"all",
"male.",
"Bishop",
"2012",
"The",
"Authors.",
"Journal",
"of",
"Child",
"Psychology",
"and",
"Psychiatry",
"2012",
"Association",
"for",
"Child",
"and",
"Adolescent",
"Mental",
"Health.",
"Published",
"by",
"Blackwell",
"Publishing,",
"9600",
"Garsington",
"Road,",
"Oxford",
"OX4",
"2DQ,",
"UK",
"and",
"350",
"Main",
"St,",
"Malden,",
"MA",
"02148,",
"USA"
] | [
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] | [
"Osteoporos",
"Int",
"(2012)",
"23:2219–2226",
"DOI",
"10.1007/s00198-011-1854-0",
"ORIGINAL",
"ARTICLE",
"Growth",
"hormone",
"effects",
"on",
"cortical",
"bone",
"dimensions",
"in",
"young",
"adults",
"with",
"childhood-onset",
"growth",
"hormone",
"deficiency",
"L.",
"Hyldstrup",
"&",
"G.",
"S.",
"Conway",
"&",
"K.",
"Racz",
"&",
"A.",
"Keller",
"&",
"P.",
"Chanson",
"&",
"M.",
"Zacharin",
"&",
"A.",
"L.",
"Lysgaard",
"&",
"A.",
"H.",
"Andreasen",
"&",
"A.-M.",
"Kappelgaard",
"Received:",
"11",
"August",
"2011",
"/",
"Accepted:",
"26",
"October",
"2011",
"/",
"Published",
"online:",
"29",
"November",
"2011",
"#",
"The",
"Author(s)",
"2011.",
"This",
"article",
"is",
"published",
"with",
"open",
"access",
"at",
"Springerlink.com",
"Abstract",
"Summary",
"Growth",
"hormone",
"(GH)",
"treatment",
"in",
"young",
"adults",
"with",
"childhood-onset",
"GH",
"deficiency",
"has",
"beneficial",
"effects",
"on",
"bone",
"mass.",
"The",
"present",
"study",
"shows",
"that",
"cortical",
"bone",
"dimensions",
"also",
"benefit",
"from",
"GH",
"treatment,",
"with",
"endosteal",
"L.",
"Hyldstrup",
"(*)",
":",
"A.",
"L.",
"Lysgaard",
"Department",
"of",
"Endocrinology",
"(541),",
"Hvidovre",
"University",
"Hospital,",
"DK-2650",
"Hvidovre,",
"Denmark",
"e-mail:",
"hyld@dadlnet.dk",
"G.",
"S.",
"Conway",
"Department",
"of",
"Endocrinology",
"and",
"Diabetes,",
"University",
"College",
"London",
"Hospitals,",
"London,",
"UK",
"K.",
"Racz",
"2nd",
"Department",
"of",
"Medicine,",
"Semmelweis",
"University,",
"Budapest,",
"Hungary",
"A.",
"Keller",
"Children’s",
"Hospital,",
"University",
"of",
"Leipzig,",
"Leipzig,",
"Germany",
"P.",
"Chanson",
"Service",
"d’Endocrinologie",
"et",
"des",
"Maladies",
"de",
"la",
"Reproduction,",
"and",
"Centre",
"de",
"Référence",
"des",
"Maladies",
"Endocriniennes",
"Rares",
"de",
"la",
"Croissance,",
"Assistance-Publique",
"Hôpitaux",
"de",
"Paris,",
"Hôpital",
"de",
"Bicêtre,",
"University",
"Paris-Sud,",
"Le",
"Kremlin-Bicêtre,",
"France",
"M.",
"Zacharin",
"Department",
"of",
"Endocrinology",
"and",
"Diabetes,",
"Royal",
"Children’s",
"Hospital,",
"Parkville,",
"VIC,",
"Australia",
"A.",
"H.",
"Andreasen",
":",
"A.-M.",
"Kappelgaard",
"GHT",
"Medical",
"Affairs,",
"Global",
"Marketing,",
"Novo",
"Nordisk,",
"Bagsvaerd,",
"Denmark",
"expansion",
"and",
"increased",
"cortical",
"thickness",
"leading",
"to",
"improved",
"bone",
"strength.",
"Introduction",
"In",
"young",
"adults",
"with",
"childhood-onset",
"growth",
"hormone",
"deficiency",
"(CO",
"GHD),",
"GH",
"treatment",
"after",
"final",
"height",
"is",
"reached",
"has",
"been",
"shown",
"to",
"have",
"beneficial",
"effects",
"on",
"spine",
"and",
"hip",
"bone",
"mineral",
"density.",
"The",
"objective",
"of",
"the",
"study",
"was",
"to",
"evaluate",
"the",
"influence",
"of",
"GH",
"on",
"cortical",
"bone",
"dimensions.",
"Methods",
"Patients",
"(n",
"=",
"160;",
"mean",
"age,",
"21.2",
"years;",
"63%",
"males)",
"with",
"CO",
"GHD",
"were",
"randomised",
"2:1",
"to",
"GH",
"or",
"no",
"treatment",
"for",
"24",
"months.",
"Cortical",
"bone",
"dimensions",
"were",
"evaluated",
"by",
"digital",
"x-ray",
"radiogrammetry",
"of",
"the",
"metacar-",
"pal",
"bones",
"every",
"6",
"months.",
"Results",
"After",
"24",
"months,",
"cortical",
"thickness",
"was",
"increased",
"compared",
"with",
"the",
"controls",
"(6.43%,",
"CI",
"3.34",
"to",
"9.61%;",
"p=",
"0.0001)",
"and",
"metacarpal",
"index",
"(MCI)",
"(6.14%,",
"CI",
"3.95",
"to",
"8.38%;",
"p<0.0001),",
"while",
"the",
"endosteal",
"diameter",
"decreased",
"(−4.64%,",
"CI",
"−7.15",
"to",
"−2.05;",
"p<0.001).",
"Total",
"bone",
"width",
"did",
"not",
"change",
"significantly",
"(0.68%,",
"CI",
"−1.17",
"to",
"2.57%;",
"not",
"significant",
"(NS)).",
"A",
"gender",
"effect",
"was",
"seen",
"on",
"bone",
"width",
"(p",
"<",
"0.0001),",
"endosteal",
"diameter",
"(p",
"<",
"0.01)",
"and",
"cortical",
"thickness",
"(p<0.01),",
"but",
"not",
"with",
"MCI",
"(NS).",
"Conclusions",
"Cortical",
"bone",
"reacts",
"promptly",
"to",
"reinstitution",
"of",
"GH",
"beyond",
"the",
"attainment",
"of",
"final",
"height",
"by",
"increasing",
"the",
"cortical",
"thickness",
"through",
"endosteal",
"bone",
"growth.",
"This",
"leads",
"to",
"a",
"higher",
"peak",
"bone",
"mass",
"and",
"may",
"reduce",
"the",
"risk",
"of",
"cortical",
"bone",
"fragility",
"later",
"in",
"life.",
"Keywords",
"Bone",
"strength",
".",
"Cortical",
"bone",
".",
"Growth",
"hormone",
"deficiency",
".",
"Growth",
"hormone",
"treatment",
".",
"Metacarpal",
"index",
"Introduction",
"Young",
"adults",
"with",
"childhood-onset",
"growth",
"hormone",
"defi-",
"ciency",
"(CO",
"GHD)",
"have",
"lower",
"bone",
"mineral",
"density",
"than"
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] | [
"BMC",
"Public",
"Health",
"Research",
"article",
"Improvements",
"in",
"readiness",
"to",
"change",
"and",
"drinking",
"in",
"primary",
"care",
"patients",
"with",
"unhealthy",
"alcohol",
"use:",
"a",
"prospective",
"study",
"Nicolas",
"Bertholet*1,2,",
"Nicholas",
"J",
"Horton3",
"and",
"Richard",
"Saitz1,4,5",
"BioMed",
"Central",
"Open",
"Access",
"Address:",
"1Clinical",
"Addiction",
"Research",
"and",
"Education",
"(CARE)",
"Unit,",
"Section",
"of",
"General",
"Internal",
"Medicine,",
"Boston",
"Medical",
"Center,",
"Boston",
"University",
"School",
"of",
"Medicine,",
"Boston,",
"Massachusetts,",
"USA,",
"2Clinical",
"Epidemiology",
"Center,",
"Institute",
"of",
"Social",
"and",
"Preventive",
"Medicine,",
"Centre",
"Hospitalier",
"Universitaire",
"Vaudois,",
"University",
"of",
"Lausanne,",
"Lausanne,",
"Switzerland,",
"3Department",
"of",
"Mathematics",
"and",
"Statistics,",
"Smith",
"College,",
"Northampton,",
"Massachusetts,",
"USA,",
"4Youth",
"Alcohol",
"Prevention",
"Center,",
"Boston",
"University",
"School",
"of",
"Public",
"Health,",
"Boston,",
"Massachusetts,",
"USA",
"and",
"5Department",
"of",
"Epidemiology,",
"Boston",
"University",
"School",
"of",
"Public",
"Health,",
"Boston,",
"Massachusetts,",
"USA",
"Email:",
"Nicolas",
"Bertholet*",
"-",
"nberthol@bu.edu;",
"Nicholas",
"J",
"Horton",
"-",
"nhorton@email.smith.edu;",
"Richard",
"Saitz",
"-",
"rsaitz@bu.edu",
"*",
"Corresponding",
"author",
"Published:",
"9",
"April",
"2009",
"BMC",
"Public",
"Health",
"2009,",
"9:101",
"doi:10.1186/1471-2458-9-101",
"This",
"article",
"is",
"available",
"from:",
"http://www.biomedcentral.com/1471-2458/9/101",
"Received:",
"17",
"September",
"2008",
"Accepted:",
"9",
"April",
"2009",
"©",
"2009",
"Bertholet",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"The",
"course",
"of",
"alcohol",
"consumption",
"and",
"cognitive",
"dimensions",
"of",
"behavior",
"change",
"(readiness",
"to",
"change,",
"importance",
"of",
"changing",
"and",
"confidence",
"in",
"ability",
"to",
"change)",
"in",
"primary",
"care",
"patients",
"are",
"not",
"well",
"described.",
"The",
"objective",
"of",
"the",
"study",
"was",
"to",
"determine",
"changes",
"in",
"readiness,",
"importance",
"and",
"confidence",
"after",
"a",
"primary",
"care",
"visit,",
"and",
"6-month",
"improvements",
"in",
"both",
"drinking",
"and",
"cognitive",
"dimensions",
"of",
"behavior",
"change,",
"in",
"patients",
"with",
"unhealthy",
"alcohol",
"use.",
"Methods:",
"Prospective",
"cohort",
"study",
"of",
"patients",
"with",
"unhealthy",
"alcohol",
"use",
"visiting",
"primary",
"care",
"physicians,",
"with",
"repeated",
"assessments",
"of",
"readiness,",
"importance,",
"and",
"confidence",
"(visual",
"analogue",
"scale",
"(VAS),",
"score",
"range",
"1–10",
"points).",
"Improvements",
"6",
"months",
"later",
"were",
"defined",
"as",
"no",
"unhealthy",
"alcohol",
"use",
"or",
"any",
"increase",
"in",
"readiness,",
"importance,",
"or",
"confidence.",
"Regression",
"models",
"accounted",
"for",
"clustering",
"by",
"physician",
"and",
"adjusted",
"for",
"demographics,",
"alcohol",
"consumption",
"and",
"related",
"problems,",
"and",
"discussion",
"with",
"the",
"physician",
"about",
"alcohol.",
"Results:",
"From",
"before",
"to",
"immediately",
"after",
"the",
"primary",
"care",
"physician",
"visit,",
"patients",
"(n",
"=",
"173)",
"had",
"increases",
"in",
"readiness",
"(mean",
"+1.0",
"point),",
"importance",
"(+0.2),",
"and",
"confidence",
"(+0.5)",
"(all",
"p",
"<",
"0.002).",
"In",
"adjusted",
"models,",
"discussion",
"with",
"the",
"physician",
"about",
"alcohol",
"was",
"associated",
"with",
"increased",
"readiness",
"(+0.8,",
"p",
"=",
"0.04).",
"At",
"6",
"months,",
"many",
"participants",
"had",
"improvements",
"in",
"drinking",
"or",
"readiness",
"(62%),",
"drinking",
"or",
"importance",
"(58%),",
"or",
"drinking",
"or",
"confidence",
"(56%).",
"Conclusion:",
"Readiness,",
"importance",
"and",
"confidence",
"improve",
"in",
"many",
"patients",
"with",
"unhealthy",
"alcohol",
"use",
"immediately",
"after",
"a",
"primary",
"care",
"visit.",
"Six",
"months",
"after",
"a",
"visit,",
"most",
"patients",
"have",
"improvements",
"in",
"either",
"drinking",
"or",
"these",
"cognitive",
"dimensions",
"of",
"behavior",
"change.",
"Background",
"Unhealthy",
"alcohol",
"use",
"(the",
"spectrum",
"from",
"at-risk",
"drink-",
"ing",
"amounts",
"through",
"alcohol",
"dependence)",
"and",
"its",
"conse-",
"quences",
"represent",
"a",
"major",
"burden",
"of",
"disease",
"in",
"the",
"general",
"population",
"[1,2].",
"Among",
"those",
"with",
"unhealthy",
"alcohol",
"use,",
"brief",
"intervention",
"(BI)",
"and",
"motivational",
"interviewing",
"have",
"demonstrated",
"evidence",
"of",
"efficacy",
"[3-5].",
"In",
"primary",
"care,",
"BI",
"is",
"recommended",
"by",
"national",
"practice",
"guidelines",
"(US",
"Preventive",
"Services",
"Task",
"Force,",
"2004),",
"and,",
"as",
"part",
"of",
"BI,",
"clinicians",
"are",
"encouraged",
"to",
"assess",
"motivation",
"and",
"Page",
"1",
"of",
"9",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"Voss",
"and",
"Entschladen",
"Cell",
"Communication",
"and",
"Signaling",
"2010,",
"8:21",
"http://www.biosignaling.com/content/8/1/21",
"R",
"E",
"V",
"I",
"E",
"W",
"Open",
"Access",
"Tumor",
"interactions",
"with",
"soluble",
"factors",
"and",
"the",
"nervous",
"system",
"Melanie",
"J",
"Voss,",
"Frank",
"Entschladen*",
"Abstract",
"In",
"the",
"genomic",
"era",
"of",
"cancer",
"research,",
"the",
"development",
"of",
"metastases",
"has",
"been",
"attributed",
"to",
"mutations",
"in",
"the",
"tumor",
"that",
"enable",
"the",
"cells",
"to",
"migrate.",
"However,",
"gene",
"analyses",
"revealed",
"that",
"primary",
"tumors",
"and",
"metastases",
"were",
"in",
"some",
"cases",
"genetically",
"identical",
"and",
"the",
"question",
"was",
"raised",
"whether",
"metastasis",
"formation",
"might",
"be",
"an",
"inher-",
"ent",
"feature",
"of",
"certain",
"tumor",
"cells.",
"In",
"contradiction",
"to",
"this",
"view,",
"the",
"last",
"decade",
"of",
"cancer",
"research",
"has",
"brought",
"to",
"light,",
"that",
"tumor",
"cell",
"migration,",
"similar",
"to",
"leukocyte",
"and",
"fibroblast",
"migration,",
"is",
"a",
"highly",
"regulated",
"process.",
"The",
"ner-",
"vous",
"system",
"plays",
"an",
"important",
"role",
"in",
"this",
"regulation,",
"at",
"least",
"in",
"two",
"respects:",
"firstly,",
"neurotransmitters",
"are",
"known",
"to",
"regulate",
"the",
"migratory",
"activity",
"of",
"tumor",
"cells,",
"and",
"secondly,",
"nerve",
"fibers",
"are",
"used",
"as",
"routes",
"for",
"perineural",
"inva-",
"sion.",
"We",
"also",
"summarize",
"here",
"the",
"current",
"knowledge",
"on",
"the",
"innervation",
"of",
"tumors.",
"Such",
"a",
"process",
"might",
"establish",
"a",
"neuro-neoplastic",
"synapse,",
"with",
"the",
"close",
"interaction",
"of",
"tumor",
"cells",
"and",
"nerve",
"cells",
"supporting",
"metastasis",
"formation.",
"Introduction",
"In",
"January",
"1971,",
"the",
"US",
"president",
"Richard",
"Nixon",
"intro-",
"duced",
"in",
"his",
"State",
"of",
"the",
"Union",
"Address",
"the",
"‘War",
"on",
"Cancer’",
"with",
"the",
"aim",
"to",
"find",
"ways",
"to",
"cure",
"cancer",
"within",
"the",
"next",
"25",
"years.",
"Although",
"significant",
"efforts",
"and",
"advances",
"have",
"been",
"made",
"since",
"then,",
"we",
"are",
"still",
"in",
"a",
"war",
"with",
"cancer",
"and",
"far",
"away",
"from",
"a",
"definite",
"victory.",
"With",
"reference",
"to",
"president",
"Nixon’s",
"State",
"of",
"the",
"Union",
"Address,",
"Michael",
"Sporn",
"published",
"an",
"article",
"in",
"The",
"Lancet",
"in",
"1996,",
"in",
"which",
"he",
"reviewed",
"the",
"progress",
"that",
"was",
"made",
"since",
"1971,",
"and",
"he",
"pointed",
"out",
"the",
"future",
"goals",
"of",
"cancer",
"research",
"[1].",
"One",
"key",
"statement",
"of",
"this",
"article",
"was:",
"“It",
"is",
"local",
"invasion",
"and",
"distant",
"metastasis",
"that",
"kill",
"rather",
"than",
"excessive",
"cell",
"proliferation",
"per",
"se.”",
"In",
"fact",
"today",
"over",
"90",
"percent",
"of",
"those",
"patients",
"that",
"die",
"from",
"their",
"cancer",
"disease",
"do",
"not",
"die",
"due",
"to",
"the",
"primary",
"tumor",
"but",
"due",
"to",
"the",
"development",
"of",
"metastases.",
"Thus,",
"there",
"is",
"a",
"pressing",
"need",
"of",
"research",
"on",
"how",
"metastases",
"occur,",
"and",
"on",
"ways",
"to",
"prevent",
"or",
"treat",
"this",
"ultimate",
"step",
"in",
"cancer",
"progression.",
"The",
"end",
"of",
"the",
"previous",
"century",
"was",
"called",
"the",
"geno-",
"mic",
"era",
"with",
"respect",
"not",
"only",
"to",
"cancer",
"research.",
"Deci-",
"phering",
"the",
"human",
"genome",
"was",
"probably",
"the",
"most",
"ambitious",
"project,",
"which",
"actually",
"succeeded",
"in",
"the",
"year",
"*",
"Correspondence:",
"entschladen@uni-wh.de",
"Institute",
"of",
"Immunology,",
"ZBAF,",
"Witten/Herdecke",
"University,",
"Stockumer",
"Str.",
"10,",
"58448",
"Witten,",
"Germany",
"2000",
"[2].",
"At",
"this",
"time,",
"genetic",
"models",
"for",
"the",
"develop-",
"ment",
"of",
"cancer",
"have",
"been",
"established",
"which",
"have",
"deliv-",
"ered",
"a",
"molecular",
"fundament",
"for",
"the",
"understanding",
"of",
"processes",
"in",
"cancer",
"cells.",
"One",
"of",
"the",
"earliest",
"and",
"most",
"famous",
"is",
"the",
"model",
"by",
"Fearon",
"and",
"Vogelstein",
"(1990)",
"which",
"gives",
"a",
"precise",
"line",
"of",
"genetic",
"events",
"that",
"occur",
"during",
"the",
"transformation",
"of",
"normal",
"colon",
"epithelium",
"to",
"a",
"carcinoma",
"[3].",
"However,",
"this",
"model",
"of",
"colorectal",
"tumorigenesis",
"does",
"not",
"specify",
"mutations",
"that",
"may",
"con-",
"stitute",
"the",
"step",
"from",
"carcinoma",
"to",
"metastasis.",
"Since",
"then",
"a",
"still",
"ongoing",
"debate",
"was",
"raised",
"to",
"what",
"extent",
"metastasis",
"formation",
"might",
"be",
"genetically",
"determined.",
"Bernards",
"and",
"Weinberg",
"provided",
"a",
"concept",
"that",
"the",
"ten-",
"dency",
"to",
"metastasize",
"is",
"acquired",
"early",
"in",
"tumorigenesis",
"[4].",
"This",
"assumption",
"is",
"based",
"on",
"observations",
"that",
"pri-",
"mary",
"tumors",
"are",
"genetically",
"similar",
"or",
"maybe",
"even",
"equal",
"to",
"their",
"metastases.",
"However,",
"some",
"genes",
"have",
"been",
"identified",
"that",
"are",
"associated",
"with",
"metastasis",
"formation.",
"For",
"example,",
"the",
"analysis",
"of",
"the",
"Smad4",
"gene",
"in",
"colorec-",
"tal",
"carcinomas",
"showed",
"mutations",
"in",
"7",
"percent",
"of",
"the",
"samples",
"of",
"primary",
"invasive",
"carcinoma",
"without",
"distant",
"metastasis,",
"but",
"mutations",
"in",
"35",
"percent",
"of",
"the",
"samples",
"of",
"primary",
"invasive",
"carcinoma",
"with",
"distant",
"metastasis",
"[5].",
"In",
"2008,",
"MACC1,",
"a",
"yet",
"largely",
"uncharacterized",
"pro-",
"tein",
"with",
"putative",
"adaptor",
"function,",
"was",
"also",
"shown",
"to",
"be",
"a",
"prominent",
"driver",
"of",
"colorectal",
"metastasis",
"[6].",
"More",
"recently",
"an",
"amplification",
"of",
"the",
"MTDH",
"gene",
"encoding",
"©",
"2010",
"Voss",
"and",
"Entschladen;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Vera",
"et",
"al.",
"BMC",
"Research",
"Notes",
"2011,",
"4:415",
"http://www.biomedcentral.com/1756-0500/4/415",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"A",
"R",
"T",
"I",
"C",
"L",
"E",
"Open",
"Access",
"Prolonged",
"exposure",
"for",
"the",
"treatment",
"of",
"Spanish-",
"speaking",
"Puerto",
"Ricans",
"with",
"posttraumatic",
"stress",
"disorder:",
"a",
"feasibility",
"study",
"Mildred",
"Vera1*,",
"María",
"L",
"Reyes-Rabanillo2,",
"Deborah",
"Juarbe3,",
"Coralee",
"Pérez-Pedrogo3,",
"Alicia",
"Olmo2,",
"Rafael",
"Kichic4",
"and",
"William",
"F",
"Chaplin5",
"Abstract",
"Background:",
"Most",
"of",
"the",
"empirical",
"studies",
"that",
"support",
"the",
"efficacy",
"of",
"prolonged",
"exposure",
"(PE)",
"for",
"treating",
"posttraumatic",
"stress",
"disorder",
"(PTSD)",
"have",
"been",
"conducted",
"on",
"white",
"mainstream",
"English-speaking",
"populations.",
"Although",
"high",
"PTSD",
"rates",
"have",
"been",
"reported",
"for",
"Puerto",
"Ricans,",
"the",
"appropriateness",
"of",
"PE",
"for",
"this",
"population",
"remains",
"unclear.",
"The",
"purpose",
"of",
"this",
"study",
"was",
"to",
"examine",
"the",
"feasibility",
"of",
"providing",
"PE",
"to",
"Spanish",
"speaking",
"Puerto",
"Ricans",
"with",
"PTSD.",
"Particular",
"attention",
"was",
"also",
"focused",
"on",
"identifying",
"challenges",
"faced",
"by",
"clinicians",
"with",
"limited",
"experience",
"in",
"PE.",
"This",
"information",
"is",
"relevant",
"to",
"help",
"inform",
"practice",
"implications",
"for",
"training",
"Spanish-",
"speaking",
"clinicians",
"in",
"PE.",
"Results:",
"Fourteen",
"patients",
"with",
"PTSD",
"were",
"randomly",
"assigned",
"to",
"receive",
"PE",
"(n",
"=",
"7)",
"or",
"usual",
"care",
"(UC)",
"(n",
"=",
"7).",
"PE",
"therapy",
"consisted",
"of",
"15",
"weekly",
"sessions",
"focused",
"on",
"gradually",
"confronting",
"and",
"emotionally",
"processing",
"distressing",
"trauma-related",
"memories",
"and",
"reminders.",
"Five",
"patients",
"completed",
"PE",
"treatment;",
"all",
"patients",
"attended",
"the",
"15",
"sessions",
"available",
"to",
"them.",
"In",
"UC,",
"patients",
"received",
"mental",
"health",
"services",
"available",
"within",
"the",
"health",
"care",
"setting",
"where",
"they",
"were",
"recruited.",
"They",
"also",
"had",
"the",
"option",
"of",
"self-referring",
"to",
"a",
"mental",
"health",
"provider",
"outside",
"the",
"study",
"setting.",
"The",
"Clinician-Administered",
"PTSD",
"Scale",
"(CAPS)",
"was",
"administered",
"at",
"baseline,",
"mid-treatment,",
"and",
"post-",
"treatment",
"to",
"assess",
"PTSD",
"symptom",
"severity.",
"Treatment",
"completers",
"in",
"the",
"PE",
"group",
"demonstrated",
"significantly",
"greater",
"reductions",
"in",
"PTSD",
"symptoms",
"than",
"the",
"UC",
"group.",
"Forty",
"percent",
"of",
"the",
"PE",
"patients",
"showed",
"clinically",
"meaningful",
"reductions",
"in",
"PTSD",
"symptoms",
"from",
"pre-",
"to",
"post-treatment.",
"Conclusions:",
"PE",
"appears",
"to",
"be",
"viable",
"for",
"treating",
"Puerto",
"Rican",
"Spanish-speaking",
"patients",
"with",
"PTSD.",
"This",
"therapy",
"had",
"good",
"patient",
"acceptability",
"and",
"led",
"to",
"improvements",
"in",
"PTSD",
"symptoms.",
"Attention",
"to",
"the",
"clinicians’",
"training",
"process",
"contributed",
"strongly",
"to",
"helping",
"them",
"overcome",
"the",
"challenges",
"posed",
"by",
"the",
"intervention",
"and",
"increased",
"their",
"acceptance",
"of",
"PE.",
"Background",
"Exposure",
"therapy",
"and",
"posttraumatic",
"stress",
"disorder",
"Prolonged",
"exposure",
"(PE),",
"a",
"form",
"of",
"cognitive",
"behavioral",
"therapy,",
"has",
"received",
"strong",
"support",
"for",
"of",
"the",
"treatment",
"of",
"posttraumatic",
"stress",
"disorder",
"(PTSD)",
"[1-3].",
"A",
"com-",
"mittee",
"convened",
"by",
"the",
"Institute",
"of",
"Medicine",
"(IOM)",
"to",
"assess",
"evidence",
"about",
"the",
"efficacy",
"of",
"treatments",
"for",
"PTSD",
"concluded",
"that",
"while",
"the",
"evidence",
"was",
"inadequate",
"*",
"Correspondence:",
"mildred.vera@upr.edu",
"1Center",
"for",
"Evaluation",
"and",
"Sociomedical",
"Research",
"and",
"Department",
"of",
"Health",
"Services",
"Administration,",
"School",
"of",
"Public",
"Health,",
"Medical",
"Science",
"Campus,",
"University",
"of",
"Puerto",
"Rico,",
"San",
"Juan,",
"Puerto",
"Rico",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"for",
"most",
"psychological",
"and",
"pharmacological",
"treatment",
"modalities,",
"the",
"efficacy",
"of",
"exposure",
"therapies",
"for",
"treating",
"PTSD",
"was",
"strongly",
"supported",
"[4].",
"The",
"superior",
"efficacy",
"of",
"PE",
"for",
"treating",
"PTSD",
"has",
"been",
"demonstrated",
"across",
"a",
"wide",
"range",
"of",
"traumatized",
"populations,",
"including",
"victims",
"of",
"rape,",
"violent",
"assault,",
"child",
"abuse,",
"combat-related",
"trauma,",
"motor",
"vehicle",
"accidents,",
"and",
"disasters",
"[1,5-7].",
"Although",
"strong",
"empirical",
"evidence",
"sustains",
"the",
"effi-",
"cacy",
"of",
"PE",
"for",
"PTSD,",
"the",
"adoption",
"of",
"exposure",
"therapy",
"in",
"clinical",
"practice",
"has",
"been",
"slow",
"[8-11].",
"Lack",
"of",
"adequate",
"training",
"has",
"been",
"identified",
"as",
"a",
"contributing",
"factor",
"to",
"the",
"low",
"use",
"of",
"exposure",
"therapy",
"by",
"clinicians",
"in",
"treating",
"PTSD",
"[12].",
"Other",
"common",
"obstacles",
"have",
"been",
"discussed",
"©",
"2011",
"Vera",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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368,
967,
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393,
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424,
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429,
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440,
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445,
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233,
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268,
997
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270,
983,
294,
997
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297,
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352,
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354,
983,
410,
997
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[
413,
983,
463,
997
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[
465,
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490,
997
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[
233,
999,
243,
1013
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[
247,
999,
363,
1014
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367,
999,
433,
1014
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438,
999,
491,
1013
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509,
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520,
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525,
869,
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547,
869,
589,
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869,
604,
883
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608,
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643,
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647,
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706,
869,
726,
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731,
869,
767,
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[
509,
885,
533,
899
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536,
885,
581,
899
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[
584,
885,
595,
899
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[
598,
885,
616,
899
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[
620,
885,
661,
899
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[
664,
885,
691,
899
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[
695,
885,
729,
900
],
[
732,
885,
766,
900
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509,
901,
595,
915
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600,
901,
627,
915
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[
631,
901,
654,
915
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[
658,
901,
679,
915
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684,
901,
710,
915
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[
714,
901,
767,
915
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[
509,
918,
570,
932
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[
576,
918,
594,
932
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[
601,
918,
678,
932
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684,
918,
716,
932
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[
722,
918,
743,
932
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918,
766,
932
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[
509,
955,
514,
964
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517,
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509,
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572,
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509,
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171,
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1050
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1040,
150,
1050
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151,
1040,
164,
1050
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[
166,
1040,
171,
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180,
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212,
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] | [
"e",
"n",
"i",
"c",
"i",
"d",
"e",
"M",
"l",
"a",
"t",
"n",
"e",
"m",
"i",
"r",
"e",
"p",
"x",
"E",
"f",
"o",
"l",
"a",
"n",
"r",
"u",
"o",
"J",
"e",
"h",
"T",
"CORRESPONDENCE",
"A.Villa:",
"villa.anna@hsr.it",
"B",
"R",
"I",
"E",
"F",
"D",
"E",
"F",
"I",
"N",
"I",
"T",
"I",
"V",
"E",
"R",
"E",
"P",
"O",
"RT",
"The",
"Wiskott-Aldr",
"ich",
"syndrome",
"protein",
"is",
"required",
"for",
"iNKT",
"cell",
"maturation",
"and",
"function",
"Michela",
"Locci,1,2",
"Elena",
"Draghici,3",
"Francesco",
"Marangoni,3",
"Marita",
"Bosticardo,1",
"Marco",
"Catucci,3",
"Alessandro",
"Aiuti,2,3",
"Caterina",
"Cancrini,2",
"Laszlo",
"Marodi,4",
"Teresa",
"Espanol,5",
"Robbert",
"G.M.",
"Bredius,6",
"Adrian",
"J.",
"Thrasher,7",
"Ansgar",
"Schulz,8",
"Jiri",
"Litzman,9",
"Maria",
"Grazia",
"Roncarolo,1,3",
"Giulia",
"Casorati,10",
"Paolo",
"Dellabona,10",
"and",
"Anna",
"Villa3,11",
"1Vita-Salute",
"San",
"Raffaele",
"University,",
"20132",
"Milan,",
"Italy",
"2Tor",
"Vergata",
"University,",
"00133",
"Rome,",
"Italy",
"3San",
"Raffaele",
"Telethon",
"Institute",
"for",
"Gene",
"Therapy,",
"20132",
"Milan,",
"Italy",
"4Department",
"of",
"Infectious",
"and",
"Pediatric",
"Immunology,",
"University",
"of",
"Debrecen",
"Medical",
"and",
"Health",
"Science",
"Center,",
"H4012",
"Debrecen,",
"Hungary",
"5Paediatric",
"Immunology",
"and",
"Infectious",
"Disease",
"Unit,",
"Vall",
"d’Hebron",
"Hospital,",
"08035",
"Barcelona,",
"Spain",
"6Department",
"of",
"Pediatrics,",
"Leiden",
"University",
"Medical",
"Center,",
"2300",
"RC",
"Leiden,",
"Netherlands",
"7Institute",
"of",
"Child",
"Health,",
"University",
"College",
"London",
"and",
"Great",
"Ormond",
"Street",
"Hospital",
"for",
"Children,",
"WCIN",
"1EH",
"London,",
"England,",
"UK",
"8Department",
"of",
"Pediatrics",
"and",
"Adolescent",
"Medicine,",
"University",
"Hospital",
"Ulm,",
"89075",
"Ulm,",
"Germany",
"9Department",
"of",
"Clinical",
"Immunology",
"and",
"Allergology,",
"Faculty",
"of",
"Medicine,",
"Masaryk",
"University,",
"St.",
"Anne’s",
"University",
"Hospital,",
"656",
"91",
"Brno,",
"Czech",
"Republic",
"10Experimental",
"Immunology",
"Unit,",
"Cancer",
"Immunotherapy",
"and",
"Gene",
"Therapy",
"Program,",
"Dipartimento",
"di",
"Biotecnologie,",
"San",
"Raffaele",
"Scientific",
"Institute,",
"20132",
"Milan,",
"Italy",
"11Istituto",
"Tecnologie",
"Biomediche,",
"Consiglio",
"Nazionale",
"delle",
"Ricerche,",
"20090",
"Segrate-Milan,",
"Italy",
"The",
"Wiskott-Aldrich",
"syndrome",
"(WAS)",
"protein",
"(WASp)",
"is",
"a",
"regulator",
"of",
"actin",
"cytoskeleton",
"in",
"hematopoietic",
"cells.",
"Mutations",
"of",
"the",
"WASp",
"gene",
"cause",
"WAS.",
"Although",
"WASp",
"is",
"in-",
"volved",
"in",
"various",
"immune",
"cell",
"functions,",
"its",
"role",
"in",
"invariant",
"natural",
"killer",
"T",
"(iNKT)",
"cells",
"has",
"never",
"been",
"investigated.",
"Defects",
"of",
"iNKT",
"cells",
"could",
"indeed",
"contribute",
"to",
"several",
"WAS",
"features,",
"such",
"as",
"recurrent",
"infections",
"and",
"high",
"tumor",
"incidence.",
"We",
"found",
"a",
"profound",
"reduction",
"of",
"circulating",
"iNKT",
"cells",
"in",
"WAS",
"patients,",
"directly",
"correlating",
"with",
"the",
"severity",
"of",
"clinical",
"phenotype.",
"To",
"better",
"characterize",
"iNKT",
"cell",
"defect",
"in",
"the",
"absence",
"of",
"WASp,",
"we",
"analyzed",
"was/",
"mice.",
"iNKT",
"cell",
"numbers",
"were",
"significantly",
"reduced",
"in",
"the",
"thymus",
"and",
"periphery",
"of",
"was/",
"mice",
"as",
"compared",
"with",
"wild-type",
"controls.",
"Moreover",
"analysis",
"of",
"was/",
"iNKT",
"cell",
"maturation",
"revealed",
"a",
"complete",
"arrest",
"at",
"the",
"CD44+",
"NK1.1",
"intermediate",
"stage.",
"Notably,",
"generation",
"of",
"BM",
"chimeras",
"demonstrated",
"a",
"was/",
"iNKT",
"cell-autonomous",
"devel-",
"opmental",
"defect.",
"was/",
"iNKT",
"cells",
"were",
"also",
"functionally",
"impaired,",
"as",
"suggested",
"by",
"the",
"reduced",
"secretion",
"of",
"interleukin",
"4",
"and",
"interferon",
"",
"upon",
"in",
"vivo",
"activation.",
"Altogether,",
"these",
"results",
"demonstrate",
"the",
"relevance",
"of",
"WASp",
"in",
"integrating",
"signals",
"critical",
"for",
"develop-",
"ment",
"and",
"functional",
"differentiation",
"of",
"iNKT",
"cells",
"and",
"suggest",
"that",
"defects",
"in",
"these",
"cells",
"may",
"play",
"a",
"role",
"in",
"WAS",
"pathology.",
"Invariant",
"natural",
"killer",
"T",
"(iNKT)",
"cells",
"consti-",
"tute",
"a",
"peculiar",
"T",
"lymphocyte",
"subset,",
"which",
"is",
"characterized",
"by",
"the",
"coexpression",
"of",
"NK",
"mark-",
"ers",
"and",
"an",
"invariant",
"TCR-",
"chain",
"(V14J18",
"in",
"mouse",
"or",
"V24J18",
"in",
"human),",
"which",
"pairs",
"with",
"a",
"restricted",
"number",
"of",
"TCR-",
"chains",
"(V8,",
"V7,",
"and",
"V2",
"in",
"mice",
"and",
"V11",
"in",
"human).",
"iNKT",
"cells",
"recognize",
"glycolipid",
"antigens,",
"such",
"as",
"-galactosylceramide",
"(-GalCer),",
"presented",
"in",
"the",
"context",
"of",
"CD1d",
"molecules",
"(1).",
"iNKT",
"cells",
"develop",
"in",
"the",
"thymus",
"from",
"CD4+",
"CD8+",
"double-positive",
"(DP)",
"cells",
"that",
"have",
"randomly",
"rearranged",
"the",
"semiinvariant",
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866,
625,
878
],
[
628,
866,
678,
878
],
[
681,
866,
706,
878
],
[
709,
866,
755,
878
],
[
759,
866,
778,
878
],
[
549,
878,
573,
890
],
[
575,
878,
621,
890
],
[
623,
878,
655,
890
],
[
658,
878,
752,
890
],
[
557,
891,
576,
903
],
[
580,
891,
605,
903
],
[
608,
891,
651,
903
],
[
655,
891,
665,
903
],
[
669,
891,
686,
903
],
[
690,
891,
719,
903
],
[
722,
891,
736,
903
],
[
739,
891,
763,
903
],
[
768,
891,
777,
903
],
[
549,
903,
563,
915
],
[
566,
903,
599,
915
],
[
602,
903,
619,
915
],
[
622,
903,
634,
915
],
[
637,
903,
652,
915
],
[
656,
903,
702,
915
],
[
705,
903,
732,
915
],
[
736,
903,
750,
915
],
[
753,
903,
777,
915
],
[
549,
916,
559,
928
],
[
562,
916,
597,
928
],
[
601,
916,
610,
928
],
[
614,
916,
629,
928
],
[
632,
916,
653,
928
],
[
656,
916,
725,
928
],
[
729,
916,
777,
928
],
[
549,
928,
585,
940
],
[
588,
928,
621,
940
],
[
625,
928,
638,
940
],
[
641,
928,
667,
940
],
[
671,
928,
720,
940
],
[
723,
928,
740,
940
],
[
743,
928,
777,
940
],
[
549,
941,
590,
953
],
[
594,
941,
604,
953
],
[
607,
941,
648,
953
],
[
652,
941,
692,
953
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[
695,
941,
704,
953
],
[
708,
941,
777,
953
],
[
549,
953,
579,
965
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[
581,
953,
620,
965
],
[
557,
966,
575,
978
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[
577,
966,
609,
978
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[
612,
966,
642,
978
],
[
644,
966,
663,
978
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[
665,
966,
685,
978
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[
687,
966,
699,
978
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[
701,
966,
726,
978
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[
728,
966,
738,
978
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[
740,
966,
778,
978
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[
549,
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595,
990
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[
597,
978,
634,
990
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[
636,
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674,
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[
557,
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1003
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599,
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1003
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] | [
"Research",
"|",
"Children’s",
"Health",
"Exposure",
"to",
"Asbestos-Containing",
"Vermiculite",
"Ore",
"and",
"Respiratory",
"Symptoms",
"among",
"Individuals",
"Who",
"Were",
"Children",
"While",
"the",
"Mine",
"Was",
"Active",
"in",
"Libby,",
"Montana",
"Lisa",
"C.",
"Vinikoor,1",
"Theodore",
"C.",
"Larson,2",
"Thomas",
"F.",
"Bateson,3",
"and",
"Linda",
"Birnbaum4",
"1U.S.",
"Environmental",
"Protection",
"Agency,",
"Research",
"Triangle",
"Park,",
"North",
"Carolina,",
"USA;",
"2Agency",
"for",
"Toxic",
"Substances",
"and",
"Disease",
"Registry,",
"Atlanta,",
"Georgia,",
"USA;",
"3U.S.",
"Environmental",
"Protection",
"Agency,",
"Washington,",
"DC,",
"USA;",
"4National",
"Institute",
"of",
"Environmental",
"Health",
"Sciences,",
"National",
"Institutes",
"of",
"Health,",
"Department",
"of",
"Health",
"and",
"Human",
"Services,",
"Research",
"Triangle",
"Park,",
"North",
"Carolina,",
"USA",
"Background",
":",
"Libby,",
"Montana,",
"was",
"home",
"to",
"the",
"largest",
"vermiculite",
"ore",
"mine",
"in",
"the",
"United",
"States.",
"The",
"processing,",
"use,",
"and",
"transport",
"of",
"the",
"ore,",
"which",
"was",
"contaminated",
"with",
"amphibole",
"asbestos,",
"led",
"to",
"generalized",
"contamination",
"of",
"the",
"community.",
"The",
"mine",
"closed",
"in",
"1990.",
"o",
"Bjectivs",
":",
"We",
"examined",
"the",
"prevalence",
"of",
"respiratory",
"symptoms",
"in",
"2000–2001",
"and",
"their",
"associa-",
"tion",
"with",
"history",
"of",
"vermiculite",
"exposure",
"among",
"people",
"who",
"were",
"≤",
"18",
"years",
"of",
"age",
"when",
"the",
"mine",
"closed.",
"Methods",
":",
"Information",
"on",
"respiratory",
"symptoms",
"and",
"exposure",
"history",
"was",
"collected",
"by",
"question-",
"naire",
"in",
"2000–2001,",
"at",
"which",
"time",
"participants",
"were",
"10–29",
"years",
"old.",
"Logistic",
"regression",
"was",
"used",
"to",
"model",
"the",
"associations",
"between",
"exposures",
"and",
"outcomes",
"adjusted",
"for",
"age,",
"sex,",
"and",
"tobacco",
"smoke",
"exposure.",
"r",
"esult",
":",
"Of",
"the",
"1,003",
"individuals",
"included",
"in",
"the",
"study,",
"10.8%",
"reported",
"usually",
"having",
"a",
"cough,",
"14.5%",
"reported",
"experiencing",
"shortness",
"of",
"breath",
"when",
"walking",
"up",
"a",
"slight",
"hill",
"or",
"hurrying",
"on",
"level",
"ground,",
"and",
"5.9%",
"reported",
"having",
"coughed",
"up",
"bloody",
"phlegm",
"in",
"the",
"past",
"year.",
"These",
"respiratory",
"symptoms",
"were",
"positively",
"associated",
"with",
"frequently",
"handling",
"vermiculite",
"insulation",
"compared",
"with",
"never",
"handling",
"vermiculite",
"insulation.",
"We",
"found",
"no",
"association",
"between",
"vermiculite",
"insulation",
"in",
"the",
"house",
"and",
"respiratory",
"symptoms.",
"Respiratory",
"symptoms",
"were",
"associated",
"with",
"other",
"vermiculite",
"expo-",
"sures",
"as",
"well,",
"and",
"the",
"number",
"and",
"frequency",
"of",
"these",
"activities",
"showed",
"a",
"positive",
"trend",
"with",
"usually",
"having",
"a",
"cough.",
"We",
"found",
"no",
"association",
"between",
"any",
"of",
"the",
"activities",
"and",
"abnormal",
"spirometry.",
"c",
"onclusi",
":",
"These",
"data",
"suggest",
"that",
"residents",
"of",
"Libby,",
"Montana,",
"who",
"were",
"children",
"when",
"the",
"mine",
"closed",
"experienced",
"some",
"respiratory",
"symptoms",
"associated",
"with",
"asbestos-contaminated",
"ver-",
"miculite",
"exposure.",
"k",
"ey",
"words",
":",
"asbestos,",
"children,",
"Libby,",
"Montana,",
"respiratory",
"symptoms,",
"spirometry,",
"vermiculite",
"ore.",
"Environ",
"Health",
"Perspect",
"118:1033–1038",
"(2010).",
"doi:10.1289/ehp.0901680",
"[Online",
"23",
"March",
"2010]",
"Libby",
"is",
"a",
"small",
"community",
"located",
"in",
"the",
"Kootenai",
"River",
"Valley",
"of",
"northwestern",
"Montana",
"approximately",
"6",
"miles",
"southwest",
"of",
"Zonolite",
"Mountain,",
"a",
"mountain",
"containing",
"high",
"concentrations",
"of",
"vermiculite",
"ore.",
"The",
"ore",
"was",
"mined",
"beginning",
"in",
"the",
"1920s",
"by",
"the",
"Zonolite",
"Company",
"and",
"then",
"later",
"by",
"W.R.",
"Grace,",
"which",
"bought",
"the",
"mine",
"in",
"1963.",
"It",
"is",
"estimated",
"that",
"between",
"1924",
"and",
"1990,",
"when",
"the",
"mine",
"was",
"closed,",
"a",
"total",
"of",
"5.8",
"million",
"tons",
"of",
"vermiculite",
"ore",
"was",
"mined",
"and",
"dis-",
"tributed",
"(Kuntz",
"et",
"al.",
"2009),",
"making",
"Zonolite",
"Mountain",
"the",
"largest",
"vermiculite",
"ore",
"mine",
"in",
"the",
"United",
"States.",
"In",
"addition",
"to",
"the",
"mine,",
"processing,",
"exfoliation,",
"and",
"shipping",
"prepara-",
"tions",
"were",
"performed",
"in",
"Libby.",
"The",
"ore",
"was",
"then",
"used",
"in",
"many",
"products",
"ranging",
"from",
"insulation",
"to",
"soil",
"additives",
"and",
"fertilizers.",
"The",
"vermiculite",
"ore",
"contained",
"amphibole",
"asbestos.",
"Libby",
"amphibole",
"asbestos",
"was",
"deter-",
"mined",
"to",
"be",
"composed",
"of",
"tremolite,",
"winchite,",
"and",
"richterite",
"(Meeker",
"et",
"al.",
"2003).",
"The",
"International",
"Agency",
"for",
"Research",
"on",
"Cancer",
"recently",
"concluded",
"that",
"“all",
"forms",
"of",
"asbestos",
"are",
"‘carcinogenic",
"to",
"humans’”",
"and",
"that",
"“min-",
"eral",
"substances",
"(e.g.,",
"talc",
"or",
"vermiculite)",
"that",
"contain",
"asbestos",
"should",
"also",
"be",
"regarded",
"as",
"‘carcinogenic",
"to",
"humans’”",
"(Straif",
"et",
"al.",
"2009).",
"As",
"with",
"other",
"forms",
"of",
"asbestos,",
"exposure",
"to",
"Libby",
"amphibole",
"asbestos",
"has",
"been",
"shown",
"to",
"negatively",
"affect",
"human",
"health.",
"Occupational",
"studies",
"have",
"shown",
"increased",
"morbidity",
"and",
"mortality",
"(specifically",
"from",
"respiratory",
"can-",
"cers",
"and",
"other",
"respiratory",
"diseases,",
"including",
"asbestosis)",
"associated",
"with",
"exposure",
"to",
"the",
"asbestos-contaminated",
"vermiculite",
"from",
"Libby",
"(Amandus",
"and",
"Wheeler",
"1987;",
"Amandus",
"et",
"al.",
"1987;",
"McDonald",
"et",
"al.",
"1986,",
"2004;",
"Sullivan",
"2007).",
"Studies",
"have",
"also",
"shown",
"increased",
"morbidity",
"and",
"mortality",
"among",
"individuals",
"living",
"in",
"Libby,",
"Montana,",
"who",
"did",
"not",
"work",
"at",
"the",
"mine",
"[Agency",
"for",
"Toxic",
"Substances",
"and",
"Disease",
"Registry",
"(ATSDR)",
"2000,",
"2002;",
"Muravov",
"et",
"al.",
"2005;",
"Noonan",
"et",
"al.",
"2006;",
"Peipins",
"et",
"al.",
"2003;",
"Whitehouse",
"et",
"al.",
"2008].",
"Health",
"effects",
"continue",
"to",
"be",
"seen",
"in",
"for-",
"mer",
"workers",
"and",
"community",
"members.",
"In",
"2000–2001",
"the",
"ATSDR",
"began",
"a",
"screening",
"program",
"for",
"individuals",
"living",
"and/or",
"work-",
"ing",
"in",
"Libby.",
"Using",
"these",
"data",
"researchers",
"have",
"found",
"positive",
"associations",
"between",
"asbestos-contaminated",
"vermiculite",
"exposure",
"and",
"pleural",
"abnormalities",
"seen",
"by",
"radiograph",
"(Peipins",
"et",
"al.",
"2003)",
"and",
"self-reported",
"history",
"of",
"systemic",
"autoimmune",
"diseases",
"(Noonan",
"et",
"al.",
"2006).",
"Despite",
"the",
"mine’s",
"closure,",
"there",
"Environmental",
"Health",
"Perspectives",
"•",
"volume",
"118",
"|",
"number",
"7",
"|",
"July",
"2010",
"is",
"concern",
"about",
"the",
"long-term",
"effects",
"of",
"the",
"mining",
"operation",
"for",
"both",
"those",
"exposed",
"in",
"childhood",
"and",
"those",
"exposed",
"to",
"lingering",
"environmental",
"contamination.",
"This",
"age",
"group",
"is",
"of",
"particular",
"importance",
"because",
"lung",
"development",
"continues",
"through",
"adolescence",
"until",
"about",
"18",
"years",
"of",
"age",
"in",
"girls",
"and",
"the",
"early",
"20s",
"in",
"boys.",
"Previous",
"research",
"has",
"shown",
"reduced",
"lung",
"development",
"in",
"children",
"10–18",
"years",
"of",
"age",
"who",
"were",
"exposed",
"to",
"ambient",
"air",
"pollution",
"(Bateson",
"and",
"Schwartz",
"2008;",
"Gauderman",
"et",
"al.",
"2004).",
"Using",
"the",
"avail-",
"able",
"ATSDR",
"survey",
"data,",
"we",
"examined",
"the",
"prevalence",
"of",
"respiratory",
"symptoms",
"and",
"their",
"association",
"with",
"vermiculite",
"exposure",
"among",
"individuals",
"who",
"were",
"no",
"older",
"than",
"18",
"years",
"of",
"age",
"while",
"the",
"mine",
"was",
"in",
"operation",
"and",
"who",
"were",
"continually",
"exposed",
"through",
"linger-",
"ing",
"environmental",
"contamination.",
"This",
"has",
"not",
"been",
"addressed",
"by",
"previous",
"research.",
"Materials",
"and",
"Methods",
"In",
"2000",
"and",
"2001,",
"ATSDR",
"conducted",
"a",
"study",
"of",
"individuals",
"who",
"resided,",
"worked,",
"attended",
"school,",
"or",
"participated",
"in",
"other",
"activities",
"in",
"the",
"Libby",
"area",
"for",
"at",
"least",
"6",
"months",
"before",
"31",
"December",
"1990.",
"In-person",
"interviews",
"and",
"medical",
"tests",
"were",
"performed",
"in",
"2000",
"(July–November)",
"and",
"2001",
"(July–September).",
"Trained",
"interviewers",
"administered",
"a",
"computer-assisted",
"question-",
"naire",
"to",
"obtain",
"information",
"on",
"demographics,",
"residential",
"history,",
"household",
"contact",
"with",
"a",
"W.R.",
"Grace",
"employee,",
"occupational",
"his-",
"tory,",
"recreational",
"activity",
"history,",
"history",
"of",
"other",
"potential",
"vermiculite",
"exposures,",
"indi-",
"vidual",
"and",
"household",
"members’",
"smoking",
"status/history,",
"medical",
"history,",
"and",
"current",
"symptoms/illnesses.",
"Parents",
"completed",
"proxy",
"interviews",
"for",
"children",
"<",
"18",
"years",
"of",
"age.",
"In",
"Address",
"correspondence",
"to",
"L.C.",
"Vinikoor,",
"U.S.",
"Environmental",
"Protection",
"Agency,",
"MD",
"B243-01,",
"109",
"T.W.",
"Alexander",
"Dr.,",
"Research",
"Triangle",
"Park,",
"NC",
"27711",
"USA.",
"Telephone:",
"(919)",
"541-2931.",
"Fax:",
"(919)",
"541-4284.",
"E-mail:",
"vinikoor.lisa@epa.gov",
"The",
"views",
"expressed",
"in",
"this",
"article",
"are",
"those",
"of",
"the",
"authors",
"and",
"do",
"not",
"necessarily",
"reflect",
"the",
"views",
"or",
"policies",
"of",
"the",
"U.S.",
"Environmental",
"Protection",
"Agency,",
"Agency",
"for",
"Toxic",
"Substances",
"and",
"Disease",
"Registry,",
"or",
"National",
"Institute",
"of",
"Environmental",
"Health",
"Sciences.",
"The",
"authors",
"declare",
"they",
"have",
"no",
"actual",
"or",
"potential",
"competing",
"financial",
"interests.",
"Received",
"10",
"November",
"2009;",
"accepted",
"12",
"March",
"2010.",
"1033"
] | [
16,
16,
16,
16,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
8,
6,
6,
6,
6,
6,
6,
6,
6,
6,
6,
6,
6,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
5,
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] | [
"Color",
"Stability",
"of",
"Silicone",
"or",
"Acrylic",
"Denture",
"Liners:",
"An",
"in",
"Vitro",
"Investigation",
"Gulfem",
"Erguna,",
"DDS,",
"PhD",
"Isil",
"Cekic",
"Nagasb,",
"DDS",
"AbstrAct",
"Objectives:",
"The",
"aim",
"of",
"this",
"study",
"was",
"to",
"compare",
"the",
"color",
"stability",
"of",
"three",
"acrylic",
"based",
"hard",
"liners",
"(Ufi",
"gel",
"hard,",
"Dura-Liner",
"II,",
"Tokuso",
"Rebase)",
"and",
"two",
"silicone",
"based",
"soft",
"liners",
"(Ufi",
"gel",
"perma-",
"nent,",
"Molloplast",
"B)",
"by",
"using",
"the",
"colorimeter.",
"Methods:",
"Sixty",
"disc-shaped",
"samples,",
"with",
"uniform",
"size",
"of",
"10",
"mm",
"diameter",
"and",
"2",
"mm",
"in",
"thick-",
"ness",
"were",
"fabricated",
"for",
"each",
"material.",
"Thirty",
"samples",
"were",
"made",
"as",
"control",
"group",
"in",
"distilled",
"water",
"and",
"the",
"remaining",
"thirty",
"samples",
"were",
"weathered",
"in",
"accelerated",
"aging",
"chamber.",
"Color",
"mea-",
"surements",
"were",
"made",
"before",
"and",
"after",
"distilled",
"water",
"and",
"aging.",
"Data",
"were",
"statistically",
"analyzed",
"using",
"nonparametric",
"Kruskal-Wallis",
"and",
"Mann-Whitney",
"U",
"tests.",
"Results:",
"Data",
"showed",
"that",
"there",
"are",
"significant",
"differences",
"among",
"materials",
"in",
"both",
"after",
"dis-",
"tilled",
"water",
"and",
"aging",
"treatments",
"(P<.001).",
"These",
"results",
"indicated",
"that",
"the",
"most",
"discolored",
"liner",
"material",
"was",
"Dura",
"Liner",
"II",
"after",
"aging",
"(∆E*=16.30)",
"and",
"the",
"least",
"discolored",
"material",
"was",
"Ufi",
"gel",
"permanent",
"after",
"distilled",
"water",
"(∆E*=0.41).",
"Conclusions:",
"Based",
"on",
"the",
"results",
"of",
"this",
"study,",
"silicone",
"based",
"liner",
"materials",
"are",
"considered",
"to",
"be",
"more",
"color",
"stable",
"than",
"acrylic",
"based",
"liner",
"materials.",
"(Eur",
"J",
"Dent",
"2007;1:144-151)",
"Key",
"words:",
"Silicone;",
"Acrylic",
"liners;",
"Color",
"stability.",
"IntroducIno",
"Denture",
"lining",
"materials",
"are",
"widely",
"used",
"for",
"the",
"base",
"of",
"a",
"denture",
"to",
"reduce",
"pain",
"or",
"to",
"improve",
"the",
"fit",
"between",
"the",
"denture",
"and",
"mucous",
"membrane.1",
"They",
"act",
"as",
"a",
"cushion",
"and",
"provide",
"an",
"even",
"distri-",
"bution",
"of",
"functional",
"load",
"onto",
"the",
"stress-bearing",
"mucosa.2",
"Application",
"of",
"a",
"soft",
"lining",
"material",
"to",
"the",
"dentures",
"can",
"also",
"increase",
"the",
"patient’s",
"mas-",
"ticatory",
"performance,",
"biting",
"force",
"and",
"improve",
"the",
"chewing",
"rhythm.3",
"Denture",
"lining",
"materials",
"can",
"be",
"classified",
"a",
"Associate",
"Professor,",
"Department",
"of",
"Prosthodontics,",
"Faculty",
"of",
"Dentistry,",
"Gazi",
"University,",
"Ankara,",
"Türkiye",
"b",
"Research",
"Assistant,",
"Department",
"of",
"Prosthodontics,",
"Faculty",
"of",
"Dentistry,",
"Gazi",
"University,",
"Ankara,",
"Türkiye",
"Corresponding",
"Author:",
"Dr.",
"Gulfem",
"Ergun",
"Address:",
"Süslü",
"sok.",
"14/9Tandoğan/Ankara",
"06580",
"Türkiye",
"Tel.:",
"+90",
"312",
"213",
"97",
"01",
"Fax:",
"+90",
"312",
"223",
"92",
"26",
"E-mail",
":",
"gulfem@gazi.edu.tr,",
"ergungulfem@yahoo.com.",
"as",
"provisional",
"or",
"permanent,",
"silicone",
"rubber",
"or",
"acrylic",
"resin,",
"and",
"can",
"be",
"either",
"chemically",
"or",
"heat",
"polymerized.4",
"A",
"provisional",
"liner",
"is",
"the",
"one",
"used",
"intraorally",
"for",
"up",
"to",
"30",
"days",
"and",
"a",
"long-term",
"liner",
"is",
"categorized",
"as",
"the",
"one",
"that",
"maintains",
"its",
"soft-",
"ness",
"and",
"elasticity",
"for",
"more",
"than",
"30",
"days.5",
"Fur-",
"thermore,",
"in",
"a",
"study,",
"a",
"long",
"term",
"liner",
"was",
"clas-",
"sified",
"to",
"be",
"the",
"one",
"used",
"for",
"1",
"year",
"or",
"longer.6",
"Silicone",
"based",
"lining",
"materials",
"are",
"basically",
"di-",
"methylsiloxane",
"polymers",
"and",
"do",
"not",
"contain",
"plas-",
"ticizer",
"to",
"produce",
"softening",
"effect.7",
"These",
"lining",
"materials",
"are",
"hydrophobic;",
"this",
"reduces",
"water",
"sorption,",
"but",
"simultaneously",
"inhibits",
"good",
"affin-",
"ity",
"to",
"the",
"supporting",
"tissues.8",
"Acrylic",
"based",
"lining",
"materials",
"are",
"composed",
"of",
"the",
"powder",
"consisting",
"of",
"a",
"higher",
"methacrylate",
"polymer",
"(usually",
"poly",
"ethyl",
"methacrylate)",
"and",
"a",
"liquid",
"of",
"a",
"higher",
"meth-",
"acrylate",
"monomer",
"(e.g.",
"ethyl,",
"n-butyl),",
"in",
"addition",
"a",
"plasticizer,",
"commonly",
"a",
"phythalate.9,10",
"When",
"im-",
"144",
"European",
"Journal",
"of",
"Dentistry"
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] | [
"BIOINFORMATICS",
"APPLICATIONS",
"NOTE",
"Vol.",
"28",
"no.",
"21",
"2012,",
"pages",
"2845–2846",
"doi:10.1093/bioinformatics/bts532",
"Sequence",
"analysis",
"Advance",
"Access",
"publication",
"September",
"8,",
"2012",
"Pythoscape:",
"a",
"framework",
"for",
"generation",
"of",
"large",
"protein",
"similarity",
"networks",
"Alan",
"E.",
"Barber",
"II",
"and",
"Patricia",
"C.",
"Babbitt*",
"Associate",
"Editor:",
"Martin",
"Bishop",
"Department",
"of",
"Bioengineering",
"and",
"Therapeutic",
"Sciences,",
"University",
"of",
"California,",
"San",
"Francisco,",
"CA",
"94158,",
"USA",
"ABSTRACT",
"Pythoscape",
"is",
"a",
"framework",
"implemented",
"in",
"Python",
"for",
"processing",
"large",
"protein",
"similarity",
"networks",
"for",
"visualization",
"in",
"other",
"software",
"packages.",
"Protein",
"similarity",
"networks",
"are",
"graphical",
"representations",
"of",
"sequence,",
"structural",
"and",
"other",
"similarities",
"among",
"proteins",
"for",
"which",
"pairwise",
"all-by-all",
"similarity",
"connections",
"have",
"been",
"calculated.",
"Mapping",
"of",
"biological",
"and",
"other",
"information",
"to",
"network",
"nodes",
"or",
"edges",
"enables",
"hypothesis",
"creation",
"about",
"sequence–structure–func-",
"tion",
"relationships",
"across",
"sets",
"of",
"related",
"proteins.",
"Pythoscape",
"provides",
"several",
"options",
"to",
"calculate",
"pairwise",
"similarities",
"for",
"input",
"sequences",
"or",
"structures,",
"applies",
"filters",
"to",
"network",
"edges",
"and",
"defines",
"sets",
"of",
"similar",
"nodes",
"and",
"their",
"associated",
"data",
"as",
"single",
"nodes",
"(termed",
"representa-",
"tive",
"nodes)",
"for",
"compression",
"of",
"network",
"information",
"and",
"output",
"data",
"or",
"formatted",
"files",
"for",
"visualization.",
"Contact:",
"babbitt@cgl.ucsf.edu",
"Supplementary",
"information:",
"Supplementary",
"data",
"are",
"available",
"at",
"Bioinformatics",
"online.",
"Received",
"on",
"June",
"7,",
"2012;",
"revised",
"on",
"August",
"8,",
"2012;",
"accepted",
"on",
"August",
"23,",
"2012",
"1",
"INTRODUCTION",
"The",
"rapid",
"growth",
"of",
"databases",
"of",
"protein",
"information",
"(e.g.",
"se-",
"quences",
"and",
"structures)",
"provides",
"both",
"new",
"opportunities",
"and",
"challenges",
"for",
"analysis",
"and",
"clustering",
"by",
"similarity.",
"For",
"example,",
"global",
"analysis",
"of",
"entire",
"superfamilies",
"and",
"association",
"of",
"their",
"members",
"with",
"biological",
"information",
"and",
"other",
"types",
"of",
"meta-",
"data",
"has",
"become",
"a",
"useful",
"tool",
"for",
"functional",
"annotation",
"and",
"discovery",
"(Brown",
"and",
"Babbitt,",
"2012).",
"As",
"these",
"sets",
"become",
"larger",
"(sometimes",
"many",
"thousands",
"of",
"sequences)",
"and",
"their",
"mem-",
"bers",
"more",
"divergent,",
"their",
"fast",
"exploration",
"on",
"a",
"large-scale",
"becomes",
"less",
"feasible",
"using",
"traditional",
"approaches",
"such",
"as",
"align-",
"ments",
"and",
"trees.",
"Protein",
"similarity",
"networks",
"(PSNs)",
"enable",
"analysis",
"and",
"visual-",
"ization",
"of",
"structure–function",
"relationships",
"in",
"large",
"protein",
"data",
"sets",
"by",
"clustering",
"of",
"individual",
"protein",
"sets",
"for",
"more",
"complex",
"analysis",
"while",
"summarizing",
"‘connectivity’",
"relationships",
"among",
"the",
"clusters.",
"Mapping",
"orthogonal",
"sources",
"of",
"biological",
"informa-",
"tion",
"onto",
"PSNs",
"then",
"provides",
"a",
"powerful",
"way",
"to",
"view",
"functional",
"trends",
"across",
"the",
"set",
"that",
"can",
"be",
"interpreted",
"in",
"the",
"context",
"of",
"their",
"similarities.",
"(See",
"Atkinson",
"et",
"al.,",
"2009",
"for",
"an",
"initial",
"analysis",
"of",
"some",
"uses",
"and",
"statistical",
"validation",
"of",
"PSNs.)",
"While",
"databases",
"like",
"Similarity",
"Matrix",
"of",
"Proteins",
"(SIMAP)",
"(Rattie",
"et",
"al.,",
"2010)",
"store",
"pairwise",
"similarities,",
"and",
"plug-ins",
"*To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"available",
"with",
"software",
"such",
"as",
"Cytoscape",
"(Smoot",
"et",
"al.,",
"2011)",
"allow",
"creation",
"of",
"small",
"PSNs",
"(Wittkop",
"et",
"al.,",
"2010),",
"no",
"software",
"solution",
"exists",
"to",
"create",
"and",
"manage",
"large",
"PSNs.",
"And",
"while",
"PSNs",
"are",
"inherently",
"amenable",
"to",
"association",
"with",
"orthogonal",
"information",
"sources,",
"the",
"many",
"information",
"types",
"available",
"com-",
"plicate",
"development",
"of",
"a",
"single",
"software",
"solution",
"for",
"managing",
"such",
"diverse",
"features.",
"Pythoscape",
"addresses",
"these",
"issues",
"and",
"pro-",
"vides",
"a",
"software",
"framework",
"to",
"create",
"PSNs",
"and",
"develop",
"new",
"analyses",
"for",
"inference",
"of",
"functional",
"properties",
"in",
"proteins.",
"2",
"DESCRIPTION",
"AND",
"SIGNIFICANCE",
"Pythoscape",
"is",
"an",
"extensible",
"computational",
"framework",
"imple-",
"mented",
"in",
"Python",
"to",
"generate",
"and",
"analyze",
"PSNs.",
"For",
"the",
"user",
"interested",
"in",
"generating",
"large",
"networks,",
"the",
"Pythoscape",
"package",
"has",
"a",
"core",
"set",
"of",
"plug-ins",
"(Supplementary",
"Table",
"S1)",
"and",
"tutorials,",
"so",
"that",
"no",
"development",
"is",
"needed",
"to",
"create",
"simple",
"networks",
"painted",
"with",
"useful",
"metadata.",
"For",
"software",
"developers,",
"Pythos-",
"cape",
"provides",
"a",
"framework",
"for",
"rapid",
"modification",
"along",
"with",
"well-documented",
"application",
"programming",
"interfaces",
"for",
"devel-",
"opment",
"of",
"additional",
"plug-ins",
"using",
"new",
"sources",
"of",
"metadata.",
"Unlike",
"sparser",
"networks",
"such",
"as",
"interaction",
"networks,",
"PSNs",
"are",
"frequently",
"close",
"to",
"complete,",
"often",
"requiring",
"storage",
"and",
"management",
"of",
"large",
"quantities",
"of",
"data,",
"and",
"fast",
"calculation",
"(Supplementary",
"Table",
"S2).",
"Pythoscape",
"allows",
"for",
"flexible",
"storage",
"of",
"data",
"through",
"the",
"use",
"of",
"storage",
"interfaces.",
"Appropriate",
"stor-",
"age",
"solutions",
"can",
"be",
"chosen",
"based",
"on",
"network",
"size",
"or",
"developed",
"as",
"needed",
"allowing",
"for",
"easy",
"updating",
"for",
"faster",
"and",
"more",
"reliable",
"database",
"software",
"solutions.",
"Pythoscape",
"can",
"create,",
"store",
"and",
"manage",
"large",
"networks,",
"then,",
"using",
"representative",
"nodes",
"and",
"edges",
"to",
"compress",
"the",
"information,",
"output",
"smaller",
"summary",
"net-",
"works",
"for",
"visualization",
"(Fig.",
"1A",
"and",
"B).",
"Users",
"can",
"choose",
"how",
"distances",
"between",
"representative",
"nodes",
"are",
"calculated",
"and,",
"im-",
"portantly,",
"the",
"full",
"set",
"of",
"sequences",
"in",
"each",
"node",
"is",
"retained",
"for",
"later",
"use.",
"Additionally,",
"Pythoscape",
"has",
"plug-ins",
"for",
"creating",
"structure",
"similarity",
"networks",
"and",
"for",
"generating",
"correlations",
"for",
"edge",
"distances",
"between",
"networks",
"generated",
"from",
"a",
"set",
"of",
"sequences",
"and",
"a",
"corresponding",
"set",
"of",
"available",
"structures",
"(Supplementary",
"Table",
"S1",
"and",
"Supplementary",
"Figs.",
"S2",
"and",
"S3).",
"3",
"EXAMPLE",
"USAGE",
"Glutathione",
"transferases",
"(GSTs)",
"are",
"enzymes",
"that",
"typically",
"cata-",
"lyze",
"the",
"addition",
"of",
"glutathione",
"to",
"substrate",
"compounds.",
"They",
"play",
"roles",
"in",
"many",
"biological",
"processes,",
"including",
"metabolism",
"of",
"endogenous",
"compounds",
"and",
"xenobiotics",
"such",
"as",
"drugs.",
"Of",
"the",
"The",
"Author",
"2012.",
"Published",
"by",
"Oxford",
"University",
"Press.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
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] | [
"BMC",
"Medical",
"Research",
"Methodology",
"BioMed",
"Central",
"BR2M0e0Cs1eM,aedriccahl",
"RaesretaircchleMethodology",
"1",
"Quality",
"control",
"and",
"data-handling",
"in",
"multicentre",
"studies:",
"the",
"case",
"of",
"the",
"Multicentre",
"Project",
"for",
"Tuberculosis",
"Research",
"Teresa",
"Caloto1,",
"Consuelo",
"Huerta1,",
"Teresa",
"Moreno1,",
"Dolores",
"Guerra1,",
"José",
"Alcaide2,",
"Concha",
"Castells3,",
"José",
"I",
"Cardenal4,",
"Angela",
"Domínguez2,",
"Pilar",
"Gayoso5,",
"Gonzalo",
"Gutiérrez6,",
"Maria",
"J",
"López7,",
"Francisco",
"Muñoz8,",
"Carmen",
"Navarro9,",
"Miguel",
"Picó10,",
"Francisco",
"Pozo1,",
"José",
"R",
"Quirós11,",
"Francisco",
"Robles12,",
"José",
"M",
"Sánchez13,",
"Hermelinda",
"Vanaclocha14,",
"Tomás",
"Vega15",
"and",
"Mercedes",
"Diez*1",
"for",
"the",
"MPTR",
"Study",
"Group",
"Address:",
"1Unidad",
"de",
"Investigación",
"en",
"Tuberculosis,",
"Instituto",
"de",
"Salud",
"Carlos",
"III,",
"Sinesio",
"Delgado,",
"6,",
"28029",
"Madrid,",
"Spain;,",
"2Departamento",
"de",
"Sanidad",
"y",
"Seguridad",
"Social,",
"Dirección",
"General",
"de",
"Salud",
"Pública,",
"Travessera",
"de",
"les",
"Corts",
"131-159,",
"08028",
"Barcelona",
"Spain;,",
"3Departamento",
"de",
"Sanidad,",
"Delegación",
"Territorial,",
"María",
"Díaz",
"de",
"Haro",
"60,",
"48010",
"Bilbao",
"Spain;,",
"4Consejería",
"de",
"Bienestar",
"Social,",
"Servicio",
"Territorial,",
"Plaza",
"de",
"Alféreces",
"Provisionales",
"s/n,",
"10071",
"Caceres,",
"Spain;,",
"5Complejo",
"Hospitalario",
"Cristal-Piñor,",
"Ramón",
"Puga",
"54,",
"32005",
"Orense,",
"Spain;,",
"6Dirección",
"General",
"de",
"Salud",
"Pública,",
"Avenida",
"de",
"Francia",
"4,",
"45071",
"Toledo,",
"Spain;,",
"7Consejería",
"de",
"Salud",
"Consumo",
"y",
"Bienestar",
"Social,",
"Dirección",
"General",
"de",
"Salud",
"y",
"Consumo,",
"Villamediana",
"17,",
"26071",
"Logroño,",
"Spain;,",
"8Hospital",
"Universitario",
"de",
"Valme,",
"Carretera",
"de",
"Cádiz",
"s/n,",
"41014",
"Sevilla,",
"Spain;,",
"9Consejería",
"de",
"Sanidad",
"y",
"Política",
"Social,",
"Dirección",
"General",
"de",
"Salud,",
"Ronda",
"de",
"Levante",
"11,",
"30008",
"Murcia,",
"Spain;,",
"10Dirección",
"General",
"de",
"Salud",
"Pública,",
"Avenida",
"de",
"la",
"Innovación",
"s/n,",
"Edificio",
"Arena",
"1,",
"41020",
"Sevilla,",
"Spain;,",
"11Dirección",
"Regional",
"de",
"Salud",
"Pública,",
"General",
"Elorza",
"32,",
"33001",
"Oviedo,",
"Spain;,",
"12Dirección",
"Provincial",
"de",
"Sanidad",
"de",
"Melilla,",
"Plaza",
"1",
"de",
"Mayo",
"s/n,",
"29803",
"Melilla,",
"Spain;,",
"13Dirección",
"Provincial",
"de",
"Sanidad",
"de",
"Ceuta,",
"Carretera",
"San",
"Amaro",
"12,",
"51001",
"Ceuta,",
"Spain;,",
"14Dirección",
"General",
"de",
"Salud",
"Pública,",
"Doctor",
"Rodríguez",
"Fornos",
"4,",
"46010",
"Valencia,",
"Spain;",
"and",
"15Dirección",
"General",
"de",
"Salud",
"Pública",
"y",
"Asistencia,",
"Avenida",
"de",
"Burgos",
"5,",
"47071",
"Valladolid,",
"Spain",
"E-mail:",
"Teresa",
"Caloto",
"-",
"Teresa_caloto@merck.com;",
"Consuelo",
"Huerta",
"-",
"chuerta@ceife.es;",
"Teresa",
"Moreno",
"-",
"mmoreno@isciii.es;",
"Dolores",
"Guerra",
"-",
"lola@enterprise.eui.upm.es;",
"José",
"Alcaide",
"-",
"jalcaide@dsss.scs.es;",
"Concha",
"Castells",
"-",
"depidebi-san@eg-gv.es;",
"José",
"I",
"Cardenal",
"-",
"jicardenal@bme.es;",
"Angela",
"Domínguez",
"-",
"angelad@dsss.scs.es;",
"Pilar",
"Gayoso",
"-",
"pgayoso@cristalp.es;",
"Gonzalo",
"Gutiérrez",
"-",
"ve@jccm.es;",
"Maria",
"J",
"López",
"-",
"mjose.lopez@larioja.org;",
"Francisco",
"Muñoz",
"-",
"med000552@nacom.es;",
"Carmen",
"Navarro",
"-",
"Carmen.Navarro@carm.es;",
"Miguel",
"Picó",
"-",
"sito@arrakis.es;",
"Francisco",
"Pozo",
"-",
"fpozo@h120.es;",
"José",
"R",
"Quirós",
"-",
"ramonqg@princast.es;",
"Francisco",
"Robles",
"-",
"froblesf@camelilla.es;",
"José",
"M",
"Sánchez",
"-",
"sanfer@teleline.es;",
"Hermelinda",
"Vanaclocha",
"-",
"vanaclocha_her@gva.es;",
"Tomás",
"Vega",
"-",
"sybs.epi@dvnet.es;",
"Mercedes",
"Diez*",
"-",
"mdiez@isciii.es",
"*Corresponding",
"author",
"Published:",
"21",
"December",
"2001",
"BMC",
"Medical",
"Research",
"Methodology",
"2001,",
"1:14",
"This",
"article",
"is",
"available",
"from:",
"http://www.biomedcentral.com/1471-2288/1/14",
"Received:",
"9",
"October",
"2001",
"Accepted:",
"21",
"December",
"2001",
"©",
"2001",
"Caloto",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"Verbatim",
"copying",
"and",
"redistribution",
"of",
"this",
"article",
"are",
"permitted",
"in",
"any",
"medium",
"for",
"any",
"purpose,",
"provided",
"this",
"notice",
"is",
"preserved",
"along",
"with",
"the",
"article's",
"original",
"URL.",
"Abstract",
"Background:",
"The",
"Multicentre",
"Project",
"for",
"Tuberculosis",
"Research",
"(MPTR)",
"was",
"a",
"clinical-",
"epidemiological",
"study",
"on",
"tuberculosis",
"carried",
"out",
"in",
"Spain",
"from",
"1996",
"to",
"1998.",
"In",
"total,",
"96",
"centres",
"scattered",
"all",
"over",
"the",
"country",
"participated",
"in",
"the",
"project,",
"19935",
"\"possible",
"cases\"",
"of",
"tuberculosis",
"were",
"examined",
"and",
"10053",
"finally",
"included.",
"Data-handling",
"and",
"quality",
"control",
"procedures",
"implemented",
"in",
"the",
"MPTR",
"are",
"described.",
"Methods:",
"The",
"study",
"was",
"divided",
"in",
"three",
"phases:",
"1)",
"preliminary",
"phase,",
"2)",
"field",
"work",
"3)",
"final",
"phase.",
"Quality",
"control",
"procedures",
"during",
"the",
"three",
"phases",
"are",
"described.",
"Results:",
"Preliminary",
"phase:",
"a)",
"organisation",
"of",
"the",
"research",
"team;",
"b)",
"design",
"of",
"epidemiological",
"tools;",
"training",
"of",
"researchers.",
"Field",
"work:",
"a)",
"data",
"collection;",
"b)",
"data",
"computerisation;",
"c)",
"data",
"transmission;",
"d)",
"data",
"cleaning;",
"e)",
"quality",
"control",
"audits;",
"f)",
"confidentiality.",
"Final",
"phase:",
"a)",
"final",
"data",
"cleaning;",
"b)",
"final",
"analysis.",
"Conclusion:",
"The",
"undertaking",
"of",
"a",
"multicentre",
"project",
"implies",
"the",
"need",
"to",
"work",
"with",
"a",
"heterogeneous",
"research",
"team",
"and",
"yet",
"at",
"the",
"same",
"time",
"attain",
"a",
"common",
"goal",
"by",
"following",
"a",
"homogeneous",
"methodology.",
"This",
"demands",
"an",
"additional",
"effort",
"on",
"quality",
"control.",
"Page",
"1",
"of",
"6",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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"Journal",
"of",
"Translational",
"Medicine",
"Research",
"Survivin",
"gene",
"levels",
"in",
"the",
"peripheral",
"blood",
"of",
"patients",
"with",
"gastric",
"cancer",
"independently",
"predict",
"survival",
"Loris",
"Bertazza1,2,",
"Simone",
"Mocellin*1,",
"Alberto",
"Marchet1,",
"Pierluigi",
"Pilati1,",
"Joseph",
"Gabrieli1,",
"Romano",
"Scalerta1",
"and",
"Donato",
"Nitti1",
"BioMed",
"Central",
"Open",
"Access",
"Address:",
"1Department",
"of",
"Oncological",
"&",
"Surgical",
"Sciences,",
"Section",
"of",
"Clinica",
"Chirurgica",
"2,",
"University",
"of",
"Padova,",
"via",
"Giustiniani",
"2,",
"35128,",
"Padua,",
"Italy",
"and",
"2Istituto",
"Oncologico",
"Veneto",
"IRCCS,",
"via",
"Gattamelata",
"64,",
"35128,",
"Padua,",
"Italy",
"Email:",
"Loris",
"Bertazza",
"-",
"loris.bertazza@unipd.it;",
"Simone",
"Mocellin*",
"-",
"simone.mocellin@unipd.it;",
"Alberto",
"Marchet",
"-",
"marchet@unipd.it;",
"Pierluigi",
"Pilati",
"-",
"pl.pilati@unipd.it;",
"Joseph",
"Gabrieli",
"-",
"josephgabrieli@yahoo.it;",
"Romano",
"Scalerta",
"-",
"romano.scalerta@unipd.it;",
"Donato",
"Nitti",
"-",
"donato.nitti@unipd.it",
"*",
"Corresponding",
"author",
"Published:",
"22",
"December",
"2009",
"Journal",
"of",
"Translational",
"Medicine",
"2009,",
"7:111",
"doi:10.1186/1479-5876-7-111",
"This",
"article",
"is",
"available",
"from:",
"http://www.translational-medicine.com/content/7/1/111",
"Received:",
"24",
"August",
"2009",
"Accepted:",
"22",
"December",
"2009",
"©",
"2009",
"Bertazza",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"The",
"detection",
"of",
"circulating",
"tumor",
"cells",
"(CTC)",
"is",
"considered",
"a",
"promising",
"tool",
"for",
"improving",
"risk",
"stratification",
"in",
"patients",
"with",
"solid",
"tumors.",
"We",
"investigated",
"on",
"whether",
"the",
"expression",
"of",
"CTC",
"related",
"genes",
"adds",
"any",
"prognostic",
"power",
"to",
"the",
"TNM",
"staging",
"system",
"in",
"patients",
"with",
"gastric",
"carcinoma.",
"Methods:",
"Seventy",
"patients",
"with",
"TNM",
"stage",
"I",
"to",
"IV",
"gastric",
"carcinoma",
"were",
"retrospectively",
"enrolled.",
"Peripheral",
"blood",
"samples",
"were",
"tested",
"by",
"means",
"of",
"quantitative",
"real",
"time",
"PCR",
"(qrtPCR)",
"for",
"the",
"expression",
"of",
"four",
"CTC",
"related",
"genes:",
"carcinoembryonic",
"antigen",
"(CEA),",
"cytokeratin-19",
"(CK19),",
"vascular",
"endothelial",
"growth",
"factor",
"(VEGF)",
"and",
"Survivin",
"(BIRC5).",
"Results:",
"Gene",
"expression",
"of",
"Survivin,",
"CK19,",
"CEA",
"and",
"VEGF",
"was",
"higher",
"than",
"in",
"normal",
"controls",
"in",
"98.6%,",
"97.1%,",
"42.9%",
"and",
"38.6%",
"of",
"cases,",
"respectively,",
"suggesting",
"a",
"potential",
"diagnostic",
"value",
"of",
"both",
"Survivin",
"and",
"CK19.",
"At",
"multivariable",
"survival",
"analysis,",
"TNM",
"staging",
"and",
"Survivin",
"mRNA",
"levels",
"were",
"retained",
"as",
"independent",
"prognostic",
"factors,",
"demonstrating",
"that",
"Survivin",
"expression",
"in",
"the",
"peripheral",
"blood",
"adds",
"prognostic",
"information",
"to",
"the",
"TNM",
"system.",
"In",
"contrast",
"with",
"previously",
"published",
"data,",
"the",
"transcript",
"abundance",
"of",
"CEA,",
"CK19",
"and",
"VEGF",
"was",
"not",
"associated",
"with",
"patients'",
"clinical",
"outcome.",
"Conclusions:",
"Gene",
"expression",
"levels",
"of",
"Survivin",
"add",
"significant",
"prognostic",
"value",
"to",
"the",
"current",
"TNM",
"staging",
"system.",
"The",
"validation",
"of",
"these",
"findings",
"in",
"larger",
"prospective",
"and",
"multicentric",
"series",
"might",
"lead",
"to",
"the",
"implementation",
"of",
"this",
"biomarker",
"in",
"the",
"routine",
"clinical",
"setting",
"in",
"order",
"to",
"optimize",
"risk",
"stratification",
"and",
"ultimately",
"personalize",
"the",
"therapeutic",
"management",
"of",
"these",
"patients.",
"Background",
"Gastric",
"cancer",
"represents",
"the",
"fourth",
"most",
"common",
"cancer",
"and",
"second",
"leading",
"cause",
"of",
"cancer-related",
"death",
"world-",
"wide.",
"The",
"estimated",
"current",
"incidence",
"of",
"gastric",
"cancer",
"is",
"approximately",
"16.2/100",
"000",
"persons/year",
"(world",
"stand-",
"ardized",
"rate,",
"WSR),",
"with",
"highest",
"incidences",
"in",
"Eastern",
"Page",
"1",
"of",
"8",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"Nucleic",
"Acids",
"Research,",
"2006,",
"Vol.",
"34,",
"Web",
"Server",
"issue",
"W15–W19",
"doi:10.1093/nar/gkl254",
"The",
"MIGenAS",
"integrated",
"bioinformatics",
"toolkit",
"for",
"web-based",
"sequence",
"analysis",
"Markus",
"Rampp*,",
"Thomas",
"Soddemann",
"and",
"Hermann",
"Lederer",
"Rechenzentrum",
"Garching",
"der",
"Max-Planck-Gesellschaft",
"(RZG),",
"am",
"Max-Planck-Institut",
"fu¨",
"r",
"Plasmaphysik,",
"Boltzmannstrasse",
"2,",
"85748",
"Garching,",
"Germany",
"Received",
"February",
"14,",
"2006;",
"Revised",
"March",
"13,",
"2006;",
"Accepted",
"March",
"30,",
"2006",
"ABSTRACT",
"We",
"describe",
"a",
"versatile",
"and",
"extensible",
"integrated",
"bioinformatics",
"toolkit",
"for",
"the",
"analysis",
"of",
"biological",
"sequences",
"over",
"the",
"Internet.",
"The",
"web",
"portal",
"offers",
"convenient",
"interactive",
"access",
"to",
"a",
"growing",
"pool",
"of",
"chainable",
"bioinformatics",
"software",
"tools",
"and",
"data-",
"bases",
"that",
"are",
"centrally",
"installed",
"and",
"maintained",
"by",
"the",
"RZG.",
"Currently,",
"supported",
"tasks",
"comprise",
"sequence",
"similarity",
"searches",
"in",
"public",
"or",
"user-",
"supplied",
"databases,",
"computation",
"and",
"validation",
"of",
"multiple",
"sequence",
"alignments,",
"phylogenetic",
"analysis",
"and",
"protein–structure",
"prediction.",
"Individual",
"tools",
"can",
"be",
"seamlessly",
"chained",
"into",
"pipelines",
"allowing",
"the",
"user",
"to",
"conveniently",
"process",
"complex",
"workflows",
"without",
"the",
"necessity",
"to",
"take",
"care",
"of",
"any",
"format",
"con-",
"versions",
"or",
"tedious",
"parsing",
"of",
"intermediate",
"results.",
"The",
"toolkit",
"is",
"part",
"of",
"the",
"Max-Planck",
"Integrated",
"Gene",
"Analysis",
"System",
"(MIGenAS)",
"of",
"the",
"Max",
"Planck",
"Society",
"available",
"at",
"www.migenas.org",
"(click",
"‘Start",
"Toolkit’).",
"INTRODUCTION",
"A",
"large",
"pool",
"of",
"individual",
"websites",
"offering",
"convenient",
"access",
"to",
"basic",
"bioinformatics",
"software",
"and",
"data",
"have",
"certainly",
"greatly",
"helped",
"to",
"establish",
"many",
"computational",
"methods",
"as",
"standard",
"tools",
"in",
"life",
"sciences.",
"Meanwhile,",
"almost",
"any",
"newly",
"published",
"bioinformatics",
"software",
"package",
"which",
"is",
"distrib-",
"uted",
"for",
"installation",
"on",
"PCs",
"is",
"supplemented",
"by",
"a",
"web",
"server",
"(hosted",
"by",
"the",
"software",
"developers",
"and/or",
"provided",
"for",
"down-",
"load",
"and",
"local",
"installation)",
"in",
"order",
"to",
"enhance",
"usability,",
"attract",
"and",
"guide",
"users,",
"and",
"to",
"promote",
"visibility",
"of",
"the",
"software",
"in",
"the",
"scientific",
"community.",
"NCBI’s",
"BLAST",
"services",
"are",
"the",
"proto-",
"typical",
"example.",
"Advanced",
"analysis,",
"however,",
"most",
"often",
"requires",
"the",
"con-",
"certed",
"interoperation",
"of",
"different",
"tools",
"and",
"heterogeneous",
"data.",
"Processing",
"the",
"corresponding",
"workflows",
"by",
"consecutively",
"visiting",
"websites",
"dispersed",
"over",
"the",
"Internet",
"is",
"apparently",
"very",
"cumbersome,",
"if",
"not",
"impracticable.",
"Apart",
"from",
"a",
"small",
"subset",
"of",
"well-defined",
"applications",
"which",
"are",
"well",
"supported",
"by",
"exist-",
"ing",
"special",
"purpose",
"software",
"[e.g.",
"the",
"ARB",
"package",
"for",
"sequence-based",
"phylogenetic",
"analysis",
"(1)]",
"surprisingly",
"few",
"integrated",
"software",
"environments",
"for",
"managing",
"such",
"workflows",
"of",
"basic",
"analysis",
"steps",
"in",
"a",
"versatile",
"and",
"user-friendly",
"way",
"are",
"publicly",
"available.",
"Existing",
"client–server",
"applications",
"may",
"be",
"subdivided",
"into",
"classic",
"web",
"portals",
"(2,3)",
"and—emerging",
"more",
"recently—solutions",
"based",
"on",
"so-called",
"rich",
"clients",
"for",
"harvest-",
"ing",
"services",
"and",
"data",
"which",
"are",
"dispersed",
"across",
"the",
"Internet",
"[cf.",
"Ref.",
"(4)",
"for",
"an",
"example",
"and",
"recent",
"overview;",
"see",
"also",
"www.",
"kepler-project.org].",
"Owing",
"to",
"its",
"service-oriented",
"software",
"architecture",
"our",
"sys-",
"tem",
"can",
"serve",
"both",
"purposes:",
"while",
"in",
"this",
"article",
"we",
"shall",
"mainly",
"focus",
"on",
"functionalities",
"offered",
"by",
"a",
"powerful",
"web",
"interface,",
"the",
"MIGenAS",
"infrastructure",
"also",
"provides",
"SOAP-",
"based",
"web",
"services",
"that",
"can",
"be",
"be",
"utilized",
"by",
"third-party",
"(remote)",
"client",
"applications.",
"FEATURES",
"AND",
"FUNCTIONALITIES",
"The",
"MIGenAS",
"bioinformatics",
"toolkit",
"is",
"a",
"new",
"web",
"application",
"for",
"processing",
"basic",
"bioinformatics",
"tasks",
"as",
"well",
"as",
"orchestrat-",
"ing",
"them",
"into",
"complex",
"workflows",
"within",
"a",
"single,",
"coherent",
"web",
"interface.",
"Target",
"users",
"are",
"only",
"assumed",
"to",
"be",
"familiar",
"with",
"the",
"basic",
"functionality",
"offered",
"by",
"the",
"popular",
"sequence",
"analysis",
"tools.",
"Neither",
"additional",
"computational",
"prerequisites",
"(A",
"mod-",
"ern",
"version",
"of",
"one",
"of",
"the",
"popular",
"web",
"browsers,",
"Mozilla/Firefox,",
"Opera",
"or",
"Internet",
"Explorer",
"is",
"required",
"with",
"JavaScript",
"enabled.)",
"nor",
"in-depth",
"bioinformatics",
"experience",
"is",
"considered",
"to",
"be",
"necessary",
"for",
"working",
"with",
"the",
"toolkit.",
"The",
"system",
"has",
"been",
"developed",
"with",
"support",
"of",
"the",
"MIGenAS",
"consortium",
"of",
"the",
"Max-Planck-Society.",
"Founding",
"members",
"are",
"the",
"Max-Planck-",
"Institute",
"(MPI)",
"of",
"Biochemistry",
"(Department",
"of",
"Oesterhelt),",
"MPI",
"for",
"Computer",
"Science",
"(Department",
"of",
"Lengauer),",
"MPI",
"for",
"Developmental",
"Biology",
"(Department",
"of",
"Lupas,",
"and",
"Group",
"S.C.",
"Schuster:",
"presently",
"at",
"Pennsylvania",
"State",
"Univer-",
"sity,",
"USA),",
"MPI",
"for",
"Marine",
"Microbiology",
"(Department",
"of",
"Amann)",
"and",
"the",
"RZG.",
"Services",
"are",
"provided",
"and",
"hosted",
"by",
"*To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"Tel:",
"+49",
"0",
"89",
"3299",
"2176;",
"Fax:",
"+49",
"0",
"80",
"3299",
"1301;",
"Email:",
"markus.rampp@rzg.mpg.de",
"The",
"Author",
"2006.",
"Published",
"by",
"Oxford",
"University",
"Press.",
"All",
"rights",
"reserved.",
"The",
"online",
"version",
"of",
"this",
"article",
"has",
"been",
"published",
"under",
"an",
"open",
"access",
"model.",
"Users",
"are",
"entitled",
"to",
"use,",
"reproduce,",
"disseminate,",
"or",
"display",
"the",
"open",
"access",
"version",
"of",
"this",
"article",
"for",
"non-commercial",
"purposes",
"provided",
"that:",
"the",
"original",
"authorship",
"is",
"properly",
"and",
"fully",
"attributed;",
"the",
"Journal",
"and",
"Oxford",
"University",
"Press",
"are",
"attributed",
"as",
"the",
"original",
"place",
"of",
"publication",
"with",
"the",
"correct",
"citation",
"details",
"given;",
"if",
"an",
"article",
"is",
"subsequently",
"reproduced",
"or",
"disseminated",
"not",
"in",
"its",
"entirety",
"but",
"only",
"in",
"part",
"or",
"as",
"a",
"derivative",
"work",
"this",
"must",
"be",
"clearly",
"indicated.",
"For",
"commercial",
"re-use,",
"please",
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] | [
"Tomkinson",
"et",
"al.",
"BMC",
"Clinical",
"Pharmacology",
"2011,",
"11:3",
"http://www.biomedcentral.com/1472-6904/11/3",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"A",
"R",
"T",
"I",
"C",
"L",
"E",
"Open",
"Access",
"Pharmacokinetics",
"and",
"tolerability",
"of",
"zibotentan",
"(ZD4054)",
"in",
"subjects",
"with",
"hepatic",
"or",
"renal",
"impairment:",
"two",
"open-label",
"comparative",
"studies",
"Helen",
"Tomkinson*,",
"John",
"Kemp,",
"Stuart",
"Oliver,",
"Helen",
"Swaisland,",
"Maria",
"Taboada,",
"Thomas",
"Morris",
"Abstract",
"Background:",
"Zibotentan",
"(ZD4054)",
"is",
"a",
"specific",
"endothelin",
"A",
"(ETA)",
"receptor",
"antagonist",
"being",
"investigated",
"for",
"the",
"treatment",
"of",
"prostate",
"cancer.",
"As",
"zibotentan",
"is",
"eliminated",
"by",
"renal",
"and",
"metabolic",
"routes,",
"clearance",
"may",
"be",
"reduced",
"in",
"patients",
"with",
"hepatic",
"or",
"renal",
"impairment,",
"leading",
"to",
"greater",
"drug",
"exposure.",
"Methods:",
"Open-label",
"studies",
"investigated",
"the",
"PK",
"and",
"tolerability",
"of",
"zibotentan",
"in",
"subjects",
"with",
"hepatic",
"or",
"renal",
"impairment,",
"compared",
"with",
"those",
"with",
"normal",
"organ",
"function.",
"In",
"the",
"hepatic",
"and",
"renal",
"studies,",
"respectively,",
"subjects",
"were",
"divided",
"into",
"categories",
"using",
"Child-Pugh",
"classification",
"or",
"24-hour",
"urine",
"creatinine",
"clearance",
"(mild,",
"moderate,",
"or",
"severe",
"impairment",
"and",
"normal",
"function).",
"Each",
"subject",
"received",
"a",
"single",
"oral",
"dose",
"of",
"zibotentan",
"10",
"mg",
"and",
"PK",
"sampling",
"was",
"undertaken.",
"Within",
"the",
"hepatic",
"study,",
"AUC",
"and",
"Cmax",
"were",
"expressed",
"as",
"the",
"ratio",
"of",
"geometric",
"means",
"and",
"90%",
"CI",
"for",
"each",
"impairment",
"group",
"compared",
"with",
"the",
"normal",
"function",
"group.",
"The",
"possibility",
"that",
"hepatic",
"impairment",
"had",
"a",
"clinically",
"relevant",
"effect",
"on",
"exposure",
"was",
"considered",
"if",
"the",
"upper",
"90%",
"CI",
"for",
"the",
"ratio",
"exceeded",
"2.",
"In",
"the",
"renal",
"study,",
"AUC,",
"Cmax",
"and",
"t1/2",
"were",
"analyzed",
"using",
"linear",
"regression",
"fitting",
"effects",
"for",
"creatinine",
"clearance",
"and",
"age.",
"Results:",
"In",
"the",
"hepatic",
"and",
"renal",
"studies",
"respectively,",
"32",
"subjects",
"(eight",
"per",
"group)",
"and",
"48",
"subjects",
"received",
"treatment",
"(n",
"=",
"18",
"normal,",
"n",
"=",
"12",
"mild,",
"n",
"=",
"9",
"moderate,",
"n",
"=",
"9",
"severe).",
"Zibotentan",
"Cmax",
"was",
"not",
"significantly",
"affected",
"by",
"hepatic",
"or",
"renal",
"impairment.",
"Compared",
"with",
"the",
"normal",
"function",
"group,",
"zibotentan",
"AUC",
"was",
"40%",
"(1.40;",
"90%",
"CI",
"0.91-2.17),",
"45%",
"(1.45;",
"90%",
"CI",
"0.94-2.24)",
"and",
"190%",
"(2.90;",
"90%",
"CI",
"1.88-4.49)",
"higher",
"in",
"subjects",
"with",
"mild,",
"moderate",
"and",
"severe",
"hepatic",
"impairment,",
"respectively,",
"and",
"66%",
"(1.66;",
"90%",
"CI",
"1.38-1.99),",
"89%",
"(1.89;",
"90%",
"CI",
"1.50-",
"2.39)",
"and",
"117%",
"(2.17;",
"90%",
"CI",
"1.64-2.86)",
"higher",
"in",
"subjects",
"with",
"mild,",
"moderate",
"and",
"severe",
"renal",
"impairment,",
"respectively.",
"In",
"both",
"studies",
"mean",
"t1/2",
"increased",
"and",
"zibotentan",
"clearance",
"decreased",
"with",
"the",
"degree",
"of",
"impairment.",
"Headache",
"was",
"the",
"most",
"common",
"AE",
"in",
"all",
"groups.",
"Conclusions:",
"Zibotentan",
"absorption",
"was",
"unchanged,",
"however,",
"exposure",
"was",
"higher",
"in",
"subjects",
"with",
"hepatic",
"or",
"renal",
"impairment",
"due",
"to",
"slower",
"clearance.",
"This",
"increased",
"exposure",
"did",
"not",
"result",
"in",
"differences",
"in",
"the",
"range",
"or",
"severity",
"of",
"AEs",
"observed.",
"Trial",
"Registration:",
"ClinicalTrials.gov:",
"NCT00672581",
"and",
"AstraZeneca",
"study",
"number",
"D4320C00016",
"(renal",
"trial;",
"conducted",
"in",
"Germany).",
"Background",
"Prostate",
"cancer",
"is",
"a",
"leading",
"cause",
"of",
"death",
"in",
"men",
"in",
"the",
"Western",
"world,",
"accounting",
"for",
"an",
"estimated",
"28%",
"of",
"new",
"cancer",
"cases",
"in",
"men",
"in",
"the",
"US",
"in",
"2010",
"[1].",
"Patients",
"with",
"advanced",
"prostate",
"cancer",
"are",
"initially",
"treated",
"with",
"andro-",
"gen",
"deprivation",
"therapy;",
"however,",
"disease",
"progression",
"will",
"*",
"Correspondence:",
"helen.tomkinson@astrazeneca.com",
"AstraZeneca,",
"Alderley",
"Park,",
"Macclesfield,",
"UK",
"eventually",
"occur",
"in",
"many",
"men",
"despite",
"castrate",
"serum",
"androgen",
"levels.",
"This",
"stage",
"of",
"disease",
"is",
"defined",
"as",
"castra-",
"tion-resistant",
"prostate",
"cancer",
"(CRPC)",
"for",
"which",
"treatment",
"is",
"currently",
"limited",
"to",
"further",
"hormonal",
"manipulation",
"or",
"cytotoxic",
"chemotherapy",
"[2].",
"The",
"endothelin",
"(ET)",
"axis",
"has",
"been",
"implicated",
"in",
"several",
"mechanisms",
"that",
"promote",
"cancer",
"progression.",
"Endothe-",
"lin-1",
"(ET-1)",
"acting",
"through",
"the",
"endothelin",
"A",
"(ETA)",
"©",
"2011",
"Tomkinson",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Frontiers",
"in",
"Zoology",
"Research",
"Bacterial",
"feeding",
"induces",
"changes",
"in",
"immune-related",
"gene",
"expression",
"and",
"has",
"trans-generational",
"impacts",
"in",
"the",
"cabbage",
"looper",
"(Trichoplusia",
"ni)",
"Dalial",
"Freitak*,",
"David",
"G",
"Heckel",
"and",
"Heiko",
"Vogel",
"BioMed",
"Central",
"Open",
"Access",
"Address:",
"Max",
"Planck",
"Institute",
"for",
"Chemical",
"Ecology,",
"Department",
"of",
"Entomology,",
"Hans",
"Knöll",
"Strasse",
"8,",
"07745",
"Jena,",
"Germany",
"Email:",
"Dalial",
"Freitak*",
"-",
"dfreitak@ice.mpg.de;",
"David",
"G",
"Heckel",
"-",
"heckel@ice.mpg.de;",
"Heiko",
"Vogel",
"-",
"hvogel@ice.mpg.de",
"*",
"Corresponding",
"author",
"Published:",
"7",
"May",
"2009",
"Frontiers",
"in",
"Zoology",
"2009,",
"6:7",
"doi:10.1186/1742-9994-6-7",
"This",
"article",
"is",
"available",
"from:",
"http://www.frontiersinzoology.com/content/6/1/7",
"Received:",
"17",
"December",
"2008",
"Accepted:",
"7",
"May",
"2009",
"©",
"2009",
"Freitak",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Background:",
"Poly-",
"and",
"oligophagous",
"insects",
"are",
"able",
"to",
"feed",
"on",
"various",
"host",
"plants",
"with",
"a",
"wide",
"range",
"of",
"defense",
"strategies.",
"However,",
"diverse",
"food",
"plants",
"are",
"also",
"inhabited",
"by",
"microbiota",
"differing",
"in",
"quality",
"and",
"quantity,",
"posing",
"a",
"potential",
"challenge",
"for",
"immune",
"system",
"mediated",
"homeostasis",
"in",
"the",
"herbivore.",
"Recent",
"studies",
"highlight",
"the",
"complex",
"interactions",
"between",
"environmentally",
"encountered",
"microorganisms",
"and",
"herbivorous",
"insects,",
"pointing",
"to",
"a",
"potential",
"adaptational",
"alteration",
"of",
"the",
"insects'",
"physiology.",
"We",
"performed",
"a",
"differential",
"gene",
"expression",
"analysis",
"in",
"whole",
"larvae",
"and",
"eggs",
"laid",
"by",
"parents",
"grown",
"on",
"different",
"diets",
"to",
"identify",
"potential",
"novel",
"genes",
"related",
"to",
"elevated",
"microbial",
"content",
"in",
"the",
"caterpillars'",
"food.",
"Results:",
"We",
"used",
"GeneFishing,",
"a",
"novel",
"differential",
"display",
"method,",
"to",
"study",
"the",
"effects",
"of",
"dietary",
"bacteria",
"on",
"the",
"general",
"gene",
"expression",
"in",
"different",
"life",
"stages",
"and",
"tissues",
"of",
"the",
"cabbage",
"looper",
"(Trichoplusia",
"ni).",
"We",
"were",
"able",
"to",
"visualize",
"several",
"hundred",
"transcripts",
"on",
"agarose",
"gels,",
"one",
"fifth",
"of",
"which",
"were",
"differentially",
"expressed",
"between",
"treatments.",
"The",
"largest",
"number",
"of",
"differentially",
"expressed",
"genes",
"was",
"found",
"in",
"defense-related",
"processes",
"(13)",
"and",
"in",
"recognition",
"and",
"metabolism",
"(16).",
"21",
"genes",
"were",
"picked",
"out",
"and",
"further",
"tested",
"for",
"differential",
"gene",
"expression",
"by",
"an",
"independent",
"method",
"(qRT-PCR)",
"in",
"various",
"tissues",
"of",
"larvae",
"grown",
"on",
"bacterial",
"and",
"bacteria-free",
"diet,",
"and",
"also",
"in",
"adults.",
"We",
"detected",
"a",
"number",
"of",
"genes",
"indicative",
"of",
"an",
"altered",
"physiological",
"status",
"of",
"the",
"insect,",
"depending",
"on",
"the",
"diet,",
"developmental",
"stage",
"and",
"tissue.",
"Conclusion:",
"Changes",
"in",
"immune",
"status",
"are",
"accompanied",
"by",
"specific",
"changes",
"in",
"the",
"transcript",
"levels",
"of",
"genes",
"connected",
"to",
"metabolism",
"and",
"homeostasis",
"of",
"the",
"organism.",
"Our",
"findings",
"show",
"that",
"larval",
"feeding",
"on",
"bacteria-rich",
"diet",
"leads",
"to",
"substantial",
"gene",
"expression",
"changes,",
"potentially",
"resulting",
"in",
"a",
"reorganization",
"of",
"the",
"insects'",
"metabolism",
"to",
"maintain",
"organismal",
"homeostasis,",
"not",
"only",
"in",
"the",
"larval",
"but",
"also",
"in",
"the",
"adult",
"stage.",
"Furthermore,",
"differences",
"in",
"gene",
"expression",
"levels",
"can",
"also",
"be",
"seen",
"in",
"the",
"next",
"generation,",
"strongly",
"influenced",
"by",
"parental",
"diet.",
"Background",
"Most",
"Lepidopteran",
"larvae",
"are",
"herbivorous",
"and",
"many",
"among",
"them",
"are",
"important",
"pests",
"in",
"agriculture,",
"causing",
"severe",
"damage",
"to",
"various",
"crop",
"plants",
"growing",
"in",
"monoc-",
"ultures.",
"The",
"level",
"of",
"specialization",
"even",
"within",
"a",
"Lepidop-",
"teran",
"family",
"can",
"vary",
"dramatically.",
"Larval",
"feeding",
"can",
"be",
"Page",
"1",
"of",
"11",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"organic",
"compounds",
"Acta",
"Crystallographica",
"Section",
"E",
"Structure",
"Reports",
"Online",
"ISSN",
"1600-5368",
"(20S)-22-Acetoxymethyl-6b-methoxy-",
"3a,5-dihydro-30H-cyclopropa[3a,5]-5a-",
"pregnane",
"Kamal",
"Aziz",
"Ketuly,",
"A.",
"Hamid",
"A.",
"Hadi",
"and",
"Seik",
"Weng",
"Ng*",
"Department",
"of",
"Chemistry,",
"University",
"of",
"Malaya,",
"50603",
"Kuala",
"Lumpur,",
"Malaysia",
"Correspondence",
"e-mail:",
"seikweng@um.edu.my",
"Received",
"27",
"May",
"2009;",
"accepted",
"31",
"May",
"2009",
"Key",
"indicators:",
"single-crystal",
"X-ray",
"study;",
"T",
"=",
"100",
"K;",
"mean",
"(C–C)",
"=",
"0.002",
"A˚;",
"R",
"factor",
"=",
"0.033;",
"wR",
"factor",
"=",
"0.092;",
"data-to-parameter",
"ratio",
"=",
"10.4.",
"In",
"the",
"title",
"steroid",
"derivative,",
"C25H40O3,",
"the",
"fused",
"cyclo-",
"propane",
"unit",
"that",
"corresponds",
"to",
"a",
"part",
"of",
"the",
"A",
"ring",
"has",
"a",
"-",
"configuration",
"and",
"the",
"associated",
"cyclopentane",
"ring",
"an",
"envelope-shaped",
"conformation.",
"Related",
"literature",
"For",
"the",
"synthesis",
"and",
"crystal",
"structure",
"of",
"the",
"iodo-substituted",
"compound,",
"see:",
"Ketuly",
"et",
"al.",
"(2009).",
"The",
"absolute",
"configura-",
"tion",
"of",
"the",
"acetoxymethyl",
"title",
"compound",
"is",
"that",
"of",
"the",
"iodo-",
"substituted",
"compound.",
"Experimental",
"Crystal",
"data",
"C25H40O3",
"Mr",
"=",
"388.57",
"Monoclinic,",
"P21",
"a",
"=",
"9.8222",
"(1)",
"A˚",
"b",
"=",
"7.6128",
"(1)",
"A˚",
"c",
"=",
"15.2309",
"(2)",
"A˚",
"=",
"107.604",
"(1)",
"Data",
"collection",
"Bruker",
"SMART",
"APEX",
"diffractometer",
"Absorption",
"correction:",
"none",
"10411",
"measured",
"reflections",
"Refinement",
"R[F",
"2",
">",
"2",
"(F",
"2)]",
"=",
"0.033",
"wR(F",
"2)",
"=",
"0.092",
"S",
"=",
"1.05",
"2674",
"reflections",
"258",
"parameters",
"V",
"=",
"1085.55",
"(2)",
"A˚",
"3",
"Z",
"=",
"2",
"Mo",
"K",
"radiation",
"=",
"0.08",
"mm",
"1",
"T",
"=",
"100",
"K",
"0.30",
"0.10",
"0.02",
"mm",
"2674",
"independent",
"reflections",
"2550",
"reflections",
"with",
"I",
">",
"2",
"(I)",
"Rint",
"=",
"0.023",
"1",
"restraint",
"H-atom",
"parameters",
"constrained",
"max",
"=",
"0.30",
"e",
"A˚",
"3",
"min",
"=",
"0.18",
"e",
"A˚",
"3",
"Data",
"collection:",
"APEX2",
"(Bruker,",
"2008);",
"cell",
"refinement:",
"SAINT",
"(Bruker,",
"2008);",
"data",
"reduction:",
"SAINT;",
"program(s)",
"used",
"to",
"solve",
"structure:",
"SHELXS97",
"(Sheldrick,",
"2008);",
"program(s)",
"used",
"to",
"refine",
"structure:",
"SHELXL97",
"(Sheldrick,",
"2008);",
"molecular",
"graphics:",
"X-",
"SEED",
"(Barbour,",
"2001);",
"software",
"used",
"to",
"prepare",
"material",
"for",
"publication:",
"publCIF",
"(Westrip,",
"2009).",
"We",
"thank",
"the",
"University",
"of",
"Malaya",
"for",
"supporting",
"this",
"study.",
"Supplementary",
"data",
"and",
"figures",
"for",
"this",
"paper",
"are",
"available",
"from",
"the",
"IUCr",
"electronic",
"archives",
"(Reference:",
"XU2534).",
"References",
"Barbour,",
"L.",
"J.",
"(2001).",
"J.",
"Supramol.",
"Chem.",
"1,",
"189–211.",
"Bruker",
"(2008).",
"APEX2",
"and",
"SAINT.",
"Bruker",
"AXS",
"Inc.,",
"Madison,",
"Wisconsin,",
"USA.",
"Ketuly,",
"K.",
"A.",
"A.,",
"Hadi,",
"A.",
"H.",
"&",
"Ng,",
"S.",
"W.",
"(2009).",
"Acta",
"Cryst.",
"E65,",
"o1125.",
"Sheldrick,",
"G.",
"M.",
"(2008).",
"Acta",
"Cryst.",
"A64,",
"112–122.",
"Westrip,",
"S.",
"P.",
"(2009).",
"publCIF.",
"In",
"preparation.",
"o1486",
"Ketuly",
"et",
"al.",
"doi:10.1107/S1600536809020674",
"Acta",
"Cryst.",
"(2009).",
"E65,",
"o1486"
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316,
1062,
482,
1074
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[
629,
1062,
651,
1074
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[
654,
1062,
682,
1074
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[
685,
1062,
720,
1074
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[
722,
1062,
744,
1074
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[
747,
1062,
784,
1074
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] | [
"inorganic",
"compounds",
"Acta",
"Crystallographica",
"Section",
"E",
"Structure",
"Reports",
"Online",
"ISSN",
"1600-5368",
"Robertsite,",
"Ca2MnIII3O2(PO4)3",
"3H2O",
"Marcelo",
"B.",
"Andrade,a*",
"Shaunna",
"M.",
"Morrison,a",
"Adrien",
"J.",
"Di",
"Domizio,a",
"Mark",
"N.",
"Feinglosb",
"and",
"Robert",
"T.",
"Downsa",
"aDepartment",
"of",
"Geosciences,",
"University",
"of",
"Arizona,",
"1040",
"E.",
"4th",
"Street,",
"Tucson,",
"Arizona",
"85721-0077,",
"USA,",
"and",
"bDuke",
"University",
"Medical",
"Center,",
"Box",
"3921,",
"Durham,",
"North",
"Carolina",
"27710,",
"USA",
"Correspondence",
"e-mail:",
"mabadean@terra.com.br",
"Received",
"13",
"August",
"2012;",
"accepted",
"30",
"August",
"2012",
"Key",
"indicators:",
"single-crystal",
"X-ray",
"study;",
"T",
"=",
"293",
"K;",
"mean",
"(P–O)",
"=",
"0.006",
"A˚;",
"R",
"factor",
"=",
"0.045;",
"wR",
"factor",
"=",
"0.107;",
"data-to-parameter",
"ratio",
"=",
"18.7.",
"Robertsite,",
"ideally",
"Ca2Mn3O2(PO4)3",
"3H2O",
"[calcium",
"manga-",
"nese(III)",
"tris(orthophosphate)",
"trihydrate],",
"can",
"be",
"associated",
"with",
"the",
"arseniosiderite",
"structural",
"group",
"characterized",
"by",
"the",
"general",
"formula",
"Ca2A3O2(TO4)3",
"nH2O,",
"with",
"A",
"=",
"Fe,",
"Mn;",
"T",
"=",
"As,",
"P;",
"and",
"n",
"=",
"2",
"or",
"3.",
"In",
"this",
"study,",
"single-crystal",
"X-ray",
"diffraction",
"data",
"were",
"used",
"to",
"determine",
"the",
"robertsite",
"structure",
"from",
"a",
"twinned",
"crystal",
"from",
"the",
"type",
"locality,",
"the",
"Tip",
"Top",
"mine,",
"Custer",
"County,",
"South",
"Dakota,",
"USA,",
"and",
"to",
"refine",
"anisotropic",
"displacement",
"parameters",
"for",
"all",
"atoms.",
"The",
"general",
"structural",
"feature",
"of",
"robertsite",
"resembles",
"that",
"of",
"the",
"other",
"two",
"members",
"of",
"the",
"arseniosiderite",
"group,",
"the",
"structures",
"of",
"which",
"have",
"previously",
"been",
"reported.",
"It",
"is",
"characterized",
"by",
"sheets",
"of",
"[MnO6]",
"octahedra",
"in",
"the",
"form",
"of",
"nine-membered",
"pseudo-trigonal",
"rings.",
"Located",
"at",
"the",
"center",
"of",
"each",
"nine-",
"membered",
"ring",
"is",
"a",
"PO4",
"tetrahedron,",
"and",
"the",
"other",
"eight",
"PO4",
"tetrahedra",
"sandwich",
"the",
"Mn–oxide",
"sheets.",
"The",
"six",
"different",
"Ca2+",
"ions",
"are",
"seven-coordinated",
"in",
"form",
"of",
"distorted",
"penta-",
"gonal",
"bipyramids,",
"[CaO5(H2O)2],",
"if",
"Ca—O",
"distances",
"less",
"than",
"2.85",
"A˚",
"are",
"considered.",
"Along",
"with",
"hydrogen",
"bonding",
"invol-",
"ving",
"the",
"water",
"molecules,",
"they",
"hold",
"the",
"manganese–phosphate",
"sheets",
"together.",
"All",
"nine",
"[MnO6]",
"octahedra",
"are",
"distorted",
"by",
"the",
"Jahn–Teller",
"effect.",
"Related",
"literature",
"For",
"information",
"on",
"the",
"arseniosiderite",
"group",
"minerals,",
"see:",
"Moore",
"&",
"Ito",
"(1974);",
"Moore",
"&",
"Araki",
"(1977);",
"van",
"Kauwen-",
"bergh",
"et",
"al.",
"(1988);",
"Voloshin",
"et",
"al.",
"(1982).",
"For",
"details",
"of",
"sailaufite,",
"see:",
"Wildner",
"et",
"al.",
"(2003).",
"For",
"studies",
"on",
"para-",
"robertsite,",
"see:",
"Roberts",
"et",
"al.",
"(1989);",
"Kampf",
"(2000).",
"For",
"research",
"involving",
"Mn3+",
"pairing",
"in",
"phosphate",
"minerals,",
"see:",
"Fransolet",
"(2000).",
"For",
"information",
"on",
"crystalline",
"manganese",
"phosphate-based",
"adsorbers,",
"see:",
"Kulprathipanja",
"et",
"al.",
"(2001).",
"Experimental",
"Crystal",
"data",
"Ca2Mn3O2(PO4)3",
"3H2O",
"Mr",
"=",
"615.94",
"Monoclinic,",
"Aa",
"a",
"=",
"17.3400",
"(9)",
"A˚",
"b",
"=",
"19.4464",
"(10)",
"A˚",
"c",
"=",
"11.2787",
"(6)",
"A˚",
"=",
"96.634",
"(3)",
"Data",
"collection",
"Bruker",
"APEXII",
"CCD",
"area-detector",
"diffractometer",
"Absorption",
"correction:",
"multi-scan",
"(SADABS;",
"Bruker,",
"2004)",
"Tmin",
"=",
"0.755,",
"Tmax",
"=",
"0.784",
"Refinement",
"R[F",
"2",
">",
"2",
"(F",
"2)]",
"=",
"0.045",
"wR(F",
"2)",
"=",
"0.107",
"S",
"=",
"1.02",
"12635",
"reflections",
"677",
"parameters",
"2",
"restraints",
"Table",
"1",
"Hydrogen-bond",
"geometry",
"(A˚",
").",
"V",
"=",
"3777.7",
"(3)",
"A˚",
"3",
"Z",
"=",
"12",
"Mo",
"K",
"radiation",
"=",
"4.26",
"mm",
"1",
"T",
"=",
"293",
"K",
"0.07",
"0.06",
"0.06",
"mm",
"28397",
"measured",
"reflections",
"12635",
"independent",
"reflections",
"9678",
"reflections",
"with",
"I",
">",
"2",
"(I)",
"Rint",
"=",
"0.037",
"max",
"=",
"1.74",
"e",
"A˚",
"3",
"min",
"=",
"1.09",
"e",
"A˚",
"3",
"Absolute",
"structure:",
"Flack",
"(1983),",
"5755",
"Friedel",
"pairs",
"Flack",
"parameter:",
"0.676",
"(18)",
"D",
"A",
"D",
"A",
"D",
"A",
"D",
"A",
"O25iii",
"Ow5",
"2.792",
"(7)",
"Ow1",
"O17",
"2.964",
"(7)",
"O13iv",
"Ow6",
"2.977",
"(6)",
"Ow1",
"O33",
"2.889",
"(8)",
"Ow9ii",
"Ow6",
"2.651",
"(7)",
"Ow2",
"O33",
"2.815",
"(7)",
"O9v",
"Ow7",
"2.768",
"(7)",
"Ow2",
"Ow8",
"2.655",
"(8)",
"Ow3vi",
"Ow7",
"2.645",
"(7)",
"Ow3",
"O1i",
"2.957",
"(4)",
"Ow8",
"O13",
"2.710",
"(8)",
"Ow3",
"O17",
"2.821",
"(6)",
"Ow8",
"Ow1",
"2.635",
"(7)",
"Ow4",
"O29",
"2.764",
"(7)",
"O12v",
"Ow9",
"2.989",
"(7)",
"Ow4",
"Ow9",
"2.631",
"(8)",
"O21vii",
"Ow9",
"2.743",
"(8)",
"Ow5",
"Ow7ii",
"2.682",
"(8)",
"Symmetry",
"codes:",
"(i)",
"x",
"þ",
"2;",
"1",
"y",
"þ",
"21;",
"z",
"þ",
"21;",
"(ii)",
"x;",
"y;",
"z",
"þ",
"1;",
"(iii)",
"x",
"þ",
"21;",
"y",
"þ",
"1;",
"z;",
"(iv)",
"x;",
"y",
"12;",
"z",
"þ",
"21;",
"(v)",
"x",
"þ",
"12;",
"y",
"þ",
"21;",
"z",
"12;",
"(vi)",
"x;",
"y",
"þ",
"21;",
"z",
"12;",
"(vii)",
"x;",
"y;",
"z",
"1.",
"Data",
"collection:",
"APEX2",
"(Bruker,",
"2004);",
"cell",
"refinement:",
"SAINT",
"(Bruker,",
"2004);",
"data",
"reduction:",
"SAINT;",
"program(s)",
"used",
"to",
"solve",
"structure:",
"SHELXS97",
"(Sheldrick,",
"2008);",
"program(s)",
"used",
"to",
"refine",
"structure:",
"SHELXL97",
"(Sheldrick,",
"2008);",
"molecular",
"graphics:",
"Xtal-",
"Draw",
"(Downs",
"&",
"Hall-Wallace,",
"2003);",
"software",
"used",
"to",
"prepare",
"material",
"for",
"publication:",
"publCIF",
"(Westrip,",
"2010).",
"We",
"are",
"very",
"grateful",
"to",
"A.",
"R.",
"Kampf",
"and",
"T.",
"A.",
"Loomis",
"for",
"providing",
"the",
"rare",
"pararobertsite",
"samples",
"to",
"the",
"RRUFF",
"project.",
"Support",
"of",
"this",
"study",
"was",
"given",
"by",
"the",
"Arizona",
"Science",
"Foundation,",
"CNPq",
"202469/2011-5",
"from",
"the",
"Brazilian",
"government,",
"and",
"NASA",
"NNX11AN75A,",
"Mars",
"Science",
"Laboratory",
"Investigations.",
"Any",
"opinions,",
"findings,",
"and",
"conclusions",
"or",
"recommendations",
"expressed",
"in",
"this",
"material",
"are",
"those",
"of",
"the",
"author(s)",
"and",
"do",
"not",
"reflect",
"the",
"views",
"of",
"the",
"National",
"Aeronautics",
"and",
"Space",
"Administration.",
"Supplementary",
"data",
"and",
"figures",
"for",
"this",
"paper",
"are",
"available",
"from",
"the",
"IUCr",
"electronic",
"archives",
"(Reference:",
"WM2672).",
"References",
"Bruker",
"(2004).",
"APEX2,",
"SAINT",
"and",
"SADABS.",
"Bruker",
"AXS",
"Inc.,",
"Madison,",
"Wisconsin,",
"USA.",
"i74",
"Andrade",
"et",
"al.",
"doi:10.1107/S160053681203735X",
"Acta",
"Cryst.",
"(2012).",
"E68,",
"i74–i75"
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] | [
"O",
"R",
"I",
"G",
"I",
"N",
"A",
"L",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"Lack",
"of",
"association",
"between",
"angiotensin-",
"conver",
"ting",
"enzyme",
"and",
"dementia",
"of",
"the",
"Alzheimer’s",
"type",
"in",
"an",
"elderly",
"Arab",
"population",
"in",
"Wadi",
"Ara,",
"Israel",
"Abdalla",
"Bowirrat1,2,3",
"Jing",
"Cui4",
"Kristin",
"Waraska5",
"Robert",
"P",
"Friedland10",
"Marlene",
"Oscar-Berman2,3,6",
"Lindsay",
"A",
"Farrer1,6,7,8,9",
"Amos",
"Korczyn11",
"Clinton",
"T",
"Baldwin1,5,7",
"1Genetic",
"Program,",
"2Department",
"of",
"Anatomy",
"and",
"Neurobiology,",
"3Division",
"of",
"Psychiatry,",
"4Hypertension",
"Section,",
"5Center",
"for",
"Human",
"Genetics,",
"6Department",
"of",
"Neurology,",
"7Department",
"of",
"Genetics",
"and",
"Genomics,",
"Boston",
"University",
"School",
"of",
"Medicine,",
"Boston,",
"MA,",
"USA;",
"8Department",
"of",
"Epidemiology,",
"9Department",
"of",
"Biostatistics,",
"Boston",
"University",
"School",
"of",
"Public",
"Health,",
"Boston,",
"MA,",
"USA;",
"10Department",
"of",
"Neurology,",
"Case",
"Western",
"Reserve",
"University,",
"Cleveland,",
"OH,",
"USA;",
"11Department",
"of",
"Neurology,",
"Tel",
"Aviv",
"University,",
"Tel",
"Aviv,",
"Israel",
"Correspondence:",
"Abdalla",
"Bowirrat",
"Department",
"of",
"Anatomy",
"and",
"Neurobiology,",
"Laboratory",
"of",
"Neuropsychology,",
"Boston",
"University",
"School",
"of",
"Medicine,",
"715",
"Albany",
"Street,",
"L-815",
"Boston,",
"MA",
"02118,",
"USA",
"Tel",
"+1",
"617",
"638",
"4807",
"Fax",
"+1",
"617",
"638",
"4806",
"Email",
"bowirrat@bu.edu",
"Abstract:",
"The",
"angiotensin-converting",
"enzyme",
"(ACE),",
"a",
"protease",
"involved",
"in",
"blood",
"pressure",
"regulation,",
"has",
"been",
"implicated",
"as",
"an",
"important",
"candidate",
"gene",
"for",
"Alzheimer’s",
"disease",
"(AD).",
"This",
"study",
"investigated",
"whether",
"the",
"ACE",
"gene",
"insertion–deletion",
"(ID)",
"polymorphism",
"is",
"associated",
"with",
"risk",
"of",
"developing",
"dementia",
"of",
"Alzheimer’s",
"type",
"(DAT)",
"in",
"an",
"Arab–Israeli",
"community,",
"a",
"unique",
"genetic",
"isolate",
"where",
"there",
"is",
"a",
"high",
"prevalence",
"of",
"DAT.",
"In",
"contrast",
"to",
"several",
"other",
"studies,",
"we",
"found",
"no",
"evidence",
"of",
"an",
"association",
"between",
"this",
"polymorphism",
"and",
"either",
"DAT",
"or",
"age-related",
"cognitive",
"decline",
"(ARCD).",
"Keywords:",
"angiotensin-converting",
"enzyme,",
"dementia",
"of",
"the",
"Alzheimer’s",
"type,",
"age-related",
"cognitive",
"decline,",
"insertion–deletion",
"polymorphism,",
"Arab",
"population",
"Introduction",
"Alzheimer’s",
"disease",
"(AD)",
"is",
"a",
"catastrophic",
"affliction",
"of",
"the",
"middle",
"and",
"later",
"years",
"of",
"life.",
"Clinically,",
"it",
"is",
"marked",
"by",
"an",
"irreversible",
"decline",
"in",
"mental",
"abilities,",
"including",
"progressive",
"loss",
"of",
"memory,",
"confusion,",
"and",
"dementia,",
"and",
"culminates",
"in",
"childlike",
"helplessness.",
"In",
"the",
"United",
"States,",
"the",
"incidence",
"of",
"AD",
"is",
"exponentially",
"increasing",
"and",
"is",
"projected",
"to",
"affect",
"8.64",
"million",
"people",
"by",
"the",
"year",
"2047",
"(Grossberg",
"2003).",
"Median",
"survival",
"times",
"range",
"from",
"8.3",
"years",
"for",
"persons",
"diagnosed",
"at",
"age",
"65,",
"to",
"3.4",
"years",
"for",
"persons",
"diagnosed",
"at",
"age",
"90",
"(Brookmeyer",
"et",
"al",
"2002).",
"Angiotensin-converting",
"enzyme",
"(ACE)",
"catalyzes",
"the",
"conversion",
"of",
"angiotensin",
"I",
"into",
"a",
"physiologically",
"active",
"peptide,",
"angiotensin",
"II.",
"This",
"reaction",
"is",
"an",
"important",
"process",
"in",
"blood",
"pressure",
"regulation.",
"In",
"addition",
"to",
"this",
"well",
"known",
"physiologic",
"role,",
"ACE",
"is",
"able",
"to",
"cleave",
"other",
"proteins,",
"including",
"bradykinin",
"and",
"substance",
"P,",
"and",
"has",
"been",
"shown",
"to",
"inhibit",
"and",
"cleave",
"amyloid",
"β-peptide",
"(Aβ)",
"aggregation",
"and",
"amyloid",
"plaque",
"formation",
"in",
"vitro",
"(Hu",
"et",
"al",
"2001).",
"ACE",
"may",
"contribute",
"to",
"the",
"pathogenesis",
"of",
"AD.",
"To",
"test",
"the",
"hypothesis",
"of",
"association",
"between",
"ACE",
"and",
"DAT,",
"we",
"evaluated",
"an",
"insertion–deletion",
"(ID)",
"polymorphism",
"in",
"the",
"ACE",
"gene",
"as",
"a",
"potential",
"risk",
"factor",
"for",
"dementia",
"of",
"the",
"Alzheimer’s",
"type",
"(DAT)",
"in",
"an",
"Arab",
"community",
"in",
"Wadi",
"Ara,",
"Israel.",
"The",
"population",
"comprised",
"853",
"persons",
"over",
"the",
"age",
"of",
"65",
"(Bowirrat",
"et",
"al",
"2001;",
"Bowirrat,",
"Friedland,",
"Farrer,",
"et",
"al",
"2002).",
"Family",
"studies",
"revealed",
"that",
"more",
"than",
"one-",
"third",
"of",
"DAT",
"cases",
"are",
"members",
"of",
"one",
"extended",
"family.",
"We",
"hypothesized",
"that",
"DAT",
"in",
"Wadi",
"Ara",
"may",
"be",
"due",
"to",
"a",
"founder",
"effect",
"enhanced",
"by",
"consanguinity;",
"thus,",
"a",
"specific",
"disease",
"susceptibility",
"allele",
"may",
"be",
"overrepresented",
"in",
"cognitively",
"impaired",
"subjects",
"compared",
"with",
"cognitively",
"healthy",
"residents.",
"Our",
"results",
"suggest",
"that",
"the",
"Neuropsychiatric",
"Disease",
"and",
"Treatment",
"2005:1(1)",
"73",
"–76",
"©",
"2005",
"Dove",
"Medical",
"Press",
"Limited.",
"All",
"rights",
"reserved",
"73"
] | [
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1,
1,
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1,
1,
1,
1,
1,
1,
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1,
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1,
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1,
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1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
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] | [
"Akech",
"et",
"al.",
"BMC",
"Pediatrics",
"2010,",
"10:71",
"http://www.biomedcentral.com/1471-2431/10/71",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"A",
"R",
"T",
"I",
"C",
"L",
"E",
"Open",
"Access",
"Phase",
"II",
"trial",
"of",
"isotonic",
"fluid",
"resuscitation",
"in",
"Kenyan",
"children",
"with",
"severe",
"malnutrition",
"and",
"hypovolaemia",
"Samuel",
"O",
"Akech1,",
"Japhet",
"Karisa1,",
"Phellister",
"Nakamya1,",
"Mwanamvua",
"Boga1,",
"Kathryn",
"Maitland1,2,3*",
"Abstract",
"Background:",
"Children",
"with",
"severe",
"malnutrition",
"who",
"develop",
"shock",
"have",
"a",
"high",
"mortality.",
"Contrary",
"to",
"contemporaneous",
"paediatric",
"practice,",
"current",
"guidelines",
"recommend",
"use",
"of",
"low",
"dose",
"hypotonic",
"fluid",
"resuscitation",
"(half-strength",
"Darrows/5%",
"dextrose",
"(HSD/5D).",
"We",
"evaluated",
"the",
"safety",
"and",
"efficacy",
"of",
"this",
"guideline",
"compared",
"to",
"resuscitation",
"with",
"a",
"standard",
"isotonic",
"solution.",
"Methods:",
"A",
"Phase",
"II",
"randomised",
"controlled,",
"safety",
"and",
"efficacy",
"trial",
"in",
"Kenyan",
"children",
"aged",
"over",
"6",
"months",
"with",
"severe",
"malnutrition",
"and",
"shock",
"including",
"children",
"with",
"severe",
"dehydration/shock",
"and",
"presumptive",
"septic",
"shock",
"(non-diarrhoeal",
"shock).",
"Eligible",
"children",
"were",
"randomised",
"to",
"HSD/5D",
"or",
"Ringer’s",
"Lactate",
"(RL).",
"A",
"maximum",
"of",
"two",
"boluses",
"of",
"15",
"ml/kg",
"of",
"HSD/5D",
"were",
"given",
"over",
"two",
"hours",
"(as",
"recommended",
"by",
"guidelines)",
"while",
"those",
"randomised",
"to",
"RL",
"received",
"10",
"ml/kg",
"aliquots",
"half",
"hourly",
"(maximum",
"40",
"ml/kg).",
"Primary",
"endpoint",
"was",
"resolution",
"of",
"shock",
"at",
"8",
"and",
"24",
"hours.",
"Secondary",
"outcomes",
"included",
"resolution",
"of",
"acidosis,",
"adverse",
"events",
"and",
"mortality.",
"Results:",
"61",
"children",
"were",
"enrolled:",
"41",
"had",
"shock",
"and",
"severe",
"dehydrating",
"diarrhoea,",
"20",
"had",
"presumptive",
"septic",
"shock;",
"69%",
"had",
"decompensated",
"shock.",
"By",
"8",
"hours",
"response",
"to",
"volume",
"resuscitation",
"was",
"poor",
"with",
"shock",
"persisting",
"in",
"most",
"children:-HSD/5D",
"15/22",
"(68%)",
"and",
"RL14/25",
"(52%),",
"p",
"=",
"0.39.",
"Oliguria",
"was",
"more",
"prevalent",
"at",
"8",
"hours",
"in",
"the",
"HSD/5D",
"group,",
"9/22",
"(41%),",
"compared",
"to",
"RL-3/25",
"(12%),",
"p",
"=",
"0.02.",
"Mortality",
"was",
"high,",
"HSD/5D-15/26",
"(58%)",
"and",
"RL",
"13/29(45%);",
"p",
"=",
"0.42.",
"Most",
"deaths",
"occurred",
"within",
"48",
"hours",
"of",
"admission.",
"Neither",
"pulmonary",
"oedema",
"nor",
"cardiogenic",
"failure",
"was",
"detected.",
"Conclusions:",
"Outcome",
"was",
"universally",
"poor",
"characterised",
"by",
"persistence",
"of",
"shock,",
"oliguria",
"and",
"high",
"case",
"fatality.",
"Isotonic",
"fluid",
"was",
"associated",
"with",
"modest",
"improvement",
"in",
"shock",
"and",
"survival",
"when",
"compared",
"to",
"HSD/5D",
"but",
"inconclusive",
"due",
"to",
"the",
"limitations",
"of",
"design",
"and",
"effectiveness",
"of",
"either",
"resuscitation",
"strategy.",
"Although",
"isotonic",
"fluid",
"resuscitation",
"did",
"not",
"result",
"in",
"cardiogenic",
"heart",
"failure,",
"as",
"previously",
"feared,",
"we",
"conclude",
"that",
"the",
"modest",
"volumes",
"used",
"and",
"rate",
"of",
"infusion",
"were",
"insufficient",
"to",
"promptly",
"correct",
"shock.",
"The",
"adverse",
"performance",
"of",
"the",
"recommended",
"fluid",
"resuscitation",
"guideline",
"for",
"severe",
"malnutrition",
"should",
"prompt",
"clinical",
"investigation",
"of",
"isotonic",
"fluids",
"for",
"resuscitation",
"of",
"compensated",
"shock,",
"defining",
"rate",
"and",
"volumes",
"required",
"to",
"inform",
"future",
"guidelines.",
"Trial",
"Registration:",
"The",
"trial",
"is",
"registered",
"as",
"ISCRTN:",
"61146418.",
"Background",
"Severe",
"malnutrition",
"is",
"a",
"common",
"cause",
"of",
"admission",
"to",
"hospital",
"in",
"young",
"children",
"in",
"Africa",
"and",
"outcome",
"remains",
"poor.",
"The",
"World",
"Health",
"Organization",
"(WHO)",
"10-step",
"treatment",
"has",
"improved",
"case",
"fatality,",
"in",
"some",
"*",
"Correspondence:",
"kmaitland@kilifi.kemri-wellcome.org",
"1KEMRI-Wellcome",
"Trust",
"Research",
"Programme,",
"Centre",
"for",
"Geographic",
"Medicine",
"Research-Coast,",
"Kilifi,",
"Kenya",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"settings,",
"to",
"under",
"5%",
"[1-3],",
"however,",
"in",
"African",
"hospitals",
"implementation",
"of",
"the",
"same",
"guideline",
"has",
"achieved",
"poorer",
"results",
"with",
"numerous",
"reports",
"of",
"unacceptably",
"high",
"case",
"fatality",
"rates",
"[4,5].",
"At",
"our",
"hospital",
"on",
"the",
"Ken-",
"yan",
"coast,",
"we",
"have",
"recently",
"reported",
"that",
"mortality",
"rates",
"in",
"children",
"with",
"severe",
"malnutrition,",
"treated",
"in",
"accor-",
"dance",
"with",
"WHO",
"guidelines,",
"were",
"20%.",
"Thirty",
"percent",
"of",
"the",
"fatalities",
"occurred",
"within",
"48",
"hours",
"of",
"admission",
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] | [
"SAGE-Hindawi",
"Access",
"to",
"Research",
"Stroke",
"Research",
"and",
"Treatment",
"Volume",
"2011,",
"Article",
"ID",
"304921,",
"7",
"pages",
"doi:10.4061/2011/304921",
"Review",
"Article",
"The",
"Migraine-Ischemic",
"Stroke",
"Relation",
"in",
"Young",
"Adults",
"Alessandro",
"Pezzini,1",
"Elisabetta",
"Del",
"Zotto,2",
"Alessia",
"Giossi,1",
"Irene",
"Volonghi,1",
"Paolo",
"Costa,1",
"Giorgio",
"Dalla",
"Volta,3",
"and",
"Alessandro",
"Padovani1",
"1",
"Dipartimento",
"di",
"Scienze",
"Mediche",
"e",
"Chirurgiche,",
"Clinica",
"Neurologica,",
"Universita`",
"degli",
"Studi",
"di",
"Brescia,",
"Piazzale",
"Spedali",
"Civili,",
"1,",
"25100",
"Brescia,",
"Italy",
"2",
"Dipartimento",
"di",
"Scienze",
"Biomediche",
"e",
"Biotecnologie,",
"Universita`",
"degli",
"Studi",
"di",
"Brescia,",
"25100",
"Brescia,",
"Italy",
"3",
"Unita`",
"di",
"Neurologia,",
"Istituto",
"Clinico",
"Citta`",
"di",
"Brescia,",
"25123",
"Brescia,",
"Italy",
"Correspondence",
"should",
"be",
"addressed",
"to",
"Alessandro",
"Pezzini,",
"ale",
"pezzini@hotmail.com",
"Received",
"19",
"September",
"2010;",
"Accepted",
"22",
"November",
"2010",
"Academic",
"Editor:",
"Halvor",
"Naess",
"Copyright",
"©",
"2011",
"Alessandro",
"Pezzini",
"et",
"al.",
"This",
"is",
"an",
"open",
"access",
"article",
"distributed",
"under",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"In",
"spite",
"of",
"the",
"strong",
"epidemiologic",
"evidence",
"linking",
"migraine",
"and",
"ischemic",
"stroke",
"in",
"young",
"adults,",
"the",
"mechanisms",
"explaining",
"this",
"association",
"remain",
"poorly",
"understood.",
"The",
"observation",
"that",
"stroke",
"occurs",
"more",
"frequently",
"during",
"the",
"interictal",
"phase",
"of",
"migraine",
"prompts",
"to",
"speculation",
"that",
"an",
"indirect",
"relation",
"between",
"the",
"two",
"diseases",
"might",
"exist.",
"In",
"this",
"regard,",
"four",
"major",
"issues",
"might",
"be",
"considered",
"which",
"may",
"be",
"summarized",
"as",
"follows:",
"(1)",
"the",
"migraine-ischemic",
"stroke",
"relation",
"is",
"influenced",
"by",
"specific",
"risk",
"factors",
"such",
"as",
"patent",
"foramen",
"ovale",
"or",
"endothelial",
"dysfunction",
"and",
"more",
"frequent",
"in",
"particular",
"conditions",
"like",
"spontaneous",
"cervical",
"artery",
"dissection;",
"(2)",
"migraine",
"is",
"associated",
"with",
"an",
"increased",
"prevalence",
"of",
"cardiovascular",
"risk",
"factors;",
"(3)",
"the",
"link",
"is",
"caused",
"by",
"migraine-specific",
"drugs;",
"(4)",
"migraine",
"and",
"ischemic",
"vascular",
"events",
"are",
"linked",
"via",
"a",
"genetic",
"component.",
"In",
"the",
"present",
"paper,",
"we",
"will",
"review",
"epidemiological",
"studies,",
"discuss",
"potential",
"mechanisms",
"of",
"migraine-induced",
"stroke",
"and",
"comorbid",
"ischemic",
"stroke,",
"and",
"pose",
"new",
"research",
"questions.",
"1.",
"Introduction",
"Migraine",
"affects",
"about",
"15%",
"of",
"people",
"in",
"developed",
"countries",
"[1]",
"and",
"is",
"three",
"times",
"more",
"common",
"in",
"women",
"than",
"in",
"men.",
"Patients",
"have",
"a",
"median",
"of",
"one",
"attack",
"per",
"month,",
"and",
"25%",
"have",
"at",
"least",
"two",
"attacks",
"per",
"month",
"[2].",
"Patients",
"with",
"more",
"than",
"one",
"attack",
"per",
"month",
"are",
"at",
"increased",
"risk",
"of",
"brain",
"lesions",
"[3].",
"In",
"the",
"last",
"decades,",
"several",
"studies",
"have",
"emphasized",
"the",
"high",
"prevalence",
"of",
"migraine",
"among",
"young",
"individuals",
"with",
"stroke",
"as",
"well",
"as",
"a",
"dysfunction",
"of",
"cerebral",
"arteries",
"during",
"migraine",
"attacks",
"and",
"the",
"finding",
"of",
"silent",
"infarct-like",
"brain",
"lesions",
"in",
"migraineurs,",
"thus",
"leading",
"to",
"the",
"hypothesis",
"that",
"a",
"comorbidity",
"between",
"migraine",
"and",
"cerebral",
"ischemia",
"exists",
"[4].",
"2.",
"Evidence",
"of",
"Association",
"The",
"first",
"epidemiological",
"suggestion",
"that",
"migraine",
"may",
"be",
"an",
"independent",
"risk",
"factor",
"for",
"stroke",
"came",
"from",
"the",
"Col-",
"laborative",
"Group",
"for",
"the",
"Study",
"of",
"Stroke",
"in",
"Young",
"Women,",
"published",
"in",
"1975,",
"which",
"showed",
"an",
"increased",
"relative",
"risk",
"of",
"stroke",
"with",
"migraine",
"compared",
"with",
"neighbor",
"controls",
"[5].",
"Since",
"then,",
"the",
"association",
"of",
"migraine",
"with",
"the",
"risk",
"of",
"stroke",
"has",
"been",
"investigated",
"in",
"several",
"observational",
"studies,",
"most",
"of",
"which",
"have",
"been",
"summarized",
"in",
"a",
"recent",
"meta-analysis",
"[6].",
"According",
"to",
"this",
"meta-analysis,",
"the",
"pooled",
"relative",
"risk",
"of",
"ischemic",
"stroke",
"among",
"patients",
"with",
"any",
"type",
"of",
"migraine",
"is",
"1.73",
"(95%",
"CI,",
"1.31",
"to",
"2.29).",
"The",
"relative",
"risk",
"for",
"women",
"is",
"increased",
"(RR",
"2.08,",
"95%",
"CI",
"1.13",
"to",
"3.84)",
"but",
"not",
"for",
"men",
"(RR",
"1.37,",
"95%",
"CI",
"0.89",
"to",
"2.11).",
"Stratifying",
"analysis",
"by",
"age,",
"people",
"with",
"migraine",
"aged",
"less",
"than",
"45",
"have",
"an",
"higher",
"risk",
"than",
"the",
"overall",
"group",
"(RR",
"2.65,",
"95%",
"CI",
"1.41",
"to",
"4.97),",
"which",
"was",
"further",
"increased",
"among",
"young",
"women",
"(RR",
"3.95,",
"95%",
"CI",
"2.21",
"to",
"6.04).",
"The",
"risk",
"is",
"apparently",
"more",
"than",
"tripled",
"by",
"smoking",
"(RR",
"9.09,",
"95%",
"CI",
"4.22",
"to",
"19.34)",
"and",
"more",
"pronounced",
"by",
"oral",
"contraceptives",
"(OCs)",
"use",
"(RR",
"7.02,",
"95%",
"CI",
"1.51",
"to",
"32.68).",
"In",
"line",
"with",
"this",
"analysis,",
"data",
"from",
"the",
"Stroke",
"Prevention",
"in",
"Young",
"Women",
"study",
"(SPYW)",
"showed",
"a",
"higher",
"risk",
"of",
"stroke",
"in",
"women",
"with",
"probable",
"migraine",
"with",
"visual",
"aura",
"who",
"were",
"cigarette",
"smokers",
"and",
"oral",
"contraceptive",
"users"
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] | [
"Galtier",
"BMC",
"Biology",
"2011,",
"9:61",
"http://www.biomedcentral.com/1741-7007/9/61",
"C",
"O",
"M",
"M",
"E",
"N",
"TA",
"R",
"Y",
"Open",
"Access",
"The",
"intriguing",
"evolutionary",
"dynamics",
"of",
"plant",
"mitochondrial",
"DNA",
"Nicolas",
"Galtier",
"See",
"research",
"article:",
"http://www.biomedcentral.com/1741-7007/9/64",
"Abstract",
"The",
"mitochondrial",
"genome",
"of",
"plants",
"is",
"-",
"in",
"every",
"respect",
"and",
"for",
"yet",
"unclear",
"reasons",
"-",
"very",
"different",
"from",
"the",
"well-studied",
"one",
"of",
"animals.",
"Thanks",
"to",
"next-generation",
"sequencing",
"technologies,",
"Davila",
"et",
"al.",
"precisely",
"characterized",
"the",
"role",
"played",
"by",
"recombination",
"and",
"DNA",
"repair",
"in",
"controlling",
"mitochondrial",
"variations",
"in",
"Arabidopsis",
"thaliana,",
"thus",
"opening",
"new",
"perspectives",
"on",
"the",
"long-term",
"evolution",
"of",
"this",
"intriguing",
"genome.",
"The",
"mitochondrial",
"genome",
"of",
"plants",
"is",
"a",
"challenge",
"to",
"molecular",
"evolutionary",
"biologists.",
"Its",
"content",
"is",
"highly",
"dynamic:",
"plant",
"mitochondrial",
"DNA",
"(mtDNA)",
"is",
"large",
"and",
"variable",
"in",
"size",
"(200",
"to",
"2,500",
"kb),",
"contains",
"many",
"introns",
"and",
"repeated",
"elements",
"(typically",
"90%",
"of",
"the",
"total",
"sequence),",
"and",
"experiences",
"frequent",
"gene",
"gain/loss/",
"transfer/duplication,",
"and",
"genome",
"rearrangements",
"[1].",
"Its",
"nucleotide",
"substitution",
"rate,",
"paradoxically,",
"is",
"remarkably",
"low",
"-",
"even",
"lower",
"than",
"for",
"nuclear",
"DNA.",
"These",
"features",
"are",
"in",
"sharp",
"contrast",
"with",
"the",
"highly",
"studied",
"mtDNA",
"of",
"animals,",
"which",
"is",
"small-sized,",
"structurally",
"conserved,",
"devoid",
"of",
"selfish",
"elements,",
"and",
"has",
"a",
"very",
"fast",
"nucleotide",
"substitution",
"rate",
"[2].",
"Why",
"these",
"two",
"genomes",
"behave",
"so",
"differently",
"is",
"one",
"of",
"the",
"most",
"head-scratching",
"questions",
"of",
"current",
"comparative",
"genomics.",
"The",
"study",
"by",
"Davila",
"et",
"al.",
"[3]",
"contributes",
"a",
"potentially",
"decisive",
"argument",
"by",
"connecting",
"the",
"plant",
"mtDNA",
"mutation",
"rate",
"to",
"yet",
"another",
"intriguing",
"feature",
"of",
"this",
"organellar",
"genome - recombination.",
"been",
"detected",
"in",
"various",
"species,",
"and",
"are",
"involved",
"in",
"a",
"number",
"of",
"phenotypic",
"traits,",
"including",
"thermotolerance",
"and",
"male",
"sterility.",
"The",
"nuclear-encoded",
"MSH1",
"gene,",
"which",
"is",
"the",
"product",
"of",
"fusion",
"between",
"a",
"homologue",
"of",
"the",
"bacterial",
"DNA-repair",
"gene",
"MutS",
"and",
"an",
"endonuclease",
"gene,",
"is",
"involved",
"in",
"the",
"control",
"of",
"plant",
"mtDNA",
"recom-",
"bination.",
"Using",
"next-generation",
"sequencing",
"technologies,",
"Davila",
"et",
"al.",
"[3]",
"have",
"examined",
"the",
"recombination",
"pattern",
"in",
"wild-type",
"versus",
"MSH1-mutant",
"ecotypes",
"of",
"the",
"Brassicaceae",
"Arabidopsis",
"thaliana",
"model.",
"They",
"report",
"that",
"MSH1",
"mutants",
"experience",
"mitochondrial",
"recombi-",
"nation",
"at",
"a",
"much",
"higher",
"rate",
"than",
"the",
"wild",
"type,",
"as",
"reflected",
"by",
"the",
"frequent",
"detection",
"of",
"rearranged",
"mito-",
"chondrial",
"molecules",
"generated",
"by",
"illegitimate",
"(ectopic)",
"recombination",
"between",
"repeated",
"elements.",
"Interestingly,",
"recombination",
"in",
"MSH1",
"mutants",
"is",
"shown",
"to",
"be",
"asso-",
"ciated",
"with",
"asymmetrical",
"genetic",
"exchanges:",
"in",
"a",
"window",
"of",
"a",
"few",
"hundred",
"bases",
"surrounding",
"the",
"recombination",
"breakpoint,",
"one",
"of",
"the",
"two",
"recombining",
"DNA",
"sequences",
"is",
"copied",
"and",
"pasted",
"onto",
"the",
"other",
"one.",
"This",
"process,",
"known",
"as",
"gene",
"conversion,",
"is",
"mediated",
"by",
"efficient",
"DNA",
"mismatch",
"repair",
"activity,",
"and",
"contributes",
"to",
"sequence",
"homogenization",
"of",
"recombinogenic",
"motifs.",
"An",
"analysis",
"of",
"mitochondrial",
"variations",
"across",
"72",
"natural",
"ecotypes",
"of",
"A.",
"thaliana",
"reveals",
"similar",
"patterns,",
"suggesting",
"that",
"the",
"processes",
"described",
"by",
"Davila",
"et",
"al.",
"actually",
"impact",
"on",
"the",
"evolution",
"of",
"plant",
"mtDNA.",
"This",
"study,",
"therefore,",
"provides",
"us",
"with",
"a",
"proximal",
"explanation",
"for",
"the",
"low",
"substitution",
"rate",
"of",
"plant",
"mtDNA,",
"namely",
"the",
"existence",
"of",
"efficient",
"recombination-",
"associated",
"DNA",
"repair",
"activity.",
"Ectopic",
"recombination",
"is",
"potentially",
"harmful",
"in",
"generating",
"chromosomal",
"rearrange-",
"ments",
"that",
"disrupt",
"coding",
"frames",
"or",
"impede",
"gene",
"expres-",
"DNA",
"repair:",
"keeping",
"a",
"watch",
"on",
"repeated",
"elements",
"sion",
"regulation.",
"Mechanisms",
"of",
"recombination",
"surveil-",
"Unlike",
"in",
"animal",
"mitochondria,",
"recombination",
"is",
"wide-",
"lance",
"and",
"repair",
"of",
"recombination-induced",
"DNA",
"damage,",
"spread",
"in",
"plant",
"mtDNA.",
"Recombinant",
"molecules",
"have",
"including",
"mismatch",
"repair,",
"appear",
"necessary",
"for",
"plant",
"mtDNA.",
"Animal",
"mtDNA,",
"in",
"contrast,",
"is",
"essentially",
"devoid",
"of",
"repeated",
"elements,",
"so",
"illegitimate",
"recombina-",
"tion",
"is",
"much",
"less",
"an",
"issue",
"in",
"these",
"genomes.",
"Selective",
"pressure",
"for",
"efficient",
"DNA",
"repair",
"might",
"thus",
"be",
"relaxed,",
"©",
"2011",
"Galtier;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Correspondence:",
"galtier@univ-montp2.fr",
"Université",
"Montpellier",
"2,",
"CNRS",
"UMR",
"5554",
"-",
"Institut",
"des",
"Sciences",
"de",
"l’Evolution,",
"Place",
"E",
"Bataillon",
"-",
"CC64,",
"34095",
"Montpellier,",
"France"
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] | [
"Ogden",
"et",
"al.",
"Implementation",
"Science",
"2012,",
"7:49",
"http://www.implementationscience.com/content/7/1/49",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"Implementation",
"Science",
"Open",
"Access",
"Measurement",
"of",
"implementation",
"components",
"ten",
"years",
"after",
"a",
"nationwide",
"introduction",
"of",
"empirically",
"supported",
"programs",
"–",
"a",
"pilot",
"study",
"Terje",
"Ogden*,",
"Gunnar",
"Bjørnebekk,",
"John",
"Kjøbli,",
"Joshua",
"Patras,",
"Terje",
"Christiansen,",
"Knut",
"Taraldsen",
"and",
"Nina",
"Tollefsen",
"Abstract",
"Background:",
"Ten",
"years",
"after",
"the",
"nationwide",
"dissemination",
"of",
"two",
"evidence-based",
"treatment",
"programs,",
"the",
"status",
"of",
"the",
"implementation",
"components",
"was",
"evaluated",
"in",
"a",
"cross-sectional",
"study.",
"The",
"aim",
"of",
"the",
"study",
"was",
"to",
"pilot",
"a",
"standardized",
"measure",
"of",
"implementation",
"components",
"by",
"examining",
"the",
"factor",
"structure,",
"the",
"reliabilities",
"of",
"the",
"scores,",
"and",
"their",
"association",
"with",
"implementation",
"outcome",
"variables.",
"The",
"aim",
"was",
"also",
"to",
"compare",
"implementation",
"profiles",
"of",
"the",
"two",
"evidence-based",
"programs",
"based",
"on",
"multi",
"informant",
"assessments.",
"Methods:",
"The",
"218",
"participants",
"in",
"the",
"study",
"were",
"therapists,",
"supervisors,",
"and",
"agency",
"leaders",
"working",
"with",
"Parent",
"Management",
"Training,",
"the",
"Oregon",
"model",
"(PMTO),",
"and",
"Multisystemic",
"Therapy",
"(MST)",
"in",
"Norway.",
"Interviewers",
"filled",
"in",
"an",
"electronic",
"version",
"of",
"the",
"Implementation",
"Components",
"Questionnaire",
"during",
"a",
"telephone",
"interview.",
"Results:",
"The",
"factor",
"analysis",
"of",
"the",
"eight",
"one-dimensional",
"subscales",
"resulted",
"in",
"an",
"individual",
"clinical-level",
"factor",
"and",
"an",
"organizational",
"system-level",
"factor.",
"Age,",
"experience,",
"and",
"number",
"of",
"colleagues",
"in",
"the",
"workplace",
"were",
"negatively",
"correlated",
"with",
"positive",
"ratings",
"of",
"the",
"implementation",
"process,",
"but",
"the",
"number",
"of",
"colleagues",
"working",
"with",
"the",
"same",
"program",
"predicted",
"positive",
"ratings.",
"MST",
"and",
"PMTO",
"had",
"different",
"implementation",
"profiles",
"and",
"therapists,",
"supervisors,",
"and",
"managers",
"evaluated",
"some",
"of",
"the",
"implementation",
"drivers",
"significantly",
"differently.",
"Conclusions:",
"The",
"psychometric",
"quality",
"of",
"the",
"questionnaire",
"was",
"supported",
"by",
"measures",
"of",
"internal",
"consistency,",
"factor",
"analyses",
"of",
"the",
"implementation",
"components,",
"and",
"the",
"comparisons",
"of",
"implementation",
"profiles",
"between",
"programs",
"and",
"respondent",
"groups.",
"A",
"moderate,",
"but",
"consistent",
"association",
"in",
"the",
"expected",
"direction",
"was",
"found",
"with",
"the",
"implementation",
"outcome",
"variables.",
"Keywords:",
"Implementation",
"measurement,",
"Implementation",
"components,",
"Empirically",
"supported",
"treatment",
"programs,",
"Parent",
"management",
"training,",
"Multisystemic",
"therapy",
"Background",
"Implementation",
"is",
"the",
"movement",
"of",
"evidence-based",
"pro-",
"grams",
"(EBPs)",
"from",
"science",
"to",
"practice,",
"or",
"the",
"active",
"and",
"planned",
"effort",
"to",
"mainstream",
"a",
"new",
"intervention",
"within",
"a",
"practice",
"organization",
"[1].",
"Implementation",
"also",
"describes",
"a",
"transition",
"period",
"in",
"which",
"practitioners",
"become",
"increasingly",
"skillful,",
"consistent,",
"and",
"committed",
"in",
"their",
"use",
"of",
"a",
"new",
"intervention",
"[2].",
"Even",
"if",
"new",
"intervention",
"programs",
"are",
"accepted",
"and",
"adopted,",
"they",
"are",
"not",
"necessarily",
"put",
"into",
"practice.",
"This",
"is",
"referred",
"to",
"as",
"the",
"‘knowing-doing",
"gap,’",
"in",
"which",
"practitioners",
"fail",
"to",
"do",
"what",
"might",
"improve",
"*",
"Correspondence:",
"terje.ogden@atferdssenteret.no",
"Norwegian",
"Center",
"for",
"Child",
"Behavioral",
"Development,",
"University",
"of",
"Oslo,",
"P.O.",
"Box",
"7053,",
"Majorstuen,",
"0306",
"Oslo,",
"Norway",
"performance",
"and",
"‘substitute",
"talk",
"for",
"action’",
"[3].",
"Further-",
"more,",
"when",
"interventions",
"are",
"properly",
"implemented",
"they",
"are",
"threatened",
"by",
"program",
"drift",
"or",
"dilution",
"over",
"time.",
"The",
"rather",
"slow",
"and",
"limited",
"success",
"of",
"transferring",
"EBPs",
"to",
"or-",
"dinary",
"service,",
"and",
"the",
"limited",
"impact",
"and",
"sustainability",
"of",
"programs",
"once",
"adoption",
"has",
"occurred,",
"have",
"been",
"the",
"focus",
"of",
"several",
"researchers",
"working",
"with",
"implementation",
"[4-7].",
"The",
"failure",
"of",
"EBPs",
"to",
"produce",
"expected",
"outcomes",
"may",
"be",
"attributable",
"to",
"the",
"effectiveness",
"of",
"intervention",
"or",
"the",
"qual-",
"ity",
"of",
"the",
"implementation",
"[2];",
"therefore,",
"both",
"the",
"program",
"effectiveness",
"and",
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507,
895,
568,
909
],
[
571,
895,
598,
909
],
[
601,
895,
640,
909
],
[
644,
895,
662,
909
],
[
665,
895,
690,
909
],
[
693,
895,
710,
909
],
[
713,
895,
751,
909
],
[
755,
895,
766,
909
],
[
769,
895,
776,
909
],
[
433,
912,
468,
926
],
[
470,
912,
524,
926
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[
526,
912,
575,
926
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[
578,
912,
599,
926
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[
601,
912,
645,
926
],
[
648,
912,
675,
926
],
[
677,
912,
725,
926
],
[
728,
912,
742,
926
],
[
745,
912,
776,
926
],
[
433,
929,
447,
943
],
[
451,
929,
526,
943
],
[
531,
929,
582,
943
],
[
587,
929,
598,
943
],
[
603,
929,
620,
943
],
[
626,
929,
644,
943
],
[
649,
929,
675,
943
],
[
680,
929,
700,
943
],
[
706,
929,
727,
943
],
[
732,
929,
776,
943
],
[
433,
945,
464,
959
],
[
466,
945,
473,
959
],
[
476,
945,
526,
959
],
[
529,
945,
584,
959
],
[
444,
962,
514,
976
],
[
522,
962,
582,
976
],
[
589,
962,
603,
976
],
[
610,
962,
628,
976
],
[
636,
962,
702,
976
],
[
710,
962,
732,
976
],
[
739,
962,
775,
976
],
[
433,
979,
463,
993
],
[
466,
979,
477,
993
],
[
481,
979,
537,
993
],
[
540,
979,
557,
993
],
[
560,
979,
611,
993
],
[
614,
979,
658,
993
],
[
661,
979,
704,
993
],
[
707,
979,
756,
993
],
[
759,
979,
776,
993
],
[
433,
995,
440,
1009
],
[
444,
995,
485,
1009
],
[
489,
995,
527,
1009
],
[
532,
995,
544,
1009
],
[
548,
995,
558,
1009
],
[
564,
995,
590,
1009
],
[
594,
995,
601,
1009
],
[
606,
995,
632,
1009
],
[
635,
995,
653,
1009
],
[
658,
995,
716,
1009
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[
721,
995,
748,
1009
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[
753,
995,
776,
1009
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[
70,
1032,
95,
1044
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97,
1032,
128,
1044
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130,
1032,
134,
1044
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[
137,
1032,
157,
1044
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[
159,
1032,
189,
1044
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190,
1032,
198,
1044
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201,
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249,
1044
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251,
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277,
1044
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280,
1032,
294,
1044
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[
297,
1032,
322,
1044
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[
324,
1032,
333,
1044
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[
336,
1032,
350,
1044
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[
352,
1032,
390,
1044
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[
393,
1032,
438,
1044
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[
440,
1032,
489,
1044
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[
491,
1032,
562,
1044
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[
565,
1032,
600,
1044
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[
602,
1032,
629,
1044
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[
631,
1032,
665,
1044
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[
667,
1032,
684,
1044
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[
686,
1032,
755,
1044
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758,
1032,
776,
1044
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[
70,
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125,
1056
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128,
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147,
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207,
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218,
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1056
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237,
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320,
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336,
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] | [
"292",
"Acta",
"Orthopaedica",
"2010;",
"81",
"(3):",
"292–295",
"The",
"posterior",
"approach",
"reduces",
"the",
"risk",
"of",
"thin",
"cement",
"mantles",
"with",
"a",
"straight",
"femoral",
"stem",
"design",
"Gavin",
"J",
"Macpherson,",
"Christian",
"Hank,",
"Michael",
"Schneider,",
"Morag",
"Trayner,",
"Robert",
"Elton,",
"Colin",
"R",
"Howie,",
"and",
"Steffen",
"J",
"Breusch",
"Department",
"of",
"Orthopaedic",
"Surgery,",
"University",
"of",
"Edinburgh,",
"The",
"Royal",
"Infirmary",
"of",
"Edinburgh,",
"UK",
"Correspondence:",
"steffen.breusch@ukonline.co.uk",
"Submitted",
"09-03-13.",
"Accepted",
"09-12-13",
"Background",
"and",
"purpose",
"The",
"properties",
"of",
"the",
"cement",
"mantle",
"around",
"a",
"prosthesis",
"are",
"important.",
"We",
"investigated",
"whether",
"the",
"surgical",
"approach",
"to",
"the",
"hip",
"influences",
"the",
"quality",
"and",
"thickness",
"of",
"the",
"cement",
"mantle",
"when",
"using",
"a",
"straight",
"femoral",
"stem",
"design.",
"Methods",
"In",
"a",
"consecutive",
"multi-surgeon",
"series,",
"we",
"reviewed",
"the",
"radiographs",
"of",
"270",
"patients",
"after",
"cemented",
"Exeter",
"total",
"hip",
"arthroplasty.",
"135",
"stems",
"were",
"introduced",
"using",
"an",
"antero-lateral",
"(transgluteal)",
"approach",
"and",
"135",
"stems",
"were",
"introduced",
"using",
"a",
"posterior",
"approach.",
"Anterior-posterior",
"and",
"lateral",
"radiographs",
"were",
"reviewed",
"and",
"cement",
"mantle",
"thickness",
"was",
"measured",
"in",
"Gruen",
"zones",
"1–14.",
"We",
"graded",
"cement",
"mantle",
"quality",
"according",
"to",
"the",
"Barrack",
"classification.",
"Results",
"Barrack",
"grading",
"did",
"not",
"reveal",
"any",
"difference",
"in",
"cement",
"mantle",
"quality",
"between",
"the",
"two",
"groups.",
"AP",
"and",
"lateral",
"radiographs",
"showed",
"no",
"difference",
"in",
"stem",
"alignment",
"between",
"the",
"groups.",
"The",
"risk",
"of",
"a",
"thin",
"cement",
"mantle",
"(<",
"2",
"mm)",
"was",
"lower",
"with",
"a",
"posterior",
"approach",
"(OR",
"=",
"1.8,",
"95%",
"CI:",
"1–3;",
"p",
"=",
"0.03).",
"The",
"greatest",
"risk",
"of",
"a",
"cement",
"mantle",
"thickness",
"of",
"<",
"2",
"mm",
"occurred",
"in",
"Gruen",
"zones",
"8–9",
"regardless",
"of",
"the",
"surgical",
"approach",
"used.",
"Interpretation",
"With",
"a",
"straight",
"femoral",
"stem",
"design,",
"the",
"pos-",
"terior",
"approach",
"to",
"the",
"hip",
"joint",
"appears",
"to",
"give",
"a",
"lower",
"risk",
"of",
"a",
"thin",
"cement",
"mantle.",
"Irrespective",
"of",
"the",
"approach,",
"there",
"was",
"a",
"risk",
"of",
"thin",
"cement",
"mantles",
"in",
"Gruen",
"zones",
"8",
"and",
"9,",
"which",
"highlights",
"the",
"importance",
"of",
"lateral",
"radiographs",
"in",
"the",
"postoperative",
"radio-",
"graphic",
"assessment",
"of",
"total",
"hip",
"replacements.",
"",
"There",
"is",
"no",
"data",
"available",
"that",
"defines",
"the",
"optimal",
"cement",
"mantle",
"thickness",
"in",
"total",
"hip",
"arthroplasty.",
"There",
"is,",
"however,",
"evidence",
"that",
"a",
"cement",
"mantle",
"of",
"2–3",
"mm",
"is",
"associated",
"with",
"a",
"better",
"long-term",
"radiographic",
"outcome",
"(Ebramzadeh",
"et",
"al.",
"1994,",
"Joshi",
"et",
"al.",
"1998).",
"Thin",
"cement",
"mantles",
"are",
"more",
"prone",
"to",
"crack",
"(Kwak",
"et",
"al.",
"1979,",
"Kawate",
"et",
"al.",
"1998),",
"thus",
"open-",
"ing",
"the",
"bone-cement",
"interface",
"to",
"wear",
"particles",
"and",
"fluid",
"pres-",
"sure",
"(Bartlett",
"et",
"al.",
"2008).",
"This",
"has",
"been",
"documented",
"to",
"cause",
"localized",
"osteolysis",
"(Huddleston",
"1988,",
"Anthony",
"et",
"al.",
"1990,",
"Schmalzried",
"et",
"al.",
"1997)",
"and",
"failure",
"(Olsson",
"and",
"Jernberger",
"1981,",
"Jasty",
"et",
"al",
"1991,",
"Cristofolini",
"et",
"al.",
"2007).",
"Several",
"fac-",
"tors",
"influence",
"the",
"quality",
"of",
"the",
"cement",
"mantle:",
"the",
"cement-",
"ing",
"technique",
"(Mulroy",
"et",
"al.",
"1990,",
"Britton",
"et",
"al.",
"1996,",
"Mal-",
"chau",
"and",
"Herberts",
"1998),",
"femoral",
"anatomy",
"(Crawford",
"et",
"al.",
"1999,",
"Breusch",
"et",
"al.",
"2001),",
"stem",
"design",
"and",
"instrumentation",
"(Garellick",
"et",
"al.",
"1999,",
"Östgaard",
"et",
"al.",
"2001),",
"centralizer",
"usage",
"(Berger",
"et",
"al.",
"1997),",
"and",
"stem",
"size",
"(Krismer",
"et",
"al.",
"1991,",
"Mas-",
"soud",
"et",
"al.",
"1997,",
"Scheerlinck",
"et",
"al.",
"2008).",
"Due",
"to",
"the",
"anatomical",
"shape",
"of",
"the",
"proximal",
"femur,",
"there",
"is",
"a",
"risk",
"of",
"producing",
"thin",
"cement",
"mantles",
"anterior-proximally",
"(Garellick",
"et",
"al.",
"1999,",
"Breusch",
"et",
"al.",
"2001,",
"Valdivia",
"et",
"al.",
"2001).",
"An",
"antero-lateral",
"surgical",
"approach",
"has",
"been",
"shown",
"to",
"adversely",
"affect",
"the",
"orientation",
"of",
"the",
"tip",
"of",
"the",
"femoral",
"com-",
"ponent",
"(Vaughan",
"et",
"al.",
"2007),",
"but",
"little",
"else",
"is",
"known",
"about",
"the",
"effect",
"of",
"the",
"surgical",
"approach",
"to",
"the",
"hip",
"with",
"regard",
"to",
"stem",
"alignment",
"and",
"cement",
"mantle",
"thickness",
"or",
"quality.",
"We",
"investigated",
"the",
"influence",
"of",
"surgical",
"approach",
"on",
"cement",
"mantle",
"thickness",
"and",
"cement",
"mantle",
"quality",
"using",
"the",
"straight",
"Exeter",
"femoral",
"stem",
"by",
"comparison",
"of",
"posterior",
"and",
"antero-lateral",
"approach",
"in",
"a",
"multi-surgeon",
"series.",
"Patients",
"and",
"methods",
"This",
"was",
"a",
"prospective,",
"consecutive,",
"multi-surgeon",
"series",
"of",
"270",
"cemented",
"primary",
"total",
"hip",
"replacements",
"performed",
"in",
"2005",
"at",
"our",
"university",
"teaching",
"hospital",
"(Table",
"1).",
"Patients",
"with",
"a",
"previous",
"femoral",
"osteotomy",
"were",
"not",
"included.",
"The",
"Exeter",
"stem",
"(Stryker",
"Orthopaedics,",
"Mahwah,",
"NJ)",
"was",
"used",
"in",
"all",
"cases.",
"All",
"procedures",
"were",
"carried",
"out",
"with",
"the",
"patient",
"in",
"a",
"lateral",
"decubitus",
"position.",
"135",
"patients",
"were",
"operated",
"on",
"using",
"an",
"antero-lateral",
"approach",
"to",
"the",
"hip",
"joint",
"and",
"135",
"patients",
"using",
"a",
"posterior",
"approach.",
"Preoperative",
"templating",
"on",
"AP",
"radiographs",
"was",
"under-",
"taken",
"to",
"determine",
"the",
"optimum",
"femoral",
"implant",
"allowing",
"for",
"a",
"cement",
"mantle",
"of",
"at",
"least",
"2",
"mm.",
"All",
"operations",
"were",
"per-",
"Open",
"Access",
"-",
"This",
"article",
"is",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Noncommercial",
"License",
"which",
"permits",
"any",
"noncommercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"source",
"is",
"credited.",
"DOI",
"10.3109/17453674.2010.487239"
] | [
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5,
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5,
5,
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5,
5,
5,
5,
5,
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11,
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] | [
"W638–W643",
"Nucleic",
"Acids",
"Research,",
"2005,",
"Vol.",
"33,",
"Web",
"Server",
"issue",
"doi:10.1093/nar/gki490",
"RACE:",
"Remote",
"Analysis",
"Computation",
"for",
"gene",
"Expression",
"data",
"Michael",
"Psarros,",
"Steffen",
"Heber1,",
"Manuela",
"Sick,",
"Gnanasekaran",
"Thoppae,",
"Keith",
"Harshman",
"and",
"Beate",
"Sick*",
"DNA",
"Array",
"Facility,",
"Center",
"for",
"Integrative",
"Genomics,",
"University",
"of",
"Lausanne,",
"Lausanne,",
"Switzerland",
"and",
"1Bioinformatics",
"Research",
"Center,",
"North",
"Carolina",
"State",
"University,",
"Raleigh,",
"NC,",
"USA",
"Received",
"February",
"14,",
"2005;",
"Revised",
"April",
"12,",
"2005;",
"Accepted",
"April",
"25,",
"2005",
"ABSTRACT",
"The",
"Remote",
"Analysis",
"Computation",
"for",
"gene",
"Expression",
"data",
"(RACE)",
"suite",
"is",
"a",
"collection",
"of",
"bioin-",
"formatics",
"web",
"tools",
"designed",
"for",
"the",
"analysis",
"of",
"DNA",
"microarray",
"data.",
"RACE",
"performs",
"probe-level",
"data",
"pre-",
"processing,",
"extensive",
"quality",
"checks,",
"data",
"visualiza-",
"tion",
"and",
"data",
"normalization",
"for",
"Affymetrix",
"GeneChips.",
"In",
"addition,",
"it",
"offers",
"differential",
"expression",
"analysis",
"on",
"normalized",
"expression",
"levels",
"from",
"any",
"array",
"platform.",
"RACE",
"estimates",
"the",
"false",
"discovery",
"rates",
"of",
"lists",
"of",
"potentially",
"regulated",
"genes",
"and",
"provides",
"a",
"Gene",
"Ontology-term",
"analysis",
"tool",
"for",
"GeneChip",
"data",
"to",
"support",
"the",
"biological",
"interpretation",
"and",
"annotation",
"of",
"results.",
"The",
"analysis",
"is",
"fully",
"automated",
"but",
"can",
"be",
"customized",
"by",
"flexible",
"parameter",
"settings.",
"To",
"offer",
"a",
"convenient",
"starting",
"point",
"for",
"subsequent",
"analyses,",
"and",
"to",
"provide",
"maximum",
"transparency,",
"the",
"R",
"scripts",
"used",
"to",
"generate",
"the",
"results",
"can",
"be",
"downloaded",
"along",
"with",
"the",
"output",
"files.",
"RACE",
"is",
"freely",
"available",
"for",
"use",
"at",
"http://race.unil.ch.",
"INTRODUCTION",
"DNA",
"microarrays",
"are",
"standard",
"tools",
"in",
"biology",
"and",
"medicine.",
"An",
"increasingly",
"long",
"list",
"of",
"applications",
"includes",
"the",
"identi-",
"fication",
"of",
"gene",
"expression",
"changes",
"associated",
"with",
"changes",
"in",
"cell",
"state",
"(1,2),",
"classifying",
"clinical",
"samples",
"based",
"on",
"the",
"under-",
"lying",
"pathological",
"characteristics",
"(3,4),",
"drug",
"development",
"(5)",
"and",
"the",
"functional",
"annotation",
"of",
"genes",
"(6).",
"A",
"typical",
"micro-",
"array",
"experiment",
"might",
"measure",
"expression",
"levels",
"of",
"tens",
"of",
"thousands",
"of",
"genes,",
"and",
"systematic",
"variations",
"introduced",
"into",
"the",
"datasets",
"(e.g.",
"variations",
"in",
"labeling",
"efficiencies",
"or",
"scanner",
"settings)",
"can",
"often",
"obscure",
"the",
"biological",
"variation",
"that",
"is",
"of",
"real",
"interest.",
"Furthermore,",
"once",
"differentially",
"expressed",
"genes",
"have",
"been",
"identified,",
"inferring",
"function",
"based",
"simply",
"on",
"their",
"expression",
"pattern",
"can",
"be",
"both",
"arduous",
"and",
"ineffective.",
"Hence,",
"bioinformatics",
"tools",
"that",
"facilitate",
"rigorous",
"data",
"analysis",
"and",
"interpretation",
"are",
"of",
"the",
"highest",
"importance.",
"Presented",
"here",
"is",
"Remote",
"Analysis",
"Computation",
"for",
"gene",
"Expression",
"data",
"(RACE),",
"a",
"web",
"server",
"which",
"provides",
"some",
"solutions",
"to",
"these",
"problems.",
"Microarray",
"data",
"analysis",
"typically",
"begins",
"with",
"data",
"quality",
"checks",
"and",
"data",
"normalization",
"(7).",
"Once",
"normalized",
"expres-",
"sion",
"levels",
"are",
"determined,",
"expression",
"ratios",
"can",
"be",
"calculated",
"and",
"differentially",
"expressed",
"genes",
"identified.",
"At",
"this",
"stage",
"of",
"data",
"analysis,",
"the",
"magnitude",
"and",
"significance",
"of",
"gene",
"expres-",
"sion",
"changes",
"as",
"well",
"as",
"the",
"false",
"discovery",
"rate",
"are",
"important",
"measures.",
"Once",
"a",
"list",
"of",
"differentially",
"expressed",
"genes",
"is",
"iden-",
"tified,",
"the",
"task",
"often",
"turns",
"to",
"describing",
"and",
"interpreting",
"the",
"biological",
"significance",
"of",
"the",
"results.",
"An",
"often",
"useful",
"approach",
"is",
"to",
"compile",
"a",
"list",
"of",
"the",
"Gene",
"Ontology",
"(GO)",
"terms",
"associ-",
"ated",
"with",
"the",
"differentially",
"expressed",
"genes",
"(8).",
"This",
"provides",
"an",
"overview",
"of",
"the",
"biological,",
"physiological",
"and",
"cellular",
"pro-",
"cesses",
"potentially",
"involved",
"in",
"the",
"biological",
"phenomena",
"and",
"suggests",
"directions",
"for",
"further",
"studies.",
"A",
"number",
"of",
"very",
"useful",
"web",
"tools",
"for",
"microarray",
"data",
"analysis",
"exist",
"(e.g.",
"9–13).",
"RACE",
"contributes",
"to",
"the",
"field",
"by",
"providing",
"access",
"to",
"a",
"wide",
"range",
"of",
"quality",
"checks,",
"probe-level",
"methods",
"and",
"state-of-the-art",
"normalization",
"techniques",
"for",
"Affymetrix",
"raw",
"data.",
"To",
"the",
"best",
"of",
"our",
"knowledge,",
"these",
"are",
"not",
"provided",
"by",
"any",
"other",
"publicly",
"available",
"server.",
"Addi-",
"tionally,",
"RACE",
"provides",
"tools",
"to",
"identify",
"lists",
"of",
"different-",
"ially",
"expressed",
"genes",
"and",
"to",
"determine",
"and",
"investigate",
"the",
"associated",
"GO-term",
"composition",
"of",
"those",
"genes.",
"To",
"facilitate",
"subsequent",
"analyses",
"and",
"guarantee",
"maximal",
"transparency",
"and",
"reproducibility,",
"the",
"R",
"script",
"used",
"to",
"generate",
"the",
"results",
"is",
"provided.",
"SYSTEM",
"AND",
"MODULE",
"DESIGN",
"RACE",
"is",
"divided",
"into",
"two",
"components:",
"the",
"user",
"interface",
"and",
"the",
"analysis",
"part.",
"RACE",
"uses",
"basic",
"authentication",
"provided",
"by",
"Apache.",
"HTTP",
"communication",
"is",
"exclusively",
"via",
"port",
"80,",
"making",
"the",
"system",
"easily",
"accessible",
"through",
"a",
"firewall.",
"*To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"Tel:",
"+1",
"41",
"21",
"692",
"3909;",
"Fax:",
"+1",
"41",
"21",
"692",
"3905;",
"Email:",
"Beate.Sick@unil.ch",
"The",
"Author",
"2005.",
"Published",
"by",
"Oxford",
"University",
"Press.",
"All",
"rights",
"reserved.",
"The",
"online",
"version",
"of",
"this",
"article",
"has",
"been",
"published",
"under",
"an",
"open",
"access",
"model.",
"Users",
"are",
"entitled",
"to",
"use,",
"reproduce,",
"disseminate,",
"or",
"display",
"the",
"open",
"access",
"version",
"of",
"this",
"article",
"for",
"non-commercial",
"purposes",
"provided",
"that:",
"the",
"original",
"authorship",
"is",
"properly",
"and",
"fully",
"attributed;",
"the",
"Journal",
"and",
"Oxford",
"University",
"Press",
"are",
"attributed",
"as",
"the",
"original",
"place",
"of",
"publication",
"with",
"the",
"correct",
"citation",
"details",
"given;",
"if",
"an",
"article",
"is",
"subsequently",
"reproduced",
"or",
"disseminated",
"not",
"in",
"its",
"entirety",
"but",
"only",
"in",
"part",
"or",
"as",
"a",
"derivative",
"work",
"this",
"must",
"be",
"clearly",
"indicated.",
"For",
"commercial",
"re-use,",
"please",
"contact",
"journals.permissions@oupjournals.org"
] | [
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] | [
"Pediatr",
"Nephrol",
"(2008)",
"23:1257–1267",
"DOI",
"10.1007/s00467-008-0801-6",
"ORIGINAL",
"ARTICLE",
"Glomerular",
"angiotensinogen",
"protein",
"is",
"enhanced",
"in",
"pediatric",
"IgA",
"nephropathy",
"Masanori",
"Takamatsu",
"&",
"Maki",
"Urushihara",
"&",
"Shuji",
"Kondo",
"&",
"Maki",
"Shimizu",
"&",
"Tetsuo",
"Morioka",
"&",
"Takashi",
"Oite",
"&",
"Hiroyuki",
"Kobori",
"&",
"Shoji",
"Kagami",
"Received:",
"14",
"November",
"2007",
"/",
"Revised:",
"30",
"January",
"2008",
"/",
"Accepted:",
"18",
"February",
"2008",
"/",
"Published",
"online:",
"18",
"April",
"2008",
"#",
"The",
"Author(s)",
"2008",
"Abstract",
"Enhanced",
"intrarenal",
"renin-angiotensin",
"system",
"(RAS)",
"is",
"implicated",
"in",
"the",
"development",
"and",
"progression",
"of",
"renal",
"injury.",
"To",
"investigate",
"whether",
"angiotensinogen",
"(AGT)",
"expression",
"is",
"involved",
"in",
"glomerular",
"RAS",
"activity",
"and",
"glomerular",
"injury,",
"we",
"examined",
"glomerular",
"AGT",
"expression",
"and",
"its",
"correlation",
"with",
"expression",
"of",
"other",
"RAS",
"components,",
"and",
"levels",
"of",
"glomerular",
"injury",
"in",
"samples",
"from",
"patients",
"with",
"immunoglobulin",
"A",
"nephropathy",
"(IgAN)",
"(23)",
"and",
"minor",
"glomerular",
"abnormalities",
"(MGA)",
"(8).",
"Immunohistochemistry",
"showed",
"that",
"AGT",
"protein",
"was",
"highly",
"expressed",
"by",
"glomerular",
"endothelial",
"cells",
"(GEC)",
"and",
"mesangial",
"cells",
"in",
"nephritic",
"glomeruli",
"of",
"IgAN",
"compared",
"with",
"glomeruli",
"of",
"MGA.",
"Levels",
"of",
"glomerular",
"AGT",
"protein",
"were",
"well",
"correlated",
"with",
"levels",
"of",
"glomerular",
"angiotensin",
"II",
"(ang",
"II),",
"transforming",
"growth",
"factor-β",
"(TGF-β),",
"α-smooth-muscle",
"actin,",
"glomerular",
"cell",
"M.",
"Takamatsu",
":",
"M.",
"Urushihara",
":",
"S.",
"Kondo",
":",
"M.",
"Shimizu",
":",
"S.",
"Kagami",
"(*)",
"Department",
"of",
"Pediatrics,",
"The",
"Institute",
"of",
"Health",
"Bioscience,",
"The",
"University",
"of",
"Tokushima",
"Graduate",
"School,",
"Kuramoto-cho-3-chome,",
"Tokushima",
"770-8503,",
"Japan",
"e-mail:",
"kagami@clin.med.tokushima-u.ac.jp",
"T.",
"Morioka",
":",
"T.",
"Oite",
"Department",
"of",
"Cellular",
"Physiology,",
"Institute",
"of",
"Nephrology,",
"Niigata",
"University",
"Graduate",
"School",
"of",
"Medical",
"and",
"Dental",
"Sciences,",
"Niigata,",
"Japan",
"H.",
"Kobori",
"Department",
"of",
"Medicine,",
"Tulane",
"University",
"Health",
"Sciences",
"Center,",
"New",
"Orleans,",
"LA,",
"USA",
"H.",
"Kobori",
"Department",
"of",
"Physiology,",
"Tulane",
"University",
"Health",
"Sciences",
"Center,",
"New",
"Orleans,",
"LA,",
"USA",
"number,",
"and",
"glomerulosclerosis",
"score",
"but",
"not",
"with",
"those",
"of",
"glomerular",
"angiotensin-converting",
"enzyme",
"and",
"ang",
"II",
"type",
"1",
"receptor.",
"Real-time",
"polymerase",
"chain",
"reaction",
"(RT-PCR)",
"and",
"Western",
"blot",
"analyses",
"using",
"cultured",
"human",
"GEC",
"indicated",
"that",
"ang",
"II",
"upregulated",
"AGT",
"messenger",
"ribonucleic",
"acid",
"(mRNA)",
"and",
"protein",
"expression",
"in",
"a",
"dose-",
"and",
"time-",
"dependent",
"manner.",
"These",
"data",
"suggest",
"that",
"activated",
"glomerular",
"AGT",
"expression",
"is",
"likely",
"involved",
"in",
"elevated",
"local",
"ang",
"II",
"production",
"and,",
"thereby,",
"may",
"contribute",
"to",
"increased",
"TGF-β",
"production",
"and",
"development",
"of",
"glomerular",
"injury",
"in",
"IgAN.",
"Augmentation",
"of",
"GEC-AGT",
"production",
"with",
"ang",
"II",
"stimulation",
"might",
"drive",
"further",
"glomerular",
"injury",
"in",
"a",
"positive-feedback",
"loop.",
"Keywords",
"Renin-angiotensin",
"system",
".",
"Transforming",
"growth",
"factor-β",
".",
"Glomerular",
"endothelial",
"cells",
".",
"α-smooth",
"muscle",
"actin",
".",
"Mesangial",
"cells",
"Introduction",
"Clinical",
"and",
"experimental",
"studies",
"have",
"provided",
"considerable",
"evidence",
"for",
"the",
"role",
"of",
"the",
"renin-angiotensin",
"system",
"(RAS)",
"in",
"the",
"development",
"of",
"hypertension",
"and",
"progression",
"of",
"renal",
"diseases",
"[1,",
"2].",
"It",
"is",
"now",
"established",
"that",
"all",
"components",
"of",
"the",
"RAS",
"are",
"widely",
"distributed",
"in",
"several",
"tissues,",
"including",
"the",
"kidney",
"[3,",
"4].",
"The",
"local",
"RAS",
"in",
"the",
"kidney",
"has",
"several",
"pathophysiologic",
"functions",
"for",
"not",
"only",
"regulating",
"blood",
"pressure",
"but",
"also",
"renal",
"cell",
"growth",
"and",
"production",
"of",
"glomerulosclerosis,",
"which",
"is",
"involved",
"in",
"the",
"development",
"of",
"renal",
"fibrosis",
"[5–8].",
"Indeed,",
"previous",
"studies",
"have",
"shown",
"beneficial",
"effects",
"of",
"angiotensin-converting",
"enzyme",
"inhibitor",
"(ACEi)",
"and/or",
"angiotensin",
"II",
"(ang",
"II)",
"type",
"1",
"receptor",
"(AT1R)",
"blocker",
"(ARB)",
"on",
"various",
"renal",
"diseases",
"in",
"rats",
"and",
"humans,"
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] | [
"DOI",
"10.4110/in.2009.9.3.90",
"PISSN",
"1598-2629",
"ORIGINAL",
"ARTICLE",
"The",
"Stimulation",
"of",
"CD147",
"Induces",
"MMP-9",
"Expression",
"through",
"ERK",
"and",
"NF-κB",
"in",
"Macrophages:",
"Implication",
"for",
"Atherosclerosis",
"Ju-Young",
"Kim1,",
"Won-Jung",
"Kim1,",
"Ho",
"Kim1,",
"Kyoungho",
"Suk2",
"and",
"Won-Ha",
"Lee1*",
"1The",
"School",
"of",
"Life",
"Sciences",
"and",
"Biotechnology,",
"2Department",
"of",
"Pharmacology,",
"School",
"of",
"Medicine,",
"Kyungpook",
"National",
"University,",
"Daegu",
"702-701,",
"Korea",
"Background:",
"CD147,",
"as",
"a",
"cellular",
"receptor",
"for",
"cyclophilin",
"A",
"(CypA),",
"is",
"a",
"multifunctional",
"protein",
"involved",
"in",
"tumor",
"in-",
"vasion,",
"inflammation,",
"tissue",
"remodeling,",
"neural",
"function,",
"and",
"reproduction.",
"Recent",
"observations",
"showing",
"the",
"expression",
"of",
"CD147",
"in",
"leukocytes",
"indicate",
"that",
"this",
"molecule",
"may",
"have",
"roles",
"in",
"inflammation.",
"Methods:",
"In",
"order",
"to",
"investigate",
"the",
"role",
"of",
"CD147",
"and",
"its",
"ligand",
"in",
"the",
"pathogenesis",
"of",
"athero-",
"sclerosis,",
"human",
"atherosclerotic",
"plaques",
"were",
"analyzed",
"for",
"the",
"expression",
"pattern",
"of",
"CD147",
"and",
"CypA.",
"The",
"cellular",
"re-",
"sponses",
"and",
"signaling",
"molecules",
"activated",
"by",
"the",
"stimulation",
"of",
"CD147",
"were",
"then",
"investigated",
"in",
"the",
"human",
"macrophage",
"cell",
"line,",
"THP-1,",
"which",
"expresses",
"high",
"basal",
"level",
"of",
"CD147",
"on",
"the",
"cell",
"surface.",
"Results:",
"Staining",
"of",
"both",
"CD147",
"and",
"CypA",
"was",
"detected",
"in",
"endothelial",
"cell",
"layers",
"facing",
"the",
"lu-",
"men",
"and",
"macrophage-rich",
"areas.",
"Stimulation",
"of",
"CD147",
"with",
"its",
"specific",
"monoclonal",
"antibody",
"induced",
"the",
"expression",
"of",
"matrix",
"metalloproteinase",
"(MMP)-9",
"in",
"THP-1",
"cells",
"and",
"it",
"was",
"suppressed",
"by",
"inhibitors",
"of",
"both",
"ERK",
"and",
"NF-κB.",
"Accordingly,",
"the",
"stimulation",
"of",
"CD147",
"was",
"observed",
"to",
"in-",
"duce",
"phosphorylation",
"of",
"ERK,",
"phosphorylation-associated",
"degradation",
"of",
"IκB,",
"and",
"nuclear",
"translocation",
"of",
"NF-κB",
"p65",
"and",
"p50",
"subunits.",
"Conclusion:",
"These",
"results",
"suggest",
"that",
"CD147",
"mediates",
"the",
"inflammatory",
"activation",
"of",
"macro-",
"phages",
"that",
"leads",
"to",
"the",
"induction",
"of",
"MMP-9",
"expression,",
"which",
"could",
"play",
"a",
"role",
"in",
"the",
"pathogenesis",
"of",
"inflammatory",
"diseases",
"such",
"as",
"atherosclerosis.",
"[Immune",
"Network",
"2009;9(3):90-97]",
"INTRODUCTION",
"CD147",
"(EMMPRIN/basigin/HAb18G/neurothelin/M6/TCSF),",
"which",
"has",
"two",
"immunoglobulin-like",
"extracellular",
"domains,",
"is",
"a",
"mul-",
"tifunctional",
"transmembrane",
"glycoprotein",
"with",
"short",
"(39",
"amino",
"acids",
"long)",
"intracellular",
"domain",
"(1).",
"CD147",
"plays",
"a",
"critical",
"role",
"in",
"many",
"pathological",
"and",
"physiological",
"processes",
"involv-",
"ing",
"a",
"variety",
"of",
"cell",
"types",
"such",
"as",
"various",
"cancer",
"cells,",
"leuko-",
"cytes,",
"fibroblasts,",
"and",
"endothelial",
"cells",
"(2-7).",
"As",
"a",
"tu-",
"mor-derived",
"MMP",
"inducer,",
"CD147",
"stimulates",
"fibroblast",
"and",
"endothelial",
"cells",
"to",
"facilitate",
"tumor",
"invasion,",
"metastasis,",
"and",
"angiogenesis",
"(7).",
"In",
"addition,",
"CD147",
"enhances",
"angiogenesis",
"through",
"stimulation",
"of",
"the",
"production",
"of",
"vascular",
"endothelial",
"growth",
"factor",
"(VEGF)",
"(8).",
"The",
"expression",
"of",
"CD147",
"has",
"been",
"shown",
"to",
"be",
"induced",
"in",
"activated",
"leukocytes",
"such",
"as",
"gran-",
"ulocytes,",
"lymphocytes,",
"and",
"macrophages",
"(4).",
"Stimulation",
"of",
"CD147",
"in",
"leukocytes",
"is",
"believed",
"to",
"be",
"involved",
"in",
"in-",
"flammatory",
"processes",
"associated",
"with",
"lung",
"injury,",
"rheumatoid",
"arthritis",
"(RA),",
"chronic",
"liver",
"disease,",
"heart",
"failure,",
"and",
"athero-",
"sclerosis",
"(9-13).",
"The",
"ligands",
"for",
"CD147",
"were",
"identified",
"to",
"be",
"the",
"two",
"cyclo-",
"sporin",
"A",
"binding",
"proteins:",
"cyclophilin",
"A",
"and",
"B",
"(CypA",
"and",
"CypB)",
"(14,15).",
"A",
"secreted",
"form",
"of",
"CypA,",
"which",
"are",
"expressed",
"by",
"smooth",
"muscle",
"cells",
"(SMCs)",
"and",
"macrophages",
"during",
"in-",
"flammatory",
"conditions",
"(16-18),",
"has",
"been",
"shown",
"to",
"have",
"cyto-",
"kine-like",
"functions",
"(17,19).",
"The",
"expression",
"of",
"CypA",
"and",
"CD147",
"was",
"detected",
"in",
"synovial",
"macrophages",
"of",
"RA",
"patients",
"and",
"stimulation",
"of",
"CD147",
"induced",
"NF-κB-mediated",
"ex-",
"pression",
"of",
"MMP-9",
"and",
"proinflammatory",
"cytokines",
"and",
"en-",
"Received",
"on",
"March",
"24,",
"2009.",
"Revised",
"on",
"April",
"1,",
"2009.",
"Accepted",
"on",
"April",
"15,",
"2009.",
"*Corresponding",
"Author.",
"Tel:",
"82-53-950-5388;",
"Fax:",
"82-53-943-6925;",
"E-mail:",
"whl@knu.ac.kr",
"Keywords:",
"macrophage,",
"atherosclerosis,",
"inflammation,",
"CD147,",
"cyclophilin",
"A",
"90",
"IMMUNE",
"NETWORK",
"http://www.ksimm.or.kr",
"Volume",
"9",
"Number",
"3",
"June",
"2009"
] | [
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] | [
"Kuang",
"et",
"al.",
"BMC",
"Public",
"Health",
"2012,",
"12:418",
"http://www.biomedcentral.com/1471-2458/12/418",
"R",
"E",
"S",
"E",
"A",
"R",
"C",
"H",
"A",
"R",
"T",
"I",
"C",
"L",
"E",
"Open",
"Access",
"Epidemic",
"features",
"affecting",
"the",
"performance",
"of",
"outbreak",
"detection",
"algorithms",
"Jie",
"Kuang1,",
"Wei",
"Zhong",
"Yang2,",
"Ding",
"Lun",
"Zhou1,",
"Zhong",
"Jie",
"Li2",
"and",
"Ya",
"Jia",
"Lan1*",
"Abstract",
"Background:",
"Outbreak",
"detection",
"algorithms",
"play",
"an",
"important",
"role",
"in",
"effective",
"automated",
"surveillance.",
"Although",
"many",
"algorithms",
"have",
"been",
"designed",
"to",
"improve",
"the",
"performance",
"of",
"outbreak",
"detection,",
"few",
"published",
"studies",
"have",
"examined",
"how",
"epidemic",
"features",
"of",
"infectious",
"disease",
"impact",
"on",
"the",
"detection",
"performance",
"of",
"algorithms.",
"This",
"study",
"compared",
"the",
"performance",
"of",
"three",
"outbreak",
"detection",
"algorithms",
"stratified",
"by",
"epidemic",
"features",
"of",
"infectious",
"disease",
"and",
"examined",
"the",
"relationship",
"between",
"epidemic",
"features",
"and",
"performance",
"of",
"outbreak",
"detection",
"algorithms.",
"Methods:",
"Exponentially",
"weighted",
"moving",
"average",
"(EWMA),",
"cumulative",
"sum",
"(CUSUM)",
"and",
"moving",
"percentile",
"method",
"(MPM)",
"algorithms",
"were",
"applied.",
"We",
"inserted",
"simulated",
"outbreaks",
"into",
"notifiable",
"infectious",
"disease",
"data",
"in",
"China",
"Infectious",
"Disease",
"Automated-alert",
"and",
"Response",
"System",
"(CIDARS),",
"and",
"compared",
"the",
"performance",
"of",
"the",
"three",
"algorithms",
"with",
"optimized",
"parameters",
"at",
"a",
"fixed",
"false",
"alarm",
"rate",
"of",
"5%",
"classified",
"by",
"epidemic",
"features",
"of",
"infectious",
"disease.",
"Multiple",
"linear",
"regression",
"was",
"adopted",
"to",
"analyse",
"the",
"relationship",
"of",
"the",
"algorithms’",
"sensitivity",
"and",
"timeliness",
"with",
"the",
"epidemic",
"features",
"of",
"infectious",
"diseases.",
"Results:",
"The",
"MPM",
"had",
"better",
"detection",
"performance",
"than",
"EWMA",
"and",
"CUSUM",
"through",
"all",
"simulated",
"outbreaks,",
"with",
"or",
"without",
"stratification",
"by",
"epidemic",
"features",
"(incubation",
"period,",
"baseline",
"counts",
"and",
"outbreak",
"magnitude).",
"The",
"epidemic",
"features",
"were",
"associated",
"with",
"both",
"sensitivity",
"and",
"timeliness.",
"Compared",
"with",
"long",
"incubation,",
"short",
"incubation",
"had",
"lower",
"probability",
"(β*",
"=",
"−0.13,",
"P",
"<",
"0.001)",
"but",
"needed",
"shorter",
"time",
"to",
"detect",
"outbreaks",
"(β*",
"=",
"−0.57,",
"P",
"<",
"0.001).",
"Lower",
"baseline",
"counts",
"were",
"associated",
"with",
"higher",
"probability",
"(β*",
"=",
"−0.20,",
"P",
"<",
"0.001)",
"and",
"longer",
"time",
"(β*",
"=",
"0.14,",
"P",
"<",
"0.001).",
"The",
"larger",
"outbreak",
"magnitude",
"was",
"correlated",
"with",
"higher",
"probability",
"(β*",
"=",
"0.55,",
"P",
"<",
"0.001)",
"and",
"shorter",
"time",
"(β*",
"=",
"−0.23,",
"P",
"<",
"0.001).",
"Conclusions:",
"The",
"results",
"of",
"this",
"study",
"suggest",
"that",
"the",
"MPM",
"is",
"a",
"prior",
"algorithm",
"for",
"outbreak",
"detection",
"and",
"differences",
"of",
"epidemic",
"features",
"in",
"detection",
"performance",
"should",
"be",
"considered",
"in",
"automatic",
"surveillance",
"practice.",
"Keywords:",
"Epidemic",
"feature,",
"Outbreak",
"detection",
"algorithms,",
"Performance,",
"Automated",
"infectious",
"disease",
"surveillance",
"Background",
"Infectious",
"diseases",
"remain",
"the",
"major",
"causes",
"of",
"morbidity",
"and",
"mortality",
"in",
"China",
"despite",
"substantial",
"progress",
"in",
"their",
"control",
"[1].",
"The",
"outbreaks",
"of",
"infectious",
"diseases",
"pose",
"serious",
"threats",
"on",
"public",
"health.",
"Early",
"detection",
"of",
"aberration",
"and",
"rapid",
"control",
"actions,",
"which",
"the",
"Chinese",
"Ministry",
"of",
"Health",
"has",
"taken",
"as",
"important",
"strategies",
"for",
"*",
"Correspondence:",
"lanyajia@sina.com",
"1Department",
"of",
"Occupational",
"Health,",
"West",
"China",
"School",
"of",
"Public",
"Health,",
"Sichuan",
"University,",
"17",
"South",
"Section",
"3",
"Renmin",
"Road,",
"Chengdu,",
"Sichuan",
"610041,",
"China",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"emergency",
"infectious",
"disease",
"prevention",
"and",
"control",
"[2],",
"are",
"prerequisites",
"for",
"preventing",
"the",
"spread",
"of",
"outbreaks",
"and",
"reducing",
"the",
"morbidity",
"and",
"death",
"caused",
"by",
"diseases.",
"Therefore,",
"China",
"Infectious",
"Disease",
"Automated-alert",
"and",
"Response",
"System",
"(CIDARS)",
"was",
"successfully",
"implemen-",
"ted",
"and",
"began",
"to",
"operate",
"nationwide",
"in",
"2008",
"[3].",
"At",
"the",
"end",
"of",
"2010,",
"analysis",
"results",
"of",
"the",
"operation",
"of",
"CIDARS",
"in",
"nationwide",
"showed",
"that",
"a",
"large",
"number",
"of",
"outbreaks",
"of",
"infectious",
"diseases",
"could",
"be",
"timely",
"detected,",
"but",
"it",
"was",
"also",
"found",
"that",
"there",
"were",
"many",
"of",
"false-posi-",
"tive",
"signals;",
"large",
"differences",
"existed",
"between",
"outbreak",
"signal",
"counts",
"and",
"final",
"identified",
"outbreaks",
"in",
"different",
"©",
"2012",
"Kuang",
"et",
"al.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"Neuropsychiatric",
"Disease",
"and",
"Treatment",
"Open",
"Access",
"Full",
"Text",
"Article",
"Adolescent",
"mental",
"health:",
"Challenges",
"with",
"maternal",
"noncompliance",
"Dovepress",
"open",
"access",
"to",
"scientific",
"and",
"medical",
"research",
"C",
"A",
"S",
"E",
"R",
"E",
"P",
"O",
"R",
"T",
"Vicki",
"A",
"Nejtek",
"Sarah",
"Hardy",
"Scott",
"Winter",
"University",
"of",
"North",
"Texas",
"Health",
"Science",
"Center,",
"Fort",
"Worth,",
"TX,",
"USA",
"Correspondence:",
"Vicki",
"A",
"Nejtek",
"University",
"of",
"North",
"Texas",
"Health",
"Science",
"Center",
"at",
"Fort",
"Worth,",
"Department",
"of",
"Psychiatry",
"and",
"Behavioral",
"Health,",
"3500",
"Camp",
"Bowie",
"Blvd.,",
"PCC",
"4.462,",
"Fort",
"Worth,",
"TX",
"76107,",
"USA",
"Tel",
"+1",
"817",
"735",
"0640",
"Fax",
"+1",
"817",
"735",
"0643",
"Email",
"vnejtek@hsc.unt.edu",
"submit",
"your",
"manuscript",
"|",
"www.dovepress.com",
"Dovepress",
"Abstract:",
"The",
"leading",
"cause",
"of",
"suicide",
"ideation,",
"attempts,",
"and",
"completion",
"in",
"adolescents",
"is",
"persistent",
"and",
"unresolved",
"parental",
"conflict.",
"National",
"statistics",
"show",
"extremely",
"high",
"rates",
"of",
"childhood",
"neglect",
"and",
"abuse",
"are",
"perpetrated",
"most",
"often",
"by",
"single",
"mothers.",
"Psychiatric",
"disorders",
"arising",
"from",
"maternal–child",
"dysfunction",
"are",
"well-documented.",
"However,",
"resources",
"to",
"prevent",
"offspring",
"victimization",
"are",
"lacking.",
"Here,",
"we",
"report",
"maternal",
"neglect",
"of",
"a",
"15-year-old",
"male",
"brought",
"to",
"the",
"psychiatric",
"emergency",
"room",
"for",
"suicidal",
"ideation.",
"An",
"inpatient",
"treatment",
"plan",
"including",
"pharmacotherapy,",
"family",
"therapy",
"and",
"psychological",
"testing",
"was",
"initiated.",
"The",
"patient’s",
"mother",
"failed",
"to",
"attend",
"clinic",
"appointments",
"or",
"family",
"therapy",
"sessions.",
"Clinician",
"attempts",
"to",
"engage",
"the",
"mother",
"in",
"the",
"treatment",
"plan",
"was",
"met",
"with",
"verbal",
"assaults,",
"aggression,",
"and",
"threatening",
"behavior.",
"The",
"patient",
"decompensated",
"in",
"relation",
"to",
"the",
"mother’s",
"actions.",
"Child",
"Protective",
"Services",
"were",
"contacted",
"and",
"a",
"follow-up",
"assessment",
"with",
"the",
"patient",
"and",
"mother",
"is",
"pending.",
"Psychiatric",
"treatment",
"of",
"the",
"mother",
"may",
"be",
"a",
"necessary",
"intervention",
"and",
"prevention",
"regimen",
"for",
"both",
"the",
"adolescent",
"and",
"the",
"mother.",
"Without",
"consistent",
"Child",
"Protective",
"Services",
"oversight,",
"medical",
"and",
"psychosocial",
"follow-up,",
"the",
"prognosis",
"and",
"quality",
"of",
"life",
"for",
"this",
"adolescent",
"is",
"considered",
"very",
"poor.",
"Stringent",
"mental",
"health",
"law",
"and",
"institutional",
"policies",
"are",
"needed",
"to",
"adequately",
"intercede",
"and",
"protect",
"adolescents",
"with",
"mental",
"illness.",
"Keywords:",
"adolescent,",
"suicide,",
"maternal",
"treatment",
"noncompliance,",
"maternal",
"neglect",
"Over",
"the",
"last",
"few",
"years",
"in",
"the",
"United",
"States,",
"childhood",
"neglect",
"and",
"abuse",
"has",
"increased",
"from",
"∼92%",
"to",
"almost",
"94%.",
"National",
"statistics",
"show",
"extremely",
"high",
"rates",
"of",
"childhood",
"neglect",
"(34.1%)",
"and",
"abuse",
"(26.4%)",
"perpetrated",
"most",
"often",
"by",
"single",
"mothers",
"(25.5%).1",
"During",
"the",
"last",
"50",
"years,",
"attachment",
"theory",
"research",
"clearly",
"shows",
"that",
"maternal",
"neglect",
"and",
"abuse",
"is",
"a",
"fundamental",
"trigger",
"of",
"childhood",
"mental",
"illness",
"that",
"lasts",
"a",
"lifetime.2–4",
"While",
"the",
"etiology",
"of",
"psychiatric",
"disorders",
"arising",
"from",
"maternal-child",
"dysfunction",
"is",
"well-documented,",
"prevention",
"resources",
"to",
"halt",
"the",
"rise",
"of",
"victimization",
"of",
"offspring",
"are",
"seriously",
"lacking.",
"Here,",
"we",
"report",
"maternal",
"neglect",
"and",
"possible",
"abuse",
"as",
"described",
"in",
"a",
"case",
"of",
"treatment",
"noncompliance",
"for",
"a",
"mentally",
"ill",
"and",
"suicidal",
"adolescent",
"inpatient.",
"The",
"mother",
"of",
"a",
"15-year-old",
"biracial",
"male",
"with",
"a",
"history",
"of",
"attention",
"deficit",
"hyperactivity",
"disorder",
"brought",
"her",
"son",
"to",
"the",
"psychiatric",
"emergency",
"room",
"for",
"suicidal",
"ideation.",
"She",
"reported",
"that",
"her",
"son",
"had",
"threatened",
"to",
"kill",
"himself",
"with",
"a",
"gun",
"and",
"that",
"she",
"found",
"bullets",
"in",
"his",
"possession.",
"The",
"son",
"denied",
"suicidal",
"ideation,",
"but",
"admitted",
"to",
"sadness,",
"chronic",
"frustration,",
"and",
"fear",
"while",
"living",
"with",
"his",
"mother",
"and",
"two",
"sisters.",
"He",
"described",
"an",
"altercation",
"with",
"his",
"sisters",
"that",
"precipitated",
"his",
"suicidal",
"threats",
"which",
"consequently",
"led",
"to",
"his",
"psychiatric",
"emergency",
"room",
"admission.",
"Neuropsychiatric",
"Disease",
"and",
"Treatment",
"2010:6",
"67–69",
"©",
"2010",
"Nejtek",
"et",
"al,",
"publisher",
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] | [
"Health",
"and",
"Quality",
"of",
"Life",
"Outcomes",
"BioMed",
"Central",
"Research",
"Open",
"Access",
"Reliability",
"of",
"a",
"1-week",
"recall",
"period",
"for",
"the",
"Medical",
"Outcomes",
"Study",
"Sleep",
"Scale",
"(MOS-SS)",
"in",
"patients",
"with",
"fibromyalgia",
"Alesia",
"Sadosky*1,",
"Ellen",
"Dukes1",
"and",
"Chris",
"Evans2",
"Address:",
"1Pfizer",
"Global",
"Outcomes",
"Research,",
"235",
"East",
"42nd",
"Street,",
"New",
"York,",
"NY",
"10017,",
"USA",
"and",
"2Mapi",
"Values,",
"15",
"Court",
"Square,",
"Suite",
"620,",
"Boston,",
"MA",
"02108,",
"USA",
"Email:",
"Alesia",
"Sadosky*",
"-",
"alesia.sadosky@pfizer.com;",
"Ellen",
"Dukes",
"-",
"ellen.dukes@pfizer.com;",
"Chris",
"Evans",
"-",
"chris.evans@mapivalues.com",
"*",
"Corresponding",
"author",
"Published:",
"10",
"February",
"2009",
"Health",
"and",
"Quality",
"of",
"Life",
"Outcomes",
"2009,",
"7:12",
"doi:10.1186/1477-7525-7-12",
"This",
"article",
"is",
"available",
"from:",
"http://www.hqlo.com/content/7/1/12",
"Received:",
"29",
"August",
"2008",
"Accepted:",
"10",
"February",
"2009",
"©",
"2009",
"Sadosky",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Abstract",
"Objective:",
"To",
"evaluate",
"the",
"reliability",
"of",
"a",
"one-week",
"versus",
"a",
"four-week",
"recall",
"period",
"of",
"the",
"Medical",
"Outcomes",
"Study",
"Sleep",
"Scale",
"(MOS-SS)",
"in",
"patients",
"with",
"fibromyalgia",
"(FM).",
"Methods:",
"The",
"MOS-SS",
"was",
"administered",
"by",
"mail",
"to",
"patients",
"with",
"a",
"confirmed",
"diagnosis",
"of",
"FM",
"and",
"a",
"current",
"pain",
"rating",
"of",
">",
"2",
"(0–10",
"point",
"numerical",
"rating",
"scale)",
"recruited",
"through",
"newspapers,",
"support",
"groups,",
"and",
"the",
"Internet.",
"Reliability",
"of",
"MOS-SS",
"subscale",
"domains",
"was",
"evaluated",
"using",
"test-",
"retest",
"methodology",
"separated",
"by",
"a",
"1–3",
"day",
"interval",
"for",
"the",
"4-week",
"recall",
"period",
"and",
"a",
"7-day",
"interval",
"for",
"the",
"1-week",
"recall",
"period.",
"Patient",
"Impression",
"of",
"Change",
"was",
"evaluated",
"for",
"sleep,",
"and",
"for",
"patients",
"with",
"no",
"change,",
"the",
"intraclass",
"correlation",
"coefficient",
"(ICC)",
"and",
"the",
"Pearson",
"correlation",
"coefficient",
"was",
"calculated",
"for",
"MOS-SS",
"subscales.",
"Results:",
"Of",
"129",
"patients",
"enrolled,",
"91.3%",
"were",
"female,",
"mean",
"age",
"was",
"49.4",
"±",
"11.0",
"years;",
"self-rated",
"FM",
"severity",
"was",
"moderate-to-severe",
"in",
"88.1%",
"of",
"patients.",
"MOS-SS",
"subscale",
"scores",
"were",
"similar",
"for",
"both",
"recall",
"periods",
"with",
"little",
"variation",
"between",
"test-retest.",
"The",
"9-item",
"Sleep",
"Problems",
"Index",
"scores",
"ranged",
"from",
"57.2",
"±",
"14.5",
"to",
"61.9",
"±",
"15.8",
"across",
"all",
"assessments",
"and",
"demonstrated",
"high",
"reliability",
"which",
"was",
"similar",
"for",
"the",
"1-week",
"(ICC",
"0.81)",
"and",
"4-week",
"(ICC",
"0.89)",
"recall",
"periods.",
"For",
"the",
"other",
"MOS-SS",
"subscales,",
"the",
"1-week",
"recall",
"period",
"also",
"showed",
"good",
"reliability,",
"which",
"was",
"consistent",
"for",
"the",
"ICC",
"and",
"Pearson",
"correlation",
"coefficients.",
"Conclusion:",
"A",
"1-week",
"recall",
"period",
"is",
"adequately",
"reliable",
"for",
"use",
"of",
"the",
"MOS-SS",
"in",
"studies",
"evaluating",
"sleep",
"disturbance",
"in",
"patients",
"with",
"FM.",
"Although",
"the",
"etiology",
"of",
"fibromyalgia",
"(FM)",
"is",
"uncertain,",
"it",
"is",
"generally",
"diagnosed",
"according",
"to",
"the",
"American",
"Col-",
"lege",
"of",
"Rheumatology",
"(ACR)",
"criteria,",
"which",
"include",
"chronic,",
"widespread",
"pain",
"for",
"at",
"least",
"3",
"months,",
"and",
"the",
"presence",
"of",
"11",
"out",
"of",
"18",
"tender",
"points",
"[1].",
"It",
"has",
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"esti-",
"mated",
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"[2].",
"In",
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"the",
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"0.5%",
"to",
"5%,",
"also",
"with",
"a",
"higher",
"prevalence",
"among",
"women",
"[3].",
"FM",
"is",
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"with",
"a",
"substantial",
"socioeconomic",
"burden",
"resulting",
"from",
"excess",
"health",
"resource",
"utilization,",
"reduc-",
"tions",
"in",
"productivity",
"and",
"quality",
"of",
"life,",
"and",
"a",
"health",
"sta-",
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"that",
"is",
"poorer",
"than",
"other",
"chronic",
"pain",
"conditions",
"such",
"as",
"rheumatoid",
"arthritis",
"and",
"osteoarthritis",
"[4-7].",
"This",
"bur-",
"Page",
"1",
"of",
"6",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"Sensors",
"2010,",
"10,",
"5063-5073;",
"doi:10.3390/s100505063",
"OPEN",
"ACCESS",
"sensors",
"ISSN",
"1424-8220",
"www.mdpi.com/journal/sensors",
"Article",
"Novel",
"Microwave-Assisted",
"Synthesis",
"of",
"Poly(D,L-lactide):",
"The",
"Influence",
"of",
"Monomer/Initiator",
"Molar",
"Ratio",
"on",
"the",
"Product",
"Properties",
"Ljubisa",
"Nikolic",
"1,*,",
"Ivan",
"Ristic",
"2,",
"Borivoj",
"Adnadjevic",
"3,",
"Vesna",
"Nikolic",
"1,",
"Jelena",
"Jovanovic",
"3",
"and",
"Mihajlo",
"Stankovic",
"1",
"1",
"2",
"3",
"Faculty",
"of",
"Technology,",
"University",
"of",
"Nis,",
"Bulevar",
"oslobodjenja",
"124,",
"16000",
"Leskovac,",
"Serbia;",
"E-Mails:",
"nvesna@yahoo.com",
"(V.N.);",
"mstankovic_99@yahoo.com",
"(M.S.)",
"Faculty",
"of",
"Technology,",
"University",
"of",
"Novi",
"Sad,",
"Cara",
"Lazara",
"1,",
"21000",
"Novi",
"Sad,",
"Serbia;",
"E-Mail:",
"ivancekaris@yahoo.com",
"Faculty",
"for",
"Physical",
"Chemistry,",
"University",
"of",
"Belgrade,",
"Studentski",
"trg",
"12-16,",
"11000",
"Belgrade,",
"Serbia;",
"E-Mails:",
"adnadjevic@nadlanu.com",
"(B.A.);",
"jelenaj@ffh.bg.ac.yu",
"(J.J.)",
"*",
"Author",
"to",
"whom",
"correspondence",
"should",
"be",
"addressed;",
"E-Mail:",
"nljubisa@yahoo.com.",
"Received:",
"29",
"March",
"2010;",
"in",
"revised",
"form:",
"26",
"April",
"2010",
"/",
"Accepted:",
"28",
"April",
"2010",
"/",
"Published:",
"20",
"May",
"2010",
"Abstract:",
"Poly(D,L-lactide)",
"synthesis",
"using",
"tin(II)",
"2-ethylhexanoate",
"initiated",
"ring-opening",
"polymerization",
"(ROP)",
"takes",
"over",
"30",
"hours",
"in",
"bulk",
"at",
"120",
"°C.",
"The",
"use",
"of",
"microwave",
"makes",
"the",
"same",
"bulk",
"polymerization",
"process",
"with",
"the",
"same",
"initiator",
"much",
"faster",
"and",
"energy",
"saving,",
"with",
"a",
"reaction",
"time",
"of",
"about",
"30",
"minutes",
"at",
"100",
"°C.",
"Here,",
"the",
"poly(lactide)",
"synthesis",
"was",
"done",
"in",
"a",
"microwave",
"reactor,",
"using",
"frequency",
"of",
"2.45",
"GHz",
"and",
"maximal",
"power",
"of",
"150",
"W.",
"The",
"reaction",
"temperature",
"was",
"controlled",
"via",
"infra-red",
"system",
"for",
"in-bulk-",
"measuring,",
"and",
"was",
"maintained",
"at",
"100",
"°C.",
"Different",
"molar",
"ratios",
"of",
"monomer",
"and",
"initiator,",
"[M]/[I],",
"of",
"1,000,",
"5,000",
"and",
"10,000",
"were",
"used.",
"The",
"achieved",
"average",
"molar",
"masses",
"for",
"the",
"obtained",
"polymers",
"(determined",
"by",
"gel",
"permeation",
"chromatography)",
"were",
"in",
"the",
"interval",
"from",
"26,700",
"to",
"112,500",
"g/mol.",
"The",
"polydispersion",
"index",
"was",
"from",
"2.436",
"to",
"3.425.",
"For",
"applicative",
"purposes,",
"the",
"obtained",
"material",
"was",
"purified",
"during",
"the",
"procedure",
"of",
"microsphere",
"preparation.",
"Microspheres",
"were",
"obtained",
"by",
"spraying",
"a",
"fine",
"fog",
"of",
"polymer",
"(D,L-lactide)",
"solution",
"in",
"tetrahydrofuran",
"into",
"the",
"water",
"solution",
"of",
"poly(vinyl",
"alcohol)",
"with",
"intensive",
"stirring."
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] | [
"6454–6465",
"Nucleic",
"Acids",
"Research,",
"2009,",
"Vol.",
"37,",
"No.",
"19",
"doi:10.1093/nar/gkp650",
"Published",
"online",
"26",
"August",
"2009",
"Yeast",
"genome",
"analysis",
"identifies",
"chromosomal",
"translocation,",
"gene",
"conversion",
"events",
"and",
"several",
"sites",
"of",
"Ty",
"element",
"insertion",
"Yoshiyuki",
"Shibata,",
"Ankit",
"Malhotra,",
"Stefan",
"Bekiranov",
"and",
"Anindya",
"Dutta*",
"Department",
"of",
"Biochemistry",
"and",
"Molecular",
"Genetics,",
"University",
"of",
"Virginia,",
"Charlottesville,",
"VA",
"22908,",
"USA",
"Received",
"April",
"3,",
"2009;",
"Revised",
"July",
"20,",
"2009;",
"Accepted",
"July",
"20,",
"2009",
"ABSTRACT",
"Paired",
"end",
"mapping",
"of",
"chromosomal",
"fragments",
"has",
"been",
"used",
"in",
"human",
"cells",
"to",
"identify",
"numerous",
"structural",
"variations",
"in",
"chromosomes",
"of",
"individuals",
"and",
"of",
"cancer",
"cell",
"lines;",
"however,",
"the",
"molecular,",
"biological",
"and",
"bioinformatics",
"methods",
"for",
"this",
"technology",
"are",
"still",
"in",
"development.",
"Here,",
"we",
"present",
"a",
"parallel",
"bioinformatics",
"approach",
"to",
"analyze",
"chromosomal",
"paired-end",
"tag",
"(ChromPET)",
"sequence",
"data",
"and",
"demonstrate",
"its",
"application",
"in",
"identifying",
"gene",
"rearrangements",
"in",
"the",
"model",
"organism",
"Saccharomyces",
"cerevisiae.",
"We",
"detected",
"several",
"expected",
"events,",
"including",
"a",
"chromo-",
"somal",
"rearrangement",
"of",
"the",
"nonessential",
"arm",
"of",
"chromosome",
"V",
"induced",
"by",
"selective",
"pressure,",
"rearrangements",
"introduced",
"during",
"strain",
"construc-",
"tion",
"and",
"gene",
"conversion",
"at",
"the",
"MAT",
"locus.",
"In",
"addition,",
"we",
"discovered",
"several",
"unannotated",
"Ty",
"element",
"insertions",
"that",
"are",
"present",
"in",
"the",
"reference",
"yeast",
"strain,",
"but",
"not",
"in",
"the",
"reference",
"genome",
"sequence,",
"suggesting",
"a",
"few",
"revisions",
"are",
"necessary",
"in",
"the",
"latter.",
"These",
"data",
"demonstrate",
"that",
"application",
"of",
"the",
"chromPET",
"technique",
"to",
"a",
"genetically",
"tractable",
"organism",
"like",
"yeast",
"provides",
"an",
"easy",
"screen",
"for",
"studying",
"the",
"mechanisms",
"of",
"chromosomal",
"rearrangements",
"during",
"the",
"propaga-",
"tion",
"of",
"a",
"species.",
"INTRODUCTION",
"The",
"precise",
"identification",
"of",
"sites",
"of",
"chromosomal",
"trans-",
"locations,",
"deletions",
"and",
"insertions",
"holds",
"the",
"promise",
"of",
"cataloging",
"recurrent",
"gene",
"rearrangements",
"in",
"diseases.",
"This",
"has",
"been",
"the",
"primary",
"impetus",
"for",
"the",
"development",
"of",
"paired",
"end",
"mapping",
"techniques",
"in",
"humans",
"(1,2).",
"The",
"basic",
"principle",
"is",
"to",
"identify",
"the",
"short",
"sequences",
"at",
"the",
"ends",
"of",
"linear",
"genomic",
"DNA",
"fragments",
"of",
"a",
"specified",
"size.",
"In",
"contrast",
"to",
"a",
"complete",
"sequencing",
"strategy,",
"mapping",
"the",
"‘paired-end-tag’",
"(PET)",
"sequences",
"back",
"to",
"the",
"genome",
"allows",
"one",
"to",
"identify",
"structural",
"variations",
"such",
"as",
"insertions,",
"inversions",
"and",
"translocations",
"with",
"far",
"fewer",
"sequence",
"reads.",
"Unlike",
"array",
"Comparative",
"Genomic",
"Hybridization",
"(a-CGH),",
"PET",
"analysis",
"provides",
"quantita-",
"tive",
"digital",
"information",
"with",
"no",
"detectable",
"signal",
"satura-",
"tion",
"and",
"ability",
"to",
"sample",
"rare",
"events",
"by",
"sequencing",
"more",
"DNA.",
"In",
"addition,",
"a",
"significant",
"advantage",
"to",
"sequencing",
"is",
"the",
"identification",
"of",
"the",
"specific",
"genomic",
"location",
"of",
"these",
"chromosomal",
"rearrangements,",
"and",
"the",
"emphasis",
"till",
"now",
"has",
"been",
"on",
"identifying",
"such",
"structural",
"variations",
"in",
"unique",
"chromosomal",
"sequences.",
"In",
"clinical",
"samples,",
"such",
"disease-specific",
"junctional",
"fragments",
"can",
"be",
"useful",
"molecular",
"markers",
"for",
"the",
"diagnosis",
"of",
"various",
"diseases.",
"Many",
"oncogenes",
"can",
"be",
"activated",
"by",
"recurrent",
"chromo-",
"somal",
"aberration",
"and",
"are",
"frequently",
"observed",
"in",
"hematological",
"and",
"solid",
"tumors.",
"For",
"example,",
"the",
"t(9;22)(q34;q11)",
"translocation",
"results",
"in",
"the",
"fusion",
"of",
"the",
"BCR",
"and",
"ABL1",
"genes",
"in",
"chronic",
"myelogenous",
"leukemia,",
"and",
"the",
"t(8;14)(q24;q32)",
"translocation",
"fuses",
"MYC",
"with",
"the",
"immunoglobulin",
"heavy",
"chain",
"gene",
"in",
"Burkitt",
"lymphoma",
"(3,4).",
"Recently,",
"paired-end",
"mapping",
"studies",
"have",
"revealed",
"extensive",
"structural",
"variation",
"in",
"the",
"human",
"genome",
"(5,6)",
"and",
"identified",
"somatically",
"acquired",
"rearrangements",
"in",
"cancer",
"(7–9).",
"This",
"raises",
"the",
"question",
"of",
"the",
"presence",
"and",
"extent",
"of",
"similar",
"structural",
"variation",
"in",
"other",
"model",
"organisms.",
"In",
"this",
"study,",
"we",
"establish",
"the",
"experimental",
"and",
"computational",
"methodology",
"for",
"paired-end",
"mapping",
"and",
"use",
"it",
"to",
"study",
"structural",
"variation",
"in",
"Saccharomyces",
"cerevisiae.",
"Saccharomyces",
"cerevisiae",
"is",
"a",
"useful",
"eukaryotic",
"model",
"organism",
"for",
"establishing",
"PET",
"applications",
"for",
"several",
"reasons.",
"Specifically,",
"it",
"is",
"easy",
"to",
"produce",
"uniform",
"population",
"of",
"cells,",
"since",
"S.",
"cerevisiae",
"grow",
"stably",
"as",
"either",
"a",
"haploid",
"or",
"diploid",
"and",
"are",
"genetically",
"tractable.",
"The",
"S.",
"cerevisiae",
"genome",
"is",
"12",
"Mbp,",
"which",
"is",
"2",
"orders",
"of",
"magnitude",
"smaller",
"than",
"the",
"human",
"genome.",
"In",
"addition,",
"S.",
"cerevisiae",
"is",
"used",
"as",
"a",
"model",
"organism",
"for",
"system",
"biology",
"and",
"has",
"a",
"well-annotated",
"*To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"Tel:",
"+1",
"(434)",
"924",
"1227;",
"Fax:",
"+1",
"(434)",
"924",
"5069;",
"Email:",
"ad8q@virginia.edu",
"The",
"authors",
"wish",
"it",
"to",
"be",
"known",
"that,",
"in",
"their",
"opinion,",
"the",
"first",
"two",
"authors",
"should",
"be",
"regarded",
"as",
"joint",
"First",
"Authors",
"The",
"Author(s)",
"2009.",
"Published",
"by",
"Oxford",
"University",
"Press.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://creativecommons.org/licenses/",
"by-nc/2.5/uk/)",
"which",
"permits",
"unrestricted",
"non-commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
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] | [
"HH",
"Kwon",
"and",
"KH",
"Kim",
"Ann",
"Dermatol",
"Vol.",
"24,",
"No.",
"1,",
"2012",
"CASE",
"REPORT",
"http://dx.doi.org/10.5021/ad.2012.24.1.66",
"Intravenous",
"Immunoglobulin",
"Treatment",
"in",
"a",
"Child",
"with",
"Resistant",
"Atopic",
"Dermatitis",
"Hyuck",
"Hoon",
"Kwon,",
"M.D.,",
"Kyu",
"Han",
"Kim,",
"M.D.,",
"Ph.D.",
"Department",
"of",
"Dermatology,",
"Seoul",
"National",
"University",
"College",
"of",
"Medicine,",
"Seoul,",
"Korea",
"In",
"a",
"subgroup",
"of",
"patients",
"suffering",
"from",
"atopic",
"dermatitis",
"(AD),",
"treatment",
"is",
"quite",
"difficult",
"even",
"after",
"taking",
"oral",
"immunosuppressants.",
"High-dose",
"intravenous",
"immunoglo-",
"bulin",
"(IVIG)",
"treatment",
"has",
"been",
"reported",
"to",
"be",
"beneficial",
"for",
"them",
"in",
"a",
"few",
"uncontrolled",
"trials.",
"Herein",
"we",
"report",
"a",
"case",
"of",
"intractable",
"AD",
"in",
"a",
"5-year-old",
"girl",
"who",
"had",
"significant",
"clinical",
"improvement",
"after",
"receiving",
"3",
"cycles",
"of",
"IVIG",
"treatment",
"(2",
"g/kg)",
"without",
"notable",
"side",
"effects.",
"Since",
"the",
"first",
"infusion",
"of",
"IVIG,",
"the",
"patient’s",
"skin",
"lesions",
"improved",
"steadily",
"and",
"the",
"improvement",
"persisted",
"until",
"the",
"8-month",
"follow-up.",
"The",
"eczema",
"area",
"and",
"severity",
"index",
"score",
"decreased",
"remarkably,",
"while",
"immunologic",
"parameters",
"did",
"not",
"cor-",
"relate",
"with",
"clinical",
"improvement.",
"This",
"case",
"suggests",
"that",
"IVIG",
"therapy",
"can",
"be",
"quite",
"effective",
"and",
"safe",
"for",
"children",
"with",
"resistant",
"AD.",
"(Ann",
"Dermatol",
"24(1)",
"66∼69,",
"2012)",
"-Keywords-",
"Atopic",
"dermatitis,",
"Intravenous",
"immunoglobulins",
"INTRODUCTION",
"Atopic",
"dermatitis",
"(AD)",
"is",
"one",
"of",
"the",
"most",
"common",
"derma-",
"tologic",
"diseases,",
"affecting",
"approximately",
"20%",
"of",
"children",
"living",
"in",
"industrialized",
"countries.",
"Moreover,",
"approxima-",
"tely",
"70%",
"of",
"cases",
"of",
"AD",
"affect",
"children",
"less",
"than",
"5",
"years",
"of",
"Received",
"July",
"21,",
"2010,",
"Revised",
"August",
"10,",
"2010,",
"Accepted",
"for",
"publication",
"August",
"10,",
"2010",
"Corresponding",
"author:",
"Kyu",
"Han",
"Kim,",
"M.D.,",
"Ph.D.,",
"Department",
"of",
"Dermatology,",
"Seoul",
"National",
"University",
"College",
"of",
"Medicine,",
"28",
"Yeongeon-dong,",
"Jongno-gu,",
"Seoul",
"110-744,",
"Korea.",
"Tel:",
"82-2-2072-",
"3463,",
"Fax:",
"82-2-747-5130,",
"E-mail:",
"kyuhkim@snu.ac.kr",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"Non-Commercial",
"License",
"(http://",
"creativecommons.org/licenses/by-nc/3.0)",
"which",
"permits",
"unrestricted",
"non-commercial",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"66",
"Ann",
"Dermatol",
"age1,2.",
"Most",
"cases",
"of",
"AD",
"are",
"effectively",
"treated",
"with",
"topical",
"steroids,",
"topical",
"calcineurin",
"inhibitors",
"and",
"inter-",
"mittent",
"use",
"of",
"immunosuppressive",
"agents,",
"including",
"oral",
"corticosteroids",
"and",
"cyclosporine.",
"However,",
"for",
"recalci-",
"trant",
"AD,",
"continuous",
"use",
"of",
"systemic",
"immunosuppressive",
"agents",
"is",
"used",
"but",
"is",
"limited",
"by",
"the",
"adverse",
"effects,",
"es-",
"pecially",
"for",
"children.",
"For",
"this",
"subgroup",
"of",
"patients,",
"a",
"num-",
"ber",
"of",
"clinical",
"trials",
"based",
"on",
"immunomodulatory",
"drugs",
"have",
"been",
"conducted",
"with",
"limited",
"success3-5,",
"and",
"high-",
"dose",
"intravenous",
"immunoglobulin",
"(IVIG)",
"therapy",
"has",
"been",
"reported",
"to",
"be",
"effective",
"in",
"some",
"recent",
"trials6-12;",
"in",
"particular,",
"children",
"have",
"shown",
"much",
"higher",
"responses",
"than",
"adults6-8,",
"and",
"no",
"serious",
"side",
"effects",
"accompanied",
"the",
"therapy.",
"In",
"the",
"current",
"report,",
"we",
"present",
"the",
"case",
"of",
"a",
"5-year-old",
"female",
"with",
"treatment-refractory",
"AD",
"who",
"was",
"remarkably",
"improved",
"with",
"IVIG",
"therapy",
"without",
"notable",
"side",
"effects.",
"Her",
"state",
"of",
"remission",
"continued",
"for",
"8",
"months",
"without",
"disease",
"recurrence.",
"CASE",
"REPORT",
"A",
"5-year-old",
"female",
"with",
"a",
"3-year",
"history",
"of",
"treatment-",
"refractory",
"AD",
"was",
"referred",
"to",
"our",
"Pediatric",
"Dermatology",
"Clinic.",
"She",
"had",
"failed",
"to",
"respond",
"to",
"2",
"years",
"of",
"topical",
"steroids",
"and",
"calcineurin",
"inhibitors.",
"Oral",
"steroid",
"treatments",
"as",
"an",
"inpatient",
"and",
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] | [
"Biochemistry",
"2010,",
"49,",
"2615–2626",
"2615",
"DOI:",
"10.1021/bi901516d",
"2",
"Structure",
"of",
"the",
"1,N",
"-Etheno-20-deoxyguanosine",
"Lesion",
"in",
"the",
"30-G(εdG)T-50",
"Sequence",
"Opposite",
"a",
"One-Base",
"Deletion†",
"Ganesh",
"Shanmugam,‡",
"Ivan",
"D.",
"Kozekov,‡",
"F.",
"Peter",
"Guengerich,§",
"Carmelo",
"J.",
"Rizzo,‡,§",
"and",
"Michael",
"P.",
"Stone*,‡,§",
"‡Department",
"of",
"Chemistry",
"and",
"§Department",
"of",
"Biochemistry,",
"Vanderbilt",
"Institute",
"of",
"Chemical",
"Biology,",
"Center",
"in",
"Molecular",
"Toxicology,",
"and",
"Vanderbilt-Ingram",
"Cancer",
"Center,",
"Vanderbilt",
"University,",
"Nashville,",
"Tennessee",
"37235",
"Received",
"August",
"28,",
"2009;",
"Revised",
"Manuscript",
"Received",
"November",
"19,",
"2009",
"ABSTRACT:",
"The",
"structure",
"of",
"the",
"1,N2-ethenodeoxyguanosine",
"lesion",
"(1,N2-εdG)",
"has",
"been",
"characterized",
"in",
"50-d(CGCATXGAATCC)-30",
"3",
"50-d(GGATTCATGCG)-30",
"(X",
"=",
"1,N2-εdG),",
"in",
"which",
"there",
"is",
"no",
"dC",
"opposite",
"the",
"lesion.",
"This",
"duplex",
"(named",
"the",
"1-BD",
"duplex)",
"models",
"the",
"product",
"of",
"translesion",
"bypass",
"of",
"1,N2-εdG",
"by",
"Sulfolobus",
"solfataricus",
"P2",
"DNA",
"polymerase",
"IV",
"(Dpo4)",
"[Zang,",
"H.,",
"Goodenough,",
"A.",
"K.,",
"Choi,",
"J.",
"Y.,",
"Irimia,",
"A.,",
"Loukachevitch,",
"L.",
"V.,",
"Kozekov,",
"I.",
"D.,",
"Angel,",
"K.",
"C.,",
"Rizzo,",
"C.",
"J.,",
"Egli,",
"M.,",
"and",
"Guengerich,",
"F.",
"P.",
"(2005)",
"J.",
"Biol.",
"Chem.",
"280,",
"29750-29764],",
"leading",
"to",
"a",
"one-base",
"deletion.",
"The",
"Tm",
"of",
"this",
"duplex",
"is",
"6",
"C",
"higher",
"than",
"that",
"of",
"the",
"duplex",
"in",
"which",
"dC",
"is",
"present",
"opposite",
"the",
"1,N2-εdG",
"lesion",
"and",
"8",
"C",
"higher",
"than",
"that",
"of",
"the",
"unmodified",
"1-BD",
"duplex.",
"Analysis",
"of",
"NOEs",
"between",
"the",
"1,N2-εdG",
"imidazole",
"and",
"deoxyribose",
"H10",
"protons",
"and",
"between",
"the",
"1,N2-εdG",
"etheno",
"H6",
"and",
"H7",
"protons",
"and",
"DNA",
"protons",
"establishes",
"that",
"1,N2-εdG",
"adopts",
"the",
"anti",
"conformation",
"about",
"the",
"glycosyl",
"bond",
"and",
"that",
"the",
"etheno",
"moiety",
"is",
"accommodated",
"within",
"the",
"helix.",
"The",
"resonances",
"of",
"the",
"1,N2-εdG",
"H6",
"and",
"H7",
"etheno",
"protons",
"shift",
"upfield",
"relative",
"to",
"the",
"monomer",
"1,N2-εdG,",
"attributed",
"to",
"ring",
"current",
"shielding,",
"consistent",
"with",
"their",
"intrahelical",
"location.",
"NMR",
"data",
"reveal",
"that",
"Watson-Crick",
"base",
"pairing",
"is",
"maintained",
"at",
"both",
"the",
"50",
"and",
"30",
"neighbor",
"base",
"pairs.",
"The",
"structure",
"of",
"the",
"1-BD",
"duplex",
"has",
"been",
"refined",
"using",
"molecular",
"dynamics",
"calculations",
"restrained",
"by",
"NMR-derived",
"distance",
"and",
"dihedral",
"angle",
"restraints.",
"The",
"increased",
"stability",
"of",
"the",
"1,N2-εdG",
"lesion",
"in",
"the",
"absence",
"of",
"the",
"complementary",
"dC",
"correlates",
"with",
"the",
"one-base",
"deletion",
"extension",
"product",
"observed",
"during",
"the",
"bypass",
"of",
"the",
"1,N2-εdG",
"lesion",
"by",
"the",
"Dpo4",
"polymerase,",
"suggesting",
"that",
"stabilization",
"of",
"this",
"bulged",
"intermediate",
"may",
"be",
"significant",
"with",
"regard",
"to",
"the",
"biological",
"processing",
"of",
"the",
"lesion.",
"Ethenobases",
"(1)",
"are",
"five-membered",
"annelation",
"products",
"arising",
"from",
"the",
"reactions",
"of",
"electrophiles",
"derived",
"from",
"vinyl",
"halides",
"and",
"other",
"vinyl",
"monomers,",
"including",
"chloroacetaldehyde,",
"with",
"dC,",
"dA,",
"and",
"dG",
"nucleotides",
"in",
"DNA",
"(2-9).",
"They",
"also",
"arise",
"from",
"endogenous",
"exposure",
"to",
"lipid",
"peroxidation",
"products",
"(10),",
"parti-",
"cularly",
"4,5-epoxy-2(E)-decanal",
"(11,",
"12)",
"and",
"4-hydroperoxynone-",
"nal",
"(13);",
"related",
"etheno",
"adducts",
"from",
"4-oxo-2(E)-nonenal",
"(14,",
"15),",
"4-oxohexenal",
"(16),",
"and",
"9,12-dioxo-10(E)-dodecanoic",
"acid",
"(17)",
"have",
"also",
"been",
"characterized",
"(15,",
"17).",
"The",
"1,N2-ethenodeoxy-",
"guanosine",
"(1,N2-εdG)1",
"adduct",
"(18)",
"(Scheme",
"1)",
"is",
"one",
"of",
"two",
"εdG",
"lesions,",
"the",
"other",
"being",
"the",
"N2,3-εdG",
"adduct.",
"One",
"of",
"our",
"laboratories",
"has",
"elucidated",
"the",
"mechanism",
"for",
"formation",
"of",
"†This",
"work",
"was",
"supported",
"by",
"National",
"Institutes",
"of",
"Health",
"(NIH)",
"Grants",
"P01",
"ES005355",
"(C.J.R.,",
"I.D.K.,",
"and",
"M.P.S.)",
"and",
"R01",
"ES010375",
"(F.P.G.).",
"Funding",
"for",
"the",
"NMR",
"spectrometers",
"was",
"supplied",
"by",
"Vanderbilt",
"University,",
"the",
"Vanderbilt",
"Center",
"in",
"Molecular",
"Toxicology",
"(P30",
"ES000267),",
"and",
"by",
"NIH",
"Grant",
"RR005805.",
"The",
"Vanderbilt",
"Ingram",
"Cancer",
"Center",
"is",
"supported",
"by",
"NIH",
"Grant",
"P30",
"CA068485.",
"*To",
"whom",
"correspondence",
"should",
"be",
"addressed.",
"Phone:",
"(615)",
"322-2589.",
"Fax:",
"(615)",
"322-7591.",
"E-mail:",
"michael.p.stone@vanderbilt.edu.",
"1Abbreviations:",
"1,N2-εdG,",
"3-(20-deoxy-β-D-erythro-pentofuranosyl)-",
"3,4-dihydro-9H-imidazo[1,2-a]purin-9-one",
"or",
"1,N2-etheno-20-deoxy-",
"guanosine;",
"M1dG,",
"3-(20-deoxy-β-D-erythro-pentofuranosyl)pyrimido-",
"[1,2-R]purin-10(3H)-one;",
"PdG,",
"1,N2-propano-20-deoxyguanosine;",
"1-BD,",
"one-base",
"deletion;",
"NOE,",
"nuclear",
"Overhauser",
"enhancement;",
"NOESY,",
"two-",
"dimensional",
"NOE",
"spectroscopy;",
"COSY,",
"correlation",
"spectroscopy;",
"DQF-",
"COSY,",
"double-quantum-filtered",
"correlation",
"spectroscopy;",
"TPPI,",
"time-",
"proportional",
"phase",
"increment.",
"A",
"right",
"superscript",
"refers",
"to",
"the",
"numerical",
"position",
"in",
"the",
"sequence",
"starting",
"from",
"the",
"50",
"terminus",
"of",
"chain",
"A",
"and",
"proceeding",
"to",
"the",
"30",
"terminus",
"of",
"chain",
"A",
"and",
"then",
"from",
"the",
"50",
"terminus",
"of",
"chain",
"B",
"to",
"the",
"30",
"terminus",
"of",
"chain",
"B.",
"1,N2-εdG",
"(19,",
"20).",
"It",
"has",
"been",
"detected",
"in",
"DNA",
"treated",
"with",
"vinyl",
"chloride",
"metabolites",
"(21)",
"and",
"β-carotene",
"oxidation",
"pro-",
"ducts",
"(22),",
"isolated",
"using",
"immunohistochemistry",
"techniques",
"(23),",
"and",
"identified",
"by",
"mass",
"spectrometry",
"in",
"liver",
"DNA",
"of",
"rodents",
"(24-27).",
"The",
"1,Ν2-εdG",
"lesion",
"blocks",
"the",
"Watson-Crick",
"hydrogen",
"bonding",
"face",
"of",
"dG",
"and",
"is",
"mutagenic",
"in",
"Escherichia",
"coli",
"(28)",
"and",
"in",
"mammalian",
"(29)",
"cells.",
"The",
"insertion",
"of",
"1,N2-εdG",
"into",
"a",
"30-G(1,N2-εdG)TACT-50",
"template",
"and",
"its",
"replication",
"by",
"the",
"Sulfolobus",
"solfataricus",
"P2",
"DNA",
"polymerase",
"IV",
"(Dpo4)",
"were",
"reported",
"by",
"Zang",
"et",
"al.",
"(30),",
"who",
"showed",
"that",
"dATP",
"was",
"preferentially",
"incorporated.",
"Crystallographic",
"analyses",
"(30)",
"of",
"either",
"binary",
"or",
"ternary",
"complexes",
"with",
"the",
"Dpo4",
"polymerase",
"led",
"to",
"the",
"conclusion",
"that",
"this",
"occurs",
"via",
"formation",
"of",
"a",
"“type",
"II”",
"bypass",
"structure",
"at",
"the",
"active",
"site",
"of",
"the",
"polymerase,",
"in",
"which",
"the",
"incoming",
"dATP",
"pairs",
"with",
"the",
"50",
"neighboring",
"T",
"of",
"the",
"template",
"strand,",
"as",
"opposed",
"to",
"the",
"damaged",
"1,N2-εdG",
"nucleotide",
"(31).",
"Further",
"extension",
"presumably",
"led",
"to",
"the",
"observed",
"-1",
"frameshift",
"event",
"and",
"the",
"50-CATGA-30",
"product",
"(30).",
"To",
"improve",
"our",
"understanding",
"of",
"the",
"structural",
"basis",
"of",
"-1",
"frameshift",
"events,",
"we",
"inserted",
"1,N2-εdG",
"into",
"the",
"12-mer",
"3",
"11-mer",
"duplex",
"[50-d(CGCATXGAATCC)-30",
"3",
"50-d(GGATTC_ATGCG)-30",
"(X",
"=",
"1,N2-εdG)]",
"containing",
"a",
"30-G(1,N2-εdG)TAC-50",
"template",
"sequence",
"(underlined)",
".",
"This",
"will",
"be",
"termed",
"the",
"1-BD",
"duplex",
"(Scheme",
"1).",
"It",
"models",
"the",
"situation",
"following",
"“type",
"II”",
"insertion",
"of",
"dATP",
"in",
"which",
"the",
"Dpo4",
"polymerase",
"skips",
"the",
"damaged",
"base",
"in",
"the",
"30-G(1,N2-εdG)TACT-50",
"template",
"and",
"instead",
"utilizes",
"the",
"50",
"neighbor",
"thymine",
"(underlined)",
"to",
"incorporate",
"dATP",
"(31),",
"r",
"2010",
"American",
"Chemical",
"Society",
"Published",
"on",
"Web",
"03/04/2010",
"pubs.acs.org/Biochemistry"
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] | [
"metal-organic",
"compounds",
"Acta",
"Crystallographica",
"Section",
"E",
"Structure",
"Reports",
"Online",
"ISSN",
"1600-5368",
"l-Bromido-bis{l-2,20-[4,7-diazadecane-",
"1,10-diylbis(nitrilomethanylylidene)]-",
"diphenolato}tricopper(II)",
"bromide",
"dimethylformamide",
"disolvate",
"Gervas",
"Assey,",
"Ray",
"J.",
"Butcher*",
"and",
"Yilma",
"Gultneh",
"Department",
"of",
"Chemistry,",
"Howard",
"University,",
"525",
"College",
"Street",
"NW,",
"Washington,",
"DC",
"20059,",
"USA",
"Correspondence",
"e-mail:",
"rbutcher99@yahoo.com",
"Experimental",
"Crystal",
"data",
"Received",
"21",
"July",
"2011;",
"accepted",
"1",
"August",
"2011",
"Key",
"indicators:",
"single-crystal",
"X-ray",
"study;",
"T",
"=",
"200",
"K;",
"mean",
"(C–C)",
"=",
"0.006",
"A˚;",
"disorder",
"in",
"solvent",
"or",
"counterion;",
"R",
"factor",
"=",
"0.030;",
"wR",
"factor",
"=",
"0.062;",
"data-to-",
"parameter",
"ratio",
"=",
"17.6.",
"The",
"complex",
"molecule",
"of",
"the",
"title",
"compound,",
"[Cu3Br(C22H28-",
"N4O2)2]Br",
"2C3H7NO,",
"contains",
"three",
"copper",
"atoms,",
"two",
"of",
"which",
"are",
"five-coordinate",
"within",
"a",
"square-pyramidal",
"environ-",
"ment",
"and",
"linked",
"by",
"a",
"bridging",
"Br",
"atom",
"occupying",
"the",
"apical",
"position",
"in",
"each",
"square",
"pyramid.",
"The",
"remaining",
"Cu",
"atom",
"is",
"four-coordinate",
"but",
"with",
"considerable",
"tetrahedral",
"disortion",
"[the",
"dihedral",
"angle",
"between",
"the",
"two",
"chelate",
"planes",
"is",
"69.21",
"(7)",
"].",
"There",
"are",
"two",
"molecules",
"of",
"dimethylformamide",
"(DMF)",
"present",
"as",
"solvent",
"molecules,",
"one",
"of",
"which",
"is",
"disordered",
"over",
"two",
"equivalent",
"conformations",
"with",
"occupan-",
"cies",
"of",
"0.603",
"(5)",
"and",
"0.397",
"(5).",
"The",
"amine",
"H",
"atoms",
"are",
"involved",
"in",
"both",
"inter-",
"and",
"intramolecular",
"hydrogen-bonding",
"interactions",
"with",
"the",
"Br",
"and",
"O",
"atoms",
"of",
"the",
"cation,",
"as",
"well",
"as",
"with",
"the",
"O",
"atom",
"of",
"the",
"ordered",
"DMF",
"molecule.",
"Related",
"literature",
"For",
"information",
"concerning",
"the",
"parameter,",
"see:",
"Addison",
"et",
"al.",
"(1984).",
"For",
"background",
"to",
"the",
"use",
"of",
"multi-nuclear",
"copper",
"complexes",
"in",
"metallo-enzymes",
"for",
"catalyzing",
"the",
"four-electron",
"reduction",
"of",
"oxygen",
"to",
"water,",
"see:",
"Yoon",
"et",
"al.",
"(2005);",
"Solomon",
"et",
"al.",
"(1996);",
"Mukherjee",
"et",
"al.",
"(2003);",
"Mirica",
"&",
"Stack",
"(2005);",
"Augustine",
"et",
"al.",
"(2010);",
"Chaudhuri",
"et",
"al.",
"(1992).",
"For",
"general",
"background",
"to",
"multinuclear",
"copper",
"types,",
"see:",
"Miessler",
"&",
"Tarr",
"(2005);",
"Mukherjee",
"et",
"al.",
"(2003);",
"Chen",
"et",
"al.",
"(2010);",
"Lawton",
"et",
"al.",
"(2009);",
"Hakulinen",
"et",
"al.",
"(2008).",
"For",
"information",
"concerning",
"the",
"Type",
"II",
"and",
"Type",
"III",
"site:",
"Pompidor",
"et",
"al.",
"(2008);",
"Li",
"et",
"al.",
"(2009).",
"For",
"model",
"studies",
"of",
"the",
"multi-copper",
"site:",
"Cole",
"et",
"al.",
"(1996);",
"Kataoka",
"et",
"al.",
"(2009);",
"Paine",
"et",
"al.",
"(2004).",
"[Cu3Br(C22H28N4O2)2]Br",
"2C3H7NO",
"Mr",
"=",
"1257.60",
"Hexagonal,",
"P61",
"a",
"=",
"18.7450",
"(2)",
"A˚",
"c",
"=",
"28.2531",
"(5)",
"A˚",
"V",
"=",
"8597.4",
"(2)",
"A˚",
"3",
"Data",
"collection",
"Oxford",
"Diffraction",
"Gemini",
"R",
"diffractometer",
"Absorption",
"correction:",
"multi-scan",
"(CrysAlis",
"RED;",
"Oxford",
"Diffraction,",
"2009)",
"Tmin",
"=",
"0.782,",
"Tmax",
"=",
"1.000",
"Refinement",
"R[F",
"2",
">",
"2",
"(F",
"2)]",
"=",
"0.030",
"wR(F",
"2)",
"=",
"0.062",
"S",
"=",
"0.91",
"11660",
"reflections",
"662",
"parameters",
"85",
"restraints",
"Z",
"=",
"6",
"Mo",
"K",
"radiation",
"=",
"2.55",
"mm",
"1",
"T",
"=",
"200",
"K",
"0.51",
"0.42",
"0.38",
"mm",
"95983",
"measured",
"reflections",
"11660",
"independent",
"reflections",
"8463",
"reflections",
"with",
"I",
">",
"2",
"(I)",
"Rint",
"=",
"0.070",
"H-atom",
"parameters",
"constrained",
"max",
"=",
"0.39",
"e",
"A˚",
"3",
"min",
"=",
"0.26",
"e",
"A˚",
"3",
"Absolute",
"structure:",
"Flack",
"(1983),",
"5710",
"Friedel",
"pairs",
"Flack",
"parameter:",
"0.007",
"(5)",
"Table",
"1",
"Hydrogen-bond",
"geometry",
"(A˚",
",",
").",
"D—H",
"A",
"N2A—H2AB",
"N3A—H3AB",
"N2B—H2BB",
"N3B—H3BB",
"O2B",
"Br2",
"O2A",
"O1S",
"D—H",
"0.93",
"0.93",
"0.93",
"0.93",
"H",
"A",
"2.00",
"2.50",
"2.14",
"2.39",
"D",
"A",
"2.919",
"(4)",
"3.429",
"(3)",
"3.061",
"(4)",
"3.005",
"(4)",
"D—H",
"A",
"170",
"174",
"172",
"123",
"Data",
"collection:",
"CrysAlis",
"CCD",
"(Oxford",
"Diffraction,",
"2009);",
"cell",
"refinement:",
"CrysAlis",
"RED",
"(Oxford",
"Diffraction,",
"2009);",
"data",
"reduc-",
"tion:",
"CrysAlis",
"RED;",
"program(s)",
"used",
"to",
"solve",
"structure:",
"SHELXS97",
"(Sheldrick,",
"2008);",
"program(s)",
"used",
"to",
"refine",
"structure:",
"SHELXL97",
"(Sheldrick,",
"2008);",
"molecular",
"graphics:",
"SHELXTL",
"(Sheldrick,",
"2008);",
"software",
"used",
"to",
"prepare",
"material",
"for",
"publication:",
"SHELXTL.",
"RJB",
"wishes",
"to",
"acknowledge",
"the",
"NSF–MRI",
"program",
"(grant",
"CHE-0619278)",
"for",
"funds",
"to",
"purchase",
"the",
"diffractometer.",
"GA",
"wishes",
"to",
"acknowledge",
"the",
"Howard",
"University",
"Graduate",
"School",
"of",
"Arts",
"&",
"Sciences",
"for",
"the",
"award",
"of",
"a",
"Teaching",
"Assistanceship.",
"Acta",
"Cryst.",
"(2011).",
"E67,",
"m1197–m1198",
"doi:10.1107/S160053681103090X",
"Assey",
"et",
"al.",
"m1197"
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"Malaria",
"Journal",
"Research",
"Efficacy",
"and",
"tolerability",
"of",
"four",
"antimalarial",
"combinations",
"in",
"the",
"treatment",
"of",
"uncomplicated",
"Plasmodium",
"falciparum",
"malaria",
"in",
"Senegal",
"Babacar",
"Faye*,",
"Jean-Louis",
"Ndiaye,",
"Daouda",
"Ndiaye,",
"Yemou",
"Dieng,",
"Oumar",
"Faye",
"and",
"Oumar",
"Gaye",
"Address:",
"Laboratoire",
"de",
"Parasitologie-Mycologie,",
"Faculté",
"de",
"Médecine,",
"Pharmacie",
"et",
"Odontologie.",
"Université",
"Cheikh",
"Anta",
"Diop,",
"Dakar,",
"Senegal",
"Email:",
"Babacar",
"Faye*",
"-",
"bfaye67@yahoo.fr;",
"Jean-Louis",
"Ndiaye",
"-",
"jlndiaye@yahoo.com;",
"Daouda",
"Ndiaye",
"-",
"dndiaye@hsph.harvard.edu;",
"Yemou",
"Dieng",
"-",
"Yemoud@yahoo.fr;",
"Oumar",
"Faye",
"-",
"katafaye@yahoo.fr;",
"Oumar",
"Gaye",
"-",
"ogaye@refer.sn",
"*",
"Corresponding",
"author",
"Published:",
"14",
"June",
"2007",
"Malaria",
"Journal",
"2007,",
"6:80",
"doi:10.1186/1475-2875-6-80",
"This",
"article",
"is",
"available",
"from:",
"http://www.malariajournal.com/content/6/1/80",
"Received:",
"3",
"February",
"2007",
"Accepted:",
"14",
"June",
"2007",
"©",
"2007",
"Faye",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"BioMed",
"Central",
"Open",
"Access",
"Abstract",
"Background:",
"In",
"view",
"of",
"the",
"high",
"level",
"of",
"chloroquine",
"resistance",
"in",
"many",
"countries,",
"WHO",
"has",
"recommended",
"the",
"use",
"of",
"combination",
"therapy",
"with",
"artemisinin",
"derivatives",
"in",
"the",
"treatment",
"of",
"uncomplicated",
"malaria",
"due",
"to",
"Plasmodium",
"falciparum.",
"Four",
"antimalarial",
"drug",
"combinations,",
"artesunate",
"plus",
"amodiaquine",
"(Arsucam®),",
"artesunate",
"plus",
"mefloquine",
"(Artequin®),",
"artemether",
"plus",
"lumefantrine",
"(Coartem®;",
"four",
"doses",
"and",
"six",
"doses),",
"and",
"amodiaquine",
"plus",
"sulphadoxine-",
"pyrimethamine,",
"were",
"studied",
"in",
"five",
"health",
"districts",
"in",
"Senegal.",
"Methods:",
"This",
"is",
"a",
"descriptive,",
"analytical,",
"open,",
"randomized",
"study",
"to",
"evaluate",
"the",
"efficacy",
"and",
"tolerability",
"of",
"these",
"four",
"antimalarial",
"combinations",
"in",
"the",
"treatment",
"of",
"uncomplicated",
"falciparum",
"malaria",
"using",
"the",
"2002",
"WHO",
"protocol.",
"Results:",
"All",
"drug",
"combinations",
"demonstrated",
"good",
"efficacy.",
"On",
"day",
"28,",
"all",
"combinations",
"resulted",
"in",
"an",
"excellent",
"clinical",
"and",
"parasitological",
"response",
"rate",
"of",
"100%",
"after",
"correction",
"for",
"PCR",
"results,",
"except",
"for",
"the",
"four-dose",
"artemether-lumefantrine",
"regimen",
"(96.4%).",
"Follow-up",
"of",
"approximately",
"10%",
"of",
"each",
"treatment",
"group",
"on",
"day",
"42",
"demonstrated",
"an",
"efficacy",
"of",
"100%.",
"The",
"combinations",
"were",
"well",
"tolerated",
"clinically",
"and",
"biologically.",
"No",
"unexpected",
"side-effect",
"was",
"observed",
"and",
"all",
"side-effects",
"disappeared",
"at",
"the",
"end",
"of",
"treatment.",
"No",
"serious",
"side-effect",
"requiring",
"premature",
"termination",
"of",
"treatment",
"was",
"observed.",
"Conclusion:",
"The",
"four",
"combinations",
"are",
"effective",
"and",
"well-tolerated.",
"Background",
"Approximately",
"35%",
"of",
"in-patient",
"and",
"out-patient",
"clinic",
"attendance",
"in",
"Senegal",
"are",
"due",
"to",
"malaria",
"[1].",
"Studies",
"car-",
"ried",
"out",
"by",
"staff",
"of",
"the",
"Parasitology",
"Laboratory,",
"Faculté",
"de",
"Médecine,",
"Université",
"Cheikh",
"Anta",
"Diop,",
"Dakar,",
"have",
"demonstrated",
"high",
"levels",
"of",
"resistance",
"to",
"chloroquine,",
"which",
"was",
"used",
"as",
"the",
"first-line",
"treatment",
"of",
"uncompli-",
"cated",
"malaria",
"and",
"as",
"chemoprophylaxis",
"in",
"pregnant",
"women",
"[2,3].",
"Clinical",
"failure",
"rates",
"higher",
"than",
"25%",
"have",
"been",
"observed",
"at",
"more",
"than",
"half",
"of",
"the",
"sites",
"surveyed.",
"Page",
"1",
"of",
"9",
"(page",
"number",
"not",
"for",
"citation",
"purposes)"
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] | [
"Kim",
"et",
"al.",
"BMC",
"Infectious",
"Diseases",
"2010,",
"10:315",
"http://www.biomedcentral.com/1471-2334/10/315",
"C",
"A",
"S",
"E",
"R",
"E",
"P",
"O",
"R",
"T",
"Open",
"Access",
"Enterobacter",
"nimipressuralis",
"as",
"a",
"cause",
"of",
"pseudobacteremia",
"Dong-Min",
"Kim1,4†,",
"Sook",
"Jin",
"Jang2,4†,",
"Ganesh",
"Prasad",
"Neupane1,",
"Mi-Sun",
"Jang1,5,",
"Se-Hoon",
"Kwon1,",
"Seok",
"Won",
"Kim3*,",
"Won",
"Yong",
"Kim6",
"Abstract",
"Background:",
"The",
"clinical",
"significance",
"of",
"the",
"Enterobacter",
"nimipressuralis",
"as",
"human",
"pathogens",
"remains",
"unclear.",
"Case",
"presentations:",
"The",
"microbiologic",
"culture",
"monitoring",
"system",
"of",
"sterile",
"body",
"fluids",
"revealed",
"on",
"an",
"episode",
"of",
"Enterobacter",
"cloacae",
"and",
"Enterobacter",
"amnigenus",
"in",
"blood",
"culture",
"results",
"on",
"the",
"same",
"day;",
"the",
"antibiotic",
"sensitivity",
"and",
"MIC",
"were",
"nearly",
"the",
"same",
"for",
"both",
"species.",
"First",
"patient",
"was",
"a",
"healthy",
"woman",
"with",
"postmenopausal",
"syndrome,",
"while",
"second",
"patient",
"with",
"herpes",
"zoster.",
"Both",
"patients",
"had",
"febrile",
"sensations",
"without",
"signs",
"of",
"bacteremia.",
"E.",
"amnigenus",
"was",
"also",
"cultured",
"from",
"the",
"unused",
"package",
"of",
"salined",
"cotton",
"in",
"the",
"container",
"through",
"epidemiologic",
"investigation.",
"The",
"cultured",
"Enterobacter",
"species",
"were",
"all",
"identified",
"as",
"E.",
"nimipressuralis",
"through",
"hsp60",
"gene",
"sequencing",
"and",
"infrequent-restriction-site",
"PCR",
"(IRS-PCR).",
"Conclusion:",
"When",
"an",
"unusual",
"microorganisms",
"such",
"as",
"E.",
"nimipressuralis",
"is",
"isolated",
"from",
"blood",
"of",
"a",
"patient",
"with",
"no",
"clinical",
"signs",
"of",
"sepsis,",
"a",
"pseudobacteremia",
"should",
"be",
"suspected.",
"When",
"the",
"antibiogram",
"and",
"MIC",
"test",
"results",
"of",
"bacterial",
"cultures",
"from",
"two",
"or",
"more",
"patients",
"are",
"nearly",
"the",
"same,",
"although",
"the",
"species",
"involved",
"may",
"appear",
"different,",
"it",
"may",
"be",
"necessary",
"to",
"prove",
"that",
"they",
"are",
"the",
"same",
"species",
"through",
"molecular",
"methods.",
"The",
"microbiologic",
"cultures",
"monitoring",
"system",
"will",
"probably",
"help",
"to",
"detect",
"pseudobacteremia",
"and",
"other",
"pseudo",
"infections",
"through",
"reliable",
"and",
"fast",
"identification.",
"Background",
"Chosun",
"University",
"Hospital,",
"Gwang-ju,",
"Korea,",
"is",
"a",
"650-",
"bed,",
"tertiary",
"care",
"teaching",
"hospital.",
"Every",
"day",
"in",
"our",
"hospital,",
"an",
"infectious",
"disease",
"specialist",
"monitors",
"all",
"the",
"results",
"of",
"the",
"hospital’s",
"microbiologic",
"cultures",
"from",
"ster-",
"ile",
"body",
"fluids",
"such",
"as",
"blood,",
"cerebrospinal",
"fluid",
"(CSF),",
"pleural",
"fluid,",
"ascites,",
"joint",
"fluid",
"and",
"localized",
"fluid",
"col-",
"lection",
"using",
"a",
"computerized",
"monitoring",
"system.",
"This",
"monitoring",
"system",
"revealed",
"an",
"episode",
"of",
"Enterobacter",
"nimipressuralis",
"pseudobacteremia",
"caused",
"by",
"con-",
"taminated",
"saline",
"cotton",
"during",
"the",
"preparation",
"of",
"blood",
"culture",
"samples.",
"Here",
"we",
"describe",
"two",
"cases",
"of",
"Entero-",
"bacter",
"species",
"pseudobacteremia.",
"*",
"Correspondence:",
"chosunns@hanmail.net",
"†",
"Contributed",
"equally",
"3Department",
"of",
"Neurosurgery,",
"Chosun",
"University,",
"School",
"of",
"Medicine",
"Gwangju",
"City,",
"Republic",
"of",
"Korea",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"Case",
"presentation",
"Case",
"1",
"A",
"54-year-old",
"female",
"patient",
"presented",
"with",
"myalgia",
"and",
"febrile",
"sensation",
"to",
"outpatient",
"Division",
"of",
"Gastroenterol-",
"ogy",
"and",
"Hepatology",
"in",
"Chosun",
"University",
"Hospital.",
"She",
"had",
"a",
"history",
"of",
"liver",
"cirrhosis",
"due",
"to",
"hepatitis",
"B",
"virus,",
"and",
"had",
"gone",
"surgery",
"because",
"of",
"a",
"pituitary",
"adenoma",
"1",
"year",
"ago.",
"The",
"patient",
"did",
"not",
"have",
"any",
"limitations",
"of",
"daily",
"living",
"without",
"major",
"health",
"issues",
"after",
"the",
"surgery.",
"Her",
"physical",
"examination",
"revealed",
"newly",
"formed",
"painful",
"grouped",
"vesicles",
"on",
"the",
"trunk.",
"Blood",
"culture",
"resulted",
"in",
"the",
"growth",
"of",
"Enterobacter",
"amnigenus.",
"The",
"vital",
"signs",
"and",
"laboratory",
"data",
"did",
"not",
"correlate",
"with",
"the",
"finding",
"of",
"the",
"bacteremia.",
"Antiviral",
"agent",
"for",
"the",
"herpes",
"zoster",
"was",
"used",
"with",
"improvement",
"in",
"pain",
"and",
"crust",
"formation",
"of",
"the",
"vesicles.",
"The",
"patient",
"was",
"treated",
"with",
"ciprofloxacin",
"according",
"to",
"the",
"culture",
"results.",
"The",
"follow",
"up",
"blood",
"culture",
"revealed",
"no",
"sign",
"of",
"any",
"growth",
"of",
"bacteria.",
"The",
"patient",
"was",
"discharged",
"on",
"the",
"10th",
"hospital",
"day",
"without",
"any",
"complications.",
"©",
"2010",
"Kim",
"et",
"al;",
"licensee",
"BioMed",
"Central",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License",
"(http://creativecommons.org/licenses/by/2.0),",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited."
] | [
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] | [
"Int.",
"J.",
"Mol.",
"Sci.",
"2010,",
"11,",
"354-369;",
"doi:10.3390/ijms11010354",
"OPEN",
"ACCESS",
"International",
"Journal",
"of",
"Molecular",
"Sciences",
"ISSN",
"1422-0067",
"www.mdpi.com/journal/ijms",
"Review",
"Surface",
"Modification",
"of",
"Biomedical",
"and",
"Dental",
"Implants",
"and",
"the",
"Processes",
"of",
"Inflammation,",
"Wound",
"Healing",
"and",
"Bone",
"Formation",
"Clark",
"M.",
"Stanford",
"Dows",
"Institute",
"for",
"Dental",
"Research,",
"College",
"of",
"Dentistry,",
"University",
"of",
"Iowa,",
"IA",
"52242,",
"USA;",
"E-Mail:",
"Clark-Stanford@uiowa.edu;",
"Tel.:",
"+1-319-335-7381;",
"Fax:",
"+1-319-335-8895",
"Received:",
"24",
"December",
"2009;",
"in",
"revised",
"form:",
"18",
"January",
"2010",
"/",
"Accepted:",
"20",
"January",
"2010",
"/",
"Published:",
"25",
"January",
"2010",
"Abstract:",
"Bone",
"adaptation",
"or",
"integration",
"of",
"an",
"implant",
"is",
"characterized",
"by",
"a",
"series",
"of",
"biological",
"reactions",
"that",
"start",
"with",
"bone",
"turnover",
"at",
"the",
"interface",
"(a",
"process",
"of",
"localized",
"necrosis),",
"followed",
"by",
"rapid",
"repair.",
"The",
"wound",
"healing",
"response",
"is",
"guided",
"by",
"a",
"complex",
"activation",
"of",
"macrophages",
"leading",
"to",
"tissue",
"turnover",
"and",
"new",
"osteoblast",
"differentiation",
"on",
"the",
"implant",
"surface.",
"The",
"complex",
"role",
"of",
"implant",
"surface",
"topography",
"and",
"impact",
"on",
"healing",
"response",
"plays",
"a",
"role",
"in",
"biological",
"criteria",
"that",
"can",
"guide",
"the",
"design",
"and",
"development",
"of",
"future",
"tissue-implant",
"surface",
"interfaces.",
"Keywords:",
"implant;",
"surfaces;",
"wound",
"healing;",
"macrophage",
"1.",
"Introduction",
"Endosseous",
"dental",
"implants",
"have",
"created",
"a",
"revolution",
"in",
"the",
"routine",
"approach",
"to",
"dental",
"care",
"for",
"patients",
"missing",
"one",
"or",
"more",
"teeth.",
"The",
"clinical",
"success",
"for",
"this",
"procedure",
"occurs",
"through",
"a",
"series",
"of",
"clinical",
"and",
"biological",
"steps",
"starting",
"with",
"initial",
"primary",
"stability",
"provided",
"by",
"the",
"amount,",
"quality",
"and",
"distribution",
"of",
"bone",
"within",
"the",
"proposed",
"implant",
"site",
"[1].",
"Following",
"placement",
"of",
"the",
"dental",
"implant",
"a",
"series",
"of",
"bone",
"modeling",
"and",
"remodeling",
"steps",
"take",
"place.",
"Bone",
"adaptation",
"or",
"integration",
"of",
"an",
"implant",
"is",
"characterized",
"by",
"a",
"series",
"of",
"biological",
"reactions",
"that",
"start",
"with",
"bone",
"turnover",
"at",
"the",
"interface",
"(a",
"process",
"of",
"localized",
"necrosis),",
"followed",
"by",
"rapid",
"repair",
"[2].",
"The",
"common",
"clinical",
"end",
"point",
"of",
"this",
"process",
"is",
"measured",
"by",
"a",
"lack",
"of",
"signs",
"and",
"symptoms",
"of",
"aggressive",
"chronic",
"inflammation,",
"a",
"lack",
"of",
"mobility",
"and",
"a",
"radiographic",
"assessment",
"of",
"bone",
"adapted",
"to",
"the",
"interface",
"[3,4].",
"While",
"high",
"success",
"rates",
"hold",
"for",
"certain",
"anatomic",
"regions,",
"the",
"bony",
"response",
"within",
"the",
"thin",
"cortical",
"plates",
"and",
"diminished"
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] | [
"Arrest",
"of",
"Nuclear",
"Division",
"in",
"Plasmodium",
"through",
"Blockage",
"of",
"Erythrocyte",
"Surface",
"Exposed",
"Ribosomal",
"Protein",
"P2",
"Sudipta",
"Das1,",
"Himanish",
"Basu1,",
"Reshma",
"Korde1,",
"Rita",
"Tewari2,",
"Shobhona",
"Sharma",
"1",
"*",
"1",
"Department",
"of",
"Biological",
"Sciences,",
"Tata",
"Institute",
"of",
"Fundamental",
"Research,",
"Mumbai,",
"India,",
"2",
"Centre",
"for",
"Genetics",
"and",
"Genomics,",
"Queen’s",
"Medical",
"Centre,",
"The",
"University",
"of",
"Nottingham,",
"Nottingham,",
"United",
"Kingdom",
"Abstract",
"Malaria",
"parasites",
"reside",
"inside",
"erythrocytes",
"and",
"the",
"disease",
"manifestations",
"are",
"linked",
"to",
"the",
"growth",
"inside",
"infected",
"erythrocytes",
"(IE).",
"The",
"growth",
"of",
"the",
"parasite",
"is",
"mostly",
"confined",
"to",
"the",
"trophozoite",
"stage",
"during",
"which",
"nuclear",
"division",
"occurs",
"followed",
"by",
"the",
"formation",
"of",
"cell",
"bodies",
"(schizogony).",
"The",
"mechanism",
"and",
"regulation",
"of",
"schizogony",
"are",
"poorly",
"understood.",
"Here",
"we",
"show",
"a",
"novel",
"role",
"for",
"a",
"Plasmodium",
"falciparum",
"60S",
"stalk",
"ribosomal",
"acidic",
"protein",
"P2",
"(PfP2)",
"(PFC0400w),",
"which",
"gets",
"exported",
"to",
"the",
"IE",
"surface",
"for",
"6–8",
"hrs",
"during",
"early",
"schizogony,",
"starting",
"around",
"26–28",
"hrs",
"post-",
"merozoite",
"invasion.",
"The",
"surface",
"exposure",
"is",
"demonstrated",
"using",
"multiple",
"PfP2-specific",
"monoclonal",
"antibodies,",
"and",
"is",
"confirmed",
"through",
"transfection",
"using",
"PfP2-GFP.",
"The",
"IE",
"surface-exposed",
"PfP2-protein",
"occurs",
"mainly",
"as",
"SDS-resistant",
"P2-",
"homo-tetramers.",
"Treatment",
"with",
"anti-PfP2",
"monoclonals",
"causes",
"arrest",
"of",
"IEs",
"at",
"the",
"first",
"nuclear",
"division.",
"Upon",
"removal",
"of",
"the",
"antibodies,",
"about",
"80–85%",
"of",
"synchronized",
"parasites",
"can",
"be",
"released",
"even",
"after",
"24",
"hrs",
"of",
"antibody",
"treatment.",
"It",
"has",
"been",
"reported",
"that",
"a",
"tubovesicular",
"network",
"(TVN)",
"is",
"set",
"up",
"in",
"early",
"trophozoites",
"which",
"is",
"used",
"for",
"nutrient",
"import.",
"Anti-P2",
"monoclonal",
"antibodies",
"cause",
"a",
"complete",
"fragmentation",
"of",
"TVN",
"by",
"36",
"hrs,",
"and",
"impairs",
"lipid",
"import",
"in",
"IEs.",
"These",
"may",
"be",
"downstream",
"causes",
"for",
"the",
"cell-cycle",
"arrest.",
"Upon",
"antibody",
"removal,",
"the",
"TVN",
"is",
"reconstituted,",
"and",
"the",
"cell",
"division",
"progresses.",
"Each",
"of",
"the",
"above",
"properties",
"is",
"observed",
"in",
"the",
"rodent",
"malaria",
"parasite",
"species",
"P.",
"yoelii",
"and",
"P.",
"berghei.",
"The",
"translocation",
"of",
"the",
"P2",
"protein",
"to",
"the",
"IE",
"surface",
"is",
"therefore",
"likely",
"to",
"be",
"of",
"fundamental",
"importance",
"in",
"Plasmodium",
"cell",
"division.",
"Citation:",
"Das",
"S,",
"Basu",
"H,",
"Korde",
"R,",
"Tewari",
"R,",
"Sharma",
"S",
"(2012)",
"Arrest",
"of",
"Nuclear",
"Division",
"in",
"Plasmodium",
"through",
"Blockage",
"of",
"Erythrocyte",
"Surface",
"Exposed",
"Ribosomal",
"Protein",
"P2.",
"PLoS",
"Pathog",
"8(8):",
"e1002858.",
"doi:10.1371/journal.ppat.1002858",
"Editor:",
"Joe",
"Smith,",
"Seattle",
"Biomedical",
"Research",
"Institute,",
"United",
"States",
"of",
"America",
"Received",
"February",
"14,",
"2012;",
"Accepted",
"June",
"27,",
"2012;",
"Published",
"August",
"9,",
"2012",
"Copyright:",
"2012",
"Das",
"et",
"al.",
"This",
"is",
"an",
"open-access",
"article",
"distributed",
"under",
"the",
"terms",
"of",
"the",
"Creative",
"Commons",
"Attribution",
"License,",
"which",
"permits",
"unrestricted",
"use,",
"distribution,",
"and",
"reproduction",
"in",
"any",
"medium,",
"provided",
"the",
"original",
"author",
"and",
"source",
"are",
"credited.",
"Funding:",
"This",
"work",
"was",
"supported",
"by",
"an",
"intramural",
"grant",
"from",
"Tata",
"Institute",
"of",
"Fundamental",
"Research,",
"India",
"and",
"grant",
"of",
"MRC",
"Investigator",
"Award,",
"United",
"Kingdom.",
"The",
"funders",
"had",
"no",
"role",
"in",
"study",
"design,",
"data",
"collection",
"and",
"analysis,",
"decision",
"to",
"publish,",
"or",
"preparation",
"of",
"the",
"manuscript.",
"Competing",
"Interests:",
"I",
"have",
"read",
"the",
"journal’s",
"policy",
"and",
"have",
"the",
"following",
"conflicts:",
"This",
"work",
"was",
"filed",
"for",
"Indian",
"Patent",
"on",
"17/06/11",
"and",
"the",
"patent",
"number",
"is",
"1773/MUM/2011.",
"This",
"does",
"not",
"alter",
"our",
"adherence",
"to",
"all",
"PLoS",
"Pathogens",
"policies",
"on",
"sharing",
"data",
"and",
"materials.",
"*",
"E-mail:",
"sharma@tifr.res.in",
"Introduction",
"Malaria,",
"caused",
"by",
"the",
"species",
"Plasmodium,",
"is",
"a",
"prevalent",
"tropical",
"infectious",
"disease,",
"which",
"continues",
"to",
"take",
"a",
"large",
"toll",
"on",
"lives",
"(WHO",
"guidelines,",
"2008).",
"The",
"malarial",
"pathology",
"is",
"largely",
"caused",
"by",
"the",
"cyclic",
"growth",
"of",
"the",
"parasite",
"within",
"the",
"infected",
"erythrocytes",
"(IE).",
"Very",
"little",
"is",
"known",
"about",
"molecular",
"mechanisms",
"of",
"replication",
"of",
"Plasmodium",
"in",
"the",
"erythrocytes.",
"Cell",
"division",
"in",
"Plasmodium",
"occurs",
"largely",
"through",
"a",
"schizogonic",
"process,",
"in",
"which",
"the",
"nuclei",
"divide",
"asynchronously",
"at",
"first",
"into",
"about",
"16–24",
"nuclei,",
"followed",
"by",
"the",
"formation",
"of",
"cell",
"bodies",
"[1–5].",
"Unlike",
"classical",
"eukaryotic",
"cell",
"division,",
"the",
"nuclear",
"cell",
"membrane",
"appears",
"to",
"remain",
"intact",
"during",
"such",
"divisions.",
"Similar",
"nuclear",
"division",
"without",
"cytokinesis",
"occurs",
"in",
"Drosophila",
"embryonic",
"syncytial",
"divisions",
"[6,7].",
"It",
"is",
"possible",
"that",
"such",
"a",
"form",
"of",
"cell",
"division",
"is",
"favoured",
"when",
"rapid",
"eukaryotic",
"cell",
"division",
"is",
"required,",
"such",
"as",
"in",
"the",
"case",
"of",
"Drosophila",
"embryo.",
"Certain",
"filament",
"forming",
"fungal",
"species",
"also",
"form",
"multinuclear",
"hyphal",
"compartments,",
"in",
"which",
"the",
"nuclear",
"position",
"and",
"cell",
"cycle",
"is",
"only",
"loosely",
"coordinated",
"with",
"septum",
"placement",
"[8,9].",
"This",
"type",
"of",
"nuclear",
"division",
"might",
"enable",
"cells",
"to",
"spatially",
"restrict",
"mitoses",
"within",
"a",
"shared",
"cytoplasm,",
"potentially",
"facilitating",
"local",
"responses",
"to",
"nutrients",
"or",
"other",
"environmental",
"stimuli.",
"The",
"entry",
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"PLoS",
"Pathogens",
"|",
"www.plospathogens.org",
"1",
"August",
"2012",
"|",
"Volume",
"8",
"|",
"Issue",
"8",
"|",
"e1002858"
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] | [
"e",
"n",
"i",
"c",
"i",
"d",
"e",
"M",
"l",
"a",
"t",
"n",
"e",
"m",
"i",
"r",
"e",
"p",
"x",
"E",
"f",
"o",
"l",
"a",
"n",
"r",
"u",
"o",
"J",
"e",
"h",
"T",
"CORRESPONDENCE",
"Harald",
"von",
"Boehmer:",
"harald_von_boehmer@",
"dfci.harvard.edu",
"Abbreviations",
"used:",
"array",
"CGH,",
"array-based",
"comparative",
"ge-",
"nomic",
"hybridization;",
"BMT,",
"BM",
"transfer;",
"DAPK,",
"death-",
"associated",
"protein",
"kinase;",
"DNMAML1,",
"dominant-nega-",
"tive",
"mastermind-like",
"1;",
"ICN,",
"intracellular",
"Notch;",
"SKY,",
"spec-",
"tral",
"karyotype;",
"T-ALL,",
"T",
"cell",
"acute",
"lymphoblastic",
"leukemia.",
"The",
"Rockefeller",
"University",
"Press",
"$30.00",
"J.",
"Exp.",
"Med.",
"Vol.",
"205",
"No.",
"12",
"2851-2861",
"www.jem.org/cgi/doi/10.1084/jem.20081561",
"A",
"RT",
"I",
"C",
"L",
"E",
"Oncogenesis",
"of",
"T-ALL",
"and",
"nonmalignant",
"consequences",
"of",
"overexpressing",
"intracellular",
"NOTCH1",
"Xiaoyu",
"Li,1",
"Fotini",
"Gounari,1,2",
"Alexei",
"Protopopov,1",
"Khashayarsha",
"Khazaie,1,3",
"and",
"Harald",
"von",
"Boehmer1",
"1Dana-Farber",
"Cancer",
"Institute,",
"Harvard",
"Medical",
"School,",
"Boston,",
"MA",
"02115",
"2Department",
"of",
"Medicine,",
"University",
"of",
"Chicago,",
"Chicago,",
"IL",
"60637",
"3Department",
"of",
"Microbiology-Immunology,",
"Northwestern",
"University,",
"Chicago,",
"IL",
"60611",
"Mutations",
"resulting",
"in",
"overexpression",
"of",
"intracellular",
"Notch1",
"(ICN1)",
"are",
"frequently",
"ob-",
"served",
"in",
"human",
"T",
"cell",
"acute",
"lymphoblastic",
"leukemia",
"(T-ALL).",
"We",
"have",
"determined",
"the",
"consequences",
"of",
"ICN1",
"overexpression",
"from",
"retroviral",
"vectors",
"introduced",
"into",
"bone",
"marrow",
"cells.",
"Early",
"consequences",
"are",
"the",
"generation",
"of",
"polyclonal",
"nontumorigenic",
"CD4+8+",
"T",
"cell",
"receptor",
"(TCR)-",
"+",
"cells",
"that",
"do",
"not",
"qualify",
"as",
"tumor",
"precursors",
"despite",
"the",
"observation",
"that",
"they",
"overexpress",
"Notch",
"1",
"and",
"c-Myc",
"and",
"degrade",
"the",
"tumor",
"suppressor",
"E2A",
"by",
"post-",
"translational",
"modification.",
"The",
"first",
"tumorigenic",
"cells",
"are",
"detected",
"among",
"more",
"immature",
"CD4",
"8+TCR-",
"cells",
"that",
"give",
"rise",
"to",
"monoclonal",
"tumors",
"with",
"a",
"single,",
"unique",
"TCR-",
"chain",
"and",
"diverse",
"TCR-",
"chains,",
"pinpointing",
"malignant",
"transformation",
"to",
"a",
"stage",
"after",
"pre-",
"TCR",
"signaling",
"and",
"before",
"completion",
"of",
"TCR-",
"rearrangement.",
"In",
"T-ALL,",
"E2A",
"deficiency",
"is",
"accompanied",
"by",
"further",
"transcriptional",
"up-regulation",
"of",
"c-Myc",
"and",
"concomitant",
"dysregu-",
"lation",
"of",
"the",
"c-Myc-p53",
"axis",
"at",
"the",
"transcriptional",
"level.",
"Even",
"though",
"the",
"tumors",
"consist",
"of",
"phenotypically",
"heterogeneous",
"cells,",
"no",
"evidence",
"for",
"tumor",
"stem",
"cells",
"was",
"found.",
"As",
"judged",
"by",
"array-based",
"comparative",
"genomic",
"hybridization",
"(array",
"CGH)",
"and",
"spectral",
"karyo-",
"type",
"(SKY)",
"analysis,",
"none",
"of",
"the",
"tumors",
"arise",
"because",
"of",
"genomic",
"instability.",
"Notch",
"receptors",
"play",
"an",
"important",
"role",
"in",
"cell",
"growth",
"and",
"differentiation.",
"When",
"binding",
"to",
"their",
"ligands,",
"these",
"transmembrane",
"receptors",
"un-",
"dergo",
"a",
"series",
"of",
"proteolytic",
"cleavages",
"that",
"result",
"in",
"the",
"generation",
"of",
"intracellular",
"Notch",
"(ICN),",
"which",
"regulates",
"transcription",
"in",
"a",
"transcriptional",
"complex",
"with",
"several",
"other",
"proteins",
"after",
"nu-",
"clear",
"translocation",
"(1).",
"Mutations",
"that",
"result",
"in",
"overexpression",
"of",
"ICN1",
"can",
"be",
"found",
"in",
"more",
"than",
"half",
"of",
"human",
"T",
"cell",
"acute",
"lymphoblastic",
"lymphoma",
"(T-ALL)",
"samples",
"(2–4).",
"These",
"find-",
"ings",
"have",
"sparked",
"renewed",
"interest",
"in",
"ICN1-",
"initiated",
"lymphomagenesis.",
"Recent",
"results",
"have",
"indicated",
"that",
"c-Myc",
"is",
"a",
"target",
"of",
"ICN1",
"and",
"contributes",
"in",
"a",
"major",
"way",
"to",
"the",
"growth",
"of",
"Notch-dependent",
"T-ALL",
"cell",
"lines",
"(5,",
"6).",
"However,",
"overexpression",
"of",
"c-Myc",
"by",
"itself",
"is",
"insufficient",
"to",
"cause",
"T-ALL,",
"and",
"additional",
"events",
"are",
"required",
"to",
"initiate",
"clonal",
"growth",
"of",
"tumor",
"cells",
"(7,",
"8).",
"Girard",
"et",
"al.",
"observed",
"that",
"frequent",
"proviral",
"insertions",
"into",
"the",
"Notch1",
"locus",
"en-",
"hanced",
"T-ALL",
"in",
"c-Myc",
"transgenic",
"mice,",
"sug-",
"The",
"online",
"version",
"of",
"this",
"article",
"contains",
"supplemental",
"material.",
"gesting",
"a",
"collaboration",
"of",
"c-Myc",
"and",
"Notch1",
"in",
"oncogenesis",
"that",
"may",
"result",
"from",
"the",
"obser-",
"vation",
"that",
"ICN1",
"and",
"c-Myc",
"target",
"overlap-",
"ping",
"genes",
"(5),",
"or",
"that",
"ICN1",
"targets",
"distinct",
"genes",
"that",
"facilitate",
"c-Myc–dependent",
"onco-",
"genesis.",
"One",
"of",
"the",
"genes",
"that",
"is",
"affected",
"by",
"Notch1",
"is",
"the",
"tumor",
"suppressor",
"E2A,",
"which",
"has",
"an",
"important",
"role",
"in",
"the",
"differentiation",
"of",
"T",
"and",
"B",
"lymphocytes",
"(9).",
"Crucial",
"events",
"that",
"eventually",
"lead",
"to",
"ma-",
"lignant",
"transformation",
"are",
"difficult",
"to",
"study",
"ret-",
"rospectively",
"in",
"cell",
"lines",
"with",
"unknown",
"etiology",
"that",
"may",
"have",
"accumulated",
"additional",
"muta-",
"tions",
"permitting",
"growth",
"in",
"vitro.",
"Therefore,",
"we",
"have",
"systematically",
"studied",
"the",
"consequences",
"of",
"overexpression",
"of",
"intracellular",
"Notch",
"1",
"intro-",
"duced",
"into",
"BM",
"cells",
"by",
"retroviral",
"vectors",
"(10).",
"The",
"results",
"identify",
"a",
"series",
"of",
"cellular",
"and",
"mo-",
"lecular",
"changes",
"that",
"accompany",
"the",
"generation",
"©",
"2008",
"Li",
"et",
"al.",
"This",
"article",
"is",
"distributed",
"under",
"the",
"terms",
"of",
"an",
"Attribution–Non-",
"commercial–Share",
"Alike–No",
"Mirror",
"Sites",
"license",
"for",
"the",
"first",
"six",
"months",
"after",
"the",
"publication",
"date",
"(see",
"http://www.jem.org/misc/terms.shtml).",
"After",
"six",
"months",
"it",
"is",
"available",
"under",
"a",
"Creative",
"Commons",
"License",
"(Attribution–Noncommercial–Share",
"Alike",
"3.0",
"Unported",
"license,",
"as",
"described",
"at",
"http://creativecommons.org/licenses/",
"by-nc-sa/3.0/).",
"2851"
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] | [
"RESEARCH",
"Multijurisdictional",
"Approach",
"to",
"Biosur",
"veillance,",
"Kansas",
"City",
"Mark",
"A.",
"Hoffman,*",
"Tiffany",
"H.",
"Wilkinson,†",
"Aaron",
"Bush,*",
"Wayne",
"Myers,*",
"Ron",
"G.",
"Griffin,†",
"Gerald",
"L.",
"Hoff,†",
"and",
"Rex",
"Archer†",
"An",
"electronic",
"reporting",
"system",
"for",
"a",
"network",
"of",
"22",
"lab-",
"oratories",
"was",
"implemented",
"in",
"Kansas",
"City,",
"Missouri,",
"with",
"an",
"independent",
"organization",
"acting",
"as",
"a",
"data",
"clearing-",
"house",
"between",
"the",
"reporting",
"laboratories",
"and",
"public",
"health",
"departments.",
"The",
"system",
"ran",
"in",
"tandem",
"with",
"conventional",
"reporting",
"methods.",
"Laboratory",
"test",
"orders",
"and",
"results",
"were",
"aggregated",
"and",
"mapped",
"to",
"a",
"common",
"nomenclature.",
"Reports",
"were",
"delivered",
"through",
"a",
"secure",
"Internet",
"connec-",
"tion",
"to",
"the",
"Kansas",
"City",
"Health",
"Department",
"(KCHD);",
"during",
"the",
"first",
"200",
"days",
"of",
"operation,",
"359",
"qualified",
"results",
"were",
"delivered",
"electronically",
"to",
"KCHD.",
"Data",
"were",
"received",
"more",
"quickly",
"than",
"they",
"were",
"with",
"conventional",
"reporting",
"meth-",
"ods:",
"notification",
"of",
"chlamydia",
"cases",
"arrived",
"2",
"days",
"earlier,",
"invasive",
"group",
"A",
"streptococcal",
"disease",
"cases",
"arrived",
"2.3",
"days",
"sooner,",
"and",
"salmonellosis",
"cases",
"arrived",
"2.7",
"days",
"sooner.",
"Data",
"were",
"more",
"complete",
"for",
"all",
"demographic",
"fields,",
"including",
"address,",
"age,",
"sex,",
"race,",
"and",
"date",
"of",
"birth.",
"Two",
"hundred",
"fourteen",
"cases",
"reported",
"electronically",
"were",
"not",
"received",
"by",
"conventional",
"means.",
"Bmation",
"sources",
"of",
"potential",
"value",
"in",
"detecting",
"an",
"iosurveillance",
"is",
"the",
"automated",
"monitoring",
"of",
"infor-",
"emerging",
"epidemic,",
"whether",
"naturally",
"occurring",
"or",
"the",
"result",
"of",
"bioterrorism.",
"Information",
"sources",
"that",
"can",
"be",
"monitored",
"for",
"early",
"warning",
"include",
"purchases",
"of",
"nonpre-",
"scription",
"medication",
"(1)",
"and",
"symptoms",
"reported",
"during",
"ambulatory",
"care",
"(2).",
"Although",
"these",
"sources",
"offer",
"opportu-",
"nities",
"for",
"early",
"detection,",
"they",
"may",
"also",
"lead",
"to",
"high",
"rates",
"of",
"false-positive",
"reactions.",
"A",
"more",
"definitive",
"tool",
"for",
"bio-",
"surveillance",
"is",
"the",
"electronic",
"reporting",
"of",
"diagnostic",
"results",
"confirming",
"the",
"presence",
"of",
"a",
"pathogen.",
"Heightened",
"concerns",
"about",
"bioterrorism",
"have",
"led",
"pub-",
"lic",
"health",
"organizations",
"to",
"reevaluate",
"methods",
"used",
"to",
"report",
"diseases.",
"Currently,",
"most",
"healthcare",
"providers",
"noti-",
"fy",
"public",
"health",
"organizations",
"of",
"reportable",
"diseases",
"by",
"telephone,",
"fax,",
"or",
"mail",
"(3).",
"These",
"techniques",
"generally",
"delay",
"the",
"communication",
"of",
"confirmatory",
"test",
"results",
"and",
"notification",
"of",
"the",
"appropriate",
"public",
"health",
"organization",
"*Cerner",
"Corporation,",
"Kansas",
"City,",
"Missouri,",
"USA;",
"and",
"†Kansas",
"City",
"Health",
"Department,",
"Kansas",
"City,",
"Missouri,",
"USA",
"(4).",
"Underreporting",
"is",
"a",
"major",
"concern",
"with",
"traditional",
"dis-",
"ease",
"surveillance",
"strategies",
"(5);",
"even",
"cases",
"of",
"severe",
"dis-",
"eases",
"sometimes",
"go",
"unreported",
"(6).",
"In",
"addition,",
"substantial",
"variability",
"exists",
"in",
"the",
"completeness",
"of",
"the",
"information",
"sent",
"to",
"public",
"health;",
"initial",
"reports",
"often",
"include",
"only",
"the",
"test",
"result",
"and",
"the",
"patient",
"name.",
"They",
"lack",
"demographic",
"details",
"that",
"are",
"useful",
"to",
"public",
"health",
"officials,",
"requiring",
"them",
"to",
"perform",
"followup",
"calls",
"to",
"get",
"the",
"additional",
"infor-",
"mation",
"(7).",
"These",
"delays",
"and",
"inconsistencies",
"may",
"impair",
"the",
"ability",
"of",
"public",
"health",
"officials",
"to",
"detect",
"or",
"respond",
"to",
"a",
"bioterrorist",
"event.",
"One",
"solution",
"to",
"these",
"deficiencies",
"is",
"to",
"use",
"an",
"electronic",
"system",
"to",
"report",
"disease",
"to",
"public",
"health",
"authorities.",
"Three",
"approaches",
"to",
"electronic",
"disease",
"reporting",
"are",
"feasible.",
"The",
"first",
"approach",
"(Figure",
"1A)",
"requires",
"each",
"healthcare",
"provider",
"to",
"standardize",
"clinical",
"results",
"(i.e.,",
"by",
"using",
"the",
"Systematized",
"Nomenclature",
"of",
"Medicine",
"[SNOMED])",
"before",
"sending",
"results",
"electronically",
"to",
"the",
"appropriate",
"authority.",
"Researchers",
"in",
"Pittsburgh,",
"working",
"in",
"an",
"integrated",
"delivery",
"network",
"that",
"used",
"a",
"single",
"data",
"dictionary",
"to",
"minimize",
"the",
"difficulty",
"of",
"reconciling",
"dis-",
"parate",
"coding",
"systems,",
"found",
"this",
"approach",
"effective",
"for",
"electronic",
"disease",
"reporting",
"(8).",
"However,",
"developing",
"this",
"type",
"of",
"system",
"can",
"be",
"challenging",
"because",
"of",
"the",
"difficul-",
"ty",
"in",
"updating",
"multiple",
"data",
"dictionaries",
"(translation",
"tables",
"that",
"associate",
"terms",
"from",
"multiple",
"organizations).",
"The",
"sec-",
"ond",
"approach",
"(Figure",
"1B)",
"requires",
"the",
"use",
"of",
"result",
"stan-",
"dardization",
"software",
"(which",
"collects",
"data",
"from",
"multiple",
"sites",
"and",
"attempts",
"to",
"automatically",
"associate",
"terms",
"to",
"stan-",
"dard",
"terms)",
"at",
"public",
"health",
"facilities.",
"This",
"approach",
"places",
"the",
"responsibility",
"for",
"technology",
"and",
"personnel",
"with",
"the",
"public",
"health",
"organizations.",
"The",
"third",
"approach",
"to",
"elec-",
"tronic",
"reporting",
"(Figure",
"1C)",
"involves",
"an",
"intermediary",
"organization",
"that",
"aggregates",
"the",
"data",
"and",
"distributes",
"stan-",
"dardized",
"reports",
"to",
"public",
"health",
"organizations.",
"Single",
"jurisdiction",
"systems",
"using",
"this",
"approach",
"have",
"been",
"devel-",
"oped",
"in",
"Hawaii",
"and",
"Indianapolis",
"(9,10).",
"We",
"developed",
"a",
"multiple-jurisdiction",
"data",
"clearinghouse",
"system",
"(11)",
"and",
"assessed",
"the",
"benefits",
"of",
"the",
"system",
"in",
"terms",
"of",
"timeliness,",
"data",
"completeness,",
"and",
"geographic",
"depth",
"of",
"coverage.",
"Emerging",
"Infectious",
"Diseases",
"•",
"Vol.",
"9,",
"No.",
"10,",
"October",
"2003",
"1281"
] | [
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