966 resultados para Gerard, James W. (James Watson), 1867-1951.


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[Rédigé et mis en ordre par Emile Picot] [[Elektronische Ressource]] : Bd. 1

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Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

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Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

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Adolf Schaalmann

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S.

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Israel Zangwill

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The research comparing imaginal and in vivo exposure in the treatment of clinically significant fear, recently reviewed by James (1986), is reexamined from the perspective of bioinformational theory and the concept of emotional processing. Fear is assumed to be stored in long term memory as a network of propositionally-coded information, which has to be processed if treatment is to be successful. Emotional processing is indicated by activation of fear responses and their habituation within and across treatment sessions. Consistent with the theory, our review indicates that successful treatment via imaginal and in vivo exposure is indeed related to activation and habituation of fear responses; interference with processing has a negative impact upon fear reduction, regardless of the specific treatment techniques employed. Furthermore, some apparently discrepant findings in the available research literature can be understood in terms of the theories cited. These ideas provide a useful perspective from which to plan future research efforts and to advance our understanding of the processes underlying reduction of pathological fear.

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Richard Reti

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N. H.

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J.