174 research outputs found

    Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

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    The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

    The portals 4.0.1 network programming interface.

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    This report presents a specification for the Portals 4.0 network programming interface. Portals 4.0 is intended to allow scalable, high-performance network communication between nodes of a parallel computing system. Portals 4.0 is well suited to massively parallel processing and embedded systems. Portals 4.0 represents an adaption of the data movement layer developed for massively parallel processing platforms, such as the 4500-node Intel TeraFLOPS machine. Sandia's Cplant cluster project motivated the development of Version 3.0, which was later extended to Version 3.3 as part of the Cray Red Storm machine and XT line. Version 4.0 is targeted to the next generation of machines employing advanced network interface architectures that support enhanced offload capabilities.

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    Fabrication of Nickel Nanostructure Arrays Via a Modified Nanosphere Lithography

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    In this paper, we present a modified nanosphere lithographic scheme that is based on the self-assembly and electroforming techniques. The scheme was demonstrated to fabricate a nickel template of ordered nanobowl arrays together with a nickel nanostructure array-patterned glass substrate. The hemispherical nanobowls exhibit uniform sizes and smooth interior surfaces, and the shallow nanobowls with a flat bottom on the glass substrate are interconnected as a net structure with uniform thickness. A multiphysics model based on the level set method (LSM) was built up to understand this fabricating process by tracking the interface between the growing nickel and the electrolyte. The fabricated nickel nanobowl template can be used as a mold of long lifetime in soft lithography due to the high strength of nickel. The nanostructure–patterned glass substrate can be used in optical and magnetic devices due to their shape effects. This fabrication scheme can also be extended to a wide range of metals and alloys
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