309 research outputs found

    Transport properties of graphene in the high-current limit

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    We present a detailed study of the high-current transport properties of graphene devices patterned in a four-point configuration. The current tends to saturate as the voltage across graphene is increased but never reaches the complete saturation as in metallic nanotubes. Measurements are compared to a model based on the Boltzmann equation, which includes electron scattering processes due to charged and neutral impurities, and graphene optical-phonons. The saturation is incomplete because of the competition between disorder and optical-phonon scattering

    Are caregiving responsibilities associated with non-attendance at breast screening?

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    <p>Abstract</p> <p>Background</p> <p>Previous research showed that deprived individuals are less likely to attend breast screening and those providing intense amounts of informal care tend to be more deprived than non-caregivers. The aim of this study was to examine the relationship between informal caregiving and uptake of breast screening and to determine if socio-economic gradients in screening attendance were explained by caregiving responsibilities.</p> <p>Methods</p> <p>A database of breast screening histories was linked to the Northern Ireland Longitudinal Study, which links information from census, vital events and health registration datasets. The cohort included women aged 47 - 64 at the time of the census eligible for breast screening in a three-year follow-up period. Cohort attributes were recorded at the Census. Multivariate logistic regression was used to examine the relationship between informal caregiving and uptake of screening using STATA version 10.</p> <p>Results</p> <p>37,211 women were invited for breast screening of whom 27,909 (75%) attended; 23.9% of the cohort were caregivers. Caregivers providing <20 hours of care/week were more affluent, while those providing >50 hours/week were more deprived than non-caregivers. Deprived women were significantly less likely to attend breast screening; however, this was not explained by caregiving responsibilities as caregivers were as likely as non-caregivers to attend (Odds Ratio 0.97; 95% confidence intervals 0.88, 1.06).</p> <p>Conclusions</p> <p>While those providing the most significant amounts of care tended to be more deprived, caregiving responsibilities themselves did not explain the known socio-economic gradients in breast screening attendance. More work is required to identify why more deprived women are less likely to attend breast screening.</p

    Communications Biophysics

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    Contains reports on ten research projects.National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Training Grant 5 T32 NS0704)National Science Foundation (Grant BNS80-06369)National Institutes of Health (Grant 5 R01 NS11153)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 RO1 NS12846)National Science Foundation (Grant BNS77-21751)National Institutes of Health (Grant 1 P01 NS14092)Karmazin Foundation through the Council for the Arts at MITNational Institutes of Health (Fellowship 5 F32 NS06386)National Science Foundation (Fellowship SP179-14913)National Institutes of Health (Grant 5 RO1 NS11080

    Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to pseudomonas aeruginosa infection

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    Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF) patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN)-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1) and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human macrophages infected with P. aeruginosa: untreated < treated with GM-CSF < treated with IFN-γ < treated with GM-CSF and IFN-γ

    Communications Biophysics

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    Contains reports on eight research projects split into four sections.National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 5 K04 NS00113)National Institutes of Health (Training Grant 5 T32 NS07047)National Science Foundation (Grant BNS80-06369)National Institutes of Health (Grant 5 ROl NS11153)National Institutes of Health (Fellowship 1 F32 NS06544)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 R01 NS10916)National Institutes of Health (Grant 5 RO1 NS12846)National Science Foundation (Grant BNS77-21751)National Institutes of Health (Grant 1 R01 NS14092)National Institutes of Health (Grant 2 R01 NS11680)National Institutes of Health (Grant 5 ROl1 NS11080)National Institutes of Health (Training Grant 5 T32 GM07301

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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    Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment
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