65 research outputs found

    Tumor immunosurveillance in human cancers

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    Until now, the anatomic extent of tumor (TNM classification) has been by far the most important factor to predict the prognosis of colorectal cancer patients. However, in recent years, data collected from large cohorts of human cancers demonstrated that the immune contexture of the primary tumors is an essential prognostic factor for patients’ disease-free and overall survival. Tumoral and immunological markers predicted by systems biology methods are involved in the shaping of an efficient immune reaction and can serve as targets for novel therapeutic approaches. Global analysis of tumor microenvironment showed that the nature, the functional orientation, the density, and the location of adaptive immune cells within distinct tumor regions influence the risk of relapse events. The density and the immune cell location within the tumor have a prognostic value that is superior to the TNM classification, and tumor invasion is statistically dependent on the host-immune reaction. Thus, the strength of the immune reaction could advance our understanding of cancer evolution and have important consequences in clinical practice

    Brain Deletion of Insulin Receptor Substrate 2 Disrupts Hippocampal Synaptic Plasticity and Metaplasticity

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    Diabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits and the corresponding neurophysiological structural and functional alterations are linked to both metabolic and vascular changes, related to chronic hyperglycaemia, but probably also defects in insulin action in the brain. To elucidate the specific role of brain insulin signalling in neuronal functions that are relevant for cognitive processes we have investigated the behaviour of neurons and synaptic plasticity in the hippocampus of mice lacking the insulin receptor substrate protein 2 (IRS-2)

    Environmental pollution policy of small businesses in Nigeria and Ghana: extent and impact

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    This study provides a comprehensive assessment of firms’ operation and environmental protection polices in Nigeria and Ghana, where there has been a rising industrial growth amidst low regulatory and institutional frameworks. We analyze the extents to which firms’ adoption of environmental protection policies affect their performances. We use firm-level data of 842 firms (447 for Nigeria and 395 for Ghana) distributed across different regions of both countries for our descriptive and econometric estimations. We find, among other things, that firms’ adoption of internal policies on environmental protection is dismally low in both Nigeria (32%) and Ghana (17%), with policies focused on reducing solid (38%, Nigeria; and 35%, Ghana), gaseous (22%, Nigeria; and 44%, Ghana), and liquid (24%, Nigeria; and 14%, Ghana) pollution. Training appears to be an important intervention that can help improve firms’ adoption of such policies. We also found that firms’ adoption and implementation of environmental protection policies significantly improve their performance

    Visualizing the Human Subcortex Using Ultra-high Field Magnetic Resonance Imaging

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    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

    The characteristics of large area processing plasmas

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    In order to, improve production efficiency, large-diameter wafer substrates (300-mm diameter) and large-are,a glass substrates (from 400 cm(2) to 1 m(2)) have been adopted recently. As a result, the development of large and high-density plasma source has become essential. To investigate the discharge phenomenon in the chamber that consists of embedded antenna coil in the rectangular system (1020 x 830 x 437 mm), we have developed a two-dimensional fluid simulation model. In order to check our model, the results from our simulation have been compared with available experimental data. The comparison is generally in a good agreement with experiments. Depending on the current direction and powered method, the distribution of plasma parameters has many differences. In our simulation with a chamber larger than is usually used in other experiments, we examine three effects: the distance between antenna coils, structure in the chamber, and the depth of the chamber. The parameters, which affect nonuniformity, electron temperature, and others, can be explained in a manner similar to the inductively coupled plasma source with a cylindrical chamber. Our simulation results confirm that the embedded antenna coil system with a suitable environment can be extended by many antenna coils as a. large-area plasma source.X116sciescopu
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