153 research outputs found

    Comparative study of directional solidification of Al-7 wt% Si alloys in Space and on Earth: Effects of gravity on dendrite growth and Columnar-to-equiaxed transition

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    International audienceDirectional solidification experiments of grain refined Al −7 wt% Si alloy were carried out on Earth under normal gravity conditions (1 g) and in the Material Science Laboratory on board the International Space Station in microgravity environment (μg), to investigate the impact of the gravity on the solidification microstructure and the columnar-to-equiaxed transition (CET). The increase of the dendrite growth velocity imposed by the processing conditions during the experiments leads to a size decrease of the dendrite microstructure and to a more homogeneous eutectic distribution under both 1 g and μg conditions. A progressive CET is obtained in both samples implying the existence of an intermediate region after the inception position of CET defined as the end of growth of the columnar dendrites. However, a more progressive CET and longer dendrites aligned with the applied temperature gradient are observed in presence of gravity. This difference is attributed to the convective flow on Earth. On the one hand, it carries the grains that nucleate ahead of the columnar front away into the bulk liquid phase. On the other hand, it sweeps the solute away from the dendrite tip zone. Consequently, the blocking effect is diminished, allowing extended continuous growth of the elongated dendrites

    Méthodologie de (re)conception de l'outil de production pour minimiser sa consommation d'énergie

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    Aujourd’hui, les ressources énergétiques sont limitées. La demande énergétique mondiale continue de croître. Ces deux constats nous amènent à réfléchir à la consommation énergétique et l’impact environnemental des sites industriels, notamment dans le domaine de la fabrication industrielle. Or, nous savons que l’optimisation de l’efficacité énergétique permet l’économie des ressources d’énergie, ce qui induit la diminution des impacts sur l’environnement des procédés de fabrication. Par conséquent, l’efficacité énergétique doit être considérée comme la priorité centrale du processus de conception de l’outil de production, afin d’obtenir à long terme l’objectif de « fabrication durable ». L’amélioration de l’efficacité énergétique nécessite une analyse fine des outils de production.Ainsi, il faut réaliser des modèles de consommation énergétique qui permettent d’identifier la consommation d’énergie des différents organes et des différents modes de travail de l’outil de production. A partir de ces informations, les stratégies de réduction de l’énergie consommée peuvent être identifiées et différents scénarios de (re)conception de l’outil de production peuvent être proposés. L’objectif à long terme de notre travail est de proposer une méthodologie de (re)conception d’un outil de production permettant de retenir les meilleures stratégies de réduction de sa consommation énergétique. Dans cette étude, nous présenterons d’abord un point de vue général de notre travail. Puis, nous nous intéresserons à un modèle de consommation d’énergie d’un système de production appliqué à un cas d’étude : un centre d’usinage

    Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction

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    To understand the dynamics behind the worldwide spread of the mcr-1 gene, we determined the population structure of Escherichia coli and of mobile genetic elements (MGEs) carrying the mcr-1 gene. After a systematic review of the literature we included 65 E. coli whole genome sequences (WGS), adding 6 recently sequenced travel related isolates, and 312 MLST profiles. We included 219 MGEs described in 7 Enterobacteriaceae species isolated from human, animal and environmental samples. Despite a high overall diversity, 2 lineages were observed in the E. coli population that may function as reservoirs of the mcr-1 gene, the largest of which was linked to ST10, a sequence type known for its ubiquity in human faecal samples and in food samples. No genotypic clustering by geographical origin or isolation source was observed. Amongst a total of 13 plasmid incompatibility types, the IncI2, IncX4 and IncHI2 plasmids accounted for more than 90% of MGEs carrying the mcr-1 gene. We observed significant geographical clustering with regional spread of IncHI2 plasmids in Europe and IncI2 in Asia. These findings point towards promiscuous spread of the mcr-1 gene by efficient horizontal gene transfer dominated by a limited number of plasmid incompatibility types

    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

    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

    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

    Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

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    Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies
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