55 research outputs found

    Analyse de l'exploitation des broches en UGV aéronautique

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    Le fraisage grande vitesse des pièces aéronautiques de grandes dimensions nécessite à la fois un taux d'enlèvement de copeaux important ainsi qu'une qualité de finition garantissant les tolérances de ces pièces à haute valeur ajoutée. Implantées sur des machines outils UGV, les électrobroches doivent supporter, sur des phases d'usinage de plusieurs heures, des sollicitations physiques importantes. Malgré les avancées technologiques, les broches apparaissent aujourd'hui comme le maillon faible des machines d'usinage à grande vitesse aéronautique. Ce papier propose un concept innovant de surveillance des broches d'UGV qui permet de suivre l'usure de celles-ci, particulièrement au niveau de leurs roulements à billes, cause principale de leurs défaillances. Pour cela des broches FISCHER ont été instrumentées de plusieurs accéléromètres, puis intégrées sur machines FOREST-LINE. Grâce aux signaux vibratoires enregistrés par un système de surveillance conçu spécifiquement et à partir d'un état de l'art sur la surveillance des roulements que nous avons réalisés, un critère vibratoire adapté au suivi de l'état des paliers des broches a été développé. De plus, les signaux et informations enregistrés lors de l'usinage par le même système de surveillance permettent de relier l'endommagement des roulements aux sollicitations subies par la broche lors de son utilisation afin d'assurer aussi une réelle surveillance du procédé en lui-même

    Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

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    AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N. 340541. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS). TN is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. The Biobanque Québec COVID19 is funded by FRQS, Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé. These funding agencies had no role in the design, implementation or interpretation of this study. The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of Excellence 2167 “Precision Medicine in Chronic Inflammation (PMI)” (DFG Grant: “EXC2167”). The COVID19-Host(a)ge study was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). Genotyping in COVID19-Host(a)ge was supported by a philantropic donation from Stein Erik Hagen. The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"and also by the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by "Consejeria de Salud y Familias" of the Andalusian Government. DMM is currently funded by the the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018). The Columbia University Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Columbia University. The SPGRX study was supported by the Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150. The GEN-COVID study was funded by: the MIUR grant “Dipartimenti di Eccellenza 2018-2020” to the Department of Medical Biotechnologies University of Siena, Italy; the “Intesa San Paolo 2020 charity fund” dedicated to the project NB/2020/0119; and philanthropic donations to the Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by Tuscany Region “Bando Ricerca COVID-19 Toscana” grant to the Azienda Ospedaliero Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA consortium for providing computational resources; the Network for Italian Genomes (NIG) (http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for managing specimens. Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the Dolce&Gabbana Fashion Firm is gratefully acknowledged. Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione IRCCS Cà Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- “Liver Investigation: Testing Marker Utility in Steatohepatitis”, Programme “Photonics” under grant agreement “101016726” for the project “REVEAL: Neuronal microscopy for cell behavioural examination and manipulation”, Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361. DP was supported by Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV). Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the "Fonds Erasme". The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2) study was supported by grants from Fondation Léon Fredericq and from Fonds de la Recherche Scientifique (FNRS). The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones Científicas. KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project grant to Michael Hultström (KAW 2020.0182) and the Swedish Research Council to Robert Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus Bergvalls Stiftelse. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland. These funding agencies had no role in the design, implementation or interpretation of this study.Background: There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management.Academy of Finland Fellow grant N. 323116Academy of Finland for PREDICT consortium N. 340541.Canadian Institutes of Health Research (CIHR) (365825 and 409511)Lady Davis Institute of the Jewish General HospitalCanadian Foundation for Innovation (CFI)NIH FoundationCancer Research UKGenome QuébecPublic Health Agency of CanadaMcGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS)Japan Society for the Promotion of Science for Young ScientistsCIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarshipFRQS Clinical Research ScholarshipCalcul QuébecCompute CanadaWelcome TrustMedical Research CouncEuropean UnionNational Institute for Health Research-funded BioResourceClinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation TrustKing’s College LondonGenome QuébecPublic Health Agency of CanadaMcGill Interdisciplinary Initiative in Infection and ImmunityFonds de Recherche Québec Santé(DFG Grant: “EXC2167”)(CompLS grant 031L0165)Stein Erik Hagen"Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"Instituto de Salud Carlos III (CIBERehd and CIBERER)COVID-19-GWASCOVID-PREMED initiatives"Consejeria de Salud y Familias" of the Andalusian GovernmentAndalusian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018)Columbia UniversityNational Center for Advancing Translational SciencesNIH Grant Number UL1TR001873Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150MIUR grant “Dipartimenti di Eccellenza 2018-2020”“Intesa San Paolo 2020 charity fund” dedicated to the project NB/2020/0119Tuscany Region “Bando Ricerca COVID-19 Toscana”CINECA consortiumNetwork for Italian Genomes (NIG)COVID-19 Host Genetics InitiativeGenetic Biobank of SienaEuroBioBankRD-ConnectRicerca Corrente (Italian Ministry of Health)Fondazione Humanitas per la RicercaBanca Intesa San PaoloDolce&Gabbana Fashion FirmCOVID-19 BiobankFondazione IRCCS Cà Granda MilanoMyFirst Grant AIRC n.16888Ricerca Finalizzata Ministero della Salute RF-2016-02364358Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoEuropean Union (EU) Programme Horizon 2020 (under grant agreement No. 777377)“Photonics” “101016726”Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV)"Fonds Erasme"Fondation Léon FredericqFonds de la Recherche Scientifique (FNRS)Consejo Superior de Investigaciones CientíficasGerman Research Foundation (LU 1944/3-1)SciLifeLab/KAW national COVID-19 research program project (KAW 2020.0182)Swedish Research Council (2014-02569 and 2014-07606)Jeansson Stiftelser, Magnus Bergvalls StiftelseTechnical University of Munich, Munich, GermanyGenotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finlan

    A first update on mapping the human genetic architecture of COVID-19

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    Analyse de concordance entre l'IRM de perfusion de stress et la scintigraphie myocardique (à partir des 3 premières années d'expérience nantaise)

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    L'IRM de perfusion de stress à l'adénosine est une modalité d'imagerie de l'ischémie myocardique de développement relativement récent. L'objectif de ce travail était de confronter ses résultats en comparaison avec ceux de la scintigraphie myocardique, qui est le gold standard en routine clinique dans notre centre, en lui appliquant une méthode d'analyse similaire par segments. Nous avons retrouvé une concordance dans l'interprétation de 71,25% des segments entre l'IRM de perfusion et la scintigraphie myocardique. Le plus grand nombre d'erreurs a été commis dans l'interprétation du tiers basal (faux positifs et/ou faux négatifs). Malgré le faible effectif qui en était la principale limite, ce travail peut suggérer de prêter une attention plus grande à l'analyse des segments 1, 2, 4, 5 et 11. Notre travail fait apparaître que l'IRM de perfusion seule, dans son interprétation qualitative, présente des limites liées à un manque de fiabilité pour séparer les segments normaux et modérément ischémiques, ce qui apparaît également dans la littérature. L'approche multiparamétrique de l'interprétation de l'IRM cardiaque, incluant notamment l'imagerie de rehaussement tardif et l'imagerie de la cinétique ventriculaire, apparaît prometteuse pour améliorer la fiabilité diagnostique de l'IRM cardiaque de stress.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

    The second bovine β-galactoside-α2,6-sialyltransferase (ST6Gal II): genomic organization and stimulation of its in vitro expression by IL-6 in bovine mammary epithelial cells

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    Chantier qualité GAWe have cloned a cDNA sequence encoding the second bovine β-galactoside-α2,6-sialyltransferase whose sequence shares more than 75% of identity with hST6Gal II cDNA coding sequence. The bovine gene, located on BTA 11, spans over 50 kbp with five exons (E1–E5) containing the 1488 bp open reading frame and a 5′-untranslated exon (E0). The gene expression pattern reveals a specific tissue distribution (brain, lungs, spleen, salivary, and mammary glands) compared to ST6Gal I which is ubiquitously expressed. We identified for bovine ST6Gal II three kinds of transcripts which differ by their 5′-untranslated regions. Among them, two transcripts are brain specific whereas the third one is found in all of the tissues expressing the gene. Two pFlag-bST6Gal II vector constructions were separately transfected in COS-1 cells in order to express either membrane-bound or soluble active forms of ST6Gal II. Enzymatic assays with these two forms indicated that the enzyme used the LacdiNAc structure (GalNAcβ1,4GlcNAc) as a better acceptor substrate than the Type II (Galβ1-4GlcNAc) disaccharide. Moreover, the enzyme's efficiency is improved when the acceptor substrate is provided as a free oligosaccharide rather than as a protein-bound oligosaccharide. In order to investigate the potential role of ST6Gal II during the acute phase of inflammation, we used primary cultures of bovine mammary epithelial cells which were stimulated with pro-inflammatory cytokines. It appears that the ST6Gal II gene was upregulated in cells stimulated by IL-6. This result suggested that α2,6-sialylation mediated by this gene could contribute to organism's response to infections

    Genesis of Carbonatite at Oldoinyo Lengai (Tanzania) from Olivine Nephelinite: Protracted Melt Evolution and Reactive Porous Flow in Deep Crustal Mushes

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    International audienceAbstract Carbonatites, carbon-rich magmatic rocks, are thought to form by low-degree partial melting of a relatively carbon-poor mantle followed by protracted differentiation and immiscibility. However, the nature of parental magmas and the characteristics of the early stages of differentiation that shape the subsequent crystal and liquid lines of descent remain poorly constrained. To provide new constraints, deep crustal cumulative xenoliths from Oldoinyo Lengai (East African Rift), the only active volcano erupting carbonatite magmas, were studied. We use major and volatile elements in primitive olivine-hosted melt inclusions, as well as major and trace elements in crystals, to reconstruct the conditions of formation and evolution of cumulates (pressure, temperature, composition). Xenoliths are composed of olivine, diopside, phlogopite, amphibole and accessory minerals. One remarkable feature is the presence of diopside and phlogopite oikocrysts enclosing roundish olivine chadacrysts. Melt inclusions do not have vapor bubble and have major element compositions resembling olivine nephelinite (7–10 wt % MgO after corrections for post-entrapment crystallization). The absence of vapor bubbles implies that the concentrations of volatile components (i.e. CO2, H2O, S) were not compromised by well-known post-entrapment volatile loss into the vapor bubble. Based on the melt inclusion study by SIMS, the volatile concentrations in olivine nephelinite magmas (early stage of differentiation) at Oldoinyo Lengai were 20–130 ppm S, 390–4500 ppm F, 50–540 ppm Cl, up to 6074 ppm CO2 and up to 1.5 wt % H2O. According to the calculated CO2-H2O saturation pressures and geophysical data, xenoliths from Embalulu Oltatwa document a mushy reservoir in the lower crust. Primitive olivine nephelinite melt inclusions have higher H2O contents than olivine nephelinite lavas from other further South volcanoes from the North Tanzanian Divergence (0.2–0.5 wt % H2O), suggesting that the lithospheric mantle source beneath the Oldoinyo Lengai is more hydrated than the mantle beneath the rest of North Tanzanian Divergence. We present a model in which resorption features observed in olivine chadacrysts, together with the LREE enrichments in olivine grains, are the consequences of reactive porous flows in a deep crustal mushy reservoir. We provide constraints on the major, trace and volatile element composition of the parental magmas of carbonatite series and demonstrate with Rhyolite-MELTS models that phonolites and related natrocarbonatites from Oldoinyo Lengai can be produced by protracted differentiation of olivine nephelinite melts

    A stable microtubule array drives fission yeast polarity reestablishment upon quiescence exit

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    Cells perpetually face the decision to proliferate or to stay quiescent. Here we show that upon quiescence establishment, Schizosaccharomyces pombe cells drastically rearrange both their actin and microtubule (MT) cytoskeletons and lose their polarity. Indeed, while polarity markers are lost from cell extremities, actin patches and cables are reorganized into actin bodies, which are stable actin filament containing structures. Astonishingly, MTs are also stabilized and rearranged into a novel antiparallel bundle associated with the spindle pole body, named Q-MT bundle. We have identified proteins involved in this process and propose a molecular model for Q-MT bundle formation. Finally and importantly, we reveal that Q-MT bundle elongation is involved in polarity reestablishment upon quiescence exit and thereby the efficient return to the proliferative state. Our work demonstrates that quiescent S. pombe cells assemble specific cytoskeleton structures that improve the swiftness of the transition back to proliferation

    Characterization of bovine FUT7 furthers understanding of FUT7 evolution in mammals

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    Chantier qualité GABackground: The Sialyl-Lewis X (Slex) is a well-known glycan structure involved in leukocyte homing and recruitment to inflammatory sites. SLex is well conserved among species and is mainly synthesized by FucT-VII in vertebrates. The enzyme responsible for its biosynthesis in cattle was not known.[br/] Results: We cloned a cDNA sequence encoding bovine α3-fucosyltransferase VII that shares 83% identity with its human counterpart. Located at the BTA 11 telomeric region, the 1029 bp open reading frame is spread over two different exons, E1 which also contains the unique 5'-untranslated region and E2 which includes the entire 3'-untranslated region. The bfut7 expression pattern is restricted to thymus and spleen. A single transcript leading to the synthesis of a 342 aa protein was identified. The encoded fucosyltransferase, produced as a recombinant enzyme in COS-1 cells, was shown to be specifically responsible for SLex synthesis in cattle. In addition, we showed that the gene promoter evolved from fish to mammals towards a complex system related to the immune system. But beyond the fact that the gene regulation seems to be conserved among mammals, we also identified 7 SNPs including 3 missense mutations in the coding region in a small panel of animals.[br/] Conclusions: The FUT7 sequence was highly conserved as well as the specific activity of the encoded protein FucT-VII. In addition, our in silico promoter analysis and the high rate of polymorphism suggested that its function is evolving toward a complex system related to the immune system. Furthermore, comparing bovine to human and mouse sequences, it appeared that a decrease in gene regulation was correlated with an increase in mutation rate and wider tissue expression
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