244 research outputs found

    Modélisation du comportement dynamique de portiques en béton armé consécutif à un fort endommagement structurel initial

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    Nous présentons dans cette communication des simulations complètes d'effondrement progressif de structures planes de type portiques, obtenues au moyen d'une approche discrète simplifiée. Cette démarche originale repose sur l'utilisation de macro-éléments discrets de poutre équivalents aux éléments finis de poutre de Timoshenko ; le comportement des matériaux est localisé dans des liaisons rhéologiques entre corps rigides. L'atout d'une telle approche est de permettre de décrire complètement l'évolution de la structure depuis son état initial jusqu'à sa ruine sans nécessiter, contrairement aux approches continues comme les éléments finis, l'ajout de degrés de libertés supplémentaires et une redéfinition des connectivités entre éléments

    Résistance du mortier en flexion dynamique approche non parfaitement fragile

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    La rupture des géo-matériaux, tel le mortier, est souvent considérée comme fragile et sensible à la vitesse de déformation. Pour caractériser cette rupture en traction, des essais de flexion trois points à différentes vitesses de déformation sont réalisés. Nous nous intéressons particulièrement à une gamme de vitesse peu documentée (entre 5 et 15 s−1). Différentes approches sont mises en oeuvre pour dépouiller les essais afin de déterminer la contrainte de rupture ainsi que son évolution en fonction de la vitesse de déformation. La prise en compte d'un comportement avec endommagement permet une nouvelle estimation de la contrainte en rupture

    Antioxidant actions of ovothiol-derived 4-mercaptoimidazoles: glutathione peroxidase activity and protection against peroxynitrite-induced damage

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    Abstract4-Mercaptoimidazoles derived from the naturally occurring antioxidants, ovothiols, were tested for their glutathione peroxidase-like (GSH Px-like) activity and protection against peroxynitrite-induced damage. All the thiol compounds displayed similar significant GSH Px-like activities, which are however weaker than that of the reference compound, ebselen. The inhibitions of the peroxynitrite-dependent oxidation of Evans blue dye and dihydrorhodamine 123 showed that the thiol compounds substituted on position 5 of the imidazole ring were nearly as effective as ebselen while the C-2 substituted ones were less effective. Both assays corroborate the large superiority of mercaptoimidazoles over glutathione as inhibitors of peroxynitrite-dependent oxidation

    Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of enterovirus 71 in crossing an in vitro model of human blood brain barrier

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    Human cerebral microvascular endothelial cells (hCMEC/D3 cell line) form a steady polarized barrier when cultured in vitro on a permeable membrane. Their susceptibility to enterovirus (EV) strains was analysed to investigate how these viruses may cross the blood-brain barrier. A sample of 88 virus strains was selected on phylogenetic features among 44 epidemiologically relevant types of the four EV species A-D. The EV-A71 genome was replicated at substantial rates while the infectious virus was released at extremely low but sustained rates at both barrier sides for at least 4 days. EV-A71 antigens were detected in a limited number of cells. The properties of the endothelial barrier (structure and permeability) remained intact throughout infection. The chronic EV-A71 infection was in sharp contrast with the productive infection of cytolytic EVs (e.g. echoviruses 6 and 30). The hCMEC/D3 barriers infected with the latter EVs exhibited elevated proportions of apoptotic and necrotic cells, which resulted in major injuries to the endothelial barriers with dramatic increase of paracellular permeability and virus crossing to the abluminal side. The following intracellular rearrangements were also seen: early destruction of the actin cytoskeleton, remodelling of intracellular membranes, and reorganization of the mitochondrion network in a small cluster near the perinuclear space

    Viral particles of the endogenous retrovirus ZAM from Drosophila melanogaster use a pre-existing endosome/exosome pathway for transfer to the oocyte

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    BACKGROUND: Retroviruses have evolved various mechanisms to optimize their transfer to new target cells via late endosomes. Here, we analyzed the transfer of ZAM, a retroelement from Drosophila melanogaster, from ovarian follicle cells to the oocyte at stage 9–10 of oogenesis, when an active yolk transfer is occurring between these two cell types. RESULTS: Combining genetic and microscopic approaches, we show that a functional secretory apparatus is required to tether ZAM to endosomal vesicles and to direct its transport to the apical side of follicle cells. There, ZAM egress requires an intact follicular epithelium communicating with the oocyte. When gap junctions are inhibited or yolk receptors mutated, ZAM particles fail to sort out the follicle cells. CONCLUSION: Overall, our results indicate that retrotransposons do not exclusively perform intracellular replication cycles but may usurp exosomal/endosomal traffic to be routed from one cell to another

    DNA demethylation agent 5azadC downregulates HPV16 E6 expression in cervical cancer cell lines independently of TBX2 expression

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    HPV16 is the most carcinogenic human papillomavirus and causes >50% of cervical cancers, the majority of anal cancers and 30% of oropharyngeal squamous cell carcinomas. HPV carcinogenesis relies on the continuous expression of the two main viral oncoproteins E6 and E7 that target >150 cellular proteins. Among them, epigenetic modifiers, including DNA Methyl Transferases (DNMT), are dysregulated, promoting an aberrant methylation pattern in HPV-positive cancer cells. It has been previously reported that the treatment of HPV-positive cervical cancer cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5azadC) caused the downregulation of E6 expression due to mRNA destabilization that was mediated by miR-375. Recently, the T-box transcription factor 2 (TBX2) has been demonstrated to repress HPV LCR activity. In the current study, the role of TBX2 in E6 repression was investigated in HPV16 cervical cancer cell lines following 5azadC treatment. A decrease of E6 expression was accompanied by p53 and p21 restoration. While TBX2 mRNA was upregulated in 5azadC-treated SiHa and Ca Ski cells, TBX2 protein was not detectable. Furthermore, the overexpression of TBX2 protein in cervical cancer cells did not allow the repression of E6 expression. The TBX2 transcription factor is therefore unlikely to be associated with the repression of E6 following 5azadC treatment of SiHa and Ca Ski cells. © 2020 Spandidos Publications. All rights reserved

    SNO KARST: a French network of observatories for the multidisciplinary study of critical zone processes in karst watersheds and aquifers

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    Karst aquifers and watersheds represent a major source of drinking water around the world. They are also known as complex and often highly vulnerable hydrosystems due to strong surface groundwater interactions. Improving the understanding of karst functioning is thus a major issue for an efficient management of karst groundwater resources. A comprehensive understanding of the various processes can be achieved only by studying karst systems over a wide range of spatio-temporal scales under different geological, geomorphological, climatic and soil cover settings. The objective of the French Karst National Observatory Service (SNO Karst) is to supply the international scientific community with appropriate data and tools, with the ambition of i) facilitating the collection of long-term observations of hydro-geo-chemical variables in karst, and ii) promoting knowledge-sharing and developing cross-disciplinary research on karst. The present paper provides an overview of the monitoring sites and of collective achievements such as the KarstMod modular modelling platform and the PaPRIKa toolbox. It also presents the research questions addressed within the framework of SNO Karst, along with major research results regarding i) the hydrological response of karst to climate and anthropogenic changes, ii) the influence of karst on geochemical balance of watersheds in the critical zone, and iii) the relationships between the structure and hydrological functioning of karst aquifers and watersheds

    Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe

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    In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >= 2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.Peer reviewe

    Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years.

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    [en] BACKGROUND: Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin's lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. METHODS: This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). RESULTS: After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58-4.95), p < 0.001, and HR = 2.22 (95% CI 1.43-3.45), p < 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice
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