51 research outputs found

    TORRENTIAL RAIN EVENTS OVER THE CÉVENNES-VIVARAIS REGION

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    High resolution numerical simulations of recent flash-flood events that have occurred over Mediterranean coasts are used to underline the physical mechanisms leading to the stationary of the precipitating systems and the predictability associated with such events. Three cases, including the two last extreme flash-flood events over Southeastern France, have been simulated : the 12-13 November 1999 catastrophe over the Aude region (MAP IOP16), the 8-9 September 2002 flash-flood over the Gard region and the less paroxysmal event of 13-14 October 1995 over the CĂ©vennes-Vivarais relief. Sensitivity to the initial conditions, to the Massif Central relief and to the Sea Surface Temperature (SST) has been studied

    The SURFEXv7.2 land and ocean surface platform for coupled or offline simulation of Earth surface variables and fluxes

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    CC Attribution 3.0 License.Final revised paper also available at http://www.geosci-model-dev.net/6/929/2013/gmd-6-929-2013.pdfInternational audienceSURFEX is a new externalized land and ocean surface platform that describes the surface fluxes and the evolution of four types of surface: nature, town, inland water and ocean. It can be run either coupled or in offline mode. It is mostly based on pre-existing, well validated scientific models. It can be used in offline mode (from point scale to global runs) or fully coupled with an atmospheric model. SURFEX is able to simulate fluxes of carbon dioxide, chemical species, continental aerosols, sea salt and snow particles. It also includes a data assimilation module. The main principles of the organization of the surface are described first. Then, a survey is made of the scientific module (including the coupling strategy). Finally the main applications of the code are summarized. The current applications are extremely diverse, ranging from surface monitoring and hydrology to numerical weather prediction and global climate simulations. The validation work undertaken shows that replacing the pre-existing surface models by SURFEX in these applications is usually associated with improved skill, as the numerous scientific developments contained in this community code are used to good advantage

    Scaling precipitation extremes with temperature in the Mediterranean: past climate assessment and projection in anthropogenic scenarios

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    Characterization of air-sea exchanges over the Western Mediterranean Sea during HyMeX SOP1 using the AROME-WMED model

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    International audienceAir-sea exchanges play an important role during intense weather events over the Mediterranean Sea, especially in supplying heat and moisture for heavy precipitation events, which often affect the area. Observations collected during the first Hydrological cycle in the Mediterranean Experiment (HyMeX) Special Observation Period (SOP1) over the Western Mediterranean area in autumn 2012 provide an unprecedented dataset for assessing the capabilities of numerical weather prediction systems to represent the air-sea interface and marine boundary layer during the heavy precipitation season. A HyMeX-dedicated version of Application de la Recherche a l'Operationnel a Meso-Echelle, in French (AROME) covering the whole western Mediterranean basin, named AROME-WMED, was evaluated through comparisons against moored buoys, drifting buoys and ship measurements deployed during the HyMeX campaign. A general, good agreement is found for near-surface meteorological parameters, whereas significant discrepancies are observed during strong air-sea exchange periods. The two main reasons are that (1) sea-surface temperature (SST) is kept constant during the model runs and (2) sensible heat flux is overestimated in strong wind regimes by the AROME turbulent flux parametrization. Air-sea exchanges during SOP1 were characterized thanks to AROME-WMED short-range (1-24h) forecasts. This shows some areas of strong air-sea fluxes in the Gulf of Lion and the Balearic, Ligurian and Tyrrhenian Seas. The Gulf of Lion is the area showing the highest variability of air-sea fluxes, due to dominant strong regional winds (Mistral/Tramontane). Whereas some heavy precipitation events occur without significant air-sea fluxes, all strong air-sea exchange events include, or occur only 1 or 2 days before, heavy precipitation events. A detailed analysis of an Intense Observation Period (IOP) dedicated to a heavy precipitation event (IOP13, from 12-15 October) illustrates how both dynamic (wind) and thermodynamic (temperature and humidity gradient effect) contributions influence air-sea flux evolution

    ER stress induces NLRP3 inflammasome activation and hepatocyte death

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    International audienceAbstract The incidence of chronic liver disease is constantly increasing, owing to the obesity epidemic. However, the causes and mechanisms of inflammation-mediated liver damage remain poorly understood. Endoplasmic reticulum (ER) stress is an initiator of cell death and inflammatory mechanisms. Although obesity induces ER stress, the interplay between hepatic ER stress, NLRP3 inflammasome activation and hepatocyte death signaling has not yet been explored during the etiology of chronic liver diseases. Steatosis is a common disorder affecting obese patients; moreover, 25% of these patients develop steatohepatitis with an inherent risk for progression to hepatocarcinoma. Increased plasma LPS levels have been detected in the serum of patients with steatohepatitis. We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with steatohepatitis progression. In livers from obese mice, administration of LPS or tunicamycin results in IRE1 α and PERK activation, leading to the overexpression of CHOP. This, in turn, activates the NLRP3 inflammasome, subsequently initiating hepatocyte pyroptosis (caspase-1, -11, interleukin-1 β secretion) and apoptosis (caspase-3, BH3-only proteins). In contrast, the LPS challenge is blocked by the ER stress inhibitor TUDCA, resulting in: CHOP downregulation, reduced caspase-1, caspase-11, caspase-3 activities, lowered interleukin-1 β secretion and rescue from cell death. The central role of CHOP in mediating the activation of proinflammatory caspases and cell death was characterized by performing knockdown experiments in primary mouse hepatocytes. Finally, the analysis of human steatohepatitis liver biopsies showed a correlation between the upregulation of inflammasome and ER stress markers, as well as liver injury. We demonstrate here that ER stress leads to hepatic NLRP3 inflammasome pyroptotic death, thus contributing as a novel mechanism of inflammation-mediated liver injury in chronic liver diseases. Inhibition of ER-dependent inflammasome activation and cell death pathways may represent a potential therapeutic approach in chronic liver diseases

    Hepatocyte-specific deletion of XBP1 sensitizes mice to liver injury through hyperactivation of IRE1α

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    X-box binding protein-1 (XBP1) is a transcription factor that plays a central role in controlling cellular responses to endoplasmic reticulum (ER) stress. Under stress conditions, the transcriptionally active form of XBP1 is generated via splicing of Xbp1 mRNA by the ER-resident protein inositol-requiring enzyme-1 (IRE1α). Genetic deletion of XBP1 has multiple consequences: some resulting from the loss of the transcription factor per se, and others related to compensatory activation of IRE1α. The objective of the current study was to investigate the effects of XBP1 deletion in adult mouse liver and determine to what extent they are direct or indirect. XBP1 was deleted from hepatocytes in adult Xbp1(fl/fl) mice using AAV8-Transthyretin-Cre (Xbp1(Δhep)). Xbp1(Δhep) mice exhibited no liver disease at baseline, but developed acute biochemical and histologic liver injury in response to a dietary challenge with fructose for 4 weeks. Fructose-mediated liver injury in Xbp1(Δhep) mice coincided with heightened IRE1α activity, as demonstrated by Xbp1 mRNA splicing, JNK activation, and regulated IRE1α-dependent RNA decay (RIDD). Activation of eIF2α was also evident, with associated up-regulation of the pro-apoptotic molecules CHOP, BIM, and PUMA. To determine whether the adverse consequences of liver-specific XBP1 deletion were due to XBP1 loss or heightened IRE1α activity, we repeated a fructose challenge in mice with liver-specific deletion of both XBP1 and IRE1α (Xbp1(Δhep);Ire1a(Δhep)). Xbp1(Δhep);Ire1a(Δhep) mice were protected from fructose-mediated liver injury and failed to exhibit any of the signs of ER stress seen in mice lacking XBP1 alone. The protective effect of IRE1α deletion persisted even with long-term exposure to fructose. Xbp1(Δhep) mice developed liver fibrosis at 16 weeks, but Xbp1(Δhep);Ire1a(Δhep) mice did not. Overall, the results indicate that the deleterious effects of hepatocyte-specific XBP1 deletion are due primarily to hyperactivation of IRE1α. They support further exploration of IRE1α as a contributor to acute and chronic liver diseases
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