526 research outputs found

    Extension of Beremin model to bi-modal brittle failure

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    Colloque avec actes et comité de lecture. Internationale.International audienceLa présence de zones ségrégées dans les aciers utilisés en forte épaisseur a pour effet d'abaisser la ténacité et d'augmenter la dispersion des mesures. Ce comportement s'explique qualitativement par l'observation de poches de rupture intergranulaires dans les zones ségrégées, le reste de la surface étant couvert de facettes de clivage. Le modèle de Beremin, maintenant largement utilisé pour décrire quantitativement la rupture fragile mono mode est étendu au cas bimodal (intergranulaire et clivage). Les prévisions de ce modèle sont confrontées aux mesures expérimentales de ténacité dans un acier renfermant des zones ségrégées

    Influence of P and C intergranular segregation during manufacturing and ageing on the fracture toughness of nuclear pressure vessel steels

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    International audienceMechanical tests on Charpy and CT specimens of a low alloy MnNiMo steel under two conditions, as received and thermally aged, revealed a shift of the ductile to brittle transition temperature. In this paper, an approach based on the combination of local fracture mechanics and segregation kinetics is proposed in order to describe this shift

    Sensory defects in Necdin deficient mice result from a loss of sensory neurons correlated within an increase of developmental programmed cell death

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    BACKGROUND: The human NECDIN gene is involved in a neurodevelopmental disorder, Prader-Willi syndrome (PWS). Previously we reported a mouse Necdin knock-out model with similar defects to PWS patients. Despite the putative roles attributed to Necdin, mainly from in vitro studies, its in vivo function remains unclear. In this study, we investigate sensory-motor behaviour in Necdin deficient mice. We reveal cellular defects and analyse their cause. RESULTS: We report sensory differences in Necdin deficient mice compared to wild type animals. These differences led us to investigate sensory neuron development in Necdin deficient mouse embryos. First, we describe the expression pattern of Necdin in developing DRGs and report a reduction of one-third in specified sensory neurons in dorsal roots ganglia and show that this neuronal loss is achieved by E13.5, when DRGs sensory neurons are specified. In parallel, we observed an increase of 41% in neuronal apoptosis during the wave of naturally occurring cell death at E12.5. Since it is assumed that Necdin is a P75NTR interactor, we looked at the P75NTR-expressing cell population in Necdin knock-out embryos. Unexpectedly, Necdin loss of function has no effect on p75NTR expressing neurons suggesting no direct genetic interaction between Necdin and P75NTR in this context. Although we exclude a role of Necdin in axonal outgrowth from spinal sensory neurons in early developmental stages; such a role could occur later in neuronal differentiation. Finally we also exclude an anti-proliferative role of Necdin in developing sensory neurons. CONCLUSION: Overall, our data show clearly that, in early development of the nervous system, Necdin is an anti-apoptotic or survival factor

    Stress corrosion crack initiation of Zircaloy-4 cladding tubes in an iodine vapor environment during creep, relaxation, and constant strain rate tests

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    During accidental power transient conditions with Pellet Cladding Interaction (PCI), the synergistic effect of the stress and strain imposed on the cladding by thermal expansion of the fuel, and corrosion by iodine released as a fission product, may lead to cladding failure by Stress Corrosion Cracking (SCC). In this study, internal pressure tests were conducted on unirradiated cold-worked stress-relieved Zircaloy-4 cladding tubes in an iodine vapor environment. The goal was to investigate the influence of loading type (constant pressure tests, constant circumferential strain rate tests, or constant circumferential strain tests) and test temperature (320, 350, or 380 °C) on iodine-induced stress corrosion cracking (I-SCC). The experimental results obtained with different loading types were consistent with each other. The apparent threshold hoop stress for I-SCC was found to be independent of the test temperature. SEM micrographs of the tested samples showed many pits distributed over the inner surface, which tended to coalesce into large pits in which a microcrack could initiate. A model for the time-to-failure of a cladding tube was developed using finite element simulations of the viscoplastic mechanical behavior of the material and a modified Kachanov's damage growth model. The times-to-failure predicted by this model are consistent with the experimental data

    Re-parametrisation of Adel-wheat allows reducing the experimental effort to simulate the 3D development of winter wheat

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    Eds. Risto Sievänen, Eero Nikinmaa, Christophe Godin, Anna Lintunen & Pekka NygrenA parameterisation of wheat architecture was developed, having high flexibility to simulate contrasted genotypes and growth conditions with a reasonably low number of parameters. Field measurements at 4-5 dates allowed to simulate crops from emergence to maturity with a good agreement between simulated and measured ground cover and GAI. Dynamics of leaf angles were shown to impact strongly ground cover

    Targeting Hsp27/eIF4E interaction with phenazine compound: A promising alternative for castration-resistant prostate cancer treatment

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    The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects. To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal. Specifically, the interaction of the chaperone protein Hsp27 with the initiation factor eIF4E leads to the protection of protein synthesis initiation process and enhances cell survival during cell stress induced by castration or chemotherapy. Thus, in this work we aimed at i) identifying the interaction site of the Hsp27/eIF4E complex and ii) interfere with the relevant protein/protein association mechanism involved in castration-resistant progression of prostate cancer. By a combination of experimental and modeling techniques, we proved that eIF4E interacts with the C-terminal part of Hsp27, preferentially when Hsp27 is phosphorylated. We also observed that the loss of this interaction increased cell chemo-and hormone-sensitivity. In order to find a potential inhibitor of Hsp27/eIF4E interaction, BRET assays in combination with molecular simulations identified the phenazine derivative 14 as the compound able to efficiently interfere with this protein/protein interaction, thereby inhibiting cell viability and increasing cell death in chemo- and castration-resistant prostate cancer models in vitro and in vivo

    Precipitation changes in the Mediterranean basin during the Holocene from terrestrial and marine pollen records: a model–data comparison

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    Climate evolution of the Mediterranean region during the Holocene exhibits strong spatial and temporal variability. The spatial differentiation and temporal variability, as evident from different climate proxy datasets, has remained notoriously difficult for models to reproduce. In light of this complexity, we examine the previously described evidence for (i) opposing northern and southern precipitation regimes during the Holocene across the Mediterranean basin, and (ii) an east-to-west precipitation gradient or dipole during the early Holocene, from a wet eastern Mediterranean to dry western Mediterranean. Using quantitative climate information from marine and terrestrial pollen archives, we focus on two key time intervals, the early to mid-Holocene (8000 to 6000 cal yrs BP) and the late Holocene (4000 to 2000 yrs BP), in order to test the above mentioned hypotheses on a Mediterranean-wide scale. Palynologically derived climate information is compared with the output of regional-scale climate-model simulations for the same time intervals. Quantitative pollen-based precipitation estimates were generated along a longitudinal gradient from the Alboran (West) to the Aegean Sea (East); they are derived from terrestrial pollen records from Greece, Italy and Malta as well as from pollen records obtained from marine cores. Because seasonality represents a key parameter in Mediterranean climates, special attention was given to the reconstruction of season-specific climate information, notably summer and winter precipitation. The reconstructed climatic trends corroborate a previously described north-south partition of precipitation regimes during the Holocene. During the early Holocene, relatively wet conditions occurred in the south-central and eastern Mediterranean region, while drier conditions prevailed from 45° N northwards. These patterns reversed during the late Holocene, with a wetter northern Mediterranean region and drier conditions in the east and south. More sites from the northern part of the Mediterranean basin are needed to further substantiate these observations. With regard to the existence of a west-east precipitation dipole during the Holocene, our pollen-based climate data show that the strength of this dipole is strongly linked to the seasonal parameter reconstructed: Early Holocene summers show a clear east-to-west gradient, with summer precipitation having been highest in the central and eastern Mediterranean and lowest over the western Mediterranean. In contrast, winter precipitation signals are less spatially coherent. A general drying trend occurred from the early to the late Holocene; particularly in the central and eastern Mediterranean. However, summer precipitation in the east remained above modern values, even during the late Holocene interval. Pollen-inferred precipitation estimates were compared to regional-scale climate modelling simulations based on the HadAM3 GCM coupled to the dynamic HadSM3 and the high-resolution regional HadRM3 models. Climate model outputs and pollen-inferred precipitation estimates show remarkably good overall correspondence, although many simulated patterns are of marginal statistical significance. Nevertheless, models weakly support an east to west division in summer precipitation and there are suggestions that the eastern Mediterranean experienced wetter summer and winter conditions during the early Holocene and wetter summer conditions during the late Holocene. The extent to which summer monsoonal precipitation may have existed in the southern and eastern Mediterranean during the mid-Holocene remains an outstanding question; our model, consistent with other global models, does not suggest an extension of the African monsoon into the Mediterranean. Given the difficulty in modelling future climate change in Southern Europe, more simulations based on high resolution global models and very high resolution regional downscaling, perhaps even including transient simulations, are required to fully understand the patterns of change in winter and summer circulation patterns over the Mediterranean regio

    GOing Bayesian: model-based gene set analysis of genome-scale data

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    The interpretation of data-driven experiments in genomics often involves a search for biological categories that are enriched for the responder genes identified by the experiments. However, knowledge bases such as the Gene Ontology (GO) contain hundreds or thousands of categories with very high overlap between categories. Thus, enrichment analysis performed on one category at a time frequently returns large numbers of correlated categories, leaving the choice of the most relevant ones to the user's; interpretation
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