A probabilistic model to predict the formation and propagation of crack networks in thermal fatigue

International audienceA probabilistic model is presented to predict the formation and propagation of crack networks in thermal fatigue. It is based on a random distribution of sites where cracks initiate and on the shielding phenomenon corresponding to the relaxed stress field created around cracks. Currently, the model considers only heterogeneous uniaxial stress loading even if thermal fatigue is multiaxial. However, the first simulations on a uniaxial mechanical loading representative of the stress gradient that appears in thermal fatigue shocks are in qualitative agreement with experimental results. The larger the stress amplitude, the denser the crack network and the smaller the crack sizes

On the formation of crack networks in high cycle fatigue

International audienceA probabilistic model based on an initial distribution of sites is proposed to describe different aspects of the formation, propagation and coalescence of crack networks in thermomechanical fatigue. The interaction between cracks is modeled by considering shielding effects

Phenotypic effects of genetic variants associated with autism

While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in individuals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 individuals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support individuals carrying these variants

Modélisation probabiliste de formation de réseaux de fissures de fatigue thermique

Thermal superficial crack networks have been detected in mixing zone of cooling system in nuclear power plants. Numerous experimental works have already been led to characterize initiation and propagation of these cracks. The random aspect of initiation led to propose a probabilistic model for the formation and propagation of crack networks in thermal fatigue. In a first part, uniaxial mechanical test were performed on smooth and slightly notched specimens in order to characterize the initiation of multiple cracks, their arrest due to obscuration and the coalescence phenomenon by recovery of amplification stress zones. In a second time, the probabilistic model was established under two assumptions: the continuous cracks initiation on surface, described by a Poisson point process law with threshold, and the shielding phenomenon which prohibits the initiation or the propagation of a crack if this one is in the relaxation stress zone of another existing crack. The crack propagation is assumed to follow a Paris' law based on the computation of stress intensity factors at the top and the bottom of crack. The evolution of multiaxial cracks on the surface can be followed thanks to three quantities: the shielding probability, comparable to a damage variable of the structure, the initiated crack density, representing the total number of cracks per unit surface which can be compared to experimental observations, and the propagating crack density, representing the number per unit surface of active cracks in the network. The crack sizes distribution is also computed by the model allowing an easier comparison with experimental results.Des réseaux de fissures superficielles de fatigue thermique ont été détectés dans des conduites de centrales nucléaires, plus précisément dans les zones de mélange du circuit de refroidissement du réacteur à l'arrêt. De nombreux travaux expérimentaux ont d'ores et déjà été menés pour caractériser l'apparition et la propagation de ces fissures. L'aspect aléatoire de l'apparition de celles-ci a conduit à proposer un modèle probabiliste de formation et de propagation de fissures. Dans un premier temps, des essais de fatigue mécanique uniaxiale sur des éprouvettes entaillées ont été réalisés afin de mettre en évidence le multi-amorçage de fissures, leur arrêt par obscurcissement et leur coalescence par recouvrement des zones d'amplification des contraintes. Dans un deuxième temps, le modèle probabiliste a été établi sous deux hypothèses : la germination continue de fissures en surface, grâce à une loi d'amorçage à seuil suivant un processus ponctuel de Poisson, et le processus d'obscurcissement qui interdit l'amorçage ou la propagation d'une fissure si celle-ci se situe dans la zone de relaxation des contraintes d'une autre fissure déjà existante. La propagation des fissures est assurée par une loi de type Paris basée sur des calculs de facteurs d'intensité des contraintes en pointe et en fond de fissure. L'évolution des réseaux de fissures multidirectionnelles en surface peut ainsi être suivi au moyen de trois grandeurs : la probabilité d'obscurcissement, comparable à une variable d'endommagement de la structure, la densité de fissures activées, comparable à la densité de fissure d'un réseau réel, et la densité de fissures actives qui permet de connaître le nombre de fissures qui se propagent toujours dans la zone d'étude. La distribution des tailles de fissures est également accessible permettant une comparaison plus rapide avec les résultats expérimentaux

Modélisation probabiliste de formation de réseaux de fissures de fatigue thermique

Des réseaux de fissures superficielles de fatigue thermique ont été détectés dans des conduites de centrales nucléaires, plus précisément dans les zones de mélange du circuit de refroidissement du réacteur à l arrêt. De nombreux travaux expérimentaux ont d ores et déjà été menés pour caractériser l apparition et la propagation de ces fissures. L aspect aléatoire de l apparition de celles-ci a conduit à proposer un modèle probabiliste de formation et de propagation de fissures. Dans un premier temps, des essais de fatigue mécanique uniaxiale sur des éprouvettes entaillées ont été réalisés afin de mettre en évidence le multi-amorçage de fissures, leur arrêt par obscurcissement et leur coalescence par recouvrement des zones d amplification des contraintes. Dans un deuxième temps, le modèle probabiliste a été établi sous deux hypothèses : la germination continue de fissures en surface, grâce à une loi d amorçage à seuil suivant un processus ponctuel de Poisson, et le processus d obscurcissement qui interdit l amorçage ou la propagation d une fissure si celle-ci se situe dans la zone de relaxation des contraintes d une autre fissure déjà existante. La propagation des fissures est assurée par une loi de type Paris basée sur des calculs de facteurs d intensité des contraintes en pointe et en fond de fissure. L évolution des réseaux de fissures multidirectionnelles en surface peut ainsi être suivi au moyen de trois grandeurs : la probabilité d obscurcissement, comparable à une variable d endommagement de la structure, la densité de fissures activées, comparable à la densité de fissure d un réseau réel, et la densité de fissures actives qui permet de connaître le nombre de fissures qui se propagent toujours dans la zone d étude. La distribution des tailles de fissures est également accessible permettant une comparaison plus rapide avec les résultats expérimentaux.Thermal superficial crack networks have been detected in mixing zone of cooling system in nuclear power plants. Numerous experimental works have already been led to characterize initiation and propagation of these cracks. The random aspect of initiation led to propose a probabilistic model for the formation and propagation of crack networks in thermal fatigue. In a first part, uniaxial mechanical test were performed on smooth and slightly notched specimens in order to characterize the initiation of multiple cracks, their arrest due to obscuration and the coalescence phenomenon by recovery of amplification stress zones. In a second time, the probabilistic model was established under two assumptions : the continuous cracks initiation on surface, described by a Poisson point process law with threshold, and the shielding phenomenon which prohibits the initiation or the propagation of a crack if this one is in the relaxation stress zone of another existing crack. The crack propagation is assumed to follow a Paris law based on the computation of stress intensity factors at the top and the bottom of crack. The evolution of multiaxial cracks on the surface can be followed thanks to three quantities : the shielding probability, comparable to a damage variable of the structure, the initiated crack density, representing the total number of cracks per unit surface which can be compared to experimental observations, and the propagating crack density, representing the number per unit surface of active cracks in the network. The crack sizes distribution is also computed by the model allowing an easier comparison with experimental results.CACHAN-ENS (940162301) / SudocSudocFranceF

Modèle probabiliste pour la description du faïençage thermique

Les canalisations des circuits de Refroidissement de Réacteur à l'Arrêt (RRA) de centrale nucléaire sont soumises à des chargements thermiques dans les zones de mélange entre fluides froid et chaud. Ces fluctuations thermiques entraînent la formation de réseaux de fissures ou faïençage thermique. Sous deux hypothèses principales -- la germination continue de mésofissures et la présence d'une zone d'obscurcissement autour de mésofissures existantes -- cette étude propose un modèle probabiliste permettant de caractériser la saturation du réseau ainsi que les densité de mésofissures actives, activées et stoppées en relation avec leurs tailles respectives. Cette modélisation probabiliste permet de caractériser l'état d'endommagement de la structure afin d'évaluer son intégrité. Le modèle est appliqué au cas d'un chargement estimé pour des essais de fatigue thermique afin de comparer les résultats du modèle aux différents réseaux de fissures observés expérimentalement

Differential Formation of Stress Granules in Radiosensitive and Radioresistant Head and Neck Squamous Cell Carcinoma Cells

International audiencePurpose: Stress granules (SGs) are cytoplasmic aggregates in which mRNAs and specific proteins are trapped in response to a variety of damaging agents. They participate in the cellular defense mechanisms. Currently, their mechanism of formation in response to ionizing radiation and their role in tumor-cell radiosensitivity remain elusive.Methods and materials: The kinetics of SG formation was investigated after the delivery of photon irradiation at different doses to head and neck squamous cell carcinoma cell lines with different radiosensitivities and the HeLa cervical cancer cell line (used as reference). In parallel, the response to a canonical inducer of SGs, sodium arsenite, was also studied. Immunolabeling of SG-specific proteins and mRNA fluorescence in situ hybridization enabled SG detection and quantification. Furthermore, a ribopuromycylation assay was used to assess the cell translational status. To determine whether reactive oxygen species were involved in SG formation, their scavenging or production was induced by pharmacologic pretreatment in both SCC61 and SQ20B cells.Results: Photon irradiation at different doses led to the formation of cytoplasmic foci that were positive for different SG markers. The presence of SGs gradually increased from 30 minutes to 2 hours postexposure in HeLa, SCC61, and Cal60 radiosensitive cells. In turn, the SQ20B and FaDu radioresistant cells did not form SGs. These results indicated a correlation between sensitivity to photon irradiation and SG formation. Moreover, SG formation was significantly reduced by reactive oxygen species scavenging using dimethyl sulfoxide in SCC61 cells, which supported their role in SG formation. However, a reciprocal experiment in SQ20B cells that depleted glutathione using buthionine sulfoximide did not restore SG formation in these cells.Conclusions: SGs are formed in response to irradiation in radiosensitive, but not in radioresistant, head and neck squamous cell carcinoma cells. Interestingly, compared with sodium arsenite-induced SGs, photon-induced SGs exhibited a different morphology and cellular localization. Moreover, photon-induced SGs were not associated with the inhibition of translation; rather, they depended on oxidative stress

Phenotypic effects of genetic variants associated with autism.

Funder: Institut Pasteur; doi: https://doi.org/10.13039/501100003762Funder: Fondation Bettencourt Schueller (Bettencourt Schueller Foundation); doi: https://doi.org/10.13039/501100007492Funder: Aarhus Universitet (Aarhus University); doi: https://doi.org/10.13039/100007605Funder: Københavns Universitet (University of Copenhagen); doi: https://doi.org/10.13039/501100001734Funder: Autism Speaks (Autism Speaks Inc.); doi: https://doi.org/10.13039/100000073Funder: European Federation of Pharmaceutical Industries and Associations (EFPIA); doi: https://doi.org/10.13039/100013322Funder: Autistica; doi: https://doi.org/10.13039/100011706Funder: Templeton World Charity Foundation (Templeton World Charity Foundation, Inc.); doi: https://doi.org/10.13039/501100011730Funder: RCUK | MRC | Medical Research Foundation; doi: https://doi.org/10.13039/501100009187Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: Université Paris Diderot (Paris Diderot); doi: https://doi.org/10.13039/501100005736Funder: This work was funded by the Conny-Maeva Charitable Foundation, the Cognacq Jay Foundation, the Eranet-Neuron (ALTRUISM), and the GenMed Labex.While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in individuals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 individuals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support individuals carrying these variants