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The present work focuses on the modelling of the fatigue behaviour of a 316L produced by laser powder bed fusion containing various defect populations : Lacks of fusion, corrosion pits and one electric discharge machined hemispherical defect. As shown in previous experimental studies, the crack leading up to failure systematically initiated on a single surface defect. The nature and morphology of the critical defect did not show any influence on the fatigue strength, and only its size seemed to matter. To take into account the critical defect size, models based on linear elastic fracture mechanics were implemented and identified. A modified Paris propagation law was used to model the short crack regime. This approach was used to predict S–N curve domains based on critical defects size range. PhD grant from the French region Pays de la Loire

International audience; The mechanical performances of additive manufactured (AM) material are highly dependent on the fabrication process which inevitably results in surface imperfection as well as porosity. In the present study, the high cycle fatigue (HCF) behavior of an AM stainless steel 316L is experimentally investigated to characterize and evaluate the effect of the inherent surface defects. Profilometry and Computed Tomography are used. A series of fatigue experiments is carried out under different loading modes including tension, bending, and torsion fatigue tests. For each loading condition, different surface preparations are used to investigate the effect of surface state. Fatigue tests reveal that surface treatment can improve fatigue performances, the improvements observed being higher under tension/bending loading than under torsion loading. The fractographic analysis is performed for all the available tested specimens to reveal the mechanism of fatigue crack initiation. Lack-of-fusion (LoF) defects play the predominant role in the fatigue performance of SS 316L fabricated by laser powder bed fusion (LPBF). The presence of multiple LoF defects at the surface or subsurface is detrimental to the endurance under cyclic loading. By using Murakami approach modeling the relationship between fatigue strength and defect size, it is found that the multiple clustering defects act synergistically as one large virtual crack to initiate the fatigue crack.

This study falls within the scope of the fatigue design of handling machines manufactured by the Manitou Group, which are usually composed of a chassis and a boom. These welded assemblies are subjected to fatigue loading conditions and include highly stressed zones acting as crack initiation sites. In view of the geometrical complexity of the structures, the degree of conservatism incorporated in design methods based on the usual international standards is difficult to evaluate. Alternative design approaches based on the structural stress are being developed and used by other companies such as PSA and LOHR. The present work focuses on developing a numerical approach to take into account the local stiffness of welds. The proposed strategy is based on shell finite element modelling of the assembly and an equivalent stiffness matrix for welds. This makes it possible to describe the local mechanical behaviour of seam welds with the computational cost of a shell element based model. To validate the proposed approach, a comparison in terms of stiffness is undertaken for three welded structures using solid finite element models as a reference. The proposed approach is also compared to the Manitou, Fayard and Lohr approaches.

International audience; This paper aims to study the individual and competitive effects of surface defects and microstructural compo­nents in an AM 316L by numerical methods. Based on the microstructure sensitive modeling framework, nu­merical simulations of models in different surface states with virtual quasi-realistic explicit microstructures are performed. Problems encountered during the establishment of the numerical polycrystalline aggregate model are discussed, including the grain morphology, the strongly textured microstructure with preferential crystallo­graphic directions, roughness and surface defect. A statistical method based on generalized extreme value dis­tribution along with a non-local method is used to describe the stochasticity of microstructural attributes. Simulations of differently configured explicit microstructure models are analyzed and discussed.

Weld toes and weld roots of continuously welded structures subjected to cyclic loading are critical zones in terms of the fatigue resistance. The finite element method coupled with a fatigue criterion is commonly used to ensure the correct sizing and fatigue design of welded structures. However, weld geometries are often simplified or idealized to limit computational cost. In this work, a numerical two-scale approach is proposed in order to calculate a non-local multiaxial equivalent stress at the weld toe and the weld root from a global finite element shell model. The influence of the parameters of the proposed model on the stiffness behaviour is investigated for three welded structures and for different loading cases. A comparison in terms of stiffness with other models from the literature is also proposed. The results show that the stiffness behaviour is not affected by the parameters of the proposed approach and that it is the most robust model for the different geometries and loading cases studied. The variation in the non-local multiaxial equivalent stress as a function of the parameters of the proposed approach was also studied. The comparison with full solid finite element models makes it possible to define minimum values for the different parameters studied and validates the potential of the proposed approach for the fatigue design of welded structures.

Corrosive environments are known to be detrimental to the mechanical strength of metallic alloys. In the case of 316L stainless steel, the main corrosion mechanism observed is pitting, which leads to localized rough defects. As for other materials submitted to cyclic loadings and prone to pit, corrosion defects tend to be at the core of crack initiation leading to failure. The work here-by presented will thus focus on the relationship between the fatigue performance and the presence of process or corrosion related defects for a 316L stainless steel manufactured by Laser Powder Bed Fusion (L-PBF). To do so, cylindrical samples were produced vertically, then machined to fatigue specimens in as-built state (no heat treatment). Specimens were polished in order to only characterize the bulk material and not its raw surface. The fatigue responses of three batches corresponding to three configurations of surface integrity (polished, pre-corroded and with an Electric Discharge Machined (EDM) defect) were investigated. For the polished batch, fracture surface observations showed that initiation started from a lack of fusion (LoF) surface pore in all specimens. The pre-corroded batch was prepared under potentiodynamic anodic polarization conditions in a neutral NaCl solution. On those samples, some cracks initiated on corrosion pits, depending on the severity of the corrosion applied to each sample and its initial population of defects. For the EDM batch, a hemispherical defect, at the source of all failures, was machined in the middle of the gauge length. A good correlation between Murakami’s square root of the area parameter and the fatigue strength was observed on a Kitagawa-Takahashi diagram for all tested specimens. This correlation showed an independence of the defect type (LoF, pit, machined defect) on the specimens fatigue strength. Defect morphology doesn’t seem to be an important driving force for crack initiation as ellipsoidal corrosion pits, hemispherical EDM defects and flat lacks of fusion, although very different in terms of shape, are just as harmful at equivalent sizes. This research was funded by a PhD grant from the French region Pays de la Loire.

The fatigue strength of cast aluminium alloys is known to be greatly affected by different defect types related to the manufacturing process, particularly microshrinkage pores created during the solidification phase of the casting process. Even if certain classification procedures are given in the standard ASTM E155-15 [1], the presence of defects is not readily related to the capacity of a component or a structure to meet the requirements of the mechanical technical specifications. The present study aims at establishing a clear link between certain microstructural features and the average fatigue strength. This is possible by looking for the average size of critical defects and using a relevant statistical analysis. More exactly, the Murakami approach based on the statistics of extremes is employed. The main originality of this work lies in the application of this approach to the case of a real structure submitted to high cycle fatigue damage: engine cylinder heads, used in the automotive industry. Indeed, both fatigue tests and microstructural characterizations are carried out on cylindrical specimens and real structures. The specimens are subjected to uniaxial and multiaxial loading conditions [2]. Original fatigue tests, developed by PSA to load in-service critical regions, are carried out on cylinder heads. Systematic analyses of fatigue failure surface are conducted to obtain the statistics of critical defects at the origin of the failures for both specimens and structures. In parallel, critical regions and the associated local loading mode in the structure are characterized by an appropriate high cycle fatigue analysis. The latter, combined with the fatigue test data and the statistical analysis of the critical defects, leads to a discussion about the size effect and an approach is proposed for a relevant fatigue design procedure.

In this study, the influence of geometrical defects on the High Cycle Fatigue (HCF) resistance of aluminium is investigated, with emphasis on the impact of local microstructure on fatigue crack initiation. In order to meet this objective, an experimental approach, using a commercial purity polycrystalline aluminium alloy, is proposed. First, different thermomechanical treatments are applied to the aluminium alloy to obtain two homogeneous microstructures with respective mean grain sizes of 100 and 1000 µm. Then, fatigue specimens with an artificial hemispherical surface defect of diameter 1000 µm are subjected to fully reversed stress-controlled cyclic loading conditions. In-situ observations are carried out to monitor the crack length during fatigue tests. It is noted that, for a higher grain size, the number of cycles needed for the initiation of a 100 µm-long surface crack is lower. A study of the influence of the defect size relative to the grain size is also conducted. Two sizes of defects are used, and the influence of characteristic sizes seems to be explained by the role of cyclic plasticity in the crack initiation process.

Jet engines gears are generally made of steel and are case-strengthened via thermochemical treatments such as carburizing or ni-triding causing microstructural modifications, superficial hardening and compressive residual stresses in the surface layers. These treatments increase the resistance to cyclic loads caused by contact between teeth and by the bending loads applied to the teeth. These two loading modes create high stress gradients at the surface. A large number of studies concerning the effect of thermochemical treatments on fatigue resistance have been carried out for uniaxial loads (rotating bending, tension or plane bending). Most of them were undertaken using smooth specimens, which do not correctly reproduce the stress gradient at the root of the gear teeth. A strong dependence between the loading mode and the position of the crack initiation site is also observed. The present work aims at experimentally investigating the fatigue behaviour of case hardened steel with a special focus on crack initiation and growth mechanisms. A vast experimental campaign composed of two parts is undertaken. Firstly, a Single Tooth Bending Fatigue (STBF) test is carried out on gears made of 16NiCrMo13 carburized steel. The resulting Wuhler diagram shows high scatter at certain stress levels which suggests a bi-modal behaviour, characterized by very different crack initiation kinetics. Secondly, fatigue tests conducted on notched specimens loaded in plane bending, designed to accurately reproduce the stress gradient observed at the gear tooth root are carried out to confirm this bimodal behaviour and to characterize the failure mechanisms.

This article describes a microstructural-based high cycle fatigue strength modelling approach applied to different cast Al-Si alloys used in an automotive context. Thank to different casting processes (gravity die casting and lost foam casting), associated with several heat treatment (T7 and Hot Isostatic Pressing-HIP), three alloys with very different microstructures have been obtained. In a vast experimental campaign undertaken to investigate the fatigue damage mechanisms governing these alloys under different multiaxial loading conditions, it was shown that the principal crack initiation mechanisms for the porosity-free alloy are either the formation of persistent slip bands (PSB) or the rupture and/or debonding of eutectic particles. For the porosity-containing alloys, the fatigue damage is always controlled by crack growth from pores. In order to take into account these fatigue damage mechanisms, a probabilistic model using a combination of the Dang Van and a modified LEFM criteria is proposed. The modified LEFM criterion is able to take into account the influence of the grain size on the threshold of the stress intensity factor. It is shown that for the porosity-free alloy, the predictions are good for combined tension-torsion loads with R = - 1 . However, because the crack initiation mechanisms are not the same depending on the hydrostatic stress, the predictions are non-conservative for the uniaxial and equibiaxial tension loads with R = 0.1 . For the porosity-containing alloys, the predictions are very good for the uniaxial, combined tension-torsion and equibiaxial tension loads with both R = - 1 and R = 0.1 . As observed experimentally, the proposed model can also predict a more pronounced effect of casting porosity for the uniaxial and combined tension-torsion loads, when compared to pure torsion loads.

International audience; Recent studies suggest that psoriasis may be more severe in patients with nonalcoholic fatty liver disease, particularly in those with the inflammatory stage of steatohepatitis [nonalcoholic steatohepatitis (NASH)]. Herein, we investigated the impact of diet-induced steatohepatitis on the severity of imiquimod-induced psoriasiform dermatitis. Mice fed with a high-fat diet developed steatohepatitis reminiscent of human NASH with ballooning hepatocytes and significant liver fibrosis. Mice with steatohepatitis also displayed moderate cutaneous inflammation characterized by erythema, dermalinfiltrates of CD45(+) leukocytes, and a local production of IL-17A. Moreover, steatohepatitis was associated with an epidermal activation of caspase-1 and cutaneous overexpression of IL-1 beta. Imiquimod-induced psoriasiform dermatitis was exacerbated in mice with steatohepatitis as compared to animals fed with a standard diet. Scale formation and acanthosis were aggravated, in correlation with increased IL-17A and IL-22 expression in inflamed skins. Finally, intradermal injection of IL-17A in standard diet-fed mice recapitulated the cutaneous pathology of mice with steatohepatitis. The results show that high-fat diet induced steatohepatitis aggravates the inflammation in psoriasiform dermatitis, via the cutaneous production of IL-17A. In agreement with clinical data, this description of a novel extrahepatic manifestation of NASH should sensitize dermatologists to the screening and the management of fatty liver in psoriatic patients.

International audience; The present study focuses on analysing and modelling the influence on fatigue behaviour of the surface of a hot-forged C70 connecting rod which undergoes a shot-blasting treatment. The shot-blasting heavily affects the surface and thus the fatigue properties. In addition, the forging process induces large defects which also have an effect on the fatigue strength. So as to be able to determine which aspects of the surface integrity are the most influential in fatigue, various surface states were thoroughly characterised and then tested in high cycle fatigue in bending. The various aspects studied are the surface roughness and large defects, residual stresses, microstructure and hardness. The aim of this work is to develop a fatigue design approach that can take into account both the effect of the surface defects and that of the residual stresses on fatigue.

International audience; This work is focused on the influence of defects on scatter and statistical size effect of Ti-6Al-4V alloy fabricated by the SLM process. A vast fatigue test campaign has been undertaken, for two surface conditions (as-built and machined surfaces) and two specimen geometries with different highly loaded volume sizes. It was shown, for machined specimens, that a large variety of crack initiation mechanisms is the principal origin of the fatigue scatter. Regarding the size effect, the change of the mechanism is the first order factor that governs the size effect. For as-built specimens, these effects are much less pronounced.

International audience; This study aims at investigating the effect of defect on the high cycle fatigue behavior of polycrystalline aggregates. An explicit virtual microstructure finite element model is created to conduct fatigue simulations. Different stress-based criteria frequently applied in fatigue assessment are tested with a combination of the non-local methods. Two realizations of the non-local method are used and compared. Simulation results are compared to experimental results of 316L. From the parametric simulations, better qualitative understandings on the choice of non-local method as well as its parameters are obtained. The effect of Kitagawa-Takahashi can be reproduced and explained by this proposed framework of microstructure modeling-simulation.

The analysis of materials mechanical behavior involves many computational challenges. In this work, we are addressing the transient simulation of the mechanical behavior when the time of interest is much larger than the characteristic time of the mechanical response. This situation is encountered in many applications, as for example in the simulation of materials aging, or in structural analysis when small-amplitude oscillatory loads are applied during a long period, as it occurs for example when characterizing viscoelastic behaviors by calculating the complex modulus or when addressing fatigue simulations. Moreover, in the case of viscoelastic behaviors, the constitutive equation is many times expressed in an integral form avoiding the necessity of using internal variables, fact that results in an integro-differential model. In order to efficiently simulate such a model, we explore in this work the use of a space-time separated representation. L'analyse du comportement mécanique des matériaux entraîne de nombreuses difficultés du point de vue numérique. Dans ce travail, nous allons nous focaliser sur l'une d'entre elles, celle associée à la simulation transitoire du comportement mécanique quand l'intervalle temporel d'intérêt est substantiellement plus long que le temps caractéristique associé à la réponse mécanique. Cette situation est fréquemment retrouvée dans la caractérisation rhéologique des matériaux viscoélastiques (pour la détermination du module complexe) ainsi que quand on s'attaque à la simulation de la fatigue. De plus, dans le cas des matriaux viscoélastiques, le comportement est généralement décrit par une loi de comportement intégrale qui évite le besoin d'utiliser des variables internes, donnant lieu à un modèle mécanique integro-différentiel. Pour une résolution efficace, nous analysons ici l'utilisation d'une représentation séparée en espace-temps.

International audience; The aim of this paper is to propose a flexible multiaxial modelling framework that is capable of combining two fatigue damage mechanisms so as to continuously describe the Kitagawa-Takahashi diagram. It is proposed that this diagram represents two distinct fatigue damage mechanisms: one associated with crack initiation (or microstructurally small cracks) and the other with crack propagation (or long cracks). It is further postulated that these damage mechanisms are more appropriately modelled using di erent fatigue criteria. A probabilistic modelling framework is proposed in which any two suitable fatigue criteria can be combined in order to simultaneously model both damage mechanisms and the transition between them. This framework is based on the weakest link hypothesis and results in a probabilistic Kitagawa-Takahashi type diagram.

Lien vers la version éditeur: http://www.sciencedirect.com/science/article/pii/S0167663613000288; International audience; To obtain robust estimations of the fatigue limit from energy-based fatigue criteria, constitutive laws must include a correct description of the energy balance when modeling the cyclic behavior. The present paper aims at providing a better understanding of the evolution of the energy balance at both microscopic and macroscopic scales in a medium carbon steel. First, an experimental procedure is used to estimate the amount of energy which is either stored in the material or dissipated into heat at a macroscopic scale. The energy balance is observed to be very dependent on the stress amplitude and the number of loading cycles. A model is then developed to investigate the energy balance at a microscopic scale. From the simulation results, both the stored energy and dissipated energy fields are found to be strongly scattered. The dispersion is mostly explained by the crystallographic orientation distribution and the two-phased microstructure.

This study is dedicated to the effect of the heat treatment on the fatigue strength of an automobile rear axle beam and aims to propose a suitable and reliable methodology for the fatigue design. The rear axle beam is made of sheet metal (22MnB5); the microstructure is initially ferrito-pearlitic before the heat treatment and is martensitic after. A vast experimental campaign has been undertaken to investigate the behaviour, and more specially, the fatigue damage mechanisms observed for both treated and non-treated material, under different loading conditions: tension and shear test with different load ratios. In order to test the sheet metal in shear an original fatigue test apparatus is used. A probabilistic approach using the weakest link concept is introduced to model the fatigue behaviour. This approach leads naturally to a probabilistic Kitagawa type diagram, which in this case explains the relationship between the influence of the heat treatment and the microstructural heterogeneities. Integrate in a numerical model, this methodology permit to predict the effect of a local heat treatment on the fatigue strength of the components.; International audience; This study is dedicated to the effect of the heat treatment on the fatigue strength of an automobile rear axle beam and aims to propose a suitable and reliable methodology for the fatigue design. The rear axle beam is made of sheet metal (22MnB5); the microstructure is initially ferrito-pearlitic before the heat treatment and is martensitic after. A vast experimental campaign has been undertaken to investigate the behaviour, and more specially, the fatigue damage mechanisms observed for both treated and non-treated material, under different loading conditions: tension and shear test with different load ratios. In order to test the sheet metal in shear an original fatigue test apparatus is used. A probabilistic approach using the weakest link concept is introduced to model the fatigue behaviour. This approach leads naturally to a probabilistic Kitagawa type diagram, which in this case explains the relationship between the influence of the heat treatment and the microstructural heterogeneities. Integrate in a numerical model, this methodology permit to predict the effect of a local heat treatment on the fatigue strength of the components.

In this study, various experimental methods are employed to determine the anisotropic fatigue behavior of a 25MnCrSiVB6 forged steel (Metasco MC). This material has a bainitic microstructure and contains many elongated non-metallic inclusions in the rolled direction, which are grouped into clusters. Specimens with different orientations relative to the rolling direction have been extracted from a hot rolled bar and the ability of certain experimental techniques to capture the fatigue anisotropy has been tested. Results obtained from monotonic tensile tests and Charpy impact tests show that the material has isotropic fracture strength and anisotropic ductility. The influence of the inclusion clusters is clearly demonstrated via observation of the fracture surfaces. Concerning the fatigue behavior, results from a classical staircase experimental procedure are compared to results from self-heating fatigue tests. For specimens orientated at 0° relative to the rolled direction, microcrack initiation is controlled by the material matrix and the prediction of the fatigue strength with the self-heating method has been observed to be correct. For specimens orientated at 45° and 90°, the elongated manganese sulfide inclusion clusters are the origin of crack initiation and the fatigue strength drops significantly. For this case, it appears that the self-heating method has difficulty predicting the fatigue behavior.

The approach developed demonstrates a framework using both the elastic shakedown concept and the weakest link theory to account for loading mode, loading path and data scatter in high cycle fatigue. The mesoplasticity and damage mechanisms occurring under high cycle fatigue are illustrated by means of observations conducted on a mild steel submitted to purely reversed torsion and push–pull fatigue tests. Plastic glide systems and microcracks are distributed in a very heterogeneous way at the surface of the observed smooth specimens. The microstructure and more specifically the configuration of the grain where the crack initiates and its immediate vicinity (neighbour grains and microstructural barriers) control most of the fatigue life. To account for this heterogeneous feature, a distribution of the elastic shakedown threshold is assumed and probability calculations carried out in the framework of the weakest link concept lead to a new fatigue criterion. In particular, a spatial and a directional heterogeneity factor are introduced. The former represents the way the stress is distributed within a component, while the latter is a measure of the number of highly stressed glide systems. It is then proved that the crack initiation modelling according to mesoplasticity consideration is not enough to reflect the macroscopic fatigue behaviour when changing the loading mode. The directional heterogeneity factor is indeed unable to explain alone the different fatigue limits under purely reversed tension and torsion. A normal stress effect clearly acts and can be readily introduced through a dependence of the scale factor in the initiation distribution. A key feature of this probabilistic mesoscopic approach is its directional formulation. It allows direct extensions regarding the description of glide system severity according to the orientation to the free surface and the non-local effects due to the non-uniform normal stress distribution in a component. This model is shown to be efficient when dealing with complex loading paths like under out-of-phase tension and torsion loading.

Introduction Un reseau cytokinique complexe a ete decrit dans les lesions cutanees psoriasiques et illustre le role central des cytokines pro-inflammatoires telles que l’IL-23, l’IL-22, l’IL-17, l’IL-1, l’oncostatine M et le TNFα, produites par les cellules immunitaires infiltrees. Recemment, nous avons montre que l’association d’IL-1α, IL-17A, IL-22, OSM et TNFα agit de facon synergique sur les keratinocytes en augmentant l’expression de molecules liees a l’immunite innee et a l’inflammation, telles que des chimiokines et des peptides antimicrobiens, et en inhibant leur programme de differenciation. Ceci genere un modele in vitro d’inflammation cutanee mimant certaines caracteristiques du psoriasis. Nous avons demontre que cette combinaison de cytokines constitue une signature moleculaire des lesions cutanees psoriasiques. En parallele, plusieurs approches therapeutiques anti-cytokine ont ete developpees et le TNFα constitue une cible de choix. Parmi ces traitements, l’adalimumab est une IgG1 monoclonale anti-TNFα entierement humaine qui diminue l’inflammation cutanee et le score de severite clinique d’au moins 75 % chez environ 80 % des patients. Notre objectif etait d’analyser la modification du profil transcriptomique cutane et les concentrations des cytokines circulantes chez les patients psoriasiques pendant le traitement par l’adalimumab. Materiel et methodes Les patients psoriasiques ont ete traites par l’adalimumab. Au bout de 4 et 16 semaines, l’efficacite clinique de la therapie a ete evaluee par les mesures de PASI et de DLQI. Les profils transcriptomiques cutanes avant et apres traitement ont ete determines par RT-PCR quantitative et les cytokines circulantes mesurees par immuno-analyse multiplexe. Resultats Nous observons un effet clair et rapide du traitement par l’adalimumab sur l’expression des cytokines « Th17 », de l’IL-1 et de l’oncostatine M, expliquant les modifications d’expression genique par les keratinocytes (BD2, S100A7, CXCL8, CK10) et la reponse clinique. Une persistance de l’expression des cytokines et de leurs cibles keratinocytaires est egalement observee dans certaines lesions residuelles. En revanche, les concentrations seriques de cytokines sont peu correlees a l’evolution clinique et aux profils d’expression cutanes, ce qui confirme la necessite d’une caracterisation locale des cytokines dans les lesions cutanees. Fait interessant, en plus du maintien de l’expression locale des cytokines chez les patients non repondeurs, un profil cytokinique initial chez les non-repondeurs pourrait suggerer l’identification possible de marqueurs predictifs de resistance/sensibilite au traitement par l’adalimumab. Discussion Nos donnees montrent que le ciblage du TNFα dans le psoriasis a un effet tres large sur le profil d’expression des cytokines Th17 et des marqueurs de l’inflammation de la peau, ce qui explique son efficacite clinique.

Introduction Les cultures de keratinocytes en monocouche sont couramment utilisees dans les etudes in vitro, mais celles-ci ne reproduisent pas fidelement l’architecture de l’epiderme et les caracteristiques physiologiques des differents etats de differenciation cellulaire. Dans cette etude, nous decrivons un protocole simple et rapide pour la generation d’epidermes reconstruits murins (RME) a partir de keratinocytes primaires de souriceaux. Apres avoir caracterise les differentes etapes de leur differenciation, nous analysons leur reponse a la stimulation par des cytokines proinflammatoires. Materiel et methodes Les RME sont realises a partir de keratinocytes primaires issus de peaux de souriceaux nouveau-nes cultives dans des inserts en polycarbonate dans un milieu d’ensemencement. Des l’obtention d’une monocouche cellulaire, les inserts sont passes a l’interface air-liquide au contact d’un milieu de differenciation. La caracterisation des RME est effectuee par histologie et par immunohistofluorescence pour la detection de marqueurs de differenciation incluant les keratines 14, 6, 10, la loricrine, la filaggrine, l’E-Cadherine et des connexines. Leur permeabilite est eprouvee par des tests de diffusion de la sonde fluorescente Lucifer Yellow . Enfin, la reponse des RME aux cytokines IL-17A, TNFα, IL-22, IL-1α et oncostatine M est evaluee par RT-qPCR par la mesure de l’expression de marqueurs de differenciation, de peptides antimicrobiens et de chimiokines. Resultats Notre protocole permet d’obtenir des RME qui reproduisent les caracteristiques morphologiques et phenotypiques d’un epiderme de souris en seulement 5 jours apres leur passage a l’interface air-liquide comme l’atteste l’expression des marqueurs de differenciation conforme a celle d’un epiderme natif. Les RME acquierent egalement leur fonction de barriere et sont impermeables au passage de la Lucifer Yellow . Enfin, suite a leur stimulation par des cytokines proinflammatoires, les RME repondent de maniere similaire a un epiderme in vivo par une diminution d’expression de la keratine 10, de l’involucrine et de la filaggrine et une augmentation de l’expression de mediateurs de l’inflammation tels que la chimiokine CXCL-3 et les peptides antimicrobiens S100A9 et β-defensine-3. Discussion Ce nouveau protocole permet donc de realiser rapidement et facilement des RME reproduisant fidelement l’architecture et les caracteristiques physiologiques d’un epiderme, y compris leur reponse dans un contexte inflammatoire. Conclusion Ce modele de RME permet d’etudier les mecanismes physiologiques de la peau et ouvre la perspective de realiser des RME a partir de keratinocytes issus de souris genetiquement modifiees.

In this paper, a new life prediction method for high cycle multiaxial fatigue of metallic materials is presented. It is based on a local approach introduced by Dang Van and developed by Papadopoulos, where accumulated plastic strain due to external loading is estimated at a scale of the order of a few grains. Its evaluation requires the use of a critical plane type fatigue criterion. As soon as the accumulated plastic mesostrain, considered as the damage variable, reaches a critical value, a crack is considered to be initiated. The complex and combined cases of loading (multiaxial and variable amplitude loading) can be analysed with this new method. In particular, attention is given to a description of the damaging effect of the loading path shape on fatigue strength. The application of hardening plasticity laws at the local scale allows one to estimate and sum the damage caused by elementary loading events like transitions.

Introduction Les carcinomes epidermoides cutanes (CEC) sont les cancers de la peau les plus frequents, leur physiopathologie reste mal connue et ils repondent peu aux traitements chimiotherapeutiques classiques. Pendant le developpement tumoral, une reponse inflammatoire s’installe et un dialogue s’etablit entre les cellules immunitaires et les cellules tumorales par le biais de la secretion de facteurs solubles tels que les cytokines. Ainsi, la presence d’interleukine (IL)-12 et d’interferon γ (IFNγ) est associee a une reponse antitumorale (type 1) alors que la production d’IL-4 est associee a une reponse pro-tumorale (type 2). La modification de cet equilibre cytokinique peut donc contribuer au developpement ou a la suppression de la tumeur. Le LITEC etudie le role des cytokines dans les maladies inflammatoires cutanees (psoriasis, cicatrisation pathologique). Nos travaux montrent que l’oncostatine M (OSM) module la proliferation, la migration et la differenciation des keratinocytes normaux en culture et entraine une hyperplasie epidermique chez la souris. Ainsi, nous faisons l’hypothese que l’OSM pourrait egalement agir sur les keratinocytes tumoraux et etre impliquee dans le developpement des CEC. Materiel et methodes Une etude ex vivo a permis d’etablir les profils cytokiniques de CEC humains par RT-qPCR en etudiant l’expression des cytokines du micro-environnement tumoral. Une etude in vitro a permis de caracteriser les effets de l’OSM sur les keratinocytes murins transformes de la lignee PDVC57. Enfin, nous avons etudie les profils cytokiniques de CEC murins in vivo obtenus apres injection sous-cutanee des cellules PDVC57. Resultats L’OSM, l’IL-6 et l’IL-1β sont surexprimees dans les CEC humains, temoins d’un environnement pro-inflammatoire. L’expression des marqueurs de type 1, comme l’IL-12 et l’IFNγ, est aussi augmentee. In vitro, l’OSM exerce un effet direct sur les keratinocytes tumoraux PDVC57 en entrainant la phosphorylation des proteines ERK et STAT3. Elle induit leur migration, leur proliferation et augmente l’expression de genes codant des marqueurs associes a la proliferation cellulaire comme la cytokeratine 6. Enfin, nous avons mis en place un modele murin de CEC et montre une surexpression d’OSM, d’IL-6 et d’IL-1β dans ces tumeurs, comme observe chez l’Homme. L’expression des cytokines de type 1 comme l’IFNγ et de type 2 comme l’IL-4 est aussi augmentee. Discussion Nos resultats suggerent que l’OSM jouerait un role direct sur les CEC, ce qui est en accord avec les etudes montrant l’implication de l’OSM dans le developpement du cancer du sein ou de l’endometre. Conclusion Pour confirmer le role de l’OSM, nous souhaitons analyser le developpement de ces CEC chez des souris dont le gene codant pour l’OSM a ete invalide. A terme, connaissant l’efficacite des therapies anti-cytokines dans le traitement des pathologies inflammatoires, nous esperons pouvoir utiliser ces memes approches pour le traitement des CEC.