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Mainly known for its role in immune defense and inflammation, interleukin 22 (IL-22) has emerged over the past decade as a cytokine involved in the adaptation of stem/progenitor cell activity for tissue homeostasis and repair. IL-22 is present in the brain, which harbors neural stem cells (NSC) in specific niches of which the ventricular-subventricular zone (V-SVZ) is the most important. In this study, we examined a possible effect of IL-22 on NSC in the adult mouse brain. We demonstrate that the IL-22 receptor is expressed in the V-SVZ, mainly in NSC characterized by their SOX2 expression. Addition of IL-22 to V-VSZ cell cultures resulted in an increase in NSC self-renewal, associated with a shift in NSC division mode towards symmetric proliferative divisions at the expense of differentiative divisions. Conversely, loss of IL-22 in knockout mice led to a decrease in neurosphere yield, suggesting a reduction in the NSC population, which was confirmed by the decrease in cells retaining BrdU labeling in IL-22 knockout mice. Our study supports that IL-22 is involved in the development and/or maintenance of V-VSZ NSC and opens new avenues to further investigate the role of IL-22 in NSC biology in health and disease.

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

The present study investigates the effect of the high-speed milling (HSM), grinding and anodizing processes on the high cycle fatigue strength of the AA7050 aluminum alloy. These processes are systematically applied to certain aircraft components as specified by aeronautical standards, to attain a good surface finish. In order to understand the effect of each process on the fatigue strength, a vast experimental campaign consisting of fully reversed plane bending fatigue tests has been conducted on specimens with different surface states. A polished batch, three milled batches with different surface roughness, a grinded batch and two milled then anodized batches with different surface roughness have been tested. The results show that the roughness must be highly degraded (Sa > 3 μm) in order to impact the fatigue strength. It is also shown that anodizing has slight beneficial effect on the fatigue strength in the high cycle fatigue domain studied. The experimental results show a dependence of the fatigue strength on the surface roughness via the parameter √Sa, previously proposed by the authors. This work was carried out within the FUI QUAUSI project (Grant n°FR1307003R on call n°15) with the support of industrial (Dassault Aviation, Europe Technologie, Figeac Aéro, Mecachrome, Spring Technologie, Precise, GEBE2, CETIM) and academic partners (LSN2-IUT Carquefou).

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.

International audience; In this work, stainless steel 316L obtained by Laser Powder Bed Fusion (L-PBF) has been produced and characterized. The experimental campaign focuses on the samples in the as-built state under cyclic tension-compression loadings. Low cycle fatigue (LCF) and high cycle fatigue (HCF) tests are carried out. Microstructure observations are performed before and after the loadings. As-built L-PBF 316L has a good LCF performance despite the presence of surface defects but a low fatigue limit in the HCF regime. Removing the surface roughness has a beneficial effect but does not improve the fatigue strength to that of machined wrought 316L. Observations on the microstructure of fatigue samples indicate that LCF is dominated by the local plastic deformation, which is mostly achieved by the slip in the studied material and is not sensitive to the defect. The lack-of-fusion defect impairs the fatigue resistance in the HCF regime.

International audience; The pathophysiology of primary burning mouth syndrome (BMS) remains controversial. Targeted analyses or "omics" approach of saliva provide diagnostic or pathophysiological biomarkers. This pilot study's primary objective was to explore the pathophysiology of BMS through a comparative analysis of the salivary metabolome among 26 BMS female cases and 25 age- and sex-matched control subjects. Secondary objectives included comparative analyses of inflammatory cytokines, neuroinflammatory markers, and steroid hormones among cases and control subjects, and among BMS patients according to their clinical characteristics. Salivary metabolome, neuroinflammatory markers, cytokines, and steroids were, respectively, analysed by liquid chromatography coupled with mass spectrometry, ELISA and protease activity assay, and multiparametric Luminex method. Among the 166 detected metabolites, univariate analysis did not find any discriminant metabolite between groups. Supervised multivariate analysis divided patients into 2 groups with an accuracy of 60% but did not allow significant discrimination (permutation test, P = 0.35). Among the metabolites contributing to the model, 3 belonging to the tyrosine pathway ( l -dopa, l -tyrosine, and tyramine) were involved in the discrimination between cases and control subjects, and among BMS patients according to their levels of pain. Among the detectable molecules, levels of cytokines, steroid hormones, and neuroinflammatory markers did not differ between cases and control subjects and were not associated with characteristics of BMS patients. These results do not support the involvement of steroid hormones, inflammatory cytokines, or inflammatory neurogenic mediators in the pathophysiology of pain in BMS, whereas the observed shift in tyrosine metabolism may indicate an adaptative response to chronic pain or an impaired dopaminergic transmission.

International audience; Sugar-based molecules such as heparins or natural heparan sulfate polysaccharides have been developed and widely studied for controlling heparanase (HPSE) enzymatic activity, a key player in extracellular matrix remodelling during cancer pathogenesis. However, non-enzymatic functions of HPSE have also been described in tumour mechanisms. Given their versatile properties, we hypothesized that sugar-based inhibitors may interfere with enzymatic but also non-enzymatic HPSE activities. In this work, we assessed the effects of an original marine λ-carrageenan derived oligosaccharide (λ-CO) we previously described, along with those of its native counterpart and heparins, on cell viability, proliferation, migration, and invasion of MDA-MB-231 breast cancer cells but also of sh-MDA-MB-231 cells, in which the expression of HPSE was selectively downregulated. We observed no cytotoxic and no anti-proliferative effects of our compounds but surprisingly λ-CO was the most efficient to reduce cell migration and invasion compared with heparins, and in a HPSE-dependent manner. We provided evidence that λ-CO tightly controlled a HPSE/MMP-14/MMP-2 axis, leading to reduced MMP-2 activity. Altogether, this study highlights λ-CO as a potent HPSE “modulator” capable of reducing not only the enzymatic activity of HPSE but also the functions controlled by the HPSE levels.

International audience; The renewed interest for Supersonic Civil Transport on one side and the environmental challenges that whole aeronautics sector will have to overcome in the next decades calls for an holistic evaluation of the environmental impacts of a possible reintroduction of supersonic flights after Concorde retirement in 2003. In this perspective, a research effort has been initiated by ONERA to investigate the lowest levels of environmental impacts that can be expected by a new generation of civil supersonic aircraft. This paper presents the setup and verification of different models and of a methodological design approach combining conceptual and preliminary aircraft design capabilities. This approach is intended to design a supersonic civil transport aircraft concepts that can serve to evaluate the minimum levels of environmental impacts of new supersonic aircraft integrating state-of-the-art technologies in terms of sonic boom, takeoff noise and emissions.; Le regain d'intérêt pour le transport civil supersonique d'une part et les défis environnementaux que tout le secteur aéronautique devra surmonter dans les prochaines décennies appellent à une évaluation holistique des impacts environnementaux d'une éventuelle réintroduction des vols supersoniques après la retraite du Concorde en 2003. Dans ce Dans cette perspective, un effort de recherche a été initié par l'ONERA pour étudier les niveaux d'impacts environnementaux les plus faibles que l'on puisse attendre d'une nouvelle génération d'avions supersoniques civils. Cet article présente la mise en place et la vérification de différents modèles et d'une approche de conception méthodologique combinant des capacités conceptuelles et préliminaires de conception d'avions. Cette approche vise à concevoir des concepts d'avions de transport civil supersoniques pouvant servir à évaluer les niveaux minimaux d'impacts environnementaux des nouveaux avions supersoniques intégrant des technologies de pointe en termes de bang sonique, de bruit au décollage et d'émissions.

Two cast aluminium alloys fabricated by different casting processes (gravity die-casting and lost foam casting) and showing different degrees of porosity were characterized with X-ray Computed tomography. Information concerning the pore distribution inside the investigated materials is obtained in terms of pore size and the pore positions in 3D space. Subsequently, a spatial point pattern analysis is undertaken to investigate the pore distributions. Different methods, including a nearest neighbor analysis, Ripley's K-function and Clark-Evans tests developed for 3D applications, are used to analyse the observed patterns. The results show that the Homogeneous Poisson process, which provides the Complete Spatial Randomness (CSR) is suitable to approximate the spatial distribution of the pores present in the investigated alloys. Synthetic microstructures that mimic key macroscale features of the materials in terms of pore size and the 3D spatial distribution of the pores were generated. These microstructures can be used in the probabilistic modelling of fatigue behavior.

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.

In this study, a probabilistic model based on Monte-Carlo theory is applied to predict the fatigue behavior of cast aluminum alloys. The objective of the proposed approach is to investigate the effect of porosity (i.e. the defect size distribution and spatial density) on the fatigue strength and its associated scatter for uniaxial fatigue loads with the load ratio R = 0.1. The proposed model is applied to two cast aluminum alloys with very different defect characteristics. The results for these two alloys confirm that the model can be used to predict the average fatigue strength with a relative error

Background A relationship between alcohol consumption and psoriasis has been reported, but it is unclear whether alcohol consumption aggravates psoriasis. Here, we studied the effect of chronic ethanol (EtOH) consumption in the murine model of Aldara-induced psoriasiform dermatitis. Methods C57BL/6 mice received 5% EtOH in their drinking water for 10 weeks. Dermatitis was induced from weeks 9 to 10, by applying Aldara to the shaved patch of skin on the back. Inflammation was characterized by histological and transcriptomic analyses. Results EtOH consumption aggravated Aldara-induced dermatitis. The scales were more severe, epidermal thickening was more pronounced, and cutaneous expression of Th17-related cytokines was exacerbated. Control mice simply receiving EtOH displayed minimal cutaneous inflammation, characterized by epidermal infiltrates of T lymphocytes and the overexpression of IL-17A and the Th17-recruiting chemokine CCL20. In vitro studies showed that low concentrations of EtOH induce the expression of CCL20 by murine epidermal keratinocytes. Conclusion Alcohol consumption leads to subliminar skin inflammation, which is revealed by the exacerbation of Aldara-induced experimental psoriasiform dermatitis, likely through Th17-type minimal skin inflammation. These results favor the systematic management of alcohol consumption in psoriatic patients.

Loss of melanocytes is the pathological hallmark of vitiligo, a chronic inflammatory skin depigmenting disorder induced by exaggerated immune response, including autoreactive CD8 T cells producing high levels of type 1 cytokines. However, the interplay between this inflammatory response and melanocyte disappearance remains to be fully characterized. Here, we demonstrate that vitiligo skin contains a significant proportion of suprabasal melanocytes, associated with disruption of E-cadherin expression, a major protein involved in melanocyte adhesion. This phenomenon is also observed in lesional psoriatic skin. Importantly, apoptotic melanocytes were mainly observed once cells were detached from the basal layer of the epidermis, suggesting that additional mechanism(s) could be involved in melanocyte loss. The type 1 cytokines IFN-γ and TNF-α induce melanocyte detachment through E-cadherin disruption and the release of its soluble form, partly due to MMP-9. The levels of MMP-9 are increased in the skin and sera of patients with vitiligo, and MMP-9 is produced by keratinocytes in response to IFN-γ and TNF-α. Inhibition of MMP-9 or the JAK/STAT signaling pathway prevents melanocyte detachment in vitro and in vivo. Therefore, stabilization of melanocytes in the basal layer of the epidermis by preventing E-cadherin disruption appears promising for the prevention of depigmentation occurring in vitiligo and during chronic skin inflammation.

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.

SummaryBackground Psoriasis associates several extra-cutaneous manifestations. Little is known about hepatic parameters specifically associated with psoriasis. Objective To study whether psoriasiform dermatitis is associated with liver injury. Methods We studied liver parameters of inflammation and fibrosis in a murine model of psoriasiform dermatitis induced by topical application of imiquimod for nine weeks. Results Topical treatment with imiquimod induced a form of psoriasiform dermatitis reminiscent of the human disorder, characterized by thickened and scaly skin, psoriasiform epidermal hyperplasia, altered keratinocyte differentiation, and cutaneous overexpression of interleukin-17A. Mice with dermatitis displayed hepatitis, as shown by elevation of plasma transaminase levels, as well as portal and periportal hepatitis characterized by T lymphocyte (CD3e+) and polymorphonuclear cell (Gr1+) infiltrates. The hepatitis progressed toward liver fibrogenesis, as shown by excessive Sirius red staining, consistent with the expression of alpha-smooth muscle actin by hepatic stellate cells. Conclusions These results indicate that liver inflammation and fibrosis is associated with experimental psoriasiform dermatitis. Our results suggest that psoriatic inflammation may be associated with specific liver injury. This article is protected by copyright. All rights reserved.

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.

International audience; Cast Al-Si alloys have been widely used in automotive applications with regard to their low density and excellent thermal conductivity. Many components made of these alloys are subjected to cyclic loads which can lead to fatigue failure. Furthermore, for these materials the well know size effect in fatigue, whereby the fatigue strength is reduced when the size is increased, can be significant and need to be properly evaluated. This paper analyses the role of casting defects on the fatigue strength’s size effect sensitivity. A uniaxial fatigue testing campaign (R=0.1) has been conducted using two cast aluminium alloys, fabricated by different casting processes (gravity die casting and lost foam casting), associated with the T7 heat treatment, and with different degrees of porosity. The fatigue response of different specimens (smooth and notched) with different stressed volumes has been investigated. The first part of this article is dedicated to the experimental characterization of the size effect in both alloys via the concept of the Highly Stressed Volume. The second part investigates the effect of the Highly Stressed Volume on the critical defect size via Kitagawa-Takahashi diagrams. The results show that the magnitude of the size effect and the experimental scatter are strongly linked to the characteristics of the defect population present in the alloy. It is revealed that the alloy B, with a high density of pore and a population of defects with relatively large size, shows non-significant size effect and less scatter in fatigue strength. In comparison, alloy A that exhibits a low density of pore and a population of defects of relatively small size manifests significant size effect and high scatter in fatigue strength.

This work is focused on the influence of porosity when dealing with the fatigue behaviour of TA6V alloys fabricated by the selective laser melting (SLM) process. The presence of porosity is one of the major issues facing additive manufacturing (AM) of metallic components subjected to fatigue loading. In order to study the effect of porosity on the fatigue behaviour, a vast experimental campaign has been undertaken. Seven specimen batches, fabricated by the SLM process with different building directions (horizontal, vertical and diagonal) were tested and a large amount of data was obtained. The link between the applied stress, the fatigue life and the pore size is highlighted by using generalized Kitagawa-Takahashi maps. It is shown that the effect of porosity on the fatigue strength is much more pronounced compared to the effect of the microstructure. In the modelling section, two approaches based on fracture mechanics are considered. The first one is based on the Paris law which is used to model long fatigue crack growth. The second approach was proposed by Caton et al. (2001) for modelling small fatigue crack growth. Finally, a simulation of the generalized Kitagawa-Takahashi is presented and good agreement with the experimental data is shown. This study is part of the FATAL project, managed by IRT Jules Verne (French Institute in Research and Technology in Advanced Manufacturing Technologies for Composite, Metallic and Hybrid Structures). The authors wish to associate the industrial and academic partners of this project; Respectively ACB, Arts et Métiers ParisTech, CNRS, DAHER, Ecole Centrale de Nantes, Europe Technologies, FIVES, Renault and University of Nantes.

In dermatology, image processing allows non-contact and non-invasive metrological measurements. Psoriasis is an incurable skin disease with an unknown origin. One of the most important tasks in the treatment of psoriasis is to evaluate the degree of the illness following a severity score. Dermatologists use visual and tactile senses to assess the lesions severity. In this article, we propose an automated methodology for assessing objectively the severity of psoriasis by measuring the physical parameters of the skin. Thus, from the colorimetry and geometry obtained by photometric-stereo, we determine the level of erythema and skin thickness. Our results show that for a low acquisition time, the scores obtained are highly correlated with those of dermatologists.

Wound healing is a complex physiological process that repairs a skin lesion and produces fibrous tissue. In some cases, this process can lead to hypertrophic scars (HS) or keloid scars (KS), for which the pathophysiology remains poorly understood. Previous studies have reported the presence of oncostatin M (OSM) during the wound healing process; however, the role of OSM in pathological scarring remains to be precisely elucidated. This study aims to analyse the presence and involvement of OSM in the pathological scarring process. It was conducted with 18 patients, including 9 patients with hypertrophic scarring and 9 patients with keloid scarring. Histological tissue analysis of HS and KS showed minor differences in the organization of the extracellular matrix, the inflammatory infiltrate and the keratinocyte phenotype. Transcriptomic analysis showed increased expression levels of fibronectin, collagen I, TGFβ1, β-defensin-2 and S100A7 in both pathological samples. OSM expression levels were greater in HS than in KS and control skin. In vitro, OSM inhibited TGFβ1-induced secretion of components of the extracellular matrix by normal and pathological fibroblasts. Overall, we suggest that OSM is involved in pathological wound healing processes by inhibiting the evolution of HS towards KS by controlling the fibrotic effect of TGFβ1.

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.

Selective laser melting SLM is investigated through a study of redesign and characterization of an aeronautic part made of titanium Ti6Al4V. The part must ensure an excellent static and fatigue behaviour. The methodology developed hereby follows 3 main steps: First, the influence of laser power, laser speed and hatch distance on the amount/rate of porosity is performed to define optimized process parameters. Then, the influence of building process strategy, i.e. building direction or as-built surface roughness on the static and fatigue behaviour are studied and understood by following a vast experimental campaign. Obtained properties are finally used in a topology optimization study to find the best compromise between part weight and fatigue behavior . 3 prototypes of simulated part are produced and then characterized. Fatigue tests are conducted on the component and confirm the fatigue design proposed. Obtained results are encouraging and illustrate the fatigue design optimization of a complex Additive Manufacturing component.

International audience; The aim of this study is to understand the impact of periodic surface micro-geometry patterns (obtained by High Speed Machining process) on the fatigue behavior of the AA7050 aluminium alloy and to define a proper defect acceptability criterion. It must be able to account for a large range of surface defects and of component sizes and geometries (wings, brackets, frames, etc.). A vast experimental campaign under fully reversed plane bending loads containing different surface states has been undertaken to characterize the effect of the surface topography on the fatigue behavior. The results show that the fatigue strength decreases when the surface roughness is significantly degraded. In order to predict the influence of the surface condition on the fatigue behavior, a numerical approach based on the real surface topology has been developed. It is shown that the numerically identified crack initiation sites are in agreement with the experimental results. A probabilistic approach based on the weakest link concept, associated with the definition of a stress based crack initiation threshold has beenintegrated in a FE model. This approach leads to a probabilistic diagram inspired from the Kitagawa type diagram, which explains the relationship between the surface and the scale effect on the fatigue strength.

International audience; Polycrystalline elasto-plasticity models provide a general framework for investigating the effect of microstructural heterogeneities (e.g. grains, inclusions, pores) on the high cycle fatigue behavior of metallic materials. In this work, continuum damage mechanics is used to construct a set of constitutive relations to describe the progressive degradation of certain mechanical properties at the grain scale. The damage is considered to be coupled with the elastic behavior of the material. Special care is taken to include the anisotropic aspect of fatigue damage and the effect of intragranular internal stresses. The constitutive relations are then implemented within a self-consistent model to evaluate intergranular interactions. Finally, the model is used to investigate the high cycle fatigue behavior of polycrystalline copper. It is shown that the influence of certain loading conditions on the high cycle behavior is correctly reproduced. Specifically, the application of a mean shear stress does not result in an increase in damage; however, a mean normal stress is damaging. That is, a decrease in the fatigue resistance is predicted when the mean normal stress is increased.