12 research outputs found

    Hypoelastic, hyperelastic, discrete and semi-discrete approaches for textile composite reinforcement forming

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    International audienceThe clear multi-scale structure of composite textile reinforcements leads to develop continuous and discrete approaches for their forming simulations. In this paper two continuous modelling respectively based on a hypoelastic and hyperelastic constitutive model are presented. A discrete approach is also considered in which each yarn is modelled by shell finite elements and where the contact with friction and possible sliding between the yarns are taken into account. Finally the semi-discrete approach is presented in which the shell finite element interpolation involves continuity of the displacement field but where the internal virtual work is obtained as the sum of tension, in-plane shear and bending ones of all the woven unit cells within the element. The advantages and drawbacks of the different approaches are discussed

    NET Formation in Bullous Pemphigoid Patients With Relapse Is Modulated by IL-17 and IL-23 Interplay

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    Background: DNA extracellular traps (ETs), released by neutrophils (NETs), or eosinophils (EETs), play a pathogenic role in several autoimmune disorders. However, to date, NETs have never been investigated in bullous pemphigoid (BP) with respect to clinical and immunological activities, both at baseline and at time of relapse which have been characterized with specific IL-17 and IL-23 patterns.Objective: We sought to assess whether ETs were associated with BP as well as the relative contribution of IL-17 axis cytokines to NET induction.Methods: Skin biopsy specimens were obtained from 11 patients with BP. Immuno-detection of neutrophils and eosinophils combined to DNA staining allowed us to investigate the in-situ presence of NETs and EETs using confocal scanning microscopy. NETs release was evaluated ex vivo by stimulating polymorphonuclear cells from BP patients with BP biological fluids in presence of IL-17A and IL-23 or of glucocorticoids.Results: At baseline, ETs were observed in BP lesions at the site of dermal-epidermal cleavage. Despite an important infiltrate of eosinophils, ETs were essentially associated with neutrophils in situ and were not related to BP clinical activity at diagnosis. In situ observation of NETs was associated in 6 among 8 patients with serum capacity of NET induction. Notably both blister fluid and sera from BP patients at diagnosis and at time of relapse could induce NET formation ex vivo. In contrast, a longitudinal investigation showed a decrease of NET formation with time of treatment in patients undergoing remission. Mimicking relapse, complementation of sera from BP patients with ongoing remission with either IL-17A or IL-23 increased NET formation. Conversely, IL-17A inhibited NET formation induced by serum from BP patients with relapse supplemented or not with IL-23. Finally, glucocorticoids also inhibited NET formation ex vivo in BP.Conclusion: NET formation is an associated phenomenon with BP. Furthermore, we showed that IL-23 favored NET formation, whereas the effects of IL-17A are environment dependent. Indeed, IL-17A displayed a protective effect on NET formation when associated with IL-23, showing for the first-time differential effects of these two cytokines in BP

    Différentes approches pour la simulation de la mise en forme des renforts fibreux de composites. Les intérêts de l’approche mésoscopique

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    Ce papier présente une modélisation à l'échelle mésoscopique de la simulation de la mise en forme des renforts fibreux. Le comportement mécanique de chaque constituant est alors plus simple que dans les modèles continus et des aspects difficiles dans ces derniers, tels que l’actualisation de la direction des mèches, sont intégrés naturellement. La contrepartie réside dans le très grand nombre de composants avec des contacts complexes entre eux. Les intérêts de cette approche seront détaillés

    Approche mésoscopique pour la mise en forme des renforts tissés de composites

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    La simulation de la mise en forme des renforts tissés permet d'étudier les conditions de faisabilité d'une telle opération en limitant les essais expérimentaux et donc les coûts de développement. La simulation permet d'accéder à des informations telles que la position des fibres après formage et leur état de déformation ainsi que de prédire l'apparition de défauts (plissements, détissages, rupture de fibres/mèches). La définition du comportement mécanique des tissus, nécessaire à ces simulations, peut se faire à différentes échelles. Seuls les modèles définis à l'échelle macroscopique permettent à l'heure actuelle d'effectuer ce type de simulations. Les modèles aux échelles inférieures permettent alors de définir le comportement macroscopique d'un renfort à partir de l'assemblage de ses constituants élémentaires. Le passage méso/macro (ou micro/macro) s'accompagne dans ce cas d'une perte d'information liée au passage d'une description discrète à une description continue. Le modèle que nous proposons consiste en une description à l'échelle mésoscopique des renforts permettant la simulation de pièces à l'échelle macroscopique. Cela est rendu possible par une simplification de la description mésoscopique grâce l'utilisation d'éléments de coques. Un modèle de comportement hypoélastique spécifique à la mèche est alors considéré. En particulier, la direction des fibres est strictement suivie et un comportement élastique non linéaire permettant de prendre en compte la compaction transverse est défini. L'identification et la validation du modèle sont effectuées grâce aux essais usuels de caractérisation des renforts. Outre le fait de décrire correctement le comportement en cisaillement des tissus, le modèle permet de prédire les plissements et les détissages de mèches. Des simulations de mise en forme illustrent ces capacitésWoven reinforcements forming simulation allows studying feasibility conditions of such processes limiting experimental tests and therefore development costs. Simulation allows accessing to information such as fibre positions after forming and their deformation state as well as predicting the onset of defects (wrinkles, yarns sliding, fibre/yarn fracture). The definition of the fabric mechanical behaviour necessary for these simulations can be done at different scales. Today only the macroscopic scale allows simulations of forming processes. Models at lower scales then allow to define the macroscopic behaviour of reinforcement from the assembly of their elementary components. The meso/macro (or micro/macro) transition is accompanied by an information loss due to the transition from a discrete description to a continuous one. The proposed model consist in a mesoscopic description of the reinforcement allowing the simulation of forming processes at the macroscopic scale. This is possible thanks to a simplification of the description by using shell elements. A hypoelastic behaviour specific of the yarn is then considered. In particular, fibre direction is strictly tracked and a non linear elastic behaviour is defined, allowing the consideration of the transverse compaction of the yarn. Identification and validation of the model are done using classical characterisation tests. In addition to a good description of the shearing behaviour of fabrics, the model allows the prediction of wrinkles and yarns sliding. Forming simulations illustrate these capabilitiesVILLEURBANNE-DOC'INSA LYON (692662301) / SudocSudocFranceF

    Anti-Type VII Collagen Antibodies Are Identified in a Subpopulation of Bullous Pemphigoid Patients With Relapse

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    Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by anti-BP180 and anti-BP230 autoantibodies (AAbs). Mucous membrane involvement is an uncommon clinical feature of BP which may evoke epidermolysis bullosa acquisita, another skin autoimmune disease characterized by anti-type VII collagen AAbs. We therefore evaluated the presence of anti-type VII collagen AAbs in the serum of BP patients with and without mucosal lesions at time of diagnosis and under therapy. Anti-BP180, anti-BP230, and anti-type VII collagen AAbs were measured by ELISA in the serum of unselected patients fulfilling clinical and histo/immunopathological BP criteria at baseline (n = 71) and at time of relapse (n = 24). At baseline, anti-type VII collagen AAbs were detected in 2 out of 24 patients with BP presenting with mucosal involvement, but not in patients without mucosal lesions (n = 47). At the time of relapse, 10 out of 24 BP patients either displayed a significant induction or increase of concentrations of anti-type VII collagen AAbs (P < 0.01), independently of mucosal involvement. Those 10 relapsing BP patients were also characterized by a sustained high concentration of anti-BP180 AAb, whereas the serum anti-BP230 AAb concentrations did not vary in BP patients with relapse according to the presence of anti-type VII collagen AAbs. Thus, our study showed that anti-type VII collagen along with anti-BP180 AAbs detection stratified BP patients at time of relapse, illustrating a still dysregulated immune response that could reflect a potential epitope spreading mechanism in those BP patients

    Mucosal Involvement in Bullous Pemphigoid Is Mostly Associated with Disease Severity and to Absence of Anti-BP230 Autoantibody

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    Bullous pemphigoid (BP) is the most common autoimmune bullous disease and typically affects the elderly. Binding of specific autoantibodies to BP180/230 hemidesmosomal components induces an inflammatory response leading to skin blister formation. Unusual manifestations of BP include additional mucous membrane involvement, without pathophysiological knowledge associated to the formation of these lesions. We here performed a prospective study on series of consecutive BP patients with (n = 77) and without (n = 18) mucosal involvements at baseline to further investigate why some BP patients display mucosal lesion and other not. Analysis of disease activity showed that BP patients with mucosal involvement displayed a higher total BP Disease Area Index (BPDAI) score (P = 0.008), but also higher skin and blister/erosion BPDAI scores (P = 0.02 and P = 0.001, respectively). By contrast, the erythema/urticaria BPDAI score was identical between the two groups of patients. The erythema/urticaria BPDAI score, but not the blister/erosion BPDAI score, was correlated with the serum concentration of anti-BP180 NC16A autoantibodies in patients with mucosal involvement. In multivariate analysis, the absence of anti-BP230 autoantibody was the only factor independently associated with mucosal involvement (OR 7.8; 95% CI, 3.1–19.6) (P < 0.0001). Analysis of the distribution of BP patients according to BPDAI scores revealed a shift toward higher blister/erosion BPDAI scores for BP patients with mucosal involvement. This study indicates that mucosal lesions are clinically mainly related to disease severity and immunologically to the absence of anti-BP230 antibodies

    Eosinophil Cationic Protein (ECP), a predictive marker of bullous pemphigoid severity and outcome

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    International audienceBullous Pemphigoid (BP) is an inflammatory rare autoimmune bullous dermatosis, which outcome cannot be predicted through clinical investigations. Eosinophils are the main immune infiltrated cells in BP. However, the release of Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN), and Eosinophil Cationic Protein (ECP) upon eosinophil activation has still not been evaluated with respect to BP development. MBP, EDN and ECP were measured by ELISA in serum (n = 61) and blister fluid (n = 20) of patients with BP at baseline, and in serum after 2 months of treatment (n = 41). Eosinophil activation in BP patients was illustrated at baseline by significantly higher MBP, EDN and ECP serum concentrations as compared with control subjects (n = 20), but without distinction according to disease severity or outcome. EDN and ECP values were even higher in the blister fluids (P < 0.01 and P < 0.05, respectively), whereas MBP values were lower (P < 0.001). ECP serum concentration decreased after 60 days of treatment in BP patients with ongoing remission but not in patients who later relapsed (P < 0.05). A reduction of at least 12.8 ng/mL in ECP concentrations provided a positive predictive value for remission of 81%, showing that ECP serum variation could be a useful biomarker stratifying BP patients at risk of relapse

    NET Formation in Bullous Pemphigoid Patients With Relapse Is Modulated by IL-17 and IL-23 Interplay

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    International audienceBackground: DNA extracellular traps (ETs), released by neutrophils (NETs), or eosinophils (EETs), play a pathogenic role in several autoimmune disorders. However, to date, NETs have never been investigated in bullous pemphigoid (BP) with respect to clinical and immunological activities, both at baseline and at time of relapse which have been characterized with specific IL-17 and IL-23 patterns. Objective: We sought to assess whether ETs were associated with BP as well as the relative contribution of IL-17 axis cytokines to NET induction. Methods: Skin biopsy specimens were obtained from 11 patients with BP. Immuno-detection of neutrophils and eosinophils combined to DNA staining allowed us to investigate the in-situ presence of NETs and EETs using confocal scanning microscopy. NETs release was evaluated ex vivo by stimulating polymorphonuclear cells from BP patients with BP biological fluids in presence of IL-17A and IL-23 or of glucocorticoids. Results: At baseline, ETs were observed in BP lesions at the site of dermal-epidermal cleavage. Despite an important infiltrate of eosinophils, ETs were essentially associated with neutrophils in situ and were not related to BP clinical activity at diagnosis. In situ observation of NETs was associated in 6 among 8 patients with serum capacity of NET induction. Notably both blister fluid and sera from BP patients at diagnosis and at time of relapse could induce NET formation ex vivo. In contrast, a longitudinal investigation showed a decrease of NET formation with time of treatment in patients undergoing remission. Mimicking relapse, complementation of sera from BP patients with ongoing remission with either IL-17A or IL-23 increased NET formation. Conversely, IL-17A inhibited NET formation induced by serum from BP patients with relapse supplemented or not with IL-23. Finally, glucocorticoids also inhibited NET formation ex vivo in BP. Conclusion: NET formation is an associated phenomenon with BP. Furthermore, we showed that IL-23 favored NET formation, whereas the effects of IL-17A are environment dependent. Indeed, IL-17A displayed a protective effect on NET formation when associated with IL-23, showing for the first-time differential effects of these two cytokines in BP
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