Coupled visco-mechanical and diffusion void growth modelling during composite curing

Most critical processing step during long fiber reinforced epoxy matrix composite laminate manufacturing is the polymerization stage. If not optimized, it gives birth to defects in the bulk material, such as voids. These defects are considered as possible sources of damage in the composite parts. The aim of this work is to model the evolution of void growth in thermoset composite laminates after ply collation (autoclave processes) or resin impregnation (RTM, LCM process). A coupled mechanical and diffusion model is presented to better predict the final void size at the end of polymerization. Amongst the parameter investigated, onset of pressure application and diffusive species concentration where found to have a major effect on void size evolution during curing process

Modeling of voids growth mechanisms during manufacturing composite laminates

Manufacturing composite laminates made of epoxy resin matrix and long carbon fibers is divided into several operations. The most critical one is the cross-linking stage of the thermoset resin. During this phase, uncured prepreg plies’ stacking is transformed into a structural laminate by the achievement of a three dimensional macromolecular resin network. A question of matter is the quality of the polymerization process. If not optimized, it gives birth to defects in the bulk material, such as voids. These defects are considered as possible sources of damage in the composite parts. The aim of this work is to address void growth processes in thermoset composite laminates with dynamic modelling. Diffusion phenomena of gas molecules in resin are neglected for the moment, in order to study more easily viscous effects of the polymer on gas bubbles traped inside the fluid. Once model bases are fixed and validated, an optimization study is proposed to determine the best temperature and pressure cycles which permit to minimize the final void radius

Quantification 2-D et 3-D de la porosité par analyse d’images dans les matériaux composites stratifiés aéronautiques = 2-D and 3-D void quantification with image analyses in aeronautic composite laminates

L'élaboration de structures primaires en matériau composite destinées à la production d'aéronefs est soumise à un contrôle qualité strict (contrôles non destructifs sur pièces et destructifs sur éprouvettes représentatives). Cette étape permet de valider le matériau mis en oeuvre ainsi que le bon déroulement du processus de moulage. Pour ce faire, il existe plusieurs méthodes d’analyse, chacune d'elles présente un certain nombre d’avantages mais aussi des inconvénients. Après avoir fait un rapide état de l'art des méthodes actuellement utilisées, d'une part par les industriels, et d'autre part par les laboratoires d'expertises, cette étude a pour objectif de développer un protocole expérimental simple d'application, permettant d'évaluer rapidement et le plus précisément possible le taux volumique de porosités contenu dans des plaques épaisses en carbone/époxy. L'analyse d'image sera utilisée pour quantifier les taux surfaciques de porosité. Puis, à l'aide de la stéréologie et sous certaines conditions, ces résultats 2D seront extrapolés à la troisième dimension. Les taux volumiques ainsi obtenus seront discutés et comparés à ceux déterminés via l'attaque à l’acide sulfurique

Protocole d'analyse aérodynamique de la nasalité en français: des variétés régionales aux variations cliniques

International audienceDifficiles à analyser acoustiquement, l'aérophonométrie permet d'étudier efficacement les phénomènes de nasalité par des mesures précises des phases temporelles d'ouverture/fermeture du port vélo-pharyngé et de la quantité d'air empruntant les voies oro-nasales. Ces informations sont essentielles dans la prise en charge clinique des insuffisances et fuites vélaires. Or, avant d'évaluer la variabilité de la nasalité selon la pathologie, les mécanismes impliqués peuvent être très différents selon l'origine régionale du locuteur et donc la phonologie de son parler. À ce titre, la production de voyelles nasales en français méridional mettrait en évidence un patron spécifique présentant une phase d'oralisation initiale et un appendice consonantique nasal terminal plus ou moins long, jusque-là peu décrit et analysé quantitativement (Demolin et Teston 1998 ; Clairet 2008). L'enjeu de ce travail est donc d'attester statistiquement de la systématicité de ce patron nasal méridional, dans l'objectif à plus long terme d'étudier comment il résiste aux troubles affectant le voile du palais. Ce travail s'inscrit également dans la construction d'un protocole de bilan clinique prenant en compte les spécificités des variétés dialectales des patients

Peut-on parler sous l'eau avec un embout de détendeur ? Etude articulatoire et perceptive

International audienceWe study the ability of sub aquatic divers to communicate orally by means of an air regulator mouthpeace equipped with an acoustical sensor. These specific constraints on elocution led us to carry out an aerodynamic study to check phonation, an EPG study tu observe the modification of articulation, and an analysis of labial forces involved with a special mouthpeace. Tests on intelligibility enabled us to evaluate the device in situation of real diving. In the current state, the various results let foresee a reduced but real possibility of spoken communication with a mouthpeace to certain conditionsCette étude porte sur la communication parlée de plongeurs en situation subaquatique. Les plongeurs sont équipés d'un embout de détendeur dans lequel est intégré un capteur acoustique. Les contraintes spécifiques d'une telle élocution nous ont poussé à effectuer une étude aérodynamique pour vérifier les mécanismes de phonation, une étude d'EPG pour observer les modifications de l'articulation et une analyse des forces labiales. Des tests d'intelligibilité nous ont permis d'évaluer le dispositif dans une situation de plongée réelle. Dans l'état actuel, les divers résultats laissent envisager une possibilité réduite mais réelle de communication parlée avec une embouchure

Peut-on parler sous l'eau avec un embout de détendeur ? Etude articulatoire et perceptive

International audienceWe study the ability of sub aquatic divers to communicate orally by means of an air regulator mouthpeace equipped with an acoustical sensor. These specific constraints on elocution led us to carry out an aerodynamic study to check phonation, an EPG study tu observe the modification of articulation, and an analysis of labial forces involved with a special mouthpeace. Tests on intelligibility enabled us to evaluate the device in situation of real diving. In the current state, the various results let foresee a reduced but real possibility of spoken communication with a mouthpeace to certain conditionsCette étude porte sur la communication parlée de plongeurs en situation subaquatique. Les plongeurs sont équipés d'un embout de détendeur dans lequel est intégré un capteur acoustique. Les contraintes spécifiques d'une telle élocution nous ont poussé à effectuer une étude aérodynamique pour vérifier les mécanismes de phonation, une étude d'EPG pour observer les modifications de l'articulation et une analyse des forces labiales. Des tests d'intelligibilité nous ont permis d'évaluer le dispositif dans une situation de plongée réelle. Dans l'état actuel, les divers résultats laissent envisager une possibilité réduite mais réelle de communication parlée avec une embouchure

In vitro production of cat-restricted Toxoplasma pre-sexual stages

Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described$^{1,2}$. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref. $^{1}$), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission

Prebiotic effects: metabolic and health benefits

The different compartments of the gastrointestinal tract are inhabited by populations of micro-organisms. By far the most important predominant populations are in the colon where a true symbiosis with the host exists that is a key for well-being and health. For such a microbiota, 'normobiosis' characterises a composition of the gut 'ecosystem' in which micro-organisms with potential health benefits predominate in number over potentially harmful ones, in contrast to 'dysbiosis', in which one or a few potentially harmful micro-organisms are dominant, thus creating a disease-prone situation. The present document has been written by a group of both academic and industry experts (in the ILSI Europe Prebiotic Expert Group and Prebiotic Task Force, respectively). It does not aim to propose a new definition of a prebiotic nor to identify which food products are classified as prebiotic but rather to validate and expand the original idea of the prebiotic concept (that can be translated in 'prebiotic effects'), defined as: 'The selective stimulation of growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host.' Thanks to the methodological and fundamental research of microbiologists, immense progress has very recently been made in our understanding of the gut microbiota. A large number of human intervention studies have been performed that have demonstrated that dietary consumption of certain food products can result in statistically significant changes in the composition of the gut microbiota in line with the prebiotic concept. Thus the prebiotic effect is now a well-established scientific fact. The more data are accumulating, the more it will be recognised that such changes in the microbiota's composition, especially increase in bifidobacteria, can be regarded as a marker of intestinal health. The review is divided in chapters that cover the major areas of nutrition research where a prebiotic effect has tentatively been investigated for potential health benefits. The prebiotic effect has been shown to associate with modulation of biomarkers and activity(ies) of the immune system. Confirming the studies in adults, it has been demonstrated that, in infant nutrition, the prebiotic effect includes a significant change of gut microbiota composition, especially an increase of faecal concentrations of bifidobacteria. This concomitantly improves stool quality (pH, SCFA, frequency and consistency), reduces the risk of gastroenteritis and infections, improves general well-being and reduces the incidence of allergic symptoms such as atopic eczema. Changes in the gut microbiota composition are classically considered as one of the many factors involved in the pathogenesis of either inflammatory bowel disease or irritable bowel syndrome. The use of particular food products with a prebiotic effect has thus been tested in clinical trials with the objective to improve the clinical activity and well-being of patients with such disorders. Promising beneficial effects have been demonstrated in some preliminary studies, including changes in gut microbiota composition (especially increase in bifidobacteria concentration). Often associated with toxic load and/or miscellaneous risk factors, colon cancer is another pathology for which a possible role of gut microbiota composition has been hypothesised. Numerous experimental studies have reported reduction in incidence of tumours and cancers after feeding specific food products with a prebiotic effect. Some of these studies (including one human trial) have also reported that, in such conditions, gut microbiota composition was modified (especially due to increased concentration of bifidobacteria). Dietary intake of particular food products with a prebiotic effect has been shown, especially in adolescents, but also tentatively in postmenopausal women, to increase Ca absorption as well as bone Ca accretion and bone mineral density. Recent data, both from experimental models and from human studies, support the beneficial effects of particular food products with prebiotic properties on energy homaeostasis, satiety regulation and body weight gain. Together, with data in obese animals and patients, these studies support the hypothesis that gut microbiota composition (especially the number of bifidobacteria) may contribute to modulate metabolic processes associated with syndrome X, especially obesity and diabetes type 2. It is plausible, even though not exclusive, that these effects are linked to the microbiota-induced changes and it is feasible to conclude that their mechanisms fit into the prebiotic effect. However, the role of such changes in these health benefits remains to be definitively proven. As a result of the research activity that followed the publication of the prebiotic concept 15 years ago, it has become clear that products that cause a selective modification in the gut microbiota's composition and/or activity(ies) and thus strengthens normobiosis could either induce beneficial physiological effects in the colon and also in extra-intestinal compartments or contribute towards reducing the risk of dysbiosis and associated intestinal and systemic pathologies

A Genome-Wide Collection of Mos1 Transposon Insertion Mutants for the C. elegans Research Community

Methods that use homologous recombination to engineer the genome of C. elegans commonly use strains carrying specific insertions of the heterologous transposon Mos1. A large collection of known Mos1 insertion alleles would therefore be of general interest to the C. elegans research community. We describe here the optimization of a semi-automated methodology for the construction of a substantial collection of Mos1 insertion mutant strains. At peak production, more than 5,000 strains were generated per month. These strains were then subject to molecular analysis, and more than 13,300 Mos1 insertions characterized. In addition to targeting directly more than 4,700 genes, these alleles represent the potential starting point for the engineered deletion of essentially all C. elegans genes and the modification of more than 40% of them. This collection of mutants, generated under the auspices of the European NEMAGENETAG consortium, is publicly available and represents an important research resource

Safety and efficacy of atezolizumab in patients with autoimmune disease: subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma

Aim Patients with pre-existing autoimmune disease (AID) are typically excluded from clinical trials of immune checkpoint inhibitors, and there are limited data on outcomes in this population. The single-arm international SAUL study of atezolizumab enrolled a broader ‘real-world’ patient population. We present outcomes in patients with a history of AID. Methods Patients with locally advanced/metastatic urinary tract carcinoma received atezolizumab 1200 mg every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary end-point was safety. Overall survival (OS) was a secondary end-point. Subgroup analyses of AID patients were prespecified. Results Thirty-five of 997 treated patients had AID at baseline, most commonly psoriasis ( n = 15). Compared with non-AID patients, AID patients experienced numerically more adverse events (AEs) of special interest (46% versus 30%; grade ≥3 14% versus 6%) and treatment-related grade 3/4 AEs (26% versus 12%), but without relevant increases in treatment-related deaths (0% versus 1%) or AEs necessitating treatment discontinuation (9% versus 6%). Pre-existing AID worsened in four patients (11%; two flares in two patients); three of the six flares resolved, one was resolving, and two were unresolved. Efficacy was similar in AID and non-AID patients (median OS, 8.2 versus 8.8 months, respectively; median progression-free survival, 4.4 versus 2.2 months; disease control rate, 51% versus 39%). Conclusions In 35 atezolizumab-treated patients with pre-existing AID, incidences of special- interest and treatment-related AEs appeared acceptable. AEs were manageable, rarely requiring atezolizumab discontinuation. Treating these patients requires caution, but pre-existing AID does not preclude atezolizumab therapy