Targeted long-read sequencing of the Ewing sarcoma 6p25.1 susceptibility locus identifies germline-somatic interactions with EWSR1-FLI1 binding

Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation

Etude des composites SiC/SiBC à matrice multiséquencée en fatigue cyclique à hautes températures sous air

Le comportement en fatigue cyclique sous air à hautes températures, d'un composite SiC/ SiBC à matrice multiséquencée est étudié. Les couches de matrice forment des films d'oxyde plus ou moins épais et protecteurs. En fatigue, cette oxydation est beaucoup plus faible que sur des échantillons avec des surfaces non protégées, oxydés en statique. L'évolution des paramètres d'endommagement, les observations microscopiques et les propriétés physico-chimiques, ont montré les mécanismes d'endommagement suivants : à basses températures, les faciès de rupture sont plutôt fragiles (profil droit, rupture des fils), et la fatigue intervient à l'interface fil/matrice interfil. Les durées de vie sont longues. A hautes températures, celles-ci diminuent. Les faciès de rupture présentent des fortes extractions individuelles des fibres. Le rôle de la propagation sous critique, du fluage ou de l'oxydation dépend de la température et de la contrainte appliquée, amenant à une interaction complexe.The aim of this work is to study composite behaviour observed during cyclic fatigue under air at high temperatures, in order to understand damage accumulation resulting from mechanical fatigue and oxidation, and then to evaluate fatigue lifetime. Principle of the multilayered matrix is to consume part of the incoming oxygen and to prevent access of residual oxygen to carbon interphase through microcracks, by forming sealant glasses. Cyclic fatigue tests performed in air from 25C to 1200C showed that oxidation during fatigue was low, compared to composites without neither seal-coat nor cycling loading. At low temperatures, fracture surface present short fibre pullout. Fatigue occurs at longitudinal bundle/inter-bundle matrix interface. Lifetimes are long. Whereas at high temperatures, lifetimes decrease, debonding occurs at the interface between fibre and matrix, and individual fibre pullout phenomenon is much more important. Damage mechanisms are linked to slow crack growth, creep and oxidation, whose interaction make the interpretation difficult.VILLEURBANNE-DOC'INSA LYON (692662301) / SudocSudocFranceF

A la recherche d'un Lyon disparu. Vie et mort des édifices religieux du IVe au XXe siècle

International audienc

The additive manufacturing of model polymer nanolaminates via automated spray deposition

Polymer nanocomposites represent a key addition to the palette of advanced polymeric materials available to us in the context of additive manufacturing. However, our understanding of their properties, and thus our ability to predict them and to design parts based on them, remains limited. With this in mind, nanolaminates have been formed via an additive process developed in our group and referred to as automated spray deposition; these materials have been characterized with the express purpose of better understanding the composition-structure-properties relations critical to our ability to create high performance polymeric materials by design via additive techniques. Here we present a preliminary comparison of the dynamic mechanical properties of two families of nanolaminates, essentially identical except for the polarity of the polymer phase and the strength of polymer / nanofiller interactions, with the aim of better understanding the mechanical response of such materials.Published versio

Clinical practice versus guidelines for the screening of cystic fibrosis-related diabetes: A French survey from the 47 centers

International audienc

Pillars fabrication by DSA lithography: material and process options

International audienceWe investigate the fabrication of sub-20 nm pillars by DSA lithography using PS-cylinder-forming PS-b-PMMA block copolymer (BCP). The approach is based on the removal of PMMA-matrix by either dry or wet etching to form PS pillars which act as a soft etching mask that can be further transferred to an intermediate hard one and then to the substrate. The process conditions of BCP self-assembly were optimized in terms of annealing temperature, brush layer composition and film thickness. It was demonstrated that PS/PMMA volume fractions of 50/50 in the PS-r-PMMA brush layer is the most adapted to obtain standing PS cylinders. Top-down SEM images showed a hexagonal array of PS cylinders in a PMMA matrix with a natural period of 33.5 nm (determined by Fast Fourier Transform FFT method) and CD around 15 nm. Both wet and dry etching strategies for PMMA removal were discussed. It was shown that UV exposure followed by organic solvent development is necessary to decrease pattern collapsing during PMMA removal step which is the most critical issue for pillar fabrication. PMMA removal by dry etching was shown to completely avoid this pattern collapsing. Finally, pillars etching transfer to typical organic Si containing antireflective coating and spin on carbon (SiARC/SOC) hard mask and then to the silicon substrate was demonstrated. Si pillars of 15 nm CD and 70 nm height were obtained with a straight profile shape.(c) SPIE 201

Les pratiques de récupération dans la construction : le remploi du « choin » de Fay à Lyon et à Vienne (Moyen Âge - Temps modernes)

National audienceThe reuse-recycling of objects and materials is a phenomenon frequently identified in ancient constructions. However, despite its apparent banality, archaeologists are not always able to recognize this practice. It can be seen and identified only when the material and its form and finishing deviate from the rest of the masonry. It then becomes evident and we are reminded of its ubiquity in buildings. Though the stages of the reuse-recycling process are difficult to perceive, this practice is not the result of random material recuperations. The materials are selected, as is their destination in the construction. The “choin de Fay” – a cold limestone extracted from the Bugey quarries – provides a well-identified example of reuse-recycling in the cities of Lyon and Vienne. Abundantly used in Antique monumental constructions, this stone with desirable qualities (ease of polishing, resistance to compression and frost, large pieces) was widely reused-recycled in Antiquity and throughout the Middle Ages. Based on a confrontation of more than 60 years of archaeological data and bibliographic sources, it was possible to reconstruct part of the chaîne opératoire (production sequence) from the recuperation of the material until its new use. This study thus reveals the diverse esthetic, technical and economic factors leading to reuse-recycling. It addresses questions concerning resource site ownership and the legal context surrounding these practices. The example of “choin de Fay” thus offers an opportunity to study the complexity of the practice of reuse-recycling.Le remploi – abordé comme la réutilisation ou le recyclage d’objets ou de matériaux variés – est un phénomène fréquemment rencontré, notamment dans l’analyse des constructions anciennes. Pratiqué de tout temps, il s’inscrit dans la chaîne opératoire ordi-naire de la construction. Malgré cette apparente banalité, le regard de l’archéologue ne peut pas toujours en saisir la présence. Il faut en effet qu’il revête un caractère manifeste: il se voit, se repère, lorsque son matériau, sa forme, sa finition, détonne avec le reste de la maçonnerie. Il devient alors évident et nous rappelle son omniprésence dans le bâti. Observé comme le résultat d’un processus dont on perçoit difficilement toutes les étapes, le remploi ne procède pourtant pas d’une récupération hasardeuse. Les matériaux sont choisis, tout comme leur destination dans la construction. À ce titre, le choin de Fay – calcaire froid extrait des carrières du Bugey (Ain) –, fournit un exemple de remploi bien identifié dans les villes de Lyon (Rhône) et de Vienne (Isère). Abondamment utilisée dans les constructions monumentales antiques, cette pierre aux qualités recherchées (facilité de polissage, résistance à la compression et au gel, modules de taille importante) est largement remployée dès l’Antiquité et tout au long du Moyen Âge. Le croisement de plus de 60ans de données archéologiques et de sources textuelles inédites permet de restituer une partie de la chaîne opératoire, depuis sa récupération jusqu’à sa nouvelle mise en œuvre. Son étude met en lumière la diversité des facteurs qui conduisent à ce remploi: ils sont esthétiques, techniques ou encore économiques. Elle permet de questionner la propriété des gisements et le contexte juridique qui encadre ces pratiques. Derrière l’exemple du choin de Fay, l’économie du remploi peut être ainsi abordée dans toute sa complexité

Screening strategies for glucose tolerance abnormalities and diabetes in people with cystic fibrosis

International audienc