Utilisation conjointe des méthodes des éléments discrets et des éléments finis pour modéliser la compaction de poudres céramiques uranifères agrégées

La simulation des procédés d'élaboration de pièces à partir de poudres passe par la prise en compte du caractère particulaire des matériaux mis en jeux. La méthode des éléments discrets (Discrete Element Method, DEM) est bien adaptée pour cette tâche. Elle permet de calculer le comportement d'un ensemble de particules à partir des forces de contact exercées sur chacune d'elles. Nous montrons comment la DEM peut être utilisée pour alimenter un code aux éléments finis en lois constitutives. Le code éléments finis simule quant à lui le comportement de la pièce entière lors de la compaction en matrice. Nous nous concentrons ici sur la génération des surfaces de charge et de rupture. L'application visée est la simulation de la compaction de poudres d'oxyde d'uranium qui se présentent sous forme d'agrégats poreux. Nous proposons une loi de contact adaptée pour décrire l'indentation, la décharge élastique et la décohésion de ces agrégats

Heparan sulfate as a regulator of inflammation and immunity

Heparan sulfate is found on the surface of most cell types, as well as in basement membranes and extracellular matrices. Its strong anionic properties and highly variable structure enable this glycosaminoglycan to provide binding sites for numerous protein ligands, including many soluble mediators of the immune system, and may promote or inhibit their activity. The formation of ligand binding sites on heparan sulfate (HS) occurs in a tissue- and context-specific fashion through the action of several families of enzymes, most of which have multiple isoforms with subtly different specificities. Changes in the expression levels of these biosynthetic enzymes occur in response to inflammatory stimuli, resulting in structurally different HS and acquisition or loss of binding sites for immune mediators. In this review, we discuss the multiple roles for HS in regulating immune responses, and the evidence for inflammation-associated changes to HS structure

The BMP Antagonist Follistatin-Like 1 Is Required for Skeletal and Lung Organogenesis

Follistatin-like 1 (Fstl1) is a secreted protein of the BMP inhibitor class. During development, expression of Fstl1 is already found in cleavage stage embryos and becomes gradually restricted to mesenchymal elements of most organs during subsequent development. Knock down experiments in chicken and zebrafish demonstrated a role as a BMP antagonist in early development. To investigate the role of Fstl1 during mouse development, a conditional Fstl1 KO allele as well as a Fstl1-GFP reporter mouse were created. KO mice die at birth from respiratory distress and show multiple defects in lung development. Also, skeletal development is affected. Endochondral bone development, limb patterning as well as patterning of the axial skeleton are perturbed in the absence of Fstl1. Taken together, these observations show that Fstl1 is a crucial regulator in BMP signalling during mouse development

Transforming growth factor beta signaling: The master sculptor of fingers

Transforming growth factor beta (TGF?) constitutes a large and evolutionarily conserved superfamily of secreted factors that play essential roles in embryonic development, cancer, tissue regeneration, and human degenerative pathology. Studies of this signaling cascade in the regulation of cellular and tissue changes in the three-dimensional context of a developing embryo have notably advanced in the understanding of the action mechanism of these growth factors. In this review, we address the role of TGF? signaling in the developing limb, focusing on its essential function in the morphogenesis of the autopod. As we discuss in this work, modern mouse genetic experiments together with more classical embryological approaches in chick embryos, provided very valuable information concerning the role of TGF? and Activin family members in the morphogenesis of the digits of tetrapods, including the formation of phalanxes, digital tendons, and interphalangeal joints. We emphasize the importance of the Activin and TGF? proteins as digit inducing factors and their critical interaction with the BMP signaling to sculpt the hand and foot morphology

Sp6 and Sp8 transcription factors control AER formation and dorsal-ventral patterning in limb development

The formation and maintenance of the apical ectodermal ridge (AER) is critical for the outgrowth and patterning of the vertebrate limb. The induction of the AER is a complex process that relies on integrated interactions among the Fgf, Wnt, and Bmp signaling pathways that operate within the ectoderm and between the ectoderm and the mesoderm of the early limb bud. The transcription factors Sp6 and Sp8 are expressed in the limb ectoderm and AER during limb development. Sp6 mutant mice display a mild syndactyly phenotype while Sp8 mutants exhibit severe limb truncations. Both mutants show defects in AER maturation and in dorsal-ventral patterning. To gain further insights into the role Sp6 and Sp8 play in limb development, we have produced mice lacking both Sp6 and Sp8 activity in the limb ectoderm. Remarkably, the elimination or significant reduction in Sp6;Sp8 gene dosage leads to tetra-amelia; initial budding occurs, but neither Fgf8 nor En1 are activated. Mutants bearing a single functional allele of Sp8 (Sp6-/-;Sp8+/-) exhibit a split-hand/foot malformation phenotype with double dorsal digit tips probably due to an irregular and immature AER that is not maintained in the center of the bud and on the abnormal expansion of Wnt7a expression to the ventral ectoderm. Our data are compatible with Sp6 and Sp8 working together and in a dose-dependent manner as indispensable mediators of Wnt/βcatenin and Bmp signaling in the limb ectoderm. We suggest that the function of these factors links proximal-distal and dorsal-ventral patterning

Endocytosis of Hedgehog through Dispatched Regulates Long-Range Signaling

SummaryThe proteins of the Hedgehog (Hh) family are secreted proteins exerting short- and long-range control over various cell fates in developmental patterning. The Hh gradient in Drosophila wing imaginal discs consists of apical and basolateral secreted pools, but the mechanisms governing the overall establishment of the gradient remain unclear. We investigated the relative contributions of endocytosis and recycling to control the Hh gradient. We show that, upon its initial apical secretion, Hh is re-internalized. We examined the effect of the resistance-nodulation-division transporter Dispatched (Disp) on long-range Hh signaling and unexpectedly found that Disp is specifically required for apical endocytosis of Hh. Re-internalized Hh is then regulated in a Rab5- and Rab4-dependent manner to ensure its long-range activity. We propose that Hh-producing cells integrate endocytosis and recycling as two instrumental mechanisms contributing to regulate the long-range activity of Hh

Effect of particle size in aggregated and agglomerated ceramic powders

International audienceThis work describes the compaction of agglomerated and aggregated ceramic powders with special emphasis on the role of primary particle size. Discrete element simulations are used to model weakly bonded agglomerates as well as strongly bonded aggregates. Crushing tests are carried out to obtain the characteristic strength of single agglomerate and aggregate. Microstructure evolution and stress-strain curves indicate that aggregates undergo a brittle to plastic-like transition as particle size decreases below 50 nm. It is shown that agglomerates made of nanoparticles exhibit much greater strength than those made of micron-sized particles, with an approximately inverse linear relationship with primary particle size. Simulation of the uniaxial compaction of a representative volume element of powder demonstrates that adhesive effects are responsible for the difficulty to compact nanopowders and for the heterogeneity of microstructure prior to sintering

Green strength of binder-free ceramics

International audienceThe Discrete Element Method (DEM) is used to investigate the compaction of ceramic powders by focusing on the role of primary particle and aggregate sizes. Hard aggregates of primary particles are represented as a collection of spherical particles bonded together by solid necks, which may break during compaction. Numerical simulations are performed to investigate the effect aggregate microstructure both on compaction and on the green strength of the ceramic compact. Tensile green strength originates only from van der Waals adhesion, without any action of a binder. It is shown that in such conditions, the green strength is inversely proportional to the size of the primary particles. The size of aggregates also plays a role, with smaller aggregates leading to larger green strength. The results of the simulations are compared to experimental data obtained on dioxide uranium aggregated powders, confirming the particle size effect. (C) 2012 Elsevier Ltd. All rights reserved