Simulation des assemblages par déformation. Vers une approche intégrée de l'assemblage dans la phase de dimensionnement

International audienceL'augmentation de structures multimatériaux dans de nombreuses industries conduit à une utilisation de plus en plus importante des procédés d'assemblage. Nous nous intéressons ici plus particulièrement aux procédés d'assemblage ponctuels par déformations plastiques tels que les différentes familles de rivetage ou encore de clinchage. Dans l'industrie automobile par exemple, la volonté permanente d'alléger la " caisse en blanc " conduit à l'utilisation de plus en plus fréquente de métaux légers tels que les alliages d'aluminium, ou encore de tôles polymères composite. Le point de soudure, majoritairement utilisé pour l'assemblage de tôles de carrosserie, n'est alors plus adapté. Les techniques de rivetage autopoinçonneur ou encore de clinchage représentent alors des solutions idéales, alliant facilité de pose, tenue mécanique appropriée et assemblage propre (absence de fumée, de projections, de bruit, d'eau)

Directed Pancreatic Acinar Differentiation of Mouse Embryonic Stem Cells via Embryonic Signalling Molecules and Exocrine Transcription Factors

Pluripotent embryonic stem cells (ESC) are a promising cellular system for generating an unlimited source of tissue for the treatment of chronic diseases and valuable in vitro differentiation models for drug testing. Our aim was to direct differentiation of mouse ESC into pancreatic acinar cells, which play key roles in pancreatitis and pancreatic cancer. To that end, ESC were first differentiated as embryoid bodies and sequentially incubated with activin A, inhibitors of Sonic hedgehog (Shh) and bone morphogenetic protein (BMP) pathways, fibroblast growth factors (FGF) and retinoic acid (RA) in order to achieve a stepwise increase in the expression of mRNA transcripts encoding for endodermal and pancreatic progenitor markers. Subsequent plating in Matrigel® and concomitant modulation of FGF, glucocorticoid, and folllistatin signalling pathways involved in exocrine differentiation resulted in a significant increase of mRNAs encoding secretory enzymes and in the number of cells co-expressing their protein products. Also, pancreatic endocrine marker expression was down-regulated and accompanied by a significant reduction in the number of hormone-expressing cells with a limited presence of hepatic marker expressing-cells. These findings suggest a selective activation of the acinar differentiation program. The newly differentiated cells were able to release α-amylase and this feature was greatly improved by lentiviral-mediated expression of Rbpjl and Ptf1a, two transcription factors involved in the maximal production of digestive enzymes. This study provides a novel method to produce functional pancreatic exocrine cells from ESC. © 2013 Delaspre et al.This work was supported by grants from the Instituto de Salud Carlos III (ISCIII)-FEDER (PI052738 and PI080511 to A.S.; PI100094 and Tercel RD06/0010/ 0025 to B.S.). A.S. was supported by ISCIII and the Health Department of the Generalitat de Catalunya; F.D. was the recipient of a Graduate Fellowship from ISCIII and was also supported by Tercel; M.M. was the recipient of a Graduate Fellowship from the Generalitat de Catalunya.Peer Reviewe

G-protein coupled receptor 88 knock-down in the associative striatum reduces the psychiatric symptoms in a translational model of Parkinson's disease

Running title: Gpr88 gene therapy for PD psychiatric symptoms

Traditional vs Gesture Based UAV Control

Abstract. The purpose of this investigation was to assess user preferences for controlling an autonomous system. A comparison using a virtual environment (VE) was made between a joystick based, game controller and a gesture-based system using the leap motion controller. Command functions included basic flight maneuvers and switching between the operator and drone view. Comparisons were made between the control approaches using a representative quadcopter drone. The VE was designed to minimize the cognitive loading and focus on the flight control. It is a physics-based flight simulator built in Unity3D. Participants first spend time familiarizing themselves with the basic controls and vehicle response to command inputs. They then engaged in search missions. Data was gathered on time spent performing tasks, and post test interviews were conducted to uncover user preferences. Results indicate that while th

Development of a conditionally immortalized human pancreatic β cell line

International audienceDiabetic patients exhibit a reduction in β cells, which secrete insulin to help regulate glucose homeostasis; however, little is known about the factors that regulate proliferation of these cells in human pancreas. Access to primary human β cells is limited and a challenge for both functional studies and drug discovery progress. We previously reported the generation of a human β cell line (EndoC-βH1) that was generated from human fetal pancreas by targeted oncogenesis followed by in vivo cell differentiation in mice. EndoC-βH1 cells display many functional properties of adult β cells, including expression of β cell markers and insulin secretion following glucose stimulation; however, unlike primary β cells, EndoC-βH1 cells continuously proliferate. Here, we devised a strategy to generate conditionally immortalized human β cell lines based on Cre-mediated excision of the immortalizing transgenes. The resulting cell line (EndoC-βH2) could be massively amplified in vitro. After expansion, transgenes were efficiently excised upon Cre expression, leading to an arrest of cell proliferation and pronounced enhancement of β cell–specific features such as insulin expression, content, and secretion. Our data indicate that excised EndoC-βH2 cells are highly representative of human β cells and should be a valuable tool for further analysis of human β cells

Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells

Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches

Suppression of Epithelial to Mesenchymal Transitioning (EMT) Enhances Ex Vivo Reprogramming of Human Exocrine Pancreatic Tissue towards Functional Insulin Producing β-Like Cells

Because of the lack of tissue available for islet transplantation, new sources of β-cells have been sought for the treatment of type 1 diabetes. The aim of this study was to determine whether the human exocrine-enriched fraction from the islet isolation procedure could be reprogrammed to provide additional islet tissue for transplantation. The exocrine-enriched cells rapidly dedifferentiated in culture and grew as a mesenchymal monolayer. Genetic lineage tracing confirmed that these mesenchymal cells arose, in part, through a process of epithelial-to-mesenchymal transitioning (EMT). A protocol was developed whereby transduction of these mesenchymal cells with adenoviruses containing Pdx1, Ngn3, MafA, and Pax4 generated a population of cells that were enriched in glucagon-secreting α-like cells. Transdifferentiation or reprogramming toward insulin-secreting β-cells was enhanced, however, when using unpassaged cells in combination with inhibition of EMT by inclusion of Rho-associated kinase (ROCK) and transforming growth factor-β1 inhibitors. Resultant cells were able to secrete insulin in response to glucose and on transplantation were able to normalize blood glucose levels in streptozotocin diabetic NOD/SCID mice. In conclusion, reprogramming of human exocrine-enriched tissue can be best achieved using fresh material under conditions whereby EMT is inhibited, rather than allowing the culture to expand as a mesenchymal monolayer