Numerical Simulation and Optimization of the Forging Process

International audienceThe objective of optimizing automatically industrial forming conditions in order to achieve a desired objective goal is now possible due to continuous increase of fast and parallel computers. Optimization requires that the computer simulation is accurate enough, that the material behavior is precisely identified and that the optimization parameters are properly selected. To achieve the first goal, the fundamental mechanical assumptions and the basic principles of three-dimensional finite element discretization are briefly recalled. Several important numerical developments for efficient computation of large plastic deformation are mentioned. The second requirement is fulfilled not only by experimental tests and identification of the material parameters of the constitutive law. Is it also necessary to predict the possible onset of defects such as cracking by introducing damage modeling. Before optimization, a parameter sensitivity analysis must be performed in order to select the most important factors: shape of the preform, tools geometry, etc. The practical optimization can be carried out by a evolutionary algorithm technique associated with a surface response method. Several examples of applications will be presented to illustrate the effectiveness of the procedure with the FORGE3 computer code. The optimization criterion can be on the forming force, on the material weight or on the final strength of the part

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels.

Changes in fetal DNA methylation (DNAm) of the leptin (LEP) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5-C-phosphate-G-3 (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother-child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia (p ≤ 0.002). Of these, cg05136031 and cg15758240 were also associated with BMI (β = -2.69, p = 0.05) and fat distribution (β = -0.581, p = 0.05) at 3-years-old, respectively. Maternal glycemia was associated with DNAm at cg15758240 (β = -0.01, p = 0.04) and neonatal leptinemia (β = 0.19, p = 0.004). DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycemia and neonatal leptinemia (p < 0.001). Our results support that DNAm regulation of the leptin pathway in response to maternal glycemia might be involved in programming adiposity in childhood

Monocyte depletion increases local proliferation of macrophage subsets after skeletal muscle injury

Background : Sequential accumulation of M1 and M2 macrophages is critical for skeletal muscle recovery after an acute injury. While M1 accumulation is believed to rely on monocyte infiltration, the mechanisms of M2 accumulation remain controversial, but could involve an infiltrating precursor. Yet, strong depletion of monocytes only partiallt impairs skeletal muscle healing, supporting the existence of alternative mechanisms to palliate the loss of infiltrating macrophage progenitors. The aims of this study are thus to investigate if proliferation occurs in macrophage subsets within injured skeletal muscles; and to determine if monocyte depletion leads to increased proliferation of macrophages after injury. Methods : Injury was induced by bupivacaine injection in the tibialis anterior muscle of rats. Blood monocytes were depleted by daily intravenous injections of liposome-encapsulated clodronate, starting 24 h prior to injury. In separate experiments, irradiation of hind limb was also performed to prevent resident cell proliferation. Upon euthanasia, blood and muscles were collected for flow cytometric analyses of macrophage/monocyte subsets. Results : Clodronate induced a 80%-90% depletion of monocyte but only led to 57% and 41% decrease of M1 and M2 macrophage accumulation, respectively, 2 d following injury. Conversely, the number of M1 macrophages in monocyte-depleted rats was 2.4-fold higher than in non-depleted rats 4 d after injury. This was associated with a 16-fold increase in the number of proliferative M1 macrophages, which was reduced by 46% in irradiated animals. Proliferation of M2 macrophages was increased tenfold by clodronate treatment 4 d post injury. The accumulation of M2 macrophages was partially impaired by irradiation, regardless of monocyte depletion. Conclusions : M1 and M2 subsets proliferate after skeletal muscle injury and their proliferation is enhanced under condition of monocyte depletion. Our study supports the conclusion that both infiltrating and resident precursors could contribute to M1 or M2 macrophage accumulation in muscle injury

Optimization of Metal Forming Processes for Improving Final Mechanical Strength

Available on: http://congress.cimne.com/complas2011/proceedings/International audienceThe fundamental mechanical assumptions and the basic principles of 3-dimensional FE discretization are briefly summarized. Several important numerical developments for efficient and accurate computation of large plastic deformation are discussed. Material behavior must be known precisely: material parameters of the constitutive law, thermal law and friction law must be determined by experimental tests and identification procedures by inverse modeling. Is it also necessary to avoid the possible onset of defects, such as crack opening, by introducing damage modeling in the cost function. A parameter sensitivity analysis is utilized in order to select the most important factors: shape of the preform, tools geometry, etc. The practical optimization is carried out by a genetic algorithm technique or by a surface response method. Moreover, for assessing the fatigue behavior, a more local approach is necessary in order to take into account material evolution at the micro scale

Analyse du champ électrostatique d'un nuage d'orage lors d'un fourdroiement en vol d'un Flacon 20

International audienceSince the 70’s, ONERA has been involved in the understanding and characterization of the physical processes occurring during a lightning strike to the aircraft which has led to the development of on board sensors for atmospheric characterization. In the 80’s, a first electric field mill network had been designed to measure the electrostatic field inside thundercloud. The system was installed on a CONVAIR (CV580) and a TRANSALL (C160). A new version of this electric field mill network, called AMPERA (Atmospheric Measurement of Potential and ElectRic field on Aircraft), has been developed since 2010. From September to October 2018, an in-flight campaign was performed over Corsica (France) in the framework of EXAEDRE (EXploiting new Atmospheric Electricity Data for Research and the Environment) project to investigate the electrical activity in thunderstorm. During this campaign, 8 scientific flights were done with a FALCON 20 (F20) of SAFIRE inside or in the vicinity of thunderstorm. During the flight of the 8 of October 2018, the aircraft was struck by lightning at an altitude of 8500m. The electrostatic field time variations show that a vertical electric polarization of the aircraft occurred just before the lightning strike. The inverse method to compute the components of the atmospheric electric field from the data of the electric field network is presented. The atmospheric electric field time evolution is shown. The value of the atmospheric electric field just before the lightning strike is about 90kV/m. This electric field value has been processed to be compared with the ones measured during TRANSALL campaigns. The altitude effect is taken into account by computing the reduced electric field (Electric field divided by air density). The comparison is presented taking into account the size of the aircraft and the electric field direction. To conclude a discussion is done on the electric field threshold for a lightning strike to aircraft.Dans les années 70, l'ONERA a mené des recherches pour caractériser et comprendre les processus physiques intervenant lors d'un foudroiement en vol d'un avion ce qui a conduit au développement de capteurs pour caractériser l'atmosphère. Dans les années 80, une première version de moulin à champ a été conçue pour mesurer les composantes du champ électrostatique à l'intérieur du nuage depuis un avion. Le système a été installé sur une CONVAIR (CV580) et sur un TRANSALL (C160). Une nouvelle version du système, appelé AMPERA (Atmospheric Measurement of Potential and ElectRic field on Aircraft), a été développée depuis 2010. De septembre à octobre 2018, une campagne en vol a été réalisée en Corse (France) dans le cadre du projet ANR EXAEDRE (EXploiting new Atmospheric Electricity Data for Research and the Environment) pour étudier l'activité électrique des orages.Pendant cette campagne, 8 vols scientifiques ont été réalisés par a FALCON 20 (F20) de SAFIRE à l'intérieur ou à proximité d'un nuage orageux. Pendant le vol du 8 octobre, l'avion a été foudroyé à une altitude de 8500 m. La variation temporelle du champ électrostatique montre que l'avion est polarisé verticalement au moment du foudroiement. La méthode inverse pour calculer les composantes du champ électrostatique est présentée. La valeur du champ atmosphérique au moment du foudroiement est de 90 kV/m. Ce champ électrique a été normalisé pour être comparé aux champs électriques mesurés lors des campagnes TRANSALL. L'effet de l'altitude a été prise en compte en calculant le champ électrique réduit (Champ électrique divisé par la densité de l'air). La taille de l'avion et la direction du champ électrique a été pris en compte pour la comparaison. Pour conclure, une discussion sur le seuil du champ électrique pour déclencher un foudroiement sur un avion

Purification and characterization of a protein tyrosine phosphatase containing SH2 domains.

A protein tyrosine phosphatase (PTP) containing two SH2 domains (PTP1C) was purified to near homogeneity from an adenovirus expression system by a two-step chromatographic procedure with a yield of 67%. The purified enzyme behaves as a monomer of 68 kDa on gel filtration and is totally specific for phosphotyrosyl residues. Its optimal pH is around neutrality for protein substrates such as reduced, carboxyamidomethylated, maleylated (RCM)-lysozyme and myelin basic protein but below 5 for low molecular weight compounds such as para-nitrophenyl phosphate (p-NPP) and phosphotyrosine. Furthermore, with the protein substrates, it displays an activity less than 1% of that obtained with other known PTPs but comparable activities toward p-NPP and phosphotyrosine. Its responsiveness toward the usual PTP activators (e.g. spermine) or inhibitors (e.g. vanadate, molybdate, heparin, or Zn2+) varied considerably with the nature of the substrates involved. Limited digestion with trypsin caused the cleavage of a C-terminal segment of the enzyme, giving rise to a 63-kDa fragment; this cleavage resulted in an approximately 20- and 10-fold activation of the enzyme toward RCM-lysozyme and myelin basic protein, respectively

Identification of New Targets Used by 15-deoxy-delta-12,14-Prostaglandin J2 to Stimulate Skeletal Muscle Cell Proliferation

Introduction: Clinical conduct can influence the healing of injured tissue. Eradication of inflammation seemed a promising strategy to promote musculoskeletal healing until studies showed a delayed/incomplete recovery from partial or complete elimination of inflammation. Endogenous lipid mediators biosynthesized from omega-3 and some from -6 fatty acids are molecules potentially playing important roles in the resolution of inflammation. Using such lipid mediators to treat injuries represents an attractive approach due to their anti-inflammatory and pro-resolving roles. Our goal was to identify the intracellular and/or extracellular targets used by 15-deoxy-delta-12,14-Prostaglandin J2(15Δ-PGJ2) to stimulate myoblast proliferation. Methods: Expression of D prostanoid (DP) 1 and 2 receptors was evaluated by western blotting. Proliferation of L6 myoblasts incubated with agonists and antagonists of prostaglandin (PG) D2 receptors DP1 and DP2 and of the peroxisome proliferator-activated receptor (PPAR) δ was assessed. Intracellular and extracellular concentrations of 15Δ-PGJ2 following L6 cell activation with protease-activated receptor (PAR)-2 agonist were measured by liquid chromatography coupled to tandem mass spectrometry. Results: Both DP1 and DP2 receptors are present in myoblasts. DP1 agonist did not modulate L6 myoblast proliferation, but DP2 and PPARδ agonists induced an increase. DP1 and DP2 antagonists both significantly inhibited 15Δ-PGJ2-induced stimulating effect of L6 cell proliferation (60% and 75%, respectively). 15Δ-PGJ2was present in the intracellular and extracellular compartments under basal conditions, but was not modulated by PAR-2 receptor activation. Conclusion: L6 muscle cell can produce 15Δ-PGJ2 and its effect on cell proliferation likely relies on both DP1 and DP2 receptor activation

Maternal lipid profile differs by gestational diabetes physiologic subtype

Aim To characterize lipid profiles in women with different gestational diabetes mellitus (GDM) physiologic subtypes. Methods We measured seven lipid markers (total cholesterol, LDL, HDL, triglycerides, non-esterified fatty acids (NEFA), ApoA, ApoB) in fasting plasma collected in a prospective cohort of 805 pregnant women during second trimester. We estimated insulin sensitivity and secretion using oral glucose tolerance test-based validated indices. We categorized GDM physiologic subtypes by insulin sensitivity and secretion defects defined as values below the 25th percentile among women with normal glucose tolerance (NGT), as previously established. We compared lipid markers across NGT and GDM subtypes. We explored associations between lipid markers and newborn anthropometry in the overall group and stratified by glucose tolerance status. Results Among 805 women, 67 (8.3%) developed GDM. Women with GDM had higher body mass index (BMI; 29.3 vs. 26.6 kg/m2), while ethnicity (97.3% vs. 97.0% European ancestry) and age (28 vs. 29 years) were similar. In comparison to women with NGT, women with GDM characterized by a predominant insulin sensitivity defect had significantly higher triglycerides (2.20 vs. 1.82, P = 0.002), lower HDL (1.64 vs. 1.90, P = 0.01) and higher NEFA (0.34 vs. 0.24, P < 0.0001). GDM women with a predominant insulin secretion defect differed from women with NGT with respect to NEFA (0.32 vs. 0.24, P = 0.003) while other lipid markers were similar. These associations remained significant after adjusting for maternal age and BMI. Greater maternal levels of NEFA were associated with higher birth weight z-scores in women with an insulin secretion defect (BMI-adjusted r = 0.58, P = 0.01). We did not find significant associations between other lipid markers and newborn anthropometry in other groups. Conclusion Women with GDM have distinct lipid profiles based on their GDM physiologic subtype which may not be apparent when investigating GDM as a single group