A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

High temperature strength of refractory complex concentrated alloys

Thermodynamic and mechanical properties of 15 single-phase and 11 multi-phase refractory complex concentrated alloys (RCCAs) are reported. Using the CALPHAD approach, phase diagrams for these alloys are calculated to identify the solidus (melting, Tm) temperatures and volume fractions of secondary phases. Correlations were identified between the strength drops at 1000 °C and 1200 °C and the alloy compositions, room temperature properties, melting temperatures and volume fractions of secondary phases. The influence of alloy density on the temperature dependence of specific yield strength was also explored. The conducted analysis suggests that the loss of high-temperature strength of single-phase BCC RCCAs is related to the activation of diffusion-controlled deformation mechanisms, which occurs at T ≥ 0.6 Tm, so that the alloys with higher Tm retain their strength to higher temperatures. On the other hand, a rapid decrease in strength of multi-phase RCCAs with increasing temperature above 1000 °C is probably due to dissolution of secondary phases

Using SALOME for sodium-cooled fast reactors coupled simulations

International audienc

Development and Validation of Multi-scale Thermal-Hydraulics Calculation Schemes for SFR Applications at CEA

Ref. IAEA-CN-245-455International audienceIn the framework of the ASTRID project for a Generation IV SFR, extensive RetD efforts are under way to improve and better validate the SFR thermal-hydraulics codes available at CEA. These efforts include:The development and validation of SFR-specific models in CATHARE. Developed at CEA, CATHARE is the current reference STH code for French LWR safety studies SFR-specific developments are being integrated and validated into the lastest version of the code, CATHARE3.The development and validation of TrioMC, a subchannel code specific to SFR core thermal-hydraulics. Initially created for design studies (with the aim of computing the maximum cladding temperature of a given core flow-rate map), TrioMC has been upgraded in order to compute the local behavior of the core during accidental transients.The application and validation of TrioCFD, a 3D, staggered-mesh CFD code developed at CEA, to SFR studies. TrioCFD is being used to compute flow behavior in the large plena of pool-type SFRs (hot and cold pools), as well as in the IHX primary side and in the in-core inter-wrapper gap regions.In most cases, these codes are used independently. However, in some cases, local phenomena may have a strong feedback effect on the global behavior of the reactor for instance, during passive decay-heat removal by natural convection, flows in the inter-wrapper gaps may contribute to up to 30% of the overall DHR if the heat sink is provided by DHXs in the hot pool. The strength of this contribution leads to a feed-back effect from a local (subchannel/CFD) phenomenon) to the global (system) scale.In order to model such effects, a coupling between CATHARE, TrioMC and TrioCFD has been developed at CEA and integrated into a new code MATHYS (Multiscale ASTRID Thermal-HYdraulics Simulation). Within MATHYS, TrioMC and TrioCFD are coupled at their boundaries (core outlet and hex-can sides), using a domain-decomposition approach then, the two codes are coupled with a CATHARE simulation of the complete system using a domain-overlapping method. The resulting multi-scale simulation is able to account for feedback effects between all three scales.This paper first outlines the development and validation efforts related to CATHARE, TrioMC and TrioCFD; then, the coupling algorithm underlying MATHYS is described. The final section discusses the validation of MATHYS overall approach, validation of coupled effects on existing experiments (TALL-3D for STH/CFD, PLANDTL-DHX for subchannel/CFD, PHENIX at the integral scale)

Une nouvelle approche dans la compréhension de l'interaction SiC/Ti

La morphologie de la zone de réaction du système SiC/Ti a été analysée par microscopie électronique à balayage. La composition des différents constituants a été déterminée par spectroscopie d'électrons Auger et par microsonde électronique. Les analyses montrent que la zone de réaction est constituée des trois composés Ti5Si3Cx, TiCx et Ti3Si. Le diagramme de phases du système Ti - Si - C a été complété à 900°C. Le suivi de l'évolution morphologique de la zone de réaction interfaciale en fonction du temps de recuit de diffusion à 900°C, a permis de déterminer la loi de croissance des particules de TiCx et de préciser les mécanismes en jeu dans l'interaction SiC/Ti

Thermoelectric properties of chromium disilicide prepared by mechanical alloying

CrSi and Cr1-x Fe (x) Si particles embedded in a CrSi2 matrix have been prepared by hot pressing from CrSi1.9, CrSi2, and CrSi2.1 powders produced by ball milling using either WC or stainless steel milling media. The samples were characterized by powder X-ray diffraction, scanning, and transmission electron microscopy and electron microprobe analysis. The final crystallite size of CrSi2 obtained from the XRD patterns is about 40 and 80 nm for SS- and WC-milled powders, respectively, whereas the size of the second phase inclusions in the hot pressed samples is about 1-5 mu m. The temperature dependence of the electrical resistivity, Seebeck coefficient, thermal conductivity, and figure of merit (ZT) were analyzed in the temperature range from 300 to 800 K. While the ball-milling process results in a lower electrical resistivity and thermal conductivity due to the presence of the inclusions and the refinement of the matrix microstructure, respectively, the Seebeck coefficient is negatively affected by the formation of the inclusions which leads to a modest improvement of ZT