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

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

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)

CFD analysis of the flow in the MICAS experimental facility, a water model of the hot pool of a sodium cooled fast reactor

International audienc

Numerical analysis of core thermal-hydraulic for sodium-cooled fast reactors

International audienceThe paper presents the numerical analysis of core thermal-hydraulic performed by CEA for Sodium-cooled Fast Reactors (SFR). The core thermal-hydraulic analyses are performed at three scales The individual sub-assembly, characterized by pin bundle with helical space wire. In the 1980s, a specific sub-channel scale model for SFR-type subassemblies was developed at CEA. In 2008, this model was re-implemented in the Trio_U CFD code, under the name Trio_U MC (Core Model), for use in design phase. Besides this sub-channel model, refined CFD models of the sub-assembly were also developed. Some examples (sodium or clad temperature inside the bundle) are presented.The whole sub-assemblies.The main objective is to determine the core steady-state hydraulic conditions, for specific objectives, such as obtaining a required mean outlet core temperature while keeping the maximum cladding temperature within a given limit in practice, this is achieved by allocating the fuel sub-assemblies among a number of flow-rate zones. The paper describes the methodology to determine the number and flow zones allocation and the corresponding mass flow rates with Trio_U MC, as well as the associated optimization process. The whole core, with sub-assemblies, inter-wrapper gaps and the hot pool plenum.A model for the interaction of the core sub-assemblies with the adjoining inter-wrapper gaps and with the hot pool plenum has been developed at CEA. Known as Trio_U MC2, it consists in a code coupling of Trio_U MC with a Trio_U CFD domain representing the inter-wrapper gaps and hot pool plenum. This model leads to tube temperatures in the reactor nominal state

Coupled Neutronics-Thermal-hydraulics Modelling of a Molten Salt Reactor : the Aircraft Reactor Experiment

International audienceThe CEA multiphysics tool combining the deterministic neutronics code APOLLO3 ® and the CFD platform TRUST/TrioCFD is used to model the first ever built molten salt nuclear reactor, the Aircraft Reactor Experiment. A neutronics and thermal-hydraulics models are created and coupled. Steady-state simulations are performed, in order to reproduce experiments realised on the ARE. Simulations results and experimental data are compared as a way of validating the multiphysics tool. Some differences are observed, which are probably due to some simplifications in the numerical model

Coupled Neutronics-Thermal-hydraulics Modelling of a Molten Salt Reactor : the Aircraft Reactor Experiment

International audienceThe CEA multiphysics tool combining the deterministic neutronics code APOLLO3 ® and the CFD platform TRUST/TrioCFD is used to model the first ever built molten salt nuclear reactor, the Aircraft Reactor Experiment. A neutronics and thermal-hydraulics models are created and coupled. Steady-state simulations are performed, in order to reproduce experiments realised on the ARE. Simulations results and experimental data are compared as a way of validating the multiphysics tool. Some differences are observed, which are probably due to some simplifications in the numerical model

Direct Forcing methods in Trio_U theory and applications

International audienc