Contrasting effects of peroxisome-proliferator-activated receptor (PPAR)γ agonists on membrane-associated prostaglandin E(2 )synthase-1 in IL-1β-stimulated rat chondrocytes: evidence for PPARγ-independent inhibition by 15-deoxy-Δ(12,14)prostaglandin J(2)

Microsomal prostaglandin E synthase (mPGES)-1 is a newly identified inducible enzyme of the arachidonic acid cascade with a key function in prostaglandin (PG)E(2 )synthesis. We investigated the kinetics of inducible cyclo-oxygenase (COX)-2 and mPGES-1 expression with respect to the production of 6-keto-PGF(1α )and PGE(2 )in rat chondrocytes stimulated with 10 ng/ml IL-1β, and compared their modulation by peroxisome-proliferator-activated receptor (PPAR)γ agonists. Real-time PCR analysis showed that IL-1β induced COX-2 expression maximally (37-fold) at 12 hours and mPGES-1 expression maximally (68-fold) at 24 hours. Levels of 6-keto-PGF(1α )and PGE(2 )peaked 24 hours after stimulation with IL-1β; the induction of PGE(2 )was greater (11-fold versus 70-fold, respectively). The cyclopentenone 15-deoxy-Δ(12,14)prostaglandin J(2 )(15d-PGJ(2)) decreased prostaglandin synthesis in a dose-dependent manner (0.1 to 10 μM), with more potency on PGE(2 )level than on 6-keto-PGF(1α )level (-90% versus -66% at 10 μM). A high dose of 15d-PGJ(2 )partly decreased COX-2 expression but decreased mPGES-1 expression almost completely at both the mRNA and protein levels. Rosiglitazone was poorly effective on these parameters even at 10 μM. Inhibitory effects of 10 μM 15d-PGJ(2 )were neither reduced by PPARγ blockade with GW-9662 nor enhanced by PPARγ overexpression, supporting a PPARγ-independent mechanism. EMSA and TransAM(® )analyses demonstrated that mutated IκBα almost completely suppressed the stimulating effect of IL-1β on mPGES-1 expression and PGE(2 )production, whereas 15d-PGJ(2 )inhibited NF-κB transactivation. These data demonstrate the following in IL-1-stimulated rat chondrocytes: first, mPGES-1 is rate limiting for PGE(2 )synthesis; second, activation of the prostaglandin cascade requires NF-κB activation; third, 15d-PGJ(2 )strongly inhibits the synthesis of prostaglandins, in contrast with rosiglitazone; fourth, inhibition by 15d-PGJ(2 )occurs independently of PPARγ through inhibition of the NF-κB pathway; fifth, mPGES-1 is the main target of 15d-PGJ(2)

Diffusion-controlled liquid bismuth induced intergranular embrittlement of copper

The consequences of the contact between liquid bismuth and a copper bicrystal are investigated at 500°C. Atoms of bismuth are shown to penetrate and embritlle the copper grain boundary. Grain boundary concentration profiles of bismuth are obtained on fracture surfaces by both Auger electron spectroscopy and He4+ Rutherford backscattering spectroscopy. The maximum bismuth intergranular concentration is calculated from experimental data to be about 1.7 monolayers (near the liquid bismuth / solid copper interface). The overall profiles are significantly different from typical erfc profiles and an interpretation is proposed, based on the coupling effect between grain boundary diffusion and non-linear segregation. These results allow us to conclude on the absence of grain boundary wetting for the Cu / Bi system at 500°C

Progress Report on Target Development

The present document is the D08 deliverable report of work package 1 (Target Development) from the MEGAPIE TEST project of the 5th European Framework Program. Deliverable D08 is the progress report on the activities performed within WP 1. The due date of this deliverable was the 5th month after the start of the EU project. This coincided with a technical status meeting of the MEGAPIE Initiative, that was held in March 2002 in Bologna (Italy). The content of the present document reflects the status of the MEGAPIE target development at that stage. It gives an overview of the Target Design, the related Design Support activities and the progress of the work done for the safety assessment and licensing of the target

Pressions de sublimation de N

Des mesures précises de la pression de sublimation de N2O ont été effectuées entre 125 K et 147 K. Jusqu’à présent il n’existait pas de valeurs fiables de cette grandeur au-dessous de 146 K. De nos résultats et de mesures antérieures de chaleurs spécifiques de N2O solide nous déduisons son entropie et son enthalpie à O K : s0 = 1,43 cal mol–1 K–1, h0 = – 5 799 cal mol–1. Ces grandeurs permettent de calculer, à l’aide des capacités calorifiques, les pressions de sublimation à basse température avec une meilleure précision que les mesures expérimentales