MHD instability analysis of a large scale electromagnetic pump for pemdyn facility.

International audienceThis paper focuses on numerical and experimental investigation of magnetohydrodynamic (MHD) instability which can occur in an electromagnetic induction pump (EMIP) in regimes when slip Magnetic Reynolds number (Rms) is sufficiently high. It has been reported that MHD instability produces strong non-homogeneity of flow, low frequency pressure pulsations, vibrations and drop of developed pressure therefore it should be regarded as highly unwanted phenomenon. Detailed studies of this problem must be carried out to develop better understanding about working regimes and master control of EMIP

Experimental and numerical analyses of the magnetic field spatial measurement inside an electromagnetic pump channel duct

International audienceThis article is a summary of a full paper that will be presented at the XInternational PAMIR International Conference - Fundamental and Applied MHD, to be heldfrom 20 – 24 June, in Cagliari, Italy.In the framework of the ASTRID R&D programme, it has been proposed to use anelectromagnetic (EM) induction pump in the secondary cooling system. This paper describesthe current status of the experimental and numerical analysis in progress to investigate liquidsodium flow instabilities in the PEMDYN loop with the objective of better managing the EMpump and preventing magnetohydrodynamic (MHD) instability. This paper discusses theanalysis of 3D measurements of the magnetic fields along a path inside the annular linearinduction pump (ALIP) channel measured with a Hall sensor. It also describes the numericalfinite-element models that have been built to gain a more in-depth understanding of theinterdependent MHD phenomena specific to EM pump operation. These measurements wereobtained before the operative condition so as to retrieve as much information as possible onthe EM field inside the channel pump without the fluid dynamic

Pyrrolidine dithiocarbamate activates the Nrf2 pathway in astrocytes

BACKGROUND: Endogenous defense against oxidative stress is controlled by nuclear factor erythroid 2-related factor 2 (Nrf2). The normal compensatory mechanisms to combat oxidative stress appear to be insufficient to protect against the prolonged exposure to reactive oxygen species during disease. Counterbalancing the effects of oxidative stress by up-regulation of Nrf2 signaling has been shown to be effective in various disease models where oxidative stress is implicated, including Alzheimer's disease. Stimulation of Nrf2 signaling by small-molecule activators is an appealing strategy to up-regulate the endogenous defense mechanisms of cells. METHODS: Here, we investigate Nrf2 induction by the metal chelator and known nuclear factor-κB inhibitor pyrrolidine dithiocarbamate (PDTC) in cultured astrocytes and neurons, and mouse brain. Nrf2 induction is further examined in cultures co-treated with PDTC and kinase inhibitors or amyloid-beta, and in Nrf2-deficient cultures. RESULTS: We show that PDTC is a potent inducer of Nrf2 signaling specifically in astrocytes and demonstrate the critical role of Nrf2 in PDTC-mediated protection against oxidative stress. This induction appears to be regulated by both Keap1 and glycogen synthase kinase 3β. Furthermore, the presence of amyloid-beta magnifies PDTC-mediated induction of endogenous protective mechanisms, therefore suggesting that PDTC may be an effective Nrf2 inducer in the context of Alzheimer's disease. Finally, we show that PDTC increases brain copper content and glial expression of heme oxygenase-1, and decreases lipid peroxidation in vivo, promoting a more antioxidative environment. CONCLUSIONS: PDTC activates Nrf2 and its antioxidative targets in astrocytes but not neurons. These effects may contribute to the neuroprotection observed for PDTC in models of Alzheimer's disease

Experimental and numerical analyses of the magnetic field spatial measurement inside an electromagnetic pump channel duct

International audienceIn the framework of the French Alternative Energies and Atomic Energy Commission (AEC) R&D program developing theAdvanced Sodium Technological Reactor for Industrial Demonstration (ASTRID), it has been proposed to use in secondarycooling circuit an electromagnetic induction pump (EMP) due to its superior safety features such as: no moving parts inliquid metal and absolutely hermetic construction. However, detailed studies should be carried out in order to masteroperation of EMP and prevent undesirable phenomenon called MHD instability, which influence both the pump efficiencyand operation

The LIEBE high-power target: Offline commissioning results and prospects for the production of 100^{100} Sn ISOL beams at HIE-ISOLDE

With the aim of increasing the primary beam intensity in the next generation Radioactive Ion Beam facilities, a major challenge is the production of targets capable of dissipating high beam power, particularly for molten targets. In that context, a direct molten loop target concept was proposed for short-lived isotopes for EURISOL. The circulation of molten metal enables the production of droplets enhancing the radioisotope diffusion. The concept also includes a heat exchanger ensuring thermal equilibrium under interaction with high proton beam power. A target prototype, named LIEBE, has been designed and assembled to validate this concept in the ISOLDE operation environment. The project is now in an offline commissioning phase in order to confirm the design specifications before tests under proton beam. Successful outcome of the project can lead to new beams with great interest in nuclear structure and physics studies. In particular, investigations fall short in the region around the double magic isotope 100Sn at ISOL facilities because of the lack of a suitable primary beam driver and target-ion source unit for any of the present-day facilities. Achievable 100Sn beam intensities and purities are calculated with ABRABLA and FLUKA considering the use of a high power molten lanthanum target combined with molecular tin formation and a FEBIAD ion source. The presented option takes into consideration upgrade scenarios of the primary beam at ISOLDE, going from a 1.4  GeV–2 μA to a 2 GeV–4 μA pulsed proton beam

Mitochondrial Cu,Zn-Superoxide Dismutase Mediates Pulmonary Fibrosis by Augmenting H2O2 Generation*

The release of H2O2 from alveolar macrophages has been linked to the development of pulmonary fibrosis, but little is known about its source or mechanism of production. We found that alveolar macrophages from asbestosis patients spontaneously produce high levels of H2O2 and have high expression of Cu,Zn-superoxide dismutase (SOD). Because Cu,Zn-SOD is found in the mitochondrial intermembrane space (IMS), we hypothesized that mitochondrial Cu,Zn-SOD-mediated H2O2 generation contributed to pulmonary fibrosis. Asbestos-induced translocation of Cu,Zn-SOD to the IMS was unique to macrophages and dependent on functional mitochondrial respiration and the presence of at least one of the conserved cysteines required for disulfide bond formation. These conserved cysteine residues were also necessary for enzyme activation and H2O2 generation. Cu,Zn-SOD-mediated H2O2 generation was inhibited by knockdown of the iron-sulfur protein, Rieske, in complex III. The role of Cu,Zn-SOD was biologically relevant in that Cu,Zn-SOD−/− mice generated significantly less H2O2 and had less oxidant stress in bronchoalveolar lavage fluid and lung parenchyma. Furthermore, Cu,Zn-SOD−/− mice did not develop pulmonary fibrosis, and knockdown of Cu,Zn-SOD in monocytes attenuated collagen I deposition by lung fibroblasts. Our findings demonstrate a novel mechanism for the pathogenesis of pulmonary fibrosis where the antioxidant enzyme Cu,Zn-SOD translocates to the mitochondrial IMS to increase H2O2 generation in alveolar macrophages

Inhibition of TTR aggregation-induced cell death : a new role for serum amyloid P component

BACKGROUND: Serum amyloid P component (SAP) is a glycoprotein that is universally found associated with different types of amyloid deposits. It has been suggested that it stabilizes amyloid fibrils and therefore protects them from proteolytic degradation. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we show that SAP binds not only to mature amyloid fibrils but also to early aggregates of amyloidogenic mutants of the plasma protein transthyretin (TTR). It does not inhibit fibril formation of TTR mutants, which spontaneously form amyloid in vitro at physiological pH. We found that SAP prevents cell death induced by mutant TTR, while several other molecules that are also known to decorate amyloid fibrils do not have such effect. Using a Drosophila model for TTR-associated amyloidosis, we found a new role for SAP as a protective factor in inhibition of TTR-induced toxicity. Overexpression of mutated TTR leads to a neurological phenotype with changes in wing posture. SAP-transgenic flies were crossed with mutated TTR-expressing flies and the results clearly confirmed a protective effect of SAP on TTR-induced phenotype, with an almost complete reduction in abnormal wing posture. Furthermore, we found in vivo that binding of SAP to mutated TTR counteracts the otherwise detrimental effects of aggregation of amyloidogenic TTR on retinal structure. CONCLUSIONS/SIGNIFICANCE: Together, these two approaches firmly establish the protective effect of SAP on TTR-induced cell death and degenerative phenotypes, and suggest a novel role for SAP through which the toxicity of early amyloidogenic aggregates is attenuated.Epub 2013 Feb 4.</p