Glucocorticoid receptor in astrocytes regulates midbrain dopamine neurodegeneration through connexin hemichannel activity

The precise contribution of astrocytes in neuroinflammatory process occurring in Parkinson's disease (PD) is not well characterized. In this study, using GR(Cx30CreERT2) mice that are conditionally inactivated for glucocorticoid receptor (GR) in astrocytes, we have examined the actions of astrocytic GR during dopamine neuron (DN) degeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results show significantly augmented DN loss in GR(Cx30CreERT2) mutant mice in substantia nigra (SN) compared to controls. Hypertrophy of microglia but not of astrocytes was greatly enhanced in SN of these astrocytic GR mutants intoxicated with MPTP, indicating heightened microglial reactivity compared to similarly-treated control mice. In the SN of GR astrocyte mutants, specific inflammation-associated transcripts ICAM-1, TNF-alpha and Il-1 beta as well as TNF-alpha protein levels were significantly elevated after MPTP neurotoxicity compared to controls. Interestingly, this paralleled increased connexin hemichannel activity and elevated intracellular calcium levels in astrocytes examined in acute midbrain slices from control and mutant mice treated with MPP+. The increased connexin-43 hemichannel activity was found in vivo in MPTP-intoxicated mice. Importantly, treatment of MPTP-injected GR(Cx30CreERT2) mutant mice with TAT-Gap19 peptide, a specific connexin-43 hemichannel blocker, reverted both DN loss and microglial activation; in wild-type mice there was partial but significant survival effect. In the SN of postmortem PD patients, a significant decrease in the number of astrocytes expressing nuclear GR was observed, suggesting the participation of astrocytic GR deregulation of inflammatory process in PD. Overall, these data provide mechanistic insights into GR-modulated processes in vivo, specifically in astrocytes, that contribute to a pro-inflammatory state and dopamine neurodegeneration in PD pathology

Ka-Band down converter and up converter in MCM-C technology for future telecommunication equipment

Over recent years, the miniaturization of R.F, and L.F. functions and the developments were running around the MCM technology. This paper presents the work made, then the results, to get new MCM-C generic components for use as building blocks in future Ka-Band equipment. The results show an actual reduction of weight and volume in comparison with the already advanced design made from separate micro-packages and a multi-layer polyimidc PCB for the low frequency part. This is achieved at equivalent electrical performances

Vitrification of HLLW Surrogate Solutions Containing Sulfate in a Direct-Induction Cold Crucible Melter -9136

ABSTRACT Efforts were made in the People's Republic of China to solidify legacy high level liquid waste (HLLW) by the Liquid-Fed Ceramic Melter process (LFCM) in the 1990s. This process was to be a continuous process with high throughput as in the French Marcoule Vitrification Plant (AVM) or the LFCM. In this context, the CEA (Commissariat à l'Energie Atomique is a French government-funded technological research organization) suggests the Cold Crucible Induction Melter (CCIM) technology that has been developed by the CEA since the 1980s to improve the performance of the vitrification process. In this context a series of vitrification tests has been carried out in a CCIM. CEA and AREVA have designed an integrated platform based on the CCIM technology on a sufficient scale to be used for demonstration programs of the one-step process. In 2003 a test was carried out at Marcoule in southern France on simulated HLLW with high sulfur content. In order to ensure the tests performed at Marcoule were consistent with the Chinese wasteforms, the glass frit was supplied by a Chinese Industry. The CCIM facility is described in detail, including process instrumentation. The test run is also described, including how the solution was directly fed on the surface of the molten glass. A maximum capacity was determined according to the applied process parameters including the high operating temperature. The electrical power supply characteristics are detailed and a glass mass balance is also presented covering more than seven hundred kilograms of glass produced in a sixty-hour test run

Performances and reliability predictions of optical data transmission links using a system simulator for aerospace applications

International audienceSpace missions for Earth Observation are called upon to carry a growing number of instruments in their payload, whose performances are increasing. Future space systems are therefore intended to generate huge amounts of data and a key challenge in coming years will therefore lie in the ability to transmit that significant quantity of data to ground. Thus very high data rate Payload Telemetry (PLTM) systems will be required to face the demand of the future Earth Exploration Satellite Systems and reliability is one of the major concern of such systems. An attractive approach associated with the concept of predictive modeling consists in analyzing the impact of components malfunctioning on the optical link performances taking into account the network requirements and experimental degradation laws. Reliability estimation is traditionally based on life-testing and a basic approach is to use Telcordia requirements (468GR) for optical telecommunication applications. However, due to the various interactions between components, operating lifetime of a system cannot be taken as the lifetime of the less reliable component. In this paper, an original methodology is proposed to estimate reliability of an optical communication system by using a dedicated system simulator for predictive modeling and design for reliability. At first, we present frameworks of point-to-point optical communication systems for space applications where high data rate (or frequency bandwidth), lower cost or mass saving are needed. Optoelectronics devices used in these systems can be similar to those found in terrestrial optical network. Particularly we report simulation results of transmission performances after introduction of DFB Laser diode parameters variations versus time extrapolated from accelerated tests based on terrestrial or submarine telecommunications qualification standards. Simulations are performed to investigate and predict the consequence of degradations of the Laser diode (acting as a - requency carrier) on system performances (eye diagram, quality factor and BER). The studied link consists in 4×2.5 Gbits/s WDM channels with direct modulation and equally spaced (0,8 nm) around the 1550 nm central wavelength. Results clearly show that variation of fundamental parameters such as bias current or central wavelength induces a penalization of dynamic performances of the complete WDM link. In addition different degradation kinetics of aged Laser diodes from a same batch have been implemented to build the final distribution of Q-factor and BER values after 25 years. When considering long optical distance, fiber attenuation, EDFA noise, dispersion, PMD, ... penalize network performances that can be compensated using Forward Error Correction (FEC) coding. Three methods have been investigated in the case of On-Off Keying (OOK) transmission over an unipolar optical channel corrupted by Gaussian noise. Such system simulations highlight the impact of component parameter degradations on the whole network performances allowing to optimize various time and cost consuming sensitivity analyses at the early stage of the system development. Thus the validity of failure criteria in relation with mission profiles can be evaluated representing a significant part of the general PDfR effort in particular for aerospace applications

3D active modules for high integration active antennas

This paper describes the different parts of active antenna sub-systems currently developed in Alcatel Espace. These modules are realized according to some new 3D RF packaging technologies, mainly based on moulding assembly

Coating conductive or semiconductive materials by polymerization of monomers on the surfaces.

Conductive and semiconductive materials are coated with 0.1-100-μm polymer anticorrosive films by (1) grafting diazonium salts having groups that function as polymn. initiators onto the surface and (2) radical or ring-opening polymn. of the monomers on the surface. Thus, an Fe electrode was electrolytically grafted with p-BrCHMeC6H4N2BF4, and Me methacrylate was polymd. by ATRP on the grafted surface

Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth

Mice carrying a hepatocyte-specific inactivation of the glucorticoid receptor (GR) gene show a dramatic reduction in body size. Growth hormone signaling mediated by the Stat5 transcription factors is impaired. We show that Stat5 proteins physically interact with GR and GR is present in vivo on Stat5-dependent IGF-I and ALS regulatory regions. Interestingly, mice with a DNA-binding-deficient GR but an unaltered ability to interact with STAT5 (GR(dim/dim)) have a normal body size and normal levels of Stat5-dependent mRNAs. These findings strongly support the model in which GR acts as a coactivator for Stat5-dependent transcription upon GH stimulation and reveal an essential role of hepatic GR in the control of body growth