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Rhyacian (c. 2.30–2.05 Ga) subduction-accretion and collisional processes are thought to represent an important event of crustal growth and reworking, often reported in the so-called Tranzamazonian/Eburnean granite-greenstone terranes of N/NE Brazil and West African craton. In this work, we present whole-rock geochemistry and U–Pb–Hf zircon ages for Rhyacian plutonic rocks that intrude Paleoproterozoic granite-greenstone terranes and Archean basement rocks of the Troia Massif, Borborema Province, NE Brazil. U–Pb SHRIMP zircon age of 2185 ± 4 Ma was obtained for a metatonalite sample (Mirador metatonalites). The metatonalites show geochemical affinity similar to those of adakites-like rocks, with all “classic” (slab-derived) adakitic signature (e.g. high Sr/Y, La/Yb and low HREE), but more akin to those evolved from partial melting of the metasomatized mantle wedge, followed by fractional crystallization. Zircon Hf crustal model ages of the metatonalite sample range between 2800 and 2660 Ma, evidencing that Archean crustal components contributed to its magma genesis, probably via subduction of continental-derived sediments to the mantle wedge. For potassic plutons of the Troia Massif (Bananeira suite) we obtained U–Pb SHRIMP zircon age of 2079 ± 4 Ma for a deformed quartz-monzonite with geochemical affinities similar to those derived from low-pressure partial melting of a K-rich mafic protolith. For less-deformed equigranular granites, we obtained a U–Pb LA-ICPMS zircon age of 2068 ± 5 Ma. They are high-K calc-alkaline and slightly peraluminous granites that probably derived from low-pressure partial melting of tonalitic crustal sources (metatonalites) and/or metagraywackes. Zircon Hf crustal model ages of a granite sample range from 2713 to 2535 Ma, evidencing Archean crustal contribution to magma genesis. However, two analyzed c. 2307 Ma inherited zircon grains show eHf(t) values of c. +4.87, indicating that crustal reworking of less-radiogenic Paleoproterozoic sources also participated in its genesis. Regional correlations of our results with the Paleoproterozoic record of the Troia Massif, Borborema Province and surrounding cratonic domains, suggest that the studied plutons are related to the c. 2.2–2.0 Ga Transamazonian/Eburnean orogenic cycle. The c. 2185 Ma metatonalites are associated to pre-collisional setting, while the c. 2079–2068 Ma quartz monzonites and granites evolved during collisional setting.

International audience; Experiments were performed with CH, Be, C, and SiO2 ablators interacting with high-intensity UV laser radiation (5 × 1015 W/cm2, λ = 351 nm) to determine the optimum material for hot-electron production and strong-shock generation. Significantly more hot electrons are produced in CH (up to ∼13% instantaneous conversion efficiency), while the amount is a factor of ∼2 to 3 lower in the other ablators. A larger hot-electron fraction is correlated with a higher effective ablation pressure. The higher conversion efficiency in CH is attributed to stronger damping of ion-acoustic waves because of the presence of light H ions.

Objectif de l’etude La radiotherapie stereotaxique se developpe pour les lesions primitives (carcinome hepatocellulaire) ou secondaires (metastase) du foie. Elle est proposee en cas de contre-indication a la chirurgie ou a la radiofrequence et utilisee dans notre centre depuis 2013. Notre objectif etait d’evaluer la tolerance et le controle local hepatique apres radiotherapie stereotaxique chez les patients pris en charge dans notre institution. Materiel et methode De janvier 2013 a octobre 2017, 50 patients ont ete traites par irradiation stereotaxique pour 54 lesions (28 metastases et 26 carcinomes hepatocellulaires) dans le centre hospitalier universitaire de Bordeaux. Le traitement a ete prepare par une scanographie de centrage apres pose de reperes fiduciels, compression abdominale (33,3 %) ou scanographie quadridimensionnelle (57,4 %), et realise sur accelerateur Elekta versa HD®. La dose totale etait de 45 Gy pour les carcinomes hepatocellulaires et 48 a 60 Gy pour les metastases en trois a quatre fractions. Les recidives ont ete considerees comme dans le volume en cas de progression dans le volume cible previsionnel, en bordure de volume en cas de progression a moins de 5 mm du volume cible previsionnel. Le controle local etait defini comme l’absence de recidive dans le volume ou en bordure. Les survies ont ete calculees en utilisant la methode de Kaplan–Meier. Resultats Une seule toxicite de grade IV a ete observee (ulcere gastrique) alors que 18,5 % des patients ont souffert d’une toxicite de grade I–II. Le suivi median etait de 14,8 mois [1,1–41,6]. Le volume median traite etait de 7,5 cm3 (0,1–286), avec une dose d’au plus 45 Gy pour 83 % des lesions. Huit tumeurs ont recidive dans le volume, avec une recidive metastatique diffuse intrahepatique ou a distance, une a recidive uniquement dans le volume et trois en bordure. Les probabilites de controle local etaient de 81 % et 67 % respectivement a 1 et 2 ans, celles de survie globale de 90 % et 56 % a 1 et 2 ans, sans difference significative entre les carcinomes hepatocellulaires et les metastases. La dose prescrite, le volume traite et la couverture du volume cible previsionnel n’avaient pas d’influence sur la recidive. Conclusion La radiotherapie stereotaxique hepatique a permis un taux de controle local a un an de 81 %. Les deux-tiers des recidives dans ou en bordure du volume etaient diffuses dans le foie ou a distance.

La gammagraphie (egalement appelee tir radiographique) de soudures est une operation non destructive efficace, mais qui peut etre dangereuse si elle n’est pas pratiquee dans le respect d’un corpus de regles precises et contraignantes. La zone de tirs doit etre delimitee de facon a en interdire l’acces a toute personne non habilitee. EDF œuvre a l’elimination des risques via differents leviers (materiel adapte, bonnes pratiques) tout en integrant au mieux les tirs vis-a-vis des autres operations de maintenance, afin d’augmenter la disponibilite de son parc nucleaire de production d’electricite. Cet article explore un axe original d’analyse de l’activite de tirs radiographiques : l’influence des representations de l’espace de travail et de ses utilisations. Cet article pose l’utilisation de certaines contraintes de l’espace comme elements explicatifs de difficultes dans l’activite de balisage et de realisation des tirs. Nous proposons des analyses innovantes a partir d’observations de terrain et d’une analyse theorique provenant des sciences cognitives, completees par des propositions techniques.

Imidazoline drugs exert neuroprotective effects in cerebral ischaemia models. They also have effects against mouse cerebellar and striatal neuronal death induced by N-methyl- d -aspartate (NMDA) through the blockade of NMDA currents. Here, we investigated the effects of antazoline on NMDA toxicity and current in rat hippocampal neuronal cultures, and on an in vivo model of status epilepticus. In hippocampal cultures, antazoline (30 μM) decreased NMDA-mediated neurotoxicity and also blocked the NMDA current with voltage-dependent and fast-reversible action (inhibition by 85±3% at −60 mV). Status epilepticus was induced by injecting pilocarpine (200 nmol) directly into the right pyriform cortex of male adult rats. The rats then received immediately three consecutive i.p. injections at 30-min intervals of either PBS (control group) or antazoline at 10 mg/kg (low-dose group) or at 45 mg/kg (high-dose group). During the 6-h recording, status epilepticus lasted more than 200 min in all groups. In the high-dose group only, seizures completely ceased 1 h after the third injection of antazoline, then started again 1 h later. Rats were killed 1 week later, and Cresyl Violet-stained sections of their brain were analysed for damage quantification. On the ipsilateral side to the pilocarpine injection, pyriform cortex and hippocampal CA1 and CA3 areas were significantly protected in both antazoline-treated groups, whilst prepyriform and entorhinal cortices were only in the high-dose group. On the contralateral side to the pilocarpine injection, only the hippocampal CA3 area was significantly protected in the low-dose group, but all investigated structures were in the high-dose group. In conclusion, antazoline is a potent neuroprotective drug in different models of neuronal primary culture, as previously shown in striatal and cerebellar granule neurons [Neuropharmacology 39 (2000) 2244], and here in hippocampal neurons. Antazoline is also neuroprotective in vivo in the intra-pyriform pilocarpine-induced status epilepticus model.

Astrocytes, the most abundant cell type in the central nervous system, are intimately associated with synapses. They play a pivotal role in neuronal survival and the brain inflammatory response. Some astrocytic functions are mediated by the secretion of polypeptides. Using a proteomic approach, we have identified more than 30 proteins released by cultured astrocytes. These include proteases and protease inhibitors, carrier proteins, and antioxidant proteins. Exposing astrocytes to brefeldin A, which selectively blocks secretory vesicle assembly, suppressed the release of some of these proteins. This indicates that astrocytes secrete these proteins by a classic vesicular mechanism and others by an alternative pathway. Astrocytes isolated from different brain regions secreted a similar pattern of proteins. However, the secretion of some of them, including metalloproteinase inhibitors and apolipoprotein E, was region-specific. In addition, pro-inflammatory treatments modified the profile of astrocytic protein secretion. Finally, more than two thirds of the proteins identified in the astrocyte-conditioned medium were detectable in the mouse cerebrospinal fluid, suggesting that astrocytes contribute to the cerebrospinal fluid protein content. In conclusion, this study provides the first unbiased characterization of the major proteins released by astrocytes, which may play a crucial role in the modulation of neuronal survival and function.

Apoptosis of cultured cerebellar granule neurons (CGNs) deprived of serum is prevented by K+ depolarization or moderate concentrations of N-methyl-d-aspartate (NMDA). Here, we have examined the role of the serine/threonine kinase Akt in these protective effects. The exposure of mouse CGNs to NMDA or K+ depolarization increased the phosphorylation of Akt, compared with that measured in cells incubated in a physiological K+ concentration. Only the NMDA-evoked response was reduced by inhibitors of phosphatidylinositol 3-kinase (wortmannin and LY294002) and mitogen-activated protein kinase (PD98059 and U0126). Similarly, the capacity of NMDA to inhibit apoptosis of CGNs deprived of serum was greatly reduced by these inhibitors as well as by the transfection of neurons with a catalytically inactive mutant of Akt, whereas the protective effect of K+ depolarization remained unaffected. These findings indicate that K+ depolarization and NMDA activate Akt through different signalling pathways in CGNs. Moreover, Akt mediates the anti-apoptotic effect of NMDA, but not that evoked by K+ depolarization.

This Letter presents the first experimental demonstration of the capability to launch shocks of several-hundred Mbar in spherical targets--a milestone for shock ignition [R. Betti et al., Phys. Rev. Lett. 98, 155001 (2007)]. Using the temporal delay between the launching of the strong shock at the outer surface of the spherical target and the time when the shock converges at the center, the shock-launching pressure can be inferred using radiation-hydrodynamic simulations. Peak ablation pressures exceeding 300 Mbar are inferred at absorbed laser intensities of ∼3×10(15) W/cm2. The shock strength is shown to be significantly enhanced by the coupling of suprathermal electrons with a total converted energy of up to 8% of the incident laser energy. At the end of the laser pulse, the shock pressure is estimated to exceed ∼1 Gbar because of convergence effects.

The Shock Ignition (SI) scheme (1) offers to reduce the laser requirements by relaxing the implosion phase to sub-ignition velocities and later adding an intense laser spike. Depending on laser energy, target characteristics and implosion velocity, high gains are expected (2, 3). Relevant intensities for scaled targets imploded in the velocity range from 150 to 400km/s are defined at ignition thresholds. A range of moderate implosion velocities is specified to match safe implosions. These conditions for target design are then inferred for relevant NIF and LMJ shock-ignited targets.

Shock-ignition experiments with peak laser intensities of ∼8 × 1015 W/cm2 were performed. D2 -filled plastic shells were compressed on a low adiabat by 40 of the 60 OMEGA beams. The remaining 20 beams were delayed and tightly focused onto the imploding shell to generate a strong shock. Up to 35% backscattering of laser energy was measured at the highest intensity. Hard x-ray measurements reveal a relatively low hot-electron temperature of ∼40 keV, independent of intensity and spike onset time.

SHRIMP U–Pb micro-analyses are reported for parts of complex zircons from a granulite facies enderbite from the Pium Complex in the Carajas Metallogenic Province of the Amazon Craton of Brazil. Zircons from the granulite consist of two types of grains — (a) those with oscillatory zoned cores surrounded by rims composed of two or more curved, overlapping, nebulously zoned domains distinguished by differences in cathodoluminescence intensity, and (b) grains which are composed entirely of such domains and have no obvious cores. The SHRIMP U–Pb age of 3002±14 Ma, determined for oscillatory-zoned zircon cores is interpreted as dating the parent rock of the enderbite. This age is resolved from the U–Pb age of 2859±9 Ma, determined on zircon rims, which is interpreted as a time point within the evolving granulite facies metamorphism. SHRIMP U–Pb ages of cores and rim-type zircon are generally concordant to slightly discordant where uranium contents are less than about 820 ppm, but once this value is exceeded the zircon becomes strongly discordant suggesting that a threshold value of radiation damage exists above which zircon stability with respect to Pb loss is sharply reduced. The results provide the first substantial age determination of the granulite metamorphism in the Carajas Province. The zircon U–Pb ages have not been influenced by the Transamazonian metamorphism dated at ca. 2.0–1.85 Ga from Ar–Ar and Rb–Sr mineral ages.

We have previously shown in cultured cerebellar granule neurons (Lafon-Cazal, M., Pietri, S., Culcasi, M., and Bockaert, J. (1993) Nature 364, 535-537) that upon N-methyl-D-aspartate stimulation, a nitric oxide synthase (NOS)-independent, arachidonic acid-dependent generation of superoxide free radicals (O2-.) is observed after a lag time of 10-15 min. Using the electron spin resonance spin trapping technique, we show that N-methyl-D-aspartate stimulation produced a more rapid burst of O2-. in L-arginine (L-Arg)-depleted neurons. These O2-. radicals are synthesized by NOS. KCl and kainate, which also stimulated NOS in these neurons, produced this rapid burst of O2-., which was blocked as follows: (a) in the presence of L-NG-nitro-arginine (L-Narg), and (b) by L-Arg repletion. This burst of O2-. was arachidonic acid-independent, and its time course was similar to that of nitric oxide production. It was also responsible for a weak but significant cell death that was suppressed by L-Narg and L-Arg.

Demonstrating ignition and net energy gain in the near future on MJ-class laser facilities will be a major step towards determining the feasibility of Inertial Fusion Energy (IFE), in Europe as in the United States. The current status of the French Laser MégaJoule (LMJ) programme, from the laser facility construction to the indirectly driven central ignition target design, is presented, as well as validating experimental campaigns, conducted, as part of this programme, on various laser facilities. However, the viability of the IFE approach strongly depends on our ability to address the salient questions related to efficiency of the target design and laser driver performances. In the overall framework of the European HiPER project, two alternative schemes both relying on decoupling target compression and fuel heating—fast ignition (FI) and shock ignition (SI)—are currently considered. After a brief presentation of the HiPER project's objectives, FI and SI target designs are discussed. Theoretical analysis and 2D simulations will help to understand the unresolved key issues of the two schemes. Finally, the on-going European experimental effort to demonstrate their viability on currently operated laser facilities is described.

Inertial Confinement Fusion with Shock Ignition relies on a very strong shock created by a laser pulse at an intensity of the order of 1016W/cm2. In this context, an experimental campaign at the Prague Asterix Laser System (PALS) has been carried out within the frame of the HiPER project. Two beams have been used, the first to create an extended preformed plasma (scale length of the order of hundreds of micrometers) on a planar target, the second to generate a strong shock wave. Different diagnostics were used to study both the shock breakout at the rear surface of the target and the laserplasma coupling and parametric instabilities. This paper is focused on back-scattering analysis to measure the backreflected energy and to characterize parametric instabilities such as stimulated Brillouin and Raman scattering. Our experimental data show that parametric instabilities do not play a strong role in the laser plasma coupling. Moreover, preliminary analysis of the back reflected light from the interaction region shows that less than 5% of the total incident laser energy was back-reflected, with only a small fraction of that light was originating from parametric instabilities.

We present the results of an experiment concerning laser-plasma interaction in the regime relevant to shock ignition. The interaction of high-intensity frequency tripled laser pulse with CH plasma preformed by lower intensity pre-pulse on fundamental wavelength of the kJ-class iodine laser was investigated in the planar geometry in order to estimate the coupling of the laser energy to the shock wave or parametric instabilities such as stimulated Raman or Brillouin scattering, or to the fast electrons. First the complete characterization of the hydrodynamic parameters of preformed plasma was made using crystal spectrometer to estimate the electron temperature and XUV probe to resolve the electron density profile close to the critical density region. The other part of the experiment consisted of the shock chronometry, calorimetry of the back-scattered light and hard X-ray spectrometry to evaluate the coupling to different processes. The preliminary analysis of the measurements showed rather low energy transfer of the high-intensity pulse to back-scattered light (> 5%) and no traces of any significant hot electron production were found in the X-ray spectra. © 2011 SPIE.

We introduce the concepts for the control and data handling systems of the European Solar Telescope (EST), the main functional and technical requirements for the definition of these systems, and the outcomes from the trade-off analysis to date. Concerning the telescope control, EST will have performance requirements similar to those of current medium-sized night-time telescopes. On the other hand, the science goals of EST require the simultaneous operation of three instruments and of a large number of detectors. This leads to a projected data flux that will be technologically challenging and exceeds that of most other astronomical projects. We give an overview of the reference design of the control and data handling systems for the EST to date, focusing on the more critical and innovative aspects resulting from the overall design of the telescope.

We have developed a sensitive enzymatic-immunoassay to quantify the level of gamma-enolase (a specific neuronal enzyme) which is released from cultured cells after exposure to various toxins. We show that this method can estimate selectively neuronal cell death without significantly interfering with glial cell death. Indeed, no gamma-enolase is released when glial cells are killed with free-radical producing agents. Experiments comparing the levels of neuronal cell death induced by NMDA or free-radical producing drugs, performed either by measuring gamma-enolase release or using the classical fluorescein diacetate method, yielded similar results. In addition to selectively follow neuronal death in a mixed population of neurons and glial cells, this method provides a way of determining the cell death kinetics from a single culture dish, since enolase can be measured on small samples taken from the culture medium. Finally, we propose these two methods as being complementary and useful neuronal and other cellular death indexes and also to understand the complex problem of glial influence on neuronal survival or death.

SLEEP DISORDERS MAY BE HIGHLY PREVALENT AMONG MIDDLE-AGED POPULATIONS; STUDIES HAVE REPORTED PREVALENCES RANGING FROM 10% TO 40% in working populations,1–13 with insomnia being one of the most common disorders. In addition, a 1995 study estimated the direct costs of insomnia to be more than $2 billion in France.14 Consequently, sleep disorders may be a serious public health issue because of the high prevalence of these disorders and their social and economic consequences. Poor sleep may also be associated with occupational and health-related problems, such as an increased risk of accidents, mortality, and illnesses, including, for example, coronary heart disease, diabetes, and mental disorders. Poor sleep is also associated with workplace absence due to sickness and with reduced productivity.15–18 The causes of poor sleep are complex and certainly multifactorial. Studies have reported the following risk factors for having a sleep disorder: older age, female sex, low socioeconomic status, living alone, and some environmental and occupational factors, as well as poor mental and psychological health.2–4,7–9,11,19,20 Research has been undertaken that targets sleep disorders in the working population, and numerous studies have focused on shift work and its association with sleep.21,22 The association between work and sleep has been considered to be worth studying because sleep disorders are expected to occur in people of working age and because psychosocial aspects of work, such as job stress, may be strongly related to sleep and sleep problems. Some studies have shown that measures of job stress, such as perceived stress, hectic work, high job demands, working under time pressure, low job control, high job strain, low social support at work, bad atmosphere at work, role conflicts, effort-reward imbalance, job dissatisfaction, low levels of interest in job, and job insecurity are associated with sleep disorders.1–7,9–13,19,20,23–27 These studies, however, were done on relatively small or selective samples, examined nonstandard measures for the assessment of job-related factors, or did not take adequate account of potential confounding factors such as sociodemographic factors, physical and psychological health status, or important occupational risk factors such as shift work and working hours. Furthermore, the effects of workplace bullying, considered to be one of the most damaging factors related to job stress, on sleep disorders have been understudied, and the literature in this area appears to be sparse.3,28–30 Workplace bullying is difficult to evaluate, and no consensus exists regarding its definition. Here, the definition by Leymann31 was adopted: workplace bullying or mobbing “involves hostile and unethical communication, which is directed in a systematic way by one or a few individuals mainly towards one individual who, due to mobbing, is pushed into a helpless and defenceless position, being held there by means of continuing mobbing activities.” Two approaches using self-reported questionnaires have been developed in surveys: (1) inventories of various forms of bullying and (2) self-reports of being exposed to bullying on the basis of a given definition. According to some authors, the combination of both approaches would be adequate to define cases of bullying.30,32–34 Duration and frequency of bullying would also be crucial elements. In the present study, we combined the 2 approaches: (1) the questionnaire developed by Leymann—the Leymann Inventory of Psychological Terror35—considered to have the greatest coverage and acceptable reliabilities36 and evaluating 45 forms of bullying and (2) self-report of being exposed to bullying. Studies exploring the associations between workplace bullying and health outcomes are still lacking. Nevertheless, workplace bullying has been found to be associated with absence due to sickness,37 psychosomatic complaints and somatic symptoms,38–40 and mental health outcomes, such as job-induced stress, psychological health and well-being, anxiety, depression,29,30,39–47 use of psychotropic drugs,28,30 and physician-diagnosed psychiatric morbidity.48 The objectives of this study were to examine the associations between workplace bullying and sleep disturbances. This study attempted to take the limitations described above into account; because it was based on a large and nonselective sample of the French working population, this study included a standard measure of exposure to workplace bullying and detailed information on this exposure and took into account a large number of confounding factors.

It is intriguing to note that RABV progression is interrupted neither by destruction of the infected neuron nor by the immune response. Thus, it is likely that RABV has developed a subversive strategy to avoid functional neuron impairment, which compromises the infectious cycle. Rabies virus neuroinvasiveness results from two factors: not only does neurotropic rabies virus avoid inducing neuronal cell death, but also 'protective' T cells that migrate into the infected nervous system are killed by apoptosis or inactivated, as a result of the overexpression of immunosubversive molecules such as FasL, HLA-G or B7-H1 in the infected nervous system. This suggests that the preservation of the neuronal network and the destruction of T cells that invade the nervous system in response to the infection are crucial events for rabies virus neuroinvasion and for transmission of rabies virus to another animal. Implications of these findings for rabies treatment are discussed.

To support direct-drive inertial confinement fusion experiments at the National Ignition Facility (NIF) [G. H. Miller, E. I. Moses, and C. R. Wuest, Opt. Eng. 43, 2841 (2004)] in its indirect-drive beam configuration, the polar-direct-drive (PDD) concept [S. Skupsky et al., Phys. Plasmas 11, 2763 (2004)] has been proposed. Ignition in PDD geometry requires direct-drive–specific beam smoothing, phase plates, and repointing the NIF beams toward the equator to ensure symmetric target irradiation. First experiments to study the energetics and preheat in PDD implosions at the NIF have been performed. These experiments utilize the NIF in its current configuration, including beam geometry, phase plates, and beam smoothing. Room-temperature, 2.2-mm-diam plastic shells filled with D2 gas were imploded with total drive energies ranging from ∼500 to 750 kJ with peak powers of 120 to 180 TW and peak on-target irradiances at the initial target radius from 8 × 1014 to 1.2 × 1015 W/cm2. Results from these initial experi...

Recent experiments on the Laboratory for Laser Energetics' OMEGA laser have been carried out to produce strong shocks in solid spherical targets with direct laser illumination. The shocks are launched at pressures of several hundred Mbars and reach Gbar upon convergence. The results are relevant to the validation of the shock-ignition scheme and to the development of an OMEGA experimental platform to study material properties at Gbar pressures. The experiments investigate the strength of the ablation pressure and the hot-electron production at incident laser intensities of ∼2 to 6 × 1015 W/cm2 and demonstrate ablation pressures exceeding 300 Mbar, which is crucial to developing a shock-ignition target design for the National Ignition Facility. The timing of the x-ray flash from shock convergence in the center of the solid plastic target is used to infer the ablation and shock pressures. Laser–plasma instabilities produce hot-electrons with a moderate temperature (

Achieving thermonuclear ignition using direct laser illumination relies on the capability to accelerate spherical shells to high implosion velocities while maintaining shell integrity. Ablator materials of moderate atomic number Z reduce the detrimental effects of laser–plasma instabilities in direct-drive implosions. To validate the physics of moderate-Z ablator materials for ignition target designs on the National Ignition Facility (NIF), hydro-equivalent targets are designed using pure plastic (CH), high-density carbon, and glass (SiO2) ablators. The hydrodynamic stability of these targets is investigated through two-dimensional (2D) single-mode and multimode simulations. The overall stability of these targets to laser-imprint perturbations and low-mode asymmetries makes it possible to design high-gain targets. Designs using polar-drive illumination are developed within the NIF laser system specifications. Mid-Z ablator targets are an attractive candidate for direct-drive ignition since they present better overall performance than plastic ablator targets through reduced laser–plasma instabilities and a similar hydrodynamic stability.

Rabies virus (RABV) is a pathogen well-adapted to the nervous system, where it infects neurons. RABV is transmitted by the bite of an infected animal. It enters the nervous system via a motor neuron through the neuromuscular junction, or via a sensory nerve through nerve spindles. It then travels from one neuron to the next, along the spinal cord to the brain and the salivary glands. The virions are then excreted in the saliva of the animal and can be transmitted to another host by bite. Thus preservation of neuronal network integrity is crucial for the virus to be transmitted. Successful invasion of the nervous system by RABV seems to be the result of a subversive strategy based on the survival of infected neurons. This strategy includes protection against virus-mediated apoptosis and destruction of T cells that invade the CNS in response to infection.

Rabies virus (RABV) is a pathogen well-adapted to the nervous system, where it infects neurons. RABV is transmitted by the bite of an infected animal. It enters the nervous system via a motor neuron through the neuromuscular junction, or via a sensory nerve through nerve spindles. It then travels from one neuron to the next, along the spinal cord to the brain and the salivary glands. The virions are then excreted in the saliva of the animal and can be transmitted to another host by bite. Thus preservation of neuronal network integrity is crucial for the virus to be transmitted. Successful invasion of the nervous system by RABV seems to be the result of a subversive strategy based on the survival of infected neurons. This strategy includes protection against virus-mediated apoptosis and destruction of T cells that invade the CNS in response to infection.

Rabies virus (RABV) is a pathogen well-adapted to the nervous system, where it infects the neurons. RABV is transmitted by the bite of an infected animal. It enters the nervous system via a motor neuron through the neuromuscular junction, or via a sensory nerve through nerve spindles. It then travels from one neuron to the next, along the spinal cord to the brain and the salivary glands. The virions are then excreted in the saliva of the animal and can be transmitted to another host by bite. Thus, preservation of the neuronal network integrity is crucial for the virus to be transmitted. Successful invasion of the nervous system by RABV seems to be the result of a subversive strategy based on the survival of infected neurons including protection against virus-mediated apoptosis and destruction of T cells that invade the CNS in response to infection.

DNA fragmentation is a key feature of the degradation phase of apoptosis. In this work we have developed an assay, based on radioimager (beta-IMAGER and micro-IMAGER) quantification of radioactive nick end labelling (RANEL), which is quantitative, rapid and sensitive to study in vitro and in vivo induced apoptosis. To establish the technique, in vitro apoptosis of T cell lines was induced by stimulation of the Fas receptor; cells were labelled using TdT-mediated [alpha-33P] dCTP nick end labelling, after which then radioactivity was quantified using a beta-IMAGER. We have also shown that the RANEL method can be applied to the quantification and visualisation, by micro-IMAGER analysis, of liver tissue sections from mouse Fas-induced fulminant hepatitis or from Dengue-1 virus infected individuals. Finally, this system has also been used to detect apoptosis induced by rabies virus in Jurkat T cells. These data have established a large field of application for the RANEL assay.

We analyse observations in the NaD1 line (λ 5896 A) obtained with the MSDP spectrograph of the Turret Dome of the Pic du Midi Observatory. Individual images reveal high spatial resolution and the data reduction shows the high capabilities of the spectrograph to get doppler measurements up to the limit of the resolution of the refractor (0. �� 3). Dopplershifts are obtained in the middle and high photosphere. The smallest granules 0. �� 4 show upward motions in the middle photosphere.

We report on laser-driven, strong-shock generation and hot-electron production in planar targets in the presence of a pre-plasma at shock-ignition (SI) relevant laser and pre-plasma conditions. 2-D simulations reproduce the shock dynamics well, indicating ablator shocks of up to 75 Mbar have been generated. We observe hot-electron temperatures of ∼70 keV at intensities of 1.4 × 1015 W/cm2 with multiple overlapping beams driving the two-plasmon decay instability. When extrapolated to SI-relevant intensities of ∼1016 W/cm2, the hot electron temperature will likely exceed 100 keV, suggesting that tightly focused beams without overlap are better suited for launching the ignitor shock.

Viral superantigens bind several alleles and isotypes belonging to the MHC class II and subsequently activate particular T cell families via the variable portion of the beta chain of TCR. As a result, a superantigen bridges MHC and TCR molecules, leading to activation of T and B cells. The T expansion of various TCR V beta subsets is triggered on the basis of their V beta specificity, but not on their antigenic specificity. The best known superantigens are bacterial endotoxins produced by Staphylococcus aureus. However, viruses such as mouse mammary tumor or rabies viruses encode superantigens too. The ability of superantigens to break the barriers of MHC restriction and to activate large numbers of T and B cells has led to the hypothesis that superantigens may activate autoreactive T and B cells to initiate or worsen autoimmune diseases such as diabetes, multiple sclerosis, or psoriasis.

Glutamate-induced glutamate release may be involved in the delayed neuronal death induced by N-methyl-D-aspartate (NMDA). In order to examine a possible modulatory effect of the presynaptic group III mGluRs on glutamate excitotoxicity, the effect of L-2-amino-4-phosphonobutyrate (L-AP4) was examined on NMDA-induced delayed death of mouse cerebellar granule neurons in culture. We found that L-AP4, at high concentration (in the millimolar range), inhibited in a non-competitive manner the NMDA-induced toxicity. This effect was mimicked by high concentration of L-serine-o-phosphate (L-SOP), and was inhibited by pertussis toxin (PTX) indicating the involvement of a Gi/o protein. This suggests the involvement of mGluR7 in the L-AP4 effect, and this was consistent with the detection of both mGluR7 protein and mRNA in these cultured neurons. To examine the mechanism of the L-AP4-induced protection from excitotoxic damage, the effect of L-AP4 on glutamate release was examined. L-AP4 (or = 1 mM) noncompetitively inhibited by more than 60% the glutamate release induced by NMDA during the insult. We also observed that the 10-min NMDA receptor stimulation resulted in a dramatic increase in the extracellular glutamate concentration reaching 6000% of the control value 24 h after the insult. This large increase was also inhibited when NMDA was applied in the presence ofor = 1 mM L-AP4. Part of the L-AP4-induced protection from excitotoxic damage of granule neurons may therefore result from the inhibition of the vicious cycle: dying cells release glutamate, glutamate induced cell death. The present results add to the hypothesis that presynaptic mGluRs, probably mGluR7, may be the targets of drugs decreasing glutamate release and then neuronal death observed in some pathological situations.

Nitric oxide and arachidonic acid act as inter- and intracellular messengers in the central nervous system. It is well known that the NMDA-mediated generation of nitric oxide and arachidonic acid is dependent on extracellular Ca2+. However, the role of voltage-dependent calcium channels (VDCCs) in this regard is poorly understood. We report here that NMDA-mediated nitric oxide production in striatal neuron cultures is blocked (80%) by the L-type VDCC antagonist nifedipine, but not by omega-conotoxin or omega-agatoxin IVA, antagonists of the N- and P-type VDCCs respectively. By contrast, none of the VDCC antagonists inhibited the NMDA-mediated release of arachidonic acid. These data indicate that permeation through different Ca2+ channels is responsible for the production of arachidonic acid and nitric oxide in striatal neurons.

Shock ignition [R. Betti et al., Phys. Rev. Lett. 98, 155001 (2007)] is being pursued as a viable option to achieve ignition on the National Ignition Facility (NIF). Shock-ignition target designs use a high-intensity laser spike at the end of a low-adiabat assembly pulse to launch a spherically convergent strong shock to ignite the hot spot of an imploding capsule. A shock-ignition target design for the NIF is presented. One-dimensional simulations indicate an ignition threshold factor of 4.1 with a gain of 58. A polar-drive beam-pointing configuration for shock-ignition experiments on the NIF at 750 kJ is proposed. The capsule design is shown to be robust to the various one- and two-dimensional effects and nonuniformities anticipated on the NIF. The target is predicted to ignite with a gain of 38 when including all anticipated levels of nonuniformity and system uncertainty.

Within the framework of the shock-ignition (SI) scheme, ignition conditions are reached following the separation of the compression and heating phases. First, the shell is compressed at a sub-ignition implosion velocity; then an intense laser spike is launched at the end of the main drive, leading to the propagation of a strong shock through the precompressed fuel. The minimal laser energy required for ignition of scaled deuterium–tritium (DT) targets is assessed by calculations. A semi-empiric model describing the ignitor shock generation and propagation in the fuel assembly is defined. The minimal power needed in the laser spike pulse to achieve ignition is derived from the hydrodynamic model. Optimal conditions for ignition of scaled targets are explored in terms of laser intensity, shell-implosion velocity, and target scale range for the SI process. Curves of minimal laser requirements for ignition are plotted in the energy–power diagram. The most economic and reliable conditions for ignition of a millimeter DT target are observed in the 240- to 320-km/s implosion velocity range and for the peak laser intensity ranging from ∼2 × 1015 W/cm2 up to 5 × 1015 W/cm2. These optimal conditions correspond to shock-ignited targets for a laser energy of ∼250 kJ and a laser power of 100 to 200 TW. Large, self-ignited targets are particularly attractive by offering ignition at a lower implosion velocity and a reduced laser intensity than for conventional ignition. The SI scheme allows for the compression and heating phases of the high power laser energy research facility target to be performed at a peak laser intensity below 1016 W/cm2. A better control of parametric and hydrodynamic instabilities within the SI scheme sets it as an optimal and reliable approach to attain ignition of large targets.

Shock ignition of DT capsules involves two major steps. First, the fuel is assembled by means of a low velocity conventional implosion. At stagnation, the central core has a temperature lower than the one needed for ignition. Then a second, strong spherical converging shock, launched from a high intensity laser spike, arrives to the core. This shock crosses the core, rebounds at the target center and increases the central pressure to the ignition conditions. In this work we consider this latter phase by using the Guderley self-similar solution for converging flows. Our model accounts for the fusion reaction energy deposition, thermal and radiation losses thus describing the basic physics of hot spot ignition. The ignition criterion derived from the analytical model is successfully compared with full scale hydrodynamic simulations.

Spherical shock-ignition experiments on OMEGA used a novel beam configuration that separates low-intensity compression beams and high-intensity spike beams. Significant improvements in the performance of plastic-shell, D2 implosions were observed with repointed beams. The analysis of the coupling of the high-intensity spike beam energy into the imploding capsule indicates that absorbed hot-electron energy contributes to the coupling. The backscattering of laser energy was measured to reach up to 36% at single-beam intensities of ∼8 × 1015 W/cm2. Hard x-ray measurements revealed a relatively low hot-electron temperature of ∼30 keV independent of intensity and timing. At the highest intensity, stimulated Brillouin scattering occurs near and above the quarter-critical density and the two-plasmon-decay instability is suppressed.

We have previously shown that nitric oxide blocks the N-methyl-D-aspartate (NMDA) receptor without affecting the agonist binding site. We now report that in cerebellar granule cells nitric oxide decreases the NMDA channel conductance and open probability, in voltage-dependent and -independent manners, respectively, by acting on an extracellular site different from the redox, glycine, and pH modulatory sites of the receptor-channel complex. This inhibition is not additive with those of Mg2+ and Zn2+. Moreover, removal of trace concentrations of metal ions in the external medium by means of metal ion-chelators significantly reduced the inhibitory action of nitric oxide on NMDA currents. These results indicate that divalent ions are required for the blockade of NMDA receptors by NO donors.

Glutamate is the major neurotransmitter of the mammalian brain. Stimulation of glutamate receptors, especially the subgroup of NMDA receptors, induces nitric oxide and arachidonic acid synthesis in neurons. These agents freely diffuse across membranes and thus can play roles of messengers in particular brain functions. The aim of our study was to identify these roles in in vitro and in vivo models from mouse and rat. Exaggerated stimulation of NMDA receptors leads to neurological disorders such as some types of epilepsy and neurodegenerative diseases. We show that superoxide ions, which probably result from metabolic degradation of arachidonic acid, would be responsible of the neurotoxic action of NMDA. On the other hand, we observed that nitric oxide inhibits NMDA receptors. This effect would protect animals against epileptic and neurodegenerative diseases mediated by over-stimulation of these receptors. This endogenous regulation may play important roles in the functioning of glutamatergic neurotransmission.

In striatal neurones in culture, N- methyl- d -aspartate-(NMDA) , kainate- (Kai) and K + -dependent cGMP production is entirely mediated via nitric oxide (NO). Low concentrations of lavendustin-A (⩽ 0.3 μ M), a highly specific tyrosine kinase inhibitor, reduced irreversibly and in a time-dependent manner NMDA-stimulated cGMP production. After a preincubation period of 20 min with lavendustin-A (0.3 μM), the inhibition of NMDA-induced cGMP production was equal to 56 ± 8% ( n = 6). After the same preincubation period, the IC 50 of the lavendustin-A blockade was 30 ± 15 nM. Genistein, another tyrosine kinase inhibitor also inhibited NMDA-dependent cGMP production with high potencies (⩽ 3 μ M). Whatever the tyrosine kinase inhibitor tested, the basal cGMP production remained unaffected. Kai-, K + -, and ionomycin-induced cGMP production was also inhibited by lavendustin-A, and genistein. In contrast, tyrosine kinase inhibitors were unable to block NO donor-induced cGMP production. Using patch clamp experiments, we have also found that lavendustin-A (0.3–1 μM), the most potent tyrosine kinase inhibitor used, (a) did not reduce the NMDA receptor-mediated current, (b) only slighly affected Kai receptor-mediated current (16.4 ± 3.4% inhibition) and (c) had a marked effect on voltage-sensitive Ca 2+ channel- (VSCC) mediated currents (44.4 ± 4.9% inhibition). A reduction in VSCC activity certainly explains the inhibition of K + -, Kai- and possibly part of the NMDA-induced cGMP production. However, two observations (inhibition of ionomycin-induced cGMP production and absence of inhibition of NO donor-induced cGMP production) indicated that tyrosine kinase inhibitors also inhibit another step localized between Ca 2+ entry into neurones and NO production. We have no information regarding the step involved because the cascade of kinases and phosphatases leading to NO-S regulation could be very complex. In any case, it can be concluded that a tyrosine phosphorylation is needed to obtain a full brain NO-synthase (NO-S) activity upon glutamate receptor stimulation.

Publisher Summary In cerebellar granule cells, endogenous production of NO tonically blocks N-methyl- D-aspartate (NMDA) receptors. Superoxide ions seem to be more efficient than NO at inducing NMDA neurotoxicity. Under experimental conditions, blocking NO formation did not prevent glutamate neurotoxicity in vitro or in vivo . On the contrary, complete depletion of NO synthesis increased the deleterious action of NMDA on neurons, probably by suppressing the negative feedback exerted by NO on NMDA receptors. In vitro studies showed that purified nitric oxide synthase can produce oxygenated free radicals such as superoxide ion when L-arginine concentrations are low. However, this was not the case under our experimental conditions, as indicated by the production of NO and cyclic guanosine monophosphate upon NMDA receptor stimulation, because neurons are usually not depleted in L-arginine. Moreover, under such conditions NO Arg did not suppress NMDA-induced superoxide ion production. Activation of phospholipase A 2 induced by NMDA receptor stimulation may be an important although not exclusive step in the generation of oxygen radicals and neuronal death.

Shock ignition is an inertial confinement fusion scheme where the ignition conditions are achieved in two steps. First, the DT shell is compressed at a low implosion velocity creating a central core at a low temperature and a high density. Then, a strong spherical converging shock is launched before the fuel stagnation time. It increases the central pressure and ignites the core. It is shown in this paper that this latter phase can be described analytically by using a self-similar solution to the equations of ideal hydrodynamics. A high and uniformly distributed pressure in the hot spot can be created thus providing favorable conditions for ignition. Analytic ignition criteria are obtained that relate the areal density of the compressed core with the shock velocity. The conclusions of the analytical model are confirmed in full hydrodynamic simulations.

In this study, we analysed the implication of superoxide (O2-.) and nitric oxide (NO.) free radicals and their resulting product peroxynitrite (ONOO-) in the neuronal death induced by the activation of the glutamatergic receptor of the N-methyl-D-aspartate (NMDA) subtype using cultured cerebellar granule cells. The NOl donor SIN-1 (3-morpholinosydnonimine N-ethylcarbamide), at concentrations which produced a much higher guanylate cyclase activation (i.e. NO. concentration) than NMDA, was not neurotoxic and did not increase the NMDA-induced neuronal death. The absence of involvement of NO. in NMDA-induced neuronal death was confirmed by the ineffectiveness of L-NG-nitroarginine (L-Narg) as a neuroprotective compound. Electron paramagnetic resonance (EPR) experiments, using 5,5-dimethyl pyrroline 1-oxide (DMPO) as a spin trap, indicated that NMDA receptor stimulation led to the generation of O2-. from at least 15-30 min. The generation of O2-. by xanthine (XA)-xanthine oxidase (XO) induced a neuronal death similar to that of NMDA. XA-XO-induced neuronal death was suppressed by addition of either superoxide dismutase (SOD) plus catalase (CAT), or DMPO in the incubation medium. In contrast, NMDA-induced neuronal death was widely blocked by DMPO and other spin trap compounds, but not by SOD +/- CAT. XA-XO-induced neuronal death was not potentiated by SIN-1 indicating that ONOO- is not more toxic than O2-. in our neuronal model.