984 resultados para Rameau, Jean François, b. 1716


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As a fundamental contribution to limiting the increase of debris in the Space environment, a three-year project started on 1 November 2010 financed by the European Commission under the FP-7 Space Programme. It aims at developing a universal system to be carried on board future satellites launched into low Earth orbit (LEO), to allow de-orbiting at end of life. The operational system involves a conductive tape-tether left bare of insulation to establish anodic contact with the ambient plasma as a giant Langmuir probe. The project will size the three disparate dimensions of a tape for a selected de-orbit mission and determine scaling laws to allow system design for a general mission. It will implement control laws to restrain tether dynamics in/off the orbital plane; and will carry out plasma chamber measurements and numerical simulations of tether-plasma interaction. The project also involves the design and manufacturing of subsystems: electron-ejecting plasma contactors, an electric control and power module, interface elements, tether and deployment mechanisms, tether tape/end-mass as well as current collection plus free-fall, and hypervelocity impact tests.

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BETs is a three-year project financed by the Space Program of the European Commission, aimed at developing an efficient deorbit system that could be carried on board any future satellite launched into Low Earth Orbit (LEO). The operational system involves a conductive tape-tether left bare to establish anodic contact with the ambient plasma as a giant Langmuir probe. As a part of this project, we are carrying out both numerical and experimental approaches to estimate the collected current by the positive part of the tether. This paper deals with experimental measurements performed in the IONospheric Atmosphere Simulator (JONAS) plasma chamber of the Onera-Space Environment Department. The JONAS facility is a 9- m3 vacuum chamber equipped with a plasma source providing drifting plasma simulating LEO conditions in terms of density and temperature. A thin metallic cylinder, simulating the tether, is set inside the chamber and polarized up to 1000 V. The Earth's magnetic field is neutralized inside the chamber. In a first time, tether collected current versus tether polarization is measured for different plasma source energies and densities. In complement, several types of Langmuir probes are used at the same location to allow the extraction of both ion densities and electron parameters by computer modeling (classical Langmuir probe characteristics are not accurate enough in the present situation). These two measurements permit estimation of the discrepancies between the theoretical collection laws, orbital motion limited law in particular, and the experimental data in LEO-like conditions without magnetic fields. In a second time, the spatial variations and the time evolutions of the plasma properties around the tether are investigated. Spherical and emissive Langmuir probes are also used for a more extensive characterization of the plasma in space and time dependent analysis. Results show the ion depletion because of the wake effect and the accumulation of- ions upstream of the tether. In some regimes (at large positive potential), oscillations are observed on the tether collected current and on Langmuir probe collected current in specific sites.

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Este trabalho investiga uma das formas pelas quais a condição contemporânea, assim chamada pós-moderna, exerce significativo impacto sobre a vontade humana. Numa perspectiva fenomenológica e existencial, apoiada primordialmente no pensamento de Paul Ricoeur e Paul Tillich, esta abordagem busca identificar a relação entre a condição pós-moderna e a crise contemporânea da vontade que, como hipótese de tese, encontra-se vinculada à forma pela qual é estabelecida a relação entre vontade e desejo. A pós-modernidade é analisada a partir de seu desenvolvimento sócio-cultural desde a década de 1930 e em interlocução com os pensamentos de Jean-François Lyotard e Jean Baudrillard de forma a evidenciar o desenvolvimento desta relação. Algumas perspectivas filosófico-teológicas são exploradas a partir da situação de impacto aqui em questão. São tentativas de contribuir para que a vontade redescubra seu caráter integralizador e possa considerá-lo tão imprescindível quanto seu ímpeto expansionista e dissipador, uma vez que ambos os movimentos são partes integrantes da coragem e do poder-de-ser que a fundamentam.(AU)

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Este trabalho investiga uma das formas pelas quais a condição contemporânea, assim chamada pós-moderna, exerce significativo impacto sobre a vontade humana. Numa perspectiva fenomenológica e existencial, apoiada primordialmente no pensamento de Paul Ricoeur e Paul Tillich, esta abordagem busca identificar a relação entre a condição pós-moderna e a crise contemporânea da vontade que, como hipótese de tese, encontra-se vinculada à forma pela qual é estabelecida a relação entre vontade e desejo. A pós-modernidade é analisada a partir de seu desenvolvimento sócio-cultural desde a década de 1930 e em interlocução com os pensamentos de Jean-François Lyotard e Jean Baudrillard de forma a evidenciar o desenvolvimento desta relação. Algumas perspectivas filosófico-teológicas são exploradas a partir da situação de impacto aqui em questão. São tentativas de contribuir para que a vontade redescubra seu caráter integralizador e possa considerá-lo tão imprescindível quanto seu ímpeto expansionista e dissipador, uma vez que ambos os movimentos são partes integrantes da coragem e do poder-de-ser que a fundamentam.(AU)

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Reconhecendo, a partir da constatação empírica, a multiplicidade de escolhas de crenças no Mundo e em particular na periferia urbana paulistana, reconhecemos, tambm, a emergência criativa de novas possibilidades de crer e não crer. Tal amplitude não apenas aponta para o crer (segundo as ofertas de um sem número de religiões) e o não crer (ateu e agnóstico), mas para uma escolha que poderia vir a ser silenciada e esquecida, neste binômio arcaico e obsoleto, quando alguém se dá à liberdade crer sem ter religião. Reconhecer interessadamente os sem-religião nas periferias urbanas paulistanas é dar-se conta das violências a que estes indivíduos estão submetidos: violência econômica, violência da cidadania (vulnerabilidade) e proveniente da armas (grupos x Estado). Tanto quanto a violência do esquecimento e silenciamento. A concomitância espaço-temporal dos sem-religião nas periferias, levou-nos buscar referências em teorias de secularização e de laicidade, e, a partir destas, traçar uma história do poder violento, cuja pretensão é a inelutabilidade, enquanto suas fissuras são abertas em espaços de resistências. A história da legitimação do poder que se quer único, soberano, de caráter universal, enquanto fragmenta a sociedade em indivíduos atomizados, fragilizando vínculos horizontais, e a dos surgimentos de resistências não violentas questionadoras da totalidade trágica, ao reconhecer a liberdade de ser com autonomia, enquanto se volta para a produção de partilha de bens comuns. Propomos reconhecer a igual liberdade de ser (expressa na crença da filiação divina) e de partilhar o bem comum em reconhecimentos mútuos (expressa pela ação social), uma expressão de resistência não violenta ao poder que requer a igual abdicação da liberdade pela via da fragmentação individualizante e submissão inquestionável à ordem totalizante. Os sem-religião nas periferias urbanas, nossos contemporâneos, partilhariam uma tal resistência, ao longo da história, com as melissas gregas, os profetas messiânicos hebreus, os hereges cristãos e os ateus modernos, cuja pretensão não é o poder, mas a partilha igual da liberdade e dos bens comuns. Estes laicos, de fato, seriam agentes de resistências de reconhecimento mútuos, em espaços de multiplicidade crescente, ao poder violento real na história.

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The important role of furin in the proteolytic activation of many pathogenic molecules has made this endoprotease a target for the development of potent and selective antiproteolytic agents. Here, we demonstrate the utility of the protein-based inhibitor α1-antitrypsin Portland (α1-PDX) as an antipathogenic agent that can be used prophylactically to block furin-dependent cell killing by Pseudomonas exotoxin A. Biochemical analysis of the specificity of a bacterially expressed His- and FLAG-tagged α1-PDX (α1-PDX/hf) revealed the selectivity of the α1-PDX/hf reactive site loop for furin (Ki, 600 pM) but not for other proprotein convertase family members or other unrelated endoproteases. Kinetic studies show that α1-PDX/hf inhibits furin by a slow tight-binding mechanism characteristic of serpin molecules and functions as a suicide substrate inhibitor. Once bound to furin’s active site, α1-PDX/hf partitions with equal probability to undergo proteolysis by furin at the C-terminal side of the reactive center -Arg355-Ile-Pro-Arg358-↓ or to form a kinetically trapped SDS-stable complex with the enzyme. This partitioning between the complex-forming and proteolytic pathways contributes to the ability of α1-PDX/hf to differentially inhibit members of the proprotein convertase family. Finally, we propose a structural model of the α1-PDX-reactive site loop that explains the high degree of enzyme selectivity of this serpin and which can be used to generate small molecule furin inhibitors.

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To investigate the functional role of different α1-adrenergic receptor (α1-AR) subtypes in vivo, we have applied a gene targeting approach to create a mouse model lacking the α1b-AR (α1b/−). Reverse transcription–PCR and ligand binding studies were combined to elucidate the expression of the α1-AR subtypes in various tissues of α1b +/+ and −/− mice. Total α1-AR sites were decreased by 98% in liver, 74% in heart, and 42% in cerebral cortex of the α1b −/− as compared with +/+ mice. Because of the large decrease of α1-AR in the heart and the loss of the α1b-AR mRNA in the aorta of the α1b/− mice, the in vivo blood pressure and in vitro aorta contractile responses to α1-agonists were investigated in α1b +/+ and −/− mice. Our findings provide strong evidence that the α1b-AR is a mediator of the blood pressure and the aorta contractile responses induced by α1 agonists. This was demonstrated by the finding that the mean arterial blood pressure response to phenylephrine was decreased by 45% in α1b −/− as compared with +/+ mice. In addition, phenylephrine-induced contractions of aortic rings also were decreased by 25% in α1b/− mice. The α1b-AR knockout mouse model provides a potentially useful tool to elucidate the functional specificity of different α1-AR subtypes, to better understand the effects of adrenergic drugs, and to investigate the multiple mechanisms involved in the control of blood pressure.

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In human beings of both sexes, dehydroepiandrosterone sulfate (DHEAS) circulating in blood is mostly an adrenally secreted steroid whose serum concentration (in the micromolar range and 30–50% higher in men than in women) decreases with age, toward ≈20–10% of its value in young adults during the 8th and 9th decades. The mechanism of action of DHEA and DHEAS is poorly known and may include partial transformation into sex steroids, increase of bioavailable insulin-like growth factor I, and effects on neurotransmitter receptors. Whether there is a cause-to-effect relationship between the decreasing levels of DHEAS with age and physiological and pathological manifestations of aging is still undecided, but this is of obvious theoretical and practical interest in view of the easy restoration by DHEA administration. Here we report on 622 subjects over 65 years of age, studied for the 4 years since DHEAS baseline values had been obtained, in the frame of the PAQUID program, analyzing the functional, psychological, and mental status of a community-based population in the south-west of France. We confirm the continuing decrease of DHEAS serum concentration with age, more in men than in women, even if men retain higher levels. Significantly lower values of baseline DHEAS were recorded in women in cases of functional limitation (Instrumental Activities of Daily Living), confinement, dyspnea, depressive symptomatology, poor subjective perception of health and life satisfaction, and usage of various medications. In men, there was a trend for the same correlations, even though not statistically significant in most categories. No differences in DHEAS levels were found in cases of incident dementia in the following 4 years. In men (but not in women), lower DHEAS was significantly associated with increased short-term mortality at 2 and 4 years after baseline measurement. These results, statistically established by taking into account corrections for age, sex, and health indicators, suggest the need for further careful trials of the administration of replacement doses of DHEA in aging humans. Indeed, the first noted results of such “treatment” are consistent with correlations observed here between functional and psychological status and endogenous steroid serum concentrations.

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Gene therapy is based on the vectorization of genes to target cells and their subsequent expression. Cationic amphiphile-mediated delivery of plasmid DNA is the nonviral gene transfer method most often used. We examined the supramolecular structure of lipopolyamine/plasmid DNA complexes under various condensing conditions. Plasmid DNA complexation with lipopolyamine micelles whose mean diameter was 5 nm revealed three domains, depending on the lipopolyamine/plasmid DNA ratio. These domains respectively corresponded to negatively, neutrally, and positively charged complexes. Transmission electron microscopy and x-ray scattering experiments on complexes originating from these three domains showed that although their morphology depends on the lipopolyamine/plasmid DNA ratio, their particle structure consists of ordered domains characterized by even spacing of 80 Å, irrespective of the lipid/DNA ratio. The most active lipopolyamine/DNA complexes for gene transfer were positively charged. They were characterized by fully condensed DNA inside spherical particles (diameter: 50 nm) sandwiched between lipid bilayers. These results show that supercoiled plasmid DNA is able to transform lipopolyamine micelles into a supramolecular organization characterized by ordered lamellar domains.

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The heat-shock protein 90 (Hsp90) is a cytosolic molecular chaperone that is highly abundant even at normal temperature. Specific functions for Hsp90 have been proposed based on the characterization of its interactions with certain transcription factors and kinases including Raf in vertebrates and flies. We therefore decided to address the role of Hsp90 for MAP kinase pathways in the budding yeast, an organism amenable to both genetic and biochemical analyses. We found that both basal and induced activities of the pheromone-signaling pathway depend on Hsp90. Signaling is defective in strains expressing low levels or point mutants of yeast Hsp90 (Hsp82), or human Hsp90β instead of the wild-type protein. Ste11, a yeast equivalent of Raf, forms complexes with wild-type Hsp90 and depends on Hsp90 function for accumulation. For budding yeast, Ste11 represents the first identified endogenous “substrate” of Hsp90. Moreover, Hsp90 functions in steroid receptor and pheromone signaling can be genetically separated as the Hsp82 point mutant T525I and the human Hsp90β are specifically defective for the former and the latter, respectively. These findings further corroborate the view that molecular chaperones must also be considered as transient or stable components of signal transduction pathways.

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Tradução de Jean-François Cleaver.

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Tradução de Jean-François Cleaver.

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Publicado no Diário Oficial de 12.03.88, da República Francesa, p. 3.288.

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Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (λs = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5⋅10−5) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22–23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0.001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.