993 resultados para Adam Wibby
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Comprend : [Frontispice : portrait de] Paul Verlaine. [Cote : microfilm R 89553] ; [Fig. au chap. I : portrait de] Tristan Corbière. [Cote : microfilm R 89553] ; [Fig. au chap. II : portrait d'] Arthur Rimbaud. [Cote : microfilm R 89553] ; [Fig. au chap. III : portrait de] Stéphane Mallarmé. [Cote : microfilm R 89553] ; [Fig. au chap. IV : portrait de] Marceline Desbordes-Valmore. [Cote : microfilm R 89553] ; [Fig. au chap. V : portrait de] Villiers de l'Isle-Adam. [Cote : microfilm R 89553]
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Objectives: Sequencing and annotation of the genome of Aspergillus fumigatus has dramatically changed our knowledge about the proteins potentially encoded by the fungus. Own analysis have resulted in at least 47 of them contain a signal for secretion. Among those list we want to characterize those enzymes that may have impact on fungal growth outside and particularly inside the host. We thereby want to learn more about their function in general and to identify possible novel drug targets suited to combat invasive aspergillosis. Methods: Four groups of secreted proteases have been chosen for further analysis: 1 Serine-carboxyl proteases (sedolisins). Four of them were expressed in yeast and partly in bacteria. Substrate-specificity studies and kinetics as well as protein characterization of the yeast derived proteases were performed according to standard methods. Enzyme specific polyclonal antibodies were raised in rabbits using the peptides expressed in bacteria. Expression of proteases in A. fumigatus was investigated with these antibodies and gene knockout mutants for each enzyme as a control. All the following mentioned proteases will be investigated accordingly. 2 Two metalloproteases from the M12-family, ADAM-A and ADAM-B. Both proteases are likely membrane associated and may have inherent sheddase function as their counterparts in mammals. 3 One metalloprotease of the M43 family. An orthologue of this protease in Coccidioides posadasii is known to posses immunomodulating activities. 4 One putative endoprotease of the S28-family. An orthologue in Aspergillus niger is known to digest proline-rich proteins. In A. fumigatus this enzyme may facilitate invasion through proline-rich proteins like collagen. Results: All sedolisins expressed in yeast were proteolytically active: Three of them were characterized as tripeptidyl-peptidases whereas one enzyme is an endoprotease. Corresponding knockout mutants did not reveal a specific phenotype. Expression and investigations on all above mentioned proteases as well as generation of corresponding knockout mutants and double knockout mutants for the ADAMs, respectively, is underway. Promising candidates will be investigated in animal studies for reduced virulence. Conclusions : The real existence of so far hypothetical proteases predicted by the genome project was already demonstrated for the sedolisins by a reverse genetic approach (from gene to protein). With the aim of improving basic knowledge on function of other proteases potentially crucial for fungal growth and thus for pathogenesis, other hypothetical enzymes will be investigated. Those enzymes may turn out to be ideal drug targets for antimycotic chemotherapy.
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Using Monte Carlo simulations we study the dynamics of three-dimensional Ising models with nearest-, next-nearest-, and four-spin (plaquette) interactions. During coarsening, such models develop growing energy barriers, which leads to very slow dynamics at low temperature. As already reported, the model with only the plaquette interaction exhibits some of the features characteristic of ordinary glasses: strong metastability of the supercooled liquid, a weak increase of the characteristic length under cooling, stretched-exponential relaxation, and aging. The addition of two-spin interactions, in general, destroys such behavior: the liquid phase loses metastability and the slow-dynamics regime terminates well below the melting transition, which is presumably related with a certain corner-rounding transition. However, for a particular choice of interaction constants, when the ground state is strongly degenerate, our simulations suggest that the slow-dynamics regime extends up to the melting transition. The analysis of these models leads us to the conjecture that in the four-spin Ising model domain walls lose their tension at the glassy transition and that they are basically tensionless in the glassy phase.
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Comprend : [Frontispice : scènes bibliques, saints et martyres. Christ, saint Jean-Baptiste, saint Sébastien, Adam et Eve, saint Christophe etc.] [Cote : Res m Yc 1008/Microfilm R 122295] ; [pl. en reg. p.13 : illustration de la tragédie I de Seneque "La colère d'Hercule" (Hercules furens).] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. p.57 : illustration de la tragédie II de Seneque "Thyestes".] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. en reg. p.93 : illustration de la tragédie III de Seneque "Thebais".] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. à la tragédie IV : illustration de la tragédie IIII de Seneque "Hypolite" (Hypolytus).] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. à la tragédie V : illustration de la tragédie V de Seneque "Oedipe" (Oedypus).] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. à la tragédie VI : illustration de la tragédie VI de Seneque "Les Troyennes" (Troas).] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. à la tragédie VII : illustration de la tragédie V de Seneque "Médée" (Medea).] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. à la tragédie VIII : illustration de la tragédie VIII de Seneque "Agamemnon" .] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. à la tragédie IX : illustration de la tragédie IX de Seneque "Octavie" (Octavia) . ] [Cote : Res m Yc 1008/Microfilm R 122295] ; [Fig. à la tragédie X : illustration de la tragédie X de Seneque "Hercules oetheus" .] [Cote : Res m Yc 1008/Microfilm R 122295]
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Phénomène reconnu de longue date, dont les rhéteurs et les écrivains ont même souvent vanté l'efficacité pour réaliser un portrait moral convaincant, la caractérisation langagière des personnages n'a été que peu observée selon une perspective générale, comme si son étude ne pouvait s'envisager en dehors du projet esthétique d'un auteur particulier. Cependant, on peut envisager la caractérisation langagière comme procédant d'une poétique du récit, c'est-à-dire comme un mécanisme du texte narratif, dont certaines constantes peuvent être décrites. L'objectif du présent travail est ainsi de mettre au jour les conditions, tant textuelles que contextuelles, devant être réunies pour que certains aspects des discours rapportés fassent sens en tant qu'éléments de caractérisation. La nature indirecte de ce phénomène demande en effet de porter une attention particulière à ce qui relève des conditions de production et d'interprétation du texte, autrement dit des éléments contextuels que le texte convoque (liés à la langue, aux genres, au « texte » de la culture, etc.) afin de (re)construire par inférence ce qui est dit « sans être dit ». Ainsi la caractérisation langagière reposet- elle sur la reconnaissance d'un rôle thématique endossé par le personnage, rôle défini en partie par certains « habitus » discursifs. Mais il importe également de considérer la caractérisation langagière comme un effet de la textualité. Cela concerne d'abord des unités manipulées par les auteurs (mots, structures syntaxiques, phonologie...). Néanmoins, rien ne se joue sur un unique élément ; au contraire, d'une part, il faut qu'une série de traits s'organisent en un réseau isotope, et cela de la réplique isolée au texte entier ; d'autre part, la caractérisation dérive encore des relations que le discours d'un personnage entretient avec des discours avoisinants, en premier lieu celui du narrateur. Se concentrant sur des oeuvres comiques ou satiriques des XVIIe et XVIIIe siècles, l'approche proposée ici veut également tenir compte d'une tradition rhétorique et poétique qui associe portrait moral et parole représentée, tradition encore très présente dans un tel corpus, qui a par ailleurs l'avantage de laisser entrer dans le monde de la fiction des personnages de toutes conditions, dotés de leurs langages spécifiques.
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Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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We investigate the phase transition in a strongly disordered short-range three-spin interaction model characterized by the absence of time-reversal symmetry in the Hamiltonian. In the mean-field limit the model is well described by the Adam-Gibbs-DiMarzio scenario for the glass transition; however, in the short-range case this picture turns out to be modified. The model presents a finite temperature continuous phase transition characterized by a divergent spin-glass susceptibility and a negative specific-heat exponent. We expect the nature of the transition in this three-spin model to be the same as the transition in the Edwards-Anderson model in a magnetic field, with the advantage that the strong crossover effects present in the latter case are absent.
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Este artigo apresenta uma reflexão a respeito de algumas concepções teóricas de autoridade e hierarquia, e de como essas concepções se constituem em elementos da cultura escolar que é construída na interação cotidiana, definindo formas diferenciadas de participação nas escolas. Parte do pressuposto de que a escola, como organização burocrática, tem em sua estrutura um corpo de princípios e valores dados pelo sistema educacional, por meio de leis, decretos e papéis formalmente estabelecidos, e um outro corpo de princípios e valores construídos e reelaborados no seu interior, pelos participantes do processo educacional, formando a cultura escolar. Assim, o grau de participação nas escolas se definiria em razão das concepções que seriam compartilhadas e construídas nesse processo de constituição da cultura escolar.
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At this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(¿)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity.
Yellow submarine of the Wnt/Frizzled signaling: submerging from the G protein harbor to the targets.
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The Wnt/Frizzled signaling pathway plays multiple functions in animal development and, when deregulated, in human disease. The G-protein coupled receptor (GPCR) Frizzled and its cognate heterotrimeric Gi/o proteins initiate the intracellular signaling cascades resulting in cell fate determination and polarization. In this review, we summarize the knowledge on the ligand recognition, biochemistry, modifications and interacting partners of the Frizzled proteins viewed as GPCRs. We also discuss the effectors of the heterotrimeric Go protein in Frizzled signaling. One group of these effectors is represented by small GTPases of the Rab family, which amplify the initial Wnt/Frizzled signal. Another effector is the negative regulator of Wnt signaling Axin, which becomes deactivated in response to Go action. The discovery of the GPCR properties of Frizzled receptors not only provides mechanistic understanding to their signaling pathways, but also paves new avenues for the drug discovery efforts.