La Lecture de Beauvoir : la Genèse d’une Vocation

L’expérience de la lecture est fondatrice pour un écrivain à venir. Quand il s’agit du cas de Simone de Beauvoir, elle est une grande lectrice, ses activités de lectures représentent une grande diversité au fil des ans. Géographiquement, les espaces de fréquentation pour la lecture manifestent une volonté du passage de la lecture à l’écriture. La lecture et l’écriture mimétique, en tant que stade préparatoire d’un écrivain à venir, conduisent ensuite Simone de Beauvoir à la réalisation de son projet littéraire

La Genèse Des Mémoires d’Une Jeune Fille Rangée

Simone de Beauvoir, l’écrivaine des Mémoires d’une jeune fille rangée, nourrit un projet de raconter son enfance et sa jeunesse quand elle était petite. Par la suite, ce désir de raconter son passé revient toujours dans sa tête, mais c’est à l’approche de sa cinquantaine qu’elle réalise ce vieux projet. Avant d’entamer l’entreprise autobiographique, Simone de Beauvoir satisfait dans une certaine mesure sa pulsion autobiographique dans les créations fictives. Ce désir se manifeste aussi dans sa lecture des œuvres autobiographiques, dans la tentation d’une nouvelle forme littéraire, dans l’angoisse des menaces venant du vieillissement et de la mort, et même dans l’écriture du Deuxième sexe. En 1956, après avoir publié Le Deuxième sexe et Les Mandarins et obtenu le prix Goncourt, Simone de Beauvoir a toute la légitimité pour son entreprise autobiographique, c’est alors qu’elle entreprend les Mémoires d’une jeune fille rangée.

Reconstruction of the East Asian monsoon variability since the mid-Holocene from the Pearl River estuary, southern China

The principal aim of this thesis is to reconstruct East Asian Monsoon (EAM) variability during the mid-Holocene, developing a relatively new proxy of bulk organic carbon isotopic signature (δ13C). C/N ratios and trace elements are also employed to conduct a multi-proxy case study from the Pearl River estuary, southern China. Sources of sediments within an estuary include river-derived terrestrial/freshwater input, in situ brackish-water suspended sediment and tide-derived marine input. This study assumes the three proxies can help differentiate sources of sediments relating to monsoon-driven freshwater flux and help reconstruct monsoonal precipitation history during the mid-Holocene when the sea level was relatively stable. To achieve the aims of this thesis a range of modern samples were collected from terrestrial areas, including plants and soil samples, through to estuarine areas, including seasonal estuarine suspended organic matter (SOM) and surface sediment. Results suggest that bulk organic δ13C and C/N ratios can successfully identify sources of the organic component of the estuarine sediment, and thus can be used to infer relative changes in monsoon-driven freshwater flux to the estuary. For example, more negative δ13C values reflect a greater level of contribution of freshwater organic carbon, i.e. stronger monsoonal freshwater discharge. Results also show that a combination of selected metals, such as the terrigenous metals (Fe, Mn, Co and As), can be useful for indicating sediment sources and sedimentary environment. Analysis of an estuarine core (UV1) shows that freshwater discharge from the Pearl River catchment gradually declined from 6400 to 2000 cal. years BP, suggesting a gradual weakening of summer monsoon precipitation, responding to the weakening insolation controlled by the orbital-driven precession cycle. Superimposed on this are wet/dry intervals, ranging from centennial- to millennial- scale, driven by solar activity. Changes in ENSO and high-latitude cooling events might be responsible for dry/wet events at centennial- to decadal- scale, identified during the mid-Holocene. This study also suggests that the coupling of thermal and moist conditions of the EAM might only have become stable after 4500 cal. yr BP. A sudden shift in the geochemical signature indicates agricultural activity in the Pearl River delta intensified from 2000 cal. yr BP

Kinetic and Crystallographic Studies of Drug-Resistant Mutants of HIV-1 Protease: Insights into the Drug Resistance Mechanisms

HIV-1 protease (PR) inhibitors (PIs) are important anti-HIV drugs for the treatment of AIDS and have shown great success in reducing mortality and prolonging the life of HIV-infected individuals. However, the rapid development of drug resistance is one of the major factors causing the reduced effectiveness of PIs. Consequently, various drug resistant mutants of HIV-1 PR have been extensively studied to gain insight into the mechanisms of drug resistance. In this study, the crystal structures, dimer stabilities, and kinetics data have been analyzed for wild type PR and over 10 resistant mutants including PRL24I, PRI32V, PRM46L, PRG48V, PRI50V, PRF53L, PRI54V, PRI54M, PRG73S and PRL90M. These mutations lie in varied structural regions of PR: adjacent to the active site, in the inhibitor binding site, the flap or at protein surface. The enzymatic activity and inhibition were altered in mutant PR to various degrees. Crystal structures of the mutants complexed with a substrate analog inhibitor or drugs indinavir, saquinavir and darunavir were determined at resolutions of 0.84 – 1.50 Å. Each mutant revealed distinct structural changes, which are usually located at the mutated residue, the flap and inhibitor binding sites. Moreover, darunavir was shown to bind to PR at a new site on the flap surface in PRI32V and PRM46L. The existence of this additional inhibitor binding site may explain the high effectiveness of darunavir on drug resistant mutants. Moreover, the unliganded structure PRF53L had a wider separation at the tips of the flaps than in unliganded wild type PR. The absence of flap interactions in PRF53L suggests a novel mechanism for drug resistance. Therefore, this study enhanced our understanding of the role of individual residues in the development of drug resistance and the structural basis of drug resistance mechanisms. Atomic resolution crystal structures are valuable for the design of more potent protease inhibitors to overcome the drug resistance problem