This thesis describes the synthesis of a series of dialkylaminoalkoxy derivatives of methyl p-nitrophenylacetate for testing as anti-histamine or hay fever drugs.

Le cytochrome P450 3A4 hépatique humain (CYP3A4) est le cytochrome P450 le plus abondant. Celui-ci est impliqué dans la dégradation de plus de 50% des médicaments que nous absorbons. Les cytochromes P450 forment une grande famille d'enzymes, caractérisée par la présence d'un hème au site actif, que l'on retrouve chez tous les organismes vivants. La réaction générale catalysée par les cytochromes P450 est une réaction d'oxygénation de substrats qui consomme de l'oxygène et du NADPH. L'étude du CYP3A4 nous a permis de constater que le site actif de cette enzyme est très sensible à la pression et qu'il était essentiel de privilégier un mode de lyse des cellules exprimant le CYP3A4 aux ultra-sons. L'expression en grande quantité du polypeptide a été réussie par l'utilisation en combinaison du vecteur d'expression pET-30a et de la souche Escherichia coli C41 (DE3). Les premières études de spectroscopie de résonance Raman du CYP3A4 purifié nous ont permis d'assigner le mode de vibration VFe-co comme étant situé à 476 cm"1 . De plus les spectres de résonance Raman dans la région des basses fréquences n'ont démontré qu'un très léger déplacement du mode VFeco lors de l'ajout des substrats imipramine et nifédipine. Ce résultat est compatible avec le fait que le site actif du CYP3A4 est flexible et relativement grand de sorte que la molécule de CO liée à Thème n'est presque pas été affectée par l'ajout de ces substrats.

Estudou-se em casa-de-vegetação o efeito do volume de terra no desenvolvimento das plantas de feijão e milho, na absorção de fósforo pelas culturas e na determinação do P isotopicamente trocável (Valor L), em função do periódo de desenvolvimento dessas culturas e dois níveis de fertilidade do solo quanto ao fósforo. Avaliou-se também o efeito do P na planta proveniente da semente no cálculo do Valor L (L: valor L calculado sem descontar o P proveniente da semente e L (-Ps): valor L calculado descontando o P proveniente da semente). O estudo foi realizado com Latossolo Vermelho-amarelo em vasos plásticos contendo: 0,5; 1,0; 2,0; 4,0; 8,0; 12,0 e 18,0 L de terra; com e sem adubação de P (50 mg kg-1 terra de P) e colhendo as plantas em dois períodos: 30 e 50 dias após a germinação. O delineamento experimental foi inteiramente casualizado com 3 repetições no esquema fatorial 7x2x2. As variações nos períodos de colheita e níveis de fertilidade são representadas por: E1F1 (30 dias, sem adubação), E1F2 (30 dias, adubado), E2F1 (50 dias, sem adubação) e E2F2 (50 dias, adubado). A concentração de P nas plantas não foi um parâmetro adequado para estabelecer o estado nutricional das plantas e os vasos de 0,5 e 1,0 L tiveram desenvolvimento prejudicado e conseqüentemente no conteúdo de P, não sendo também adequados para determinação do valor L. Houve efeito do P na planta proveniente da semente no valor L para volumes de terra menor que 4,0 L para plantas de feijão e 8,0 L para plantas de milho. O volume de terra de 2,0 L é recomendado para estudos do valor L e L (-Ps) em plantas de feijão para as seguintes variáveis: E1F1, E1F2, E2F1 e em plantas de milho para E1F1 e E2F1. Para valor L e L (- Ps) em plantas de feijão para E2F2 e em plantas de milho para E1F2 e E2F2, recomenda-se o volume de terra de 4,0 L. A maior produção de massa seca e de conteúdo de P em plantas de feijão E1F2 foram obtidos com 12,0 L. Vasos com volume de terra de 13,0 L são os indicados para avaliação do desenvolvimento em plantas de milho E1F2 e E2F1. Com 14,0 L de terra obteve-se o maior conteúdo de P e massa seca em plantas de feijão E1F2 e conteúdo de P em plantas de milho E1F1. O volume de terra de 15,0 L é indicado para conteúdo de P em plantas de milho E1F2. Para a obtenção da máxima produção de massa seca em feijão em ambos os solos e épocas (E2F1 e E2F2) e milho no solo adubado e 50 dias (E2F2), assim como para conteúdo de P para feijão no E2F1 e E2F2 e milho E2F2, há necessidade de se usar vaso com volume de terra maior que 18,0 L. / The effect of soil volume on the growth of bean and corn crop, phosphorus uptake and isotopically exchangeable P (L value), as affected by the plant growing period and two soil P fertility level were studied in green house. The effect of seed derived P in the plant on the L value (L: L value calculated without discounting the seed derived P and L (- Ps): L value calculated discounting the seed derived P) was also evalueted. The study was carried out in plastic pots containing: 0.5; 1.0, 2.0, 4.0, 8.0, 12.0 and 18.0 L of Red Yellow Latosol, with and without P addition (50 mg kg-1 soil P) and harvesting the plants in two periods: 30 and 50 days after seeding. The experimental design was completely randomized with 3 replications in 7x2x2 factorial scheme. The variations in harvest period and soil P fertility level are presented as: E1F1 (30 days, without P application), E1F2 (30 days, with P), E2F1 (50 days, without P) and E2F2 (50 days, with P). The plant P concentration was not an adequate parameter for establishing the plant nutritional state. The plants of 0.5 and 1.0 L pots had their growth limited, which consequently affected the P content, therefore also not being adequate for the L value determination. There was effect of seed derived P on L value for soil volumes smaller than 4.0 L for bean plants, and 8.0 L for corn plants. The 2.0 L soil volume is recommended for L and L (-Ps) values studies with bean plants to the following variables: E1F1, E1F2, E2F1 and with corn plants to E1F1 and E2F1. For L and L (-Ps) values in beans plants to E2F2 and with corn plants to E1F2 and E2F2, the 4.0 L soil volume is recommended. The highest dry matter weight and P content in E1F2 bean plants were obtained with 12.0 L soil volume. Pots with 13.0 L soil are indicated for growth evaluation of E1F2 and E2F1 corn plants. The highest P content and dry matter weigh of E1F2 bean plants and E1F1 corn plants P content were obtained with 14.0 L soil volume. The 15.0 L soil volume is suggested for the P content study with E1F2 corn plants. For obtaining maximum dry matter yield of bean plants in both soils and growth periods (E2F1 and E2F2) and of corn in P fertilized soil harvesting at 50 days (E2F2), as well as for P content of E2F1 and E2F2 bean plants and E2F2 corn plants, pots with larger soil volume than 18.0 L should be used.

Cette thèse est consacrée à l’étude des groupes linéaires définissables dans les corpsp-adiques. Les tores anisotropes jouent un rôle central tout au long de ce travail. Nousdonnons une description modèle-théorique et algébrique des Qp-tores anisotropes dedimension 1.L’étude des sous-groupes de Cartan de SL2(Qp) (où Qp est un corps élémentairementéquivalent à Qp) nous permet de donner une description complète de tous les sous-groupes définissables de SL2(Qp).Nous nous intéressons également aux groupes linéaires définissables dans des enri-chissements p-minimaux d’un corps p-adiquement clos. Nous introduisons une notionde p-connexité pour les groupes. Et nous établissons que tout groupe linéaire com-mutatif p-connexe définissable dans une telle structure est isomorphe à un groupesemi-algébrique.Enfin des résultats sur la généricité et la générosité dans SL2(Qp) sont donnés. / This thesis is dedicated to the study of linear definable groups in p-adic fields. Ani-sotropic tori play an important role in this work. We give a model-theoretic andalgebraic description of anisotropic Qp-tori of dimension 1.The study of Cartan subgroups in SL2(Qp) (where Qp is a field elementarily equi-valent to Qp) permit us to give a complete description of all definable subgroups ofSL2(Qp).We are seeing also linear groups definable in p-minimal expansions of p-adically closedfields. We introduce a notion of p-connexity for groups. We etablish that every linearcommutative p-connected group definable in such structure is isomorphic to a semi-algebraic group.Finally some results on genericity and generosity in SL2(Qp) are given.

Estudou-se em casa-de-vegetação o efeito do volume de terra no desenvolvimento das plantas de feijão e milho, na absorção de fósforo pelas culturas e na determinação do P isotopicamente trocável (Valor L), em função do periódo de desenvolvimento dessas culturas e dois níveis de fertilidade do solo quanto ao fósforo. Avaliou-se também o efeito do P na planta proveniente da semente no cálculo do Valor L (L: valor L calculado sem descontar o P proveniente da semente e L (-Ps): valor L calculado descontando o P proveniente da semente). O estudo foi realizado com Latossolo Vermelho-amarelo em vasos plásticos contendo: 0,5; 1,0; 2,0; 4,0; 8,0; 12,0 e 18,0 L de terra; com e sem adubação de P (50 mg kg-1 terra de P) e colhendo as plantas em dois períodos: 30 e 50 dias após a germinação. O delineamento experimental foi inteiramente casualizado com 3 repetições no esquema fatorial 7x2x2. As variações nos períodos de colheita e níveis de fertilidade são representadas por: E1F1 (30 dias, sem adubação), E1F2 (30 dias, adubado), E2F1 (50 dias, sem adubação) e E2F2 (50 dias, adubado). A concentração de P nas plantas não foi um parâmetro adequado para estabelecer o estado nutricional das plantas e os vasos de 0,5 e 1,0 L tiveram desenvolvimento prejudicado e conseqüentemente no conteúdo de P, não sendo também adequados para determinação do valor L. Houve efeito do P na planta proveniente da semente no valor L para volumes de terra menor que 4,0 L para plantas de feijão e 8,0 L para plantas de milho. O volume de terra de 2,0 L é recomendado para estudos do valor L e L (-Ps) em plantas de feijão para as seguintes variáveis: E1F1, E1F2, E2F1 e em plantas de milho para E1F1 e E2F1. Para valor L e L (- Ps) em plantas de feijão para E2F2 e em plantas de milho para E1F2 e E2F2, recomenda-se o volume de terra de 4,0 L. A maior produção de massa seca e de conteúdo de P em plantas de feijão E1F2 foram obtidos com 12,0 L. Vasos com volume de terra de 13,0 L são os indicados para avaliação do desenvolvimento em plantas de milho E1F2 e E2F1. Com 14,0 L de terra obteve-se o maior conteúdo de P e massa seca em plantas de feijão E1F2 e conteúdo de P em plantas de milho E1F1. O volume de terra de 15,0 L é indicado para conteúdo de P em plantas de milho E1F2. Para a obtenção da máxima produção de massa seca em feijão em ambos os solos e épocas (E2F1 e E2F2) e milho no solo adubado e 50 dias (E2F2), assim como para conteúdo de P para feijão no E2F1 e E2F2 e milho E2F2, há necessidade de se usar vaso com volume de terra maior que 18,0 L. / The effect of soil volume on the growth of bean and corn crop, phosphorus uptake and isotopically exchangeable P (L value), as affected by the plant growing period and two soil P fertility level were studied in green house. The effect of seed derived P in the plant on the L value (L: L value calculated without discounting the seed derived P and L (- Ps): L value calculated discounting the seed derived P) was also evalueted. The study was carried out in plastic pots containing: 0.5; 1.0, 2.0, 4.0, 8.0, 12.0 and 18.0 L of Red Yellow Latosol, with and without P addition (50 mg kg-1 soil P) and harvesting the plants in two periods: 30 and 50 days after seeding. The experimental design was completely randomized with 3 replications in 7x2x2 factorial scheme. The variations in harvest period and soil P fertility level are presented as: E1F1 (30 days, without P application), E1F2 (30 days, with P), E2F1 (50 days, without P) and E2F2 (50 days, with P). The plant P concentration was not an adequate parameter for establishing the plant nutritional state. The plants of 0.5 and 1.0 L pots had their growth limited, which consequently affected the P content, therefore also not being adequate for the L value determination. There was effect of seed derived P on L value for soil volumes smaller than 4.0 L for bean plants, and 8.0 L for corn plants. The 2.0 L soil volume is recommended for L and L (-Ps) values studies with bean plants to the following variables: E1F1, E1F2, E2F1 and with corn plants to E1F1 and E2F1. For L and L (-Ps) values in beans plants to E2F2 and with corn plants to E1F2 and E2F2, the 4.0 L soil volume is recommended. The highest dry matter weight and P content in E1F2 bean plants were obtained with 12.0 L soil volume. Pots with 13.0 L soil are indicated for growth evaluation of E1F2 and E2F1 corn plants. The highest P content and dry matter weigh of E1F2 bean plants and E1F1 corn plants P content were obtained with 14.0 L soil volume. The 15.0 L soil volume is suggested for the P content study with E1F2 corn plants. For obtaining maximum dry matter yield of bean plants in both soils and growth periods (E2F1 and E2F2) and of corn in P fertilized soil harvesting at 50 days (E2F2), as well as for P content of E2F1 and E2F2 bean plants and E2F2 corn plants, pots with larger soil volume than 18.0 L should be used.

Les partitions pour pipa de Dunhuang (fin dynastie Tang, début époque Song), copiées sur les manuscrits P. 3539, P. 3808 et P. 3719 conservés à la BnF ont été découvertes par Paul Pelliot en 1908 dans la grotte numéro 17 du site de Mogao en Chine. Cette thèse décrit les influences musicales et culturelles apportées en Chine par la route la soie, notamment la musique koutchéenne, puis réalise le bilan des études de ces partitions, menées depuis plus de soixante-quinze ans par les plus grands spécialistes dont Hayashi Kenzō, Ren Erbei, Rao Zongyi, Ye Dong, He Changlin, Chen Yingshi, Xi Zhenguan, Rembrandt Wolpert et François Picard. Il est admis qu’il s’agit de partitions en tablature pour un luth pipa à quatre cordes et quatre frettes, tel qu’il existait à l’époque. Les discussions en cours entre les chercheurs sur la tonalité, le rythme et le tempo, l'origine, le genre et l'organisation de ces pièces sont exposés et critiqués. Le logiciel conçu d'après mes spécifications pour faciliter leur étude et produire leur transcription sur portée est décrit. Mes propositions de transcription des vingt-cinq pièces de P. 3808 sont analysées en détail et comparées entre-elles. L'enregistrement de leur interprétation sur pipa de Nanyin, instrument actuel le plus proche des anciens luths, constitue l'aboutissement de ce travail. / The Dunhuang pipa scores (end of Tang dynasty, beginning of Song period), copied on the manuscripts P. 3539, P. 3808 and P. 3719, now kept in the BnF, were discovered by Paul Pelliot in 1908 in the Mogao cave number 17 in China. This thesis describes the musical and cultural influences brought to China by the silk road, including Kuchan music, then reviews the studies of these partitions, conducted over seventy-five years by leading experts including Hayashi Kenzō, Ren Erbei, Rao Zongyi, Ye Dong, He Changlin, Chen Yingshi, Xi Zhenguan, Rembrandt Wolpert and François Picard. It is recognized that they are tablature partitions for a pipa lute with four strings and four frets, as it existed at that time. Ongoing discussions between researchers about the tone, rhythm and tempo, origin, gender and organization of these scores are exposed and criticized. The software designed according to my specifications to facilitate their study and produce their transcription is described. My transcription proposals of the twenty-five pieces of P. 3808 are analysed in detail and compared with each other. The recording of their interpretation with a Nanyin's pipa, current instrument closest to the ancient lutes, is the culmination of that work.

Phosphorus plays a crucial role in modern p-block chemistry.1 One reason for that is the diagonal relationship between phosphorus and carbon.2 Comparable to carbon and its chemistry, phosphorus tends to form homoatomic bonds, which is explainable by the relatively high P–P single bond energy (ca. 200 kJ/mol).3 Thus, a plethora of poly-phosphorus compounds are reported in the last decades comprising of fascinating bonding motifs4 and interesting applications in coordination5-7 and synthetic8-11 chemistry, as well as in ligand design.12,13 A crucial point in the chemistry of polyphosphanes is of course the formation of P–P bonds. Numerous synthetic procedures are established and reviewed including salt metathesis,4a,14 dehalosilylation15 and dehalostannylation16 reactions, base promoted dehydrohalogenation reactions17 and dehydrogenative coupling reactions mediated by main group compounds18 or catalysis by transition metals.5,19 Moreover, dialkylamino-substituted phosphanes are used in condensation reactions to form P–P bonds since the early 1960’s. Yet these reactions need elevated temperatures, somewhat limiting the formation of polyphosphorus compounds as stated by the few examples reported.17d,20 The application of pyrazolyl-substituted phosphanes in P–P bond formation reactions is a relatively young field of research.21 Their synthesis and general chemical behavior as well as advantages in comparison to dialkylamino-substituted phosphanes is discussed in the following chapter.

在這篇論文裡, 我們探討體中之賦值的一般理論. 最主要的, 我們證明了多個賦值等價條件. 進而我們探討p進位數體中的分析, 得到ㄧ些新的現象與例子. / In this thesis, we study some general theory of valuations on a field. Especially, we obtain several equivalent conditions on the equivalence of two valuations on a field, some of them are new in the literature. Moreover, we study the $p$-adic analysis on the p-adic number fields and obtain some new phenomena and examples.

Consistent efficacy in human clinical trials has been achieved by two leading malaria vaccine candidates encoding either the P. falciparum circumsporozoite (CSP) or thrombospondin-related adhesion (TRAP) proteins. However, protection in humans relies on high antibody (Ab) titers or potent T cells, respectively, when these antigens are used individually. Therefore, a concurrent induction of both anti-CSP antibodies and TRAP-specific T cells may further improve the protective efficacy associated with these immunogens. This thesis investigates the protective potential associated with CSP and TRAP combination vaccines by employing a pre-clinical Plasmodium berghei (P. berghei) mouse malaria challenge model. Depletion of CD4⁺ and CD8⁺ T cells indicated that protection by the CSP antigen relied solely on antibodies while TRAP protected through CD8⁺ T cell responses. Moreover, the administration of relatively small amount of anti-CSP monoclonal antibodies (mAb) substantially enhanced the sub-optimal protection elicited by TRAP. A way to maximize both, anti-CSP antibodies by adenovirus/protein (Ad-P) prime-boost vaccinations and anti-TRAP T cell responses using adenovirus/modified vaccinia strain Ankara (Ad-M), was explored. Combination of the two approaches stimulated optimal humoral and cellular responses that afforded sterile protection in the C57BL/6 animal model. Additional analyses of the effector functions of Abs indicated that the efficacy of this vaccine relied on a two-stage attack against the parasite: anti-CS antibodies reduced the number of sporozoites reaching the liver, thus decreasing the number of infected hepatocytes required to be eliminated by the dual action of natural killer (NK) cells and CD8⁺ T cells. These proof-of-concept studies using a wild-type (wt) P. berghei challenge model allowed progression towards the development of human malaria Plasmodium vivax (P. vivax) vaccines using PvCSP and PvTRAP antigens. The immunogenicity of PvCSP and PvTRAP-based vaccine candidates was assessed in multiple mouse strains. Additionally, transgenic (tg) P. berghei parasites expressing P. vivax genes were generated and used to demonstrate the protective efficacy of Ad-P PvCSP and Ad-M PvTRAP vaccines.

El documento digital no refiere asesor / Presenta la definición de valor absoluto y cuerpo valuado y realiza una demostración de sus propiedades y consecuencias, se apoya en conceptos topológicos y algebraicos. Construye campos de extensión de Q usando los valores absolutos P-ádicos y para cada campo construído se responde a si es algebraicamente cerrado, completo, esféricamente completo, localmente compacto y segundo numerable, así como qué tipo de cardinal tiene y cuál es un subconjunto numerable denso. / Trabajo de suficiencia profesional