Cette thèse étend la théorie de Voronoï aux invariants d'Hermite généralisés définis par T. Watanabe pour le groupe linéaire adèlique : elle caractérise via des propriétés de perfection et d'eutaxie les maxima locaux de cet invariant en terme de formes de Humbert. Par l'extension d'inégalités et de méthodes développées dans le cas classique, elle présente les valeurs de ces constantes dans certains cas particuliers. Enfin, elle introduit pour la variété drapeau des notions de design vexillaire et de réseau fortement parfait qui fournissent via la théorie des groupes une large classe d'exemple de réseaux extrême.

L'objectif de cette thèse est d'aboutir à une meilleure compréhension des propriétés des différentes phases du titane. L'étude du titane est im- portante du point de vue fondamental car la compréhension des éléments correspondant au remplissage de la couche 3d est encore loin d'être satis- faisante. Le titane est l'un des premiers éléments de transition. Il possède un nombre encore raisonnable d'électrons à modéliser, tout en présentant les difficultés liées à la modélisation de la couche 3d. Quand les problèmes de modélisation rencontrés ne sont pas spécifiquement liés au titane, mais représentent une tendance générale parmi les éléments de transition, nous étendons notre analyse à d'autres matériaux comme le dioxyde de titane, le cuivre ou le zirconium.

L'objectif de cette thèse est d'aboutir à une meilleure compréhension du diagramme de phase du titane grâce à la théorie de la fonctionnelle de la densité. Ce diagramme comprend 3 phases: la phase alpha, la phase omega de haute pression et la phase beta de haute température. Ceci nécessite de pouvoir prédire les différences d'énergie entre phases avec une très grande précision, car ces écarts sont faibles, environ 50 meV. Or, les calculs ab initio prédisent la phase omega comme la phase la plus stable, en désaccord avec l'expérience. Ce problème existe aussi dans le dioxyde de titane et dans le zirconium. J'ai donc exploré les différentes approximations présentes afin de comprendre laquelle est en cause. Ceci m'a conduite à étudier l'influence des états de semi-coeur et de la fonctionnelle d'échange et corrélation, et à évaluer la contribution de l'énergie de point zéro. J'en ai conclu que c'est l'approximation de la fonctionnelle qui engendre une erreur significative. Une correction possible consiste à tenir compte de l'auto-interaction électronique. Cette correction appliquée aux états de semi-coeur améliore systématiquement les paramètres de maille, mais n'explique pas l'erreur sur la stabilité des phases.<br />Bien que les fonctionnelles d'échanges et corrélation usuelles ne se soient pas révélées suffisamment précises pour décrire le diagrammes de phases du titane, elles sont satisfaisantes pour prédire des propriétés moins fines, comme les constantes élastiques. Toutefois, il est nécessaire que le volume d'équilibre prédit soit précis, car j'ai mis en évidence que ces propriétés dépendent fortement du volume

Submitted by Maryse Santos (maryseeu4@gmail.com) on 2016-08-26T13:19:20Z No. of bitstreams: 1 Ingrid Karina Morales Pinilla- Dissertação de mestrado.pdf: 1065373 bytes, checksum: 0e8a077647bb4c0a7a9acbbe3fe5b9e6 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-09-19T17:32:17Z (GMT) No. of bitstreams: 1 Ingrid Karina Morales Pinilla- Dissertação de mestrado.pdf: 1065373 bytes, checksum: 0e8a077647bb4c0a7a9acbbe3fe5b9e6 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-09-19T17:34:08Z (GMT) No. of bitstreams: 1 Ingrid Karina Morales Pinilla- Dissertação de mestrado.pdf: 1065373 bytes, checksum: 0e8a077647bb4c0a7a9acbbe3fe5b9e6 (MD5) / Made available in DSpace on 2016-09-19T17:34:08Z (GMT). No. of bitstreams: 1 Ingrid Karina Morales Pinilla- Dissertação de mestrado.pdf: 1065373 bytes, checksum: 0e8a077647bb4c0a7a9acbbe3fe5b9e6 (MD5) Previous issue date: 2016-03-01 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / El presente estudio tiene como objetivo investigar, por medio de la Intertextualidad y de la Residualidad Literaria y Cultural, la retomada de valores de la Edad Media en la configuración de los personajes de los libros El Ingenioso Hidalgo Don Quijote de la Mancha (1605), de Miguel de Cervantes e Infortúnios Trágicos da Constante Florinda (1625), de Gaspar Pires de Rebelo. Se verifican vestigios de la mentalidad medieval en la construcción de algunos personajes de ambos libros: sea por la vía de la Intertextualidad de los protagonistas Don Quijote y Florinda (Leandro, en su fase masculina) con Amadís de Gaula del libro homónimo; sea por la vía de la Residualidad de los arquetipos de Eva en los personajes de las narrativas intercaladas, Leandra del Quijote I y Fausta de Constante Florinda I; y de María, madre de Jesús, en las protagonistas Dulcinea del Quijote I y Florinda de Constante Florinda I. En lo que se refiere a la reflexión teórica de la Intertextualidad se recurre, principalmente, a los estudios de Gerard Genette (1989), Affonso Romano de Sant’Anna (2003), Koch, Bentes e Cavalcante (2012). Ya, en lo tocante a la Residualidad Literaria y Cultural, se parte de los conceptos operativos de residuo, hibridación cultural, cristalización y mentalidad, apoyándose en la Teoría de la Residualidad, sistematizada por Roberto Pontes (1999) y en otros autores. / O presente estudo tem como o bjetivo investigar, por meio da Intertextualidade e da Residualidade Literária e Cultural, a retomada de valores da Idade Média na configuração dos personagens dos livros O Engenhoso Fidalgo Dom Quixote de la Mancha (1605), de Miguel de Cervantes e Infortúnios Trágicos da Constante Florinda (1625), de Gaspar Pires de Rebelo. Verificam - se vestígios da mentalidade medieval na construção de alguns personagens de ambos os livros: ora pela via da Intertextualidade dos protagonistas dom Quixote e Florinda (Leandro, na sua face masculina) com Amadis de Gaula do livro homônimo; ora pela via da Residualidade dos arquétipos de Eva nas personagens das narrativas intercaladas, Leandra do Quixote Ie Fausta de Constante Florinda I; e de Maria, mãe de Jesus, nas protagonistas Dulcinéia do Quixote I e Florinda de Constante Florinda I. No que se refere à reflexão teórica da Intertextualidade recorre -se, principalmente, aos estudos de Gerard Genette (1989), Affonso Romano de Sant’Anna (2003), Koch, Bentes e Cavalcante (2012). Já, no tocante à Residualidade Literária e Cultural, parte- se dos conceitos operacionais de resíduo, hibridação cultural, cristalização e mentalidade, apoiando -se na Teoria da Residualidade, sistematizada por Roberto Pontes (1999) e em outros autores.

In classical international law, States alone were the makers and subjects of the law. Times have changed. Contemporary international law admits, not only States as its subjects but also individuals and international organisations; it controls not just the needs of States but also the needs of individuals as it continues to venture into areas which, in the classical era, were exclusively reserved to domestic law. The fact that international law now applies to entities other than States is no longer a subject of controversy both in theory and practice. On the contrary, the question relating to whether international law could originate from a source other than through the consent of States in the positivist sense of the law has remained a question of controversy. The question has been made more complex by the multiplicity of international institutions created by States and vested with authority to perform the functions entrusted to them under international law. The functions they perform influence the behaviours and expectations of both States and individuals; but the powers they exercise belong to the States which delegated the powers. Since the powers are delegated by States, it should follow that the powers be confined by the very fact of delegation to the functions for which the powers had been granted. Such powers cannot be used for any other purpose, perhaps. With this in mind, the question sought to be answered in this work is whether the powers granted to International Court of Justice to “decide disputes” – article 38(1) of the Statute of the Court) – implicates the power of judicial lawmaking. In other words, whether rules and principles arising from the decisions of the Court can be properly referred to as rules and principles of international law. The question becomes quite intriguing when placed within the context of article 38(1)(d) and article 59 of the Statute of the Court on the one hand, and the practice of the Court and of the States appearing before it on the other hand. Articles 38(1)(d) provides: “subject to the provisions of Article 59, judicial decisions and the teachings of the most highly qualified publicists of the various nations, as subsidiary means for the determination of rules of law.” By article 59: “The decision of the Court has no binding force except between the parties and in respect of that particular case”. Notwithstanding the language of the above provisions, it is shown in this work that like judges in municipal law, judges in the ICJ lay down rules and principles having legal implications for the decisions in subsequent cases as well as for the conduct of States, in general, regarding areas within the degrees of the settled case-law of the Court. It is accordingly argued that to the extent that rules and principles in the decisions of the Court are relevant as rules and principles of international law (in subsequent decisions of the Court) to the determination of international law rights and obligations of States, judicial decisions in article 38(1)(d) are a source of international law. This is notwithstanding the unhelpful language of paragraph (d) and the influence of article 59. Concerning article 59, the writer argues that the article has no bearing on the authority of judicial decisions in article 38(1)(d); its real function being to protect the legal rights and interests of States from a decision given in a case to which they were not parties.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

L'objectif de ce travail est l'analyse de la stabilité thermodynamique et de l'inertie chimique de complexes métalliques avec des ligands ou des nanoparticules conçus pour des applications en IRM. Deux types de ligands polyaminocarboxylates ont été étudiés, ligands pour lesquels les unités complexantes sont soit linéaires soit macrocycliques.Les ligands macrocycliques étudiés sont des ligands basés sur des squelettes DO3A, substitués par des entités benzimidazole (L1H4) ou p-nitrophenylbenzimidazole (L2H3). Les données thermodynamiques indiquent que les affinités de ces ligands vis-à-vis des ions de la première série de transition (Cu(II) et Zn(II)) ou vis-à-vis des lanthanides (Gd(III) et Eu(III)) sont plus élevées que celles des complexes correspondants avec le ligand DO3A. Ce renforcement d'affinité est corrélé avec la participation des groupements benzimidazole à la sphère de coordination de chacun des métaux. L'inertie chimique du complexe Gd(III)- L1H4 a ensuite été évaluée par relaxométrie en tampon phosphate, en présence d'une quantité équimolaire de Zn(II). Dans cette expérience, le Zn(II) joue le rôle d'un compétiteur du Gd(III) c'est-à-dire qu'il peut si le complexe Gd(III)-L1H4 n'est pas inerte chimiquement, induire une libération de l'ion gadolinium. Pour Gd(III)-L1H4, aucune réaction de ce type n'a été détectée, ce qui plaide en faveur de l'inertie chimique de ce complexe.Les ligands linéaires étudiés sont des dérivés dithiolés de ligands DTPA bisamide L@1H5. Ces ligands ont été conçus pour être greffés sur des nanoparticules d'or. La stabilité thermodynamique des complexes de Cu(II), Zn(II) et Gd(III) utilisant les ligands L@1H5 et L@1H5 greffé sur nanoparticule d'or (autrement appelé L@2H3) suit l'ordre de stabilité croissant Zn(II) < Cu(II) < Gd(III). Par ailleurs, les résultats montrent que le complexe Gd(III)-L@1H5 est moins stable d'au moins deux ordres de grandeur que le complexe Gd(III)-L@2H3. Ceci suggère qu'une fois greffé sur la nanoparticule, le complexe de gadolinium correspondant gagne en stabilité. Par ailleurs, des études comparatives d'inertie chimique montre que le complexe Gd(III)-L@1H5 greffé sur la nanoparticule a une inertie chimique comparable à celle de l'agent de contraste commercial Gd-DTPA. En revanche lorsque ce complexe est seul, sa vitesse de démétallation est rapide. Le greffage du ligand L@1H5 à la surface de la nanoparticule est donc au bénéfice de la stabilité et de l'inertie chimique de son complexe de Gd(III). Ce gain de stabilité peut être attribué à l''effet de ballast' de la nanoparticule qui rigidifie la structure du complexe et limite sa démétallation. / The aim of this work is to analyse the stability of metal complexes with ligands or nanoparticles of interest in MRI and to study their transmetallation mechanisms in the presence of endogenous cations near physiological pH. Two types of polyaminocarboxylate ligands were studied for which the binding unit was either linear or macrocyclic.Macrocyclic ligands are constituted of a DO3A backbone functionalized with a benzimidazole (L1H4) or a p-nitrophenylbenzimidazole unit (L2H3). Thermodynamic data indicated that the affinities of these ligands towards first row transition metal ions (Cu(II) and Zn(II) or lanthanide ions (Gd(III) and Eu(III)) are increased compared to the corresponding ones with DO3A. This enhancement is correlated to the involvement of the benzimidazole moiety to each metal coordination sphere. For gadolinium complex Gd(III)- L1H4, its kinetic inertness was evaluated in phosphate buffer by relaxometry, in the presence of equimolar quantities of Zn(II) as a competitor. In these conditions, if the complex is not chemically inert, it would be subjected to a transmetallation reaction, that is to say that at least, gadolinium would be released. For Gd(III)-L1H4, no such reaction was detected which is in favour of kinetic inertness of Gd(III)- L1H4.Linear ligand, dithiolated DTPA bisamide L@1H5 was designed with an aim of grafting it onto gold nanoparticles. L@1H5 and the ligand grafted into gold nanoparticle,namely L@2H3, were analysed for their thermodynamic stability towards mainly Cu(II), Zn(II) and Gd(III). Whatever the system, L@1H5 or L@2H3, the general trend of increasing complex stability was Zn(II) < Cu(II) < Gd(III). Furthermore, Gd(III)-L@1H5 complex was less stable than Gd(III)-L@2H3, this latter being 2 orders of magnitude more stable at physiological pH. This suggested that the gadolinium complex stability is enhanced when the ligand is grafted onto the nanoparticle. Moreover, comparative kinetic inertness studies showed that the gadolinium complex Gd(III)-L@1H5 is not chemically inert and demetallates rapidly while the gadolinium complex grafted onto the nanoparticle exhibit almost equal kinetic inertness as Gd-DTPA (Magnevist). The bulky nanoparticle probably rigidifies the structure of the complex and prevents Gd(III)-L@2H3 from an extensive demetallation, which was a good point for the possible use of these nanoparticles in living organisms for imaging applications.

[pt] Este trabalho propõe um gráfico de controle EWMA para observações individuais ou médias amostrais, com a constante de amortecimento variando entre dois valores de acordo com o valor mais recente da estatística EWMA, para obter detecção mais rápida de alterações pequenas a moderadas na média do processo, e sem a complexidade operacional apresentada por outros esquemas adaptativos, pois o tamanho da amostra e o intervalo de amostragem são mantidos fixos. Já existe um outro trabalho propondo a variação da constante de amortecimento dos gráficos EWMA, mas com base em outro critério: Capizzi e Masarotto (2003). O esquema EWMA adaptativo foi combinado com limites de Shewhart para os valores individuais (ou médias amostrais), para acelerar a detecção de grandes deslocamentos da média do processo, também sem aumento da complexidade operacional. Os NMA1´s - números esperados de amostras até um sinal verdadeiro - foram calculados por um método de aproximação numérica usando um modelo matemático por cadeias de Markov, e comparados com os do esquema EWMA tradicional (com parâmetros fixos) e com os do esquema adaptativo de Capizzi e Masarotto (2003). O esquema proposto tende a fornecer NMA1´s menores para alterações na média acima de 1,0 desvio-padrão, e o esquema de Capizzi e Masarotto (2003) tende a fornecer NMA1´s menores para pequenas alterações. Ambos os esquemas possuem melhor desempenho que o gráfico EWMA com parâmetros fixos. Uma vantagem que pode se tornar decisiva para a adoção do esquema proposto é a simplicidade dos cálculos requeridos para o monitoramento. / [en] This work proposes an EWMA process control chart for individual observations or subgroup averages, in which the smoothing constant varies between two values according to the most recent value of the EWMA statistic, in order to achieve faster detection of small to moderate shifts in the process mean, and without the operational complexities presented by other adaptive schemes, since its sample size and sampling interval do not vary. There is one other work proposing the adaptive variation of the smoothing constant of EWMA charts, but based on a different criterion: Capizzi and Masarotto (2003). The adaptive EWMA scheme was combined with Shewhart limits for the individual values (or subgroup averages), to enhance its sensitivity to large shifts, again with no extra operational burden. The out-of-control average run lengths (ARL1´s) were calculated through a numerical approximation method based on a Markov chain model. The ARL1´s were compared of the proposed scheme, of the traditional (fixed parameter) EWMA chart and of Capizzi and Masarottos´s adaptive EWMA scheme. The proposed scheme generally provides the shortest ARL1´s for shifts in the mean above one standard deviation, and Capizzi and Masarotto´s scheme tends to outperform it for smaller shifts. Both schemes perform better than the fixed parameter EWMA. An advantage that can become decisive for the adoption of the proposed scheme is the simplicity of the calculations required for the monitoring.

Mesmo com o grande número de estudos relacionados à proteases do subtipo B e de como suas mutações podem interferir na estrutura, na resistência a inibidores e na eficiência catalítica da enzima, existe ainda uma lacuna de como as mudanças polimórficas de proteases de HIV de outros subtipos de HIV-1 interferem nesses fatores. Nesse contexto insere-se esse trabalho, que utilizou proteases de HIV-1 isoladas de pacientes brasileiros HIV-1 infectados com o subtipo F, e outros dois mutantes, sendo que um do subtipo F e outro do subtipo B para ensaios frente a seis inibidores comercialmente disponíveis: amprenavir, indinavir, lopinavir, nelfinavir, ritonavir e saquinavir. Nossos resultados experimentais revelam que os seis inibidores comerciais estudados são significantemente menos ativos para o subtipo F e para as mutantes quando comparados ao subtipo B. Além disso, os valores de vitalidade dessas proteases também são considerados maiores que os obtidos para a proteína selvagem do subtipo B. O acúmulo de mutações comumente detectadas e o polimorfismo natural tornam a protease selvagem do subtipo F cataliticamente suficiente para manter a viabilidade do vírus e garantir alto grau de resistência cruzada frente a todos os inibidores estudados. / Despite years of intense research around the world, HIV continues to represent considerable therapeutical challenge. In order to gain more insights into resistance of polymorphic mutations of existing HIV subtypes toward commercially available pharmaceutics, we studied inhibition of subtypes B and F HIV proteases (PRs) [native and two mutant enzymes clinically identified in Brazilian patients] by six commercial inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir). Our results show that all these inhibitors have significantly higher Ki values for the subtype F HIV PR (Fwt) and both mutant enzymes than that for the B subtype HIV PR (Bwt). Furthermore, the biochemical fitnesses of these proteases, or their vitalities, are also considerably higher than that of Bwt. The accumulation of commonly detected resistant mutations in HIV PRs with natural polymorphisms turns Fwt sufficiently catalytically active to guarantee the virus viability and confers it a large degree of cross resistance against all studied inhibitors.