Nesse trabalho introduzimos e desenvolvemos a teoria de hiper-ideais de aplicações multilineares contínuas e polinômios homogêneos contínuos entre espaços de Banach. A ideia central é refinar os conceitos de multi-ideais e de ideais de polinômios com o objetivo de explorar de forma mais aprofundada a natureza não-linear das aplicações envolvidas. Para isso tomamos a teoria de ideais de operadores lineares, aplicações multilineares e polinômios homogêneos, desenvolvida a partir dos trabalhos de Pietsch, tanto no caso linear como no caso multilinear, como referencial. Provamos resultados gerais para hiper-ideais, damos muitos exemplos ilustrativos, e desenvolvemos métodos para gerar hiper-ideais, tanto no caso multilinear como no caso polinomial. / In this work we introduce and develop the theory of hyper-ideals of multilinear mappings and homogeneous polynomials between Banach spaces. The main idea is to refine the concepts of multi-ideal and of ideal of polynomials with the purpose of exploring deeply the nonlinear nature of the underlying mappings. To do this we take the ideal theory of linear operators, multilinear mappings and homogeneous polynomials, developed from the works of Pietsch, both in the linear and nonlinear cases, as a reference. We prove general results for hyper-ideals, provide a number of illustrative examples, and develop methods to generate hyper-ideals of multilinear mappings, as well as of hyper-ideals of homogeneous polynomials.

Submitted by Jaqueline Silva (jtas29@gmail.com) on 2014-09-16T17:01:54Z No. of bitstreams: 2 Naves, Emílio Santiago-2014-tese.pdf: 587232 bytes, checksum: 384bbcad6790ecde844af07f4c8deed9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-09-16T17:02:18Z (GMT) No. of bitstreams: 2 Naves, Emílio Santiago-2014-tese.pdf: 587232 bytes, checksum: 384bbcad6790ecde844af07f4c8deed9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-16T17:02:18Z (GMT). No. of bitstreams: 2 Naves, Emílio Santiago-2014-tese.pdf: 587232 bytes, checksum: 384bbcad6790ecde844af07f4c8deed9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-11-08 / This work presents results for the dynamic (hyper)polarizabilities of ozone, sulfur dioxide, nitrous oxide and carbon dioxide molecules, with inclusion of vibrational corrections. The electronic contributions for the properties of interest were computed analytically at the single and double coupled cluster level through response theory. Ozone and sulfur dioxide were studied separately. For both systems, contributions of connected triple excitations were also estimated by the multiplicative correction scheme. The vibrational corrections were calculated by the perturbation theoretical method (PT). The zero-point vibrational average correction, calculated only for ozone and sulfur dioxide, proved to be small. Results also show that the pure vibrational correction is relevant for the following nonlinear optical processes: dc-Pockels effect, intensity dependent refractive index, and dc-Kerr effect. For the ozone molecule the dc-second harmonic generation effect also had a significant pure vibrational correction. In addition, pure vibrational correction was calculated according to a variational methodology proposed by our research group (VAR) for the four systems, and the results were compared with the corresponding PT results. A comparison between PT and VAR results shows that ozone is the system most sensitive to the method, while sulfur dioxide and carbon dioxide are the most well behaved. / Neste trabalho são apresentados resultados para as (hiper)polarizabilidades dinâmicas das moléculas de ozônio, dióxido de enxofre, óxido nitroso e dióxido de carbono, com inclusão de correções vibracionais. As contribuições eletrônicas das propriedades de interesse foram computadas analiticamente através da teoria de resposta no nível coupled cluster com substituições simples e duplas. O ozônio e o dióxido de enxofre foram estudados separadamente. Para ambos os sistemas, as contribuições das substituições triplas conexas também foram estimadas através do esquema de correção multiplicativa. As correções vibracionais foram calculadas por meio dométodo de perturbação teórica (PT). A correção da média vibracional de ponto zero, calculada apenas para o ozônio e o dióxido de enxofre, revelou-se pequena. Os resultados também mostram que a correção vibracional pura é relevante para os seguintes processos ópticos não lineares: efeito dc-Pockels, índice de refração dependente da intensidade e efeito dc-Kerr. Para a molécula de ozônio o efeito de geração de segundo harmônico dc também teve uma correção vibracional pura significativa. Em adição, a correção vibracional pura foi calculada segundo uma metologia variacional proposta pelo nosso grupo de pesquisa (VAR) para os quatro sistemas, e os resultados foram comparados com os respectivos resultados PT. Uma comparação entre os resultados PT e VAR mostra que o ozônio é o sistema mais sensível ao método, ao passo que o dióxido de enxofre e o dióxido de carbono são os mais bem comportados.

Pathogenesis, diagnosis and treatment, the essential domains in medical practice, seem helpless to address Alzheimer's disease (AD). With a huge mortality rate, it is looming and threatening the socioeconomic barrier. Despite many different studies, the pathogenesis of AD remains inconclusive. However, growing numbers of studies suggest oxidative stress to contribute to the initiation and progression of AD. We propose an iron hypothesis: iron mediated oxidative damage by reactive oxygen species (ROS), which induces protective roles of amyloid beta and hyper-phosphorylated tau (HP-tau) to sequester iron and limit the disease. We propose to study such mechanism using transgenic mice models for AD, inducing oxidative stress to elevate intracellular iron, and analyze its co-localization with proteins using Magnetic Resonance Imaging (MRI), 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Western blot. We report three primary findings: 1) a significant loss in T2 signal over bilateral hippocampi of transgenic mice compared to the wild types (WT) by three months, corresponding to early disease and the ability of proteins to sequestration iron. Ability of rescue treatments to impede disease progression reflected as preserved T2 signal intensities over these areas throughout our study period of nine months. 2) Concentration of zinc and its dual role in the presence or absence of oxidative stress reflected as loss of 1H NMR T2 measurement showed that higher concentrations of zinc were neuro protective when there was an active oxidative stress inducing condition, but neurotoxic and promote oxidative damage in normal condition. And 3) Different strains of mice, according to their transgene, expressed various proteins associated with AD. However, these expressions were in accordance with our iron-hypothesis.

This thesis is a commentary on Patrick McCabe's novel, The Butcher Boy, which was published in 1992. The novel is told through the perspective of the main character, Francie Brady, who through the majority of the narration is depicted as a young boy. Francie's life is riddled with tragedy with his moving from the loss of one important person in his life to another until the pain of these losses triggers a violent paranoid outburst resulting in the murder of the fixation of an obsession of his, Mrs. Nugent. This thesis looks at the events of the novel through the perspective and insight provided by Ursula K. Heise's theories of "posthistory" and the "hyper-present," as well as Paul Grainge's concepts of the "Mood" and the "Mode" of nostalgia.

Le clan « arrestine » est une superfamille de protéines adaptatrices regroupant les arrestines conventionnelles (β-arrestines et arrestines visuelles), bien décrites pour leur rôle dans la régulation des récepteurs membranaires couplés aux protéines G hétéro-trimériques et la signalisation associée et des protéines de type arrestin-like identifiées plus récemment, qui semblent partager des fonctions communes dans la régulation et le trafic de cargos membranaires. Ce travail de thèse a porté sur l'étude de la protéine arrestin-like AdcA de Dictyostelium discoideum dans l'objectif d'en définir le rôle fonctionnel. En plus de son module arrestine, caractéristique de cette famille de protéines, AdcA possède un domaine FYVE qui permet son association à la voie endocytaire, un domaine C-terminal riche en tyrosines et un domaine N-terminal riche en histidines impliqué dans son oligomérisation. Mes travaux ont permis d'établir que la protéine AdcA répond à des stress de natures diverses dont l'hyper-osmolarité, par une multi-phosphorylation massive, notamment au niveau du domaine N-terminal. La sensibilité d'AdcA à la dépolymérisation du réseau d'actine suggère un lien fonctionnel entre le cytosquelette d'actine et la cascade de signalisation menant à la phosphorylation de la protéine. En conditions de stress modéré, la phosphorylation d'AdcA est transitoire et sa déphosphorylation, en partie dépendante du facteur de transcription STATc, corrèle avec l'adaptation des cellules aux conditions de stress. Cette modification post-traductionnelle transitoire pourrait permettre de contrôler l'activité d'AdcA et d'optimiser la réponse des cellules au stress. Parallèlement, la caractérisation fonctionnelle d'un partenaire d'AdcA, la protéine FrmC, a été entreprise. FrmC est une nouvelle protéine, encore non caractérisée, présentant plusieurs domaines fonctionnels dont un domaine FERM capable de lier l'actine in vitro et un domaine à motifs LRR. Mes travaux ont notamment mis en évidence que FrmC est recrutée à la membrane plasmique et joue un rôle dans l'adhésion cellulaire. Par ailleurs, l'absence de FrmC affecte l'adaptation des cellules et la réponse d'AdcA en situation de stress hyper-osmotique. / The arrestin clan represents a large group of adaptor proteins which includes the canonical arrestins - β-arrestins and visual arrestins – well described for their role in the regulation of membrane receptors coupled to heterotrimeric G-proteins and associated signaling as well as arrestin-like proteins identified more recently that seem to share functions in the regulation and trafficking of membrane cargoes. This work focused on the study of the arrestin-like protein AdcA of Dictyostelium discoideum, to determine the functional role of this atypical member. In addition to the arrestin module common to all the members of the arrestin family, AdcA harbors a FYVE domain responsible for its association to the endocytic pathway, a C-terminal tyrosine-rich domain and an N-terminal extension rich in histidine residues mediating its oligomerization. I have established that AdcA responds to a variety of stresses such as hyperosmolarity by a massive multi-phosphorylation of the protein. Sensitivity of AdcA to changes in F-actin polymerization status suggests a link between the signaling cascade leading to AdcA phosphorylation and the actin cytoskeleton. In conditions of moderate stress, AdcA response is transient and its dephosphorylation depends on the transcription factor STATc and correlates with cell adaptation to the stress conditions. This post-translational modification of AdcA could modulate its activity and optimitize the cell response to stress. In parallel, the functional characterization of a partner of AdcA, the protein FrmC, has been undertaken. This so-far uncharacterized protein presents a multimodular structure with a FERM domain able to bind F-actin in vitro and several leucine-rich repeats (LRR). I have shown that FrmC is recruited to the plasma membrane and is involved in cell-substrate adhesion. In addition, disruption of FrmC affects cell adaptation and AdcA response in conditions of hyperosmotic stress.

Solar energy is incident on the earth's surface in both short-wave and long-wave parts of the spectrum. The short-wave part of the spectrum is of special interest to oceanographers since the vertical distribution of temperature in the top layer of the ocean is mostly determined by the vertical attenuation of short-wave radiation. There are numerous studies regarding the temperature evolution as a function of time (see Chapter 2 for details). The diurnal and seasonal variation of the heat content (and hence temperature) of the ocean is explored in this thesis. The basis for such heat budget simulation lies in the fact that the heat budget is the primary driver of ocean currents (maybe secondary to wind effects) and these circulation features affect the biological and chemical effects of that region. The vertical attenuation of light (classified to be in the 300-700 nm range) in the top layer of the ocean has been parameterized by several authors. Simpson and Dickey (1981) in their paper have listed the various attenuation schemes in use till then. This includes a single-exponential form, a bimodal exponential form, and a spectral decomposition into nine spectral bands, each with their specific exponential functions with depth. The effects of vertical light attenuation have been investigated by integrating the light models into a 1D and a 3D turbulence closure model. The main part of the thesis is the inclusion of a bottom effect in the shallow waters. Bottom serves two purposes, it reflects some light based on its albedo and it radiates the rest of the light as heat. 1-D simulation including bottom effects clearly indicates the effect of light on the temperature profile and also the corresponding effect on salinity profiles. An extension of the study includes a 3D simulation of the heat budget and the associated circulation and hydrodynamics. Intense heating due to the bottom leads to the formation of hyper-saline waters that percolate down to depths of 50 m in the summer. Such plumes have been simulated by using a 3D numerical ocean model and it is consistent with observations from the Bahamas banks.

Un spectrographe hyper-Raman très lumineux a été développé pour étudier les vibrations des matériaux. Les résultats obtenus sur ce dispositif sont comparés aux spectroscopies vibrationnelles classiques (Diffusion inélastique des neutrons, absorption infrarouge, diffusion Raman). L'analyse des règles de sélection a permis de préciser la nature des modes de vibrations dans les verres d'oxydes v-SiO2 et v-B2O3. Il a été nécessaire de s'appuyer sur les données obtenus dans des verres binaires xNa2O(1-x)SiO2 et xLi2O(1-x)B2O3, ainsi que dans une série de verres de silices densifiées de manière permanente. Nous montrons en particulier que les modes du pic boson des verres d'oxydes sont essentiellement associés à des mouvements de libration des unités structurales élémentaires qui composent le verre: tétraèdres SiO4 pour la silice et essentiellement les anneaux boroxols B3O3 dans v-B2O3. Nous observons aussi que pour ces deux verres les spectres Raman et hyper-Raman sont dominés par des modes de vibrations associés à des mouvements d'anneaux.

Les checkpoints de l'ADN coordonnent les réponses cellulaires aux dommages de l'ADN et au blocage de la réplication des cellules eucaryotes. Chez Saccharomyces cerevisiae, la protéine kinase Rad53 occupe une place centrale au sein des checkpoints de l'ADN. Afin d'identifier de nouveaux partenaires de Rad53, une approche génétique a été développée, utilisant l'allèle dominant létal RAD53-DL qui déclenche constitutivement des réponses cellulaires normalement induites par des lésions de l'ADN. Notre hypothèse est que l'absence des activateurs ou des substrats de Rad53 pourrait rétablir la croissance. Nous avons donc recherché, à l'échelle du génome de S. cerevisiae, les gènes qui suppriment la toxicité de RAD53-DL lorsqu'ils sont inactivés. 110 gènes ont été isolés et classés en groupes fonctionnels. Un groupe a particulièrement retenu notre attention. Il est composé de huit gènes dont l'inactivation confère à la cellule une hyper-résistance à plusieurs stress génotoxiques. Trois de ces gènes codent des composants du protéasome 26S, l'enzyme central du système de dégradation ubiquitine-dépendante des protéines qui joue un rôle crucial dans la plupart des processus cellulaires. Le protéasome est une structure macromoléculaire très sophistiquée composée d'une partie catalytique, la particule 20S, associée au complexe régulateur 19S, lui même formé de 2 sous-complexes, la base et le couvercle. Son assemblage comprend de nombreuses étapes ordonnées. Au moment du crible, un seul chaperon du protéasome était connu chez la levure, la protéine Ump1, impliquée dans les étapes finales de maturation du protéasome 20S. Par des analyses génétiques et biochimiques, nous avons caractérisé les cinq autres membres du groupe fonctionnel « protéasome », dont la fonction était jusqu'alors inconnue. Les gènes YLR021W, YPL144W, YLR199C et YKL206C, que nous avons baptisés POC1-4 (Proteasome Chaperone), codent 4 protéines formant deux paires de chaperons du protéasome 20S (Poc1-Poc2 et Poc3-Poc4) agissant en amont de Ump1. HSM3 code la première protéine chaperonne de la particule régulatrice du protéasome. Hsm3 s'associe avec la base du 19S et assiste son assemblage. Son rôle est également de réguler l'association du 19S en formation avec le protéasome 20S. Nous avons identifié les homologues mammifères de Poc1-4 (PAC1-4) et Hsm3 (S5b), mettant ainsi en lumière une conservation remarquable des facteurs d'assemblage du protéasome au cours de l'évolution

Ce travail de recherche concerne l'apport de l'approche Aspect à l'ingénierie des systèmes d'information (SI) en général et aux patrons de conception en particulier. L'objectif principal de ce travail est de développer des patrons à base d'aspects afin de faciliter et de guider l'ingénierie de SI par réutilisation de patrons.<br />Les patrons de conception par objets améliorent et accélèrent le développement en favorisant l'évolution, l'adaptation et la réutilisation de SI. Leur utilisation dans une approche strictement Objet pose cependant plusieurs problèmes et limites qui sont principalement liés à la dispersion et à l'enchevêtrement du code de leurs imitations dans l'implémentation des applications. L'approche Aspect permet de nouvelles solutions pour ces patrons contribuant à garder visible et isolée l'imitation de chaque patron dans le code des applications, afin de pallier à leurs problèmes d'utilisation et d'améliorer leur traçabilité et leur réutilisation.<br />Toutefois, un manque de consensus sur les concepts et mécanismes fondamentaux de l'approche Aspect et la diversité des modèles et langages de programmation proposés dans ce courant de recherche rendent difficile l'expression de structures par aspects de patrons indépendamment d'une technique de programmation par aspects particulière. Pour aborder cette difficulté, nous avons adopté une approche par métamodélisation et transformation de modèles. Nous avons basé cette approche sur un métamodèle général intégrant les particularités de l'approche Aspect et deux métamodèles spécifiques à AspectJ et Hyper/J. Les trois métamodèles proposés sont définis comme étant des extensions du métamodèle d'UML. Des règles de transformation sont également proposées.<br />Nous avons utilisé le métamodèle général pour l'expression de nouvelles solutions par aspects des patrons de conception par objets que nous considérons. Cette étude nous a permis de définir un système de huit nouveaux patrons originaux capitalisant des expertises en matière de conception par aspects. Les patrons proposés sont coordonnés et hiérarchisés ce qui permet d'offrir un cadre pour une démarche pour réaliser une conception et une programmation par aspects de qualité.

Telomeres are the outermost parts of linear chromosomes. They consist of tandemly repeated non-coding short nucleotide sequences (TTAGGG in all vertebrates), in humans spanning over the last 2 to 15 kilobase pairs of the chromosome. Due to the end-replication problem, telomeres shorten with each cellular division. A critically short telomere will trigger the cell to enter a state of cellular senescence or to apoptose. The rate of telomere shortening can be accelerated by factors such as oxidative stress and inflammation. Taken together, this contributed to making telomere length a candidate biomarker of health and aging. Studies have shown that leukocyte telomere length progressively shortens with age, and that it independent of age is associated with age-related morbidity, lifestyle factors, and mortality. This thesis was aimed at exploring the relationships of leukocyte telomere length with various functional and structural attributes of the brain. In Paper I, telomere length was shown to be longer among non-demented carriers of the apolipoprotein E (APOE) ε4 allele, a well-established risk factor for Alzheimer’s disease. However, the rate of telomere shortening was greater among the ε4 carriers, possibly due to the higher levels of oxidative stress and inflammation associated with this allele. Furthermore, performance on episodic memory tests was inversely related to telomere length among ε4 carriers. The results may contribute to a better understanding of the pathophysiology related to the APOE ε4 allele. The volume of the hippocampus, a structure in the brain critical for episodic memory function, was in Paper II found to be inversely related to telomere length among non-demented APOE ε3/ε3 carriers. No correlation between hippocampal volume and telomere length was discernible among ε4 carriers, but they fit the pattern exhibited by the ε3/ε3 carriers as they tended to have smaller hippocampi and longer telomere length compared with the ε3/ε3 carriers. The results are possibly explained by a low proliferative activity among subjects with smaller hippocampi, which might also explain the inverse association between telomere length and episodic memory performance in Paper I. In Paper III, we describe results corroborating earlier findings of shorter telomere length among individuals suffering from depression. Moreover, we found that the shorter telomere length among the patients to a large extent could be linked to a hypocortisolemic state; a state which has been associated with chronic stress. The findings corroborate the link between telomere length and stress, and underline the role of stress in depressive illness. Two prominent manifestations of the aging brain are atrophy and white matter hyperintensities. In Paper IV, we report that white matter hyperintensities and cerebral subcortical atrophy were associated with shorter telomere length in aged non-demented individuals. Cortical atrophy was not associated with telomere length. Inflammation may be the underlying cause of the associations, as it is linked to telomere attrition, subcortical atrophy, and white matter hyperintensities. Taken together, these results show that leukocyte telomere length has the potential of being used as a biomarker for structural and functional attributes of the brain. Furthermore, the findings can provide new insights into mechanisms of disease and aging of the brain