L’association entre déficits immunitaires primitifs (DIPs) et manifestations auto-immunes peut sembler paradoxale lorsque l’on aborde les DIPs comme des défauts d’immunité opposés à l’autoimmunité vue comme excès d’immunité adaptative à l’encontre du soi. Néanmoins, loin de se résumer à un simple défaut d’une ou plusieurs composantes du système immunitaire qui prédispose aux infections par divers agents pathogènes, les DIPs sont fréquemment associés à une autoimmunité; parfois révélatrice. Ainsi, les données épidémiologiques issues de registres ou de larges séries de patients atteints de DIPs s’accordent sur une prévalence globale de 25 à 30% de complications auto-immunes (au premier rang desquelles figurent les cytopénies auto-immunes). Différentes hypothèses sont avancées pour rendre compte de l’auto-immunité dans les DIPs. On peut citer : 1°) une perturbation profonde de l’homéostasie lymphocytaire, en particulier dans les déficits immunitaires combinés sévères (CID) avec lymphopénies T et B ; 2°) des défauts intrinsèques des lymphocytes B permettant une rupture de tolérance précoce des LB auto réactifs ; 3°) un comportement aberrant des LT (défaut de maturation, excès d’activation) ; 4°) une absence de lymphocytes T ou de B régulateurs ; 5°) une production inappropriée de certaines cytokines proinflammatoires comme dans les interféronopathies. Ces hypothèses concernent surtout les DIPs pédiatriques sévères. Mon travail de thèse explore la rupture de tolérance immunitaire adaptative au cours des DIPs de l’adulte par différentes approches. Nous nous sommes en particulier attachés au plus fréquent, le DICV (Déficit Immunitaire Commun Variable), déficit immunitaire humoral pas toujours bien défini sur le plan génétique et physiopathologique qui constitue un défi thérapeutique lorsqu’il est compliqué d’une auto-immunité nécessitant un traitement immunosuppresseur. / The association between primary immune deficiency (PID) and autoimmunity may seem paradoxical when PID is considered only as an immune response defect against pathogens and autoimmunity only as an excess of immunity. Nevertheless, far from being simple immune defects increasing the risk of infections, DIPs are frequently associated with autoimmunity. Even more, autoimmunes manifestations can sometimes reveal a PID. Thus, epidemiological data from registers or large series of patients with PIDs agree on an overall prevalence of 25 to 30% of autoimmune complications (with auto-immune cytopenias as first causes). Several hypotheses have been proposed with different underlying mechanisms to explain the tolerance breakdown in PIDs. We can cite : 1°) a severe disturbance of lymphocyte homeostasis, for example in severe combined immunodeficiencies ; 2°) an impaired B-cell developpement with earlystage defects of tolerance ; 3°) a dysregulation of T cells (developpement or activation impairments) ; 4°) a dysfunction of T-reg (or B-reg) ; 5°) an excess of production of proinflammatory cytokines. These hypotheses are especially true for early-onset PIDs (in infancy). In this work (PhD), we explore the mechanisms of tolerance breakdown involved in adults PIDs. We use several approaches to describe the pathways leading to autoimmunity, focusing on the most common PID in adult : CVID (common variable immunodeficiency). This syndrome is not well defined on the genetic and physiopathological level. It is still a therapeutic challenge when complicated by autoimmunity (requiring immunosuppressive therapy).

O presente trabalho analisa o tema das famílias desajustadas no sistema ficcional norte-americano. Os corpora estudados são os contos sobre a família Glass, de J. D. Salinger, e o roteiro do filme The Royal Tenenbaums, escrito por Wes Anderson e Owen Wilson. O enfoque comparatista aqui desenvolvido é duplo: de um lado, o diálogo temático entre a obra dos diferentes autores, de outro lado, a investigação sobre os modos em que os contos de Salinger e o filme dialogam com as demais artes. Desta forma, a leitura crítica aqui efetuada rastreia as estratégias intertextuais e inter-artísticas presentes nos corpora. A análise temática é desenvolvida a partir da definição de um conceito de desajuste. A inadaptação pode ser vista como uma inadequação ou reação do indivíduo ao grupo ou comunidade a que pertence, aos pensamentos, valores e modos de agir desta. Tanto os Glass quanto os Tenenbaums são irmãos que, quando crianças, foram destacadamente brilhantes em atividades comumente desempenhadas por adultos. Ao amadurecer tornaram-se pessoas problemáticas com dificuldades de relacionamento pessoal. Para chegar à síntese da leitura comparativa visualizamos três elementos comuns em ambos os corpora: o conflito do indivíduo com o mundo; a dificuldade da comunicação pessoal (além de discorrermos sobre as estratégias da comunicação ficcional) e a dificuldade em lidar com a instabilidade. Ao final, examino como tais problemas são superados pelos personagens. Além disso, também tentamos descrever como tais obras inserem-se na tradição ficcional norte-americana de produção obras cujo tema principal são as problemáticas relações familiares. / The present work analyses the theme of maladjusted families in the American fictional system. The corpora consists of the short stories about the Glass family, by J. D. Salinger, and the screenplay for The Royal Tenenbaums, written by Wes Anderson and Owen Wilson. The comparative approach here developed is twofold: on the one hand, a thematic dialogue between the different authors' works, on the other hand, a research about the ways in which Salinger's stories and the film dialogue with another arts. Thus, the critical reading searches the intertextual and interartistic strategies present in the corpora. The thematic analysis is developed from a definition of a concept of maladjustment. Maladjustment can be seen as an individual's inadequacy or reaction to the group or community to which he/she belongs, to the thoughts, to the values and ways of behaviour. Both Glass and Tenenbaums are siblings which, when children, were outstandingly brilliant in activities mainly fullfilled by adults. Coming of age they become problematical with difficulties in personal relationship. To summarize the comparative reading we highlight three elements in common to both corpora: the individual's conflict with the world; the difficult of the personal communication (besides the strategies of fictional communication) and the difficulty in deal with instability. Finally, I examine how such problems are overcome by the characters. Besides this, I also try to describe how such works are inserted in the American fictional tradition of producing works whose main theme is the problematic family relationship.

O presente trabalho analisa o tema das famílias desajustadas no sistema ficcional norte-americano. Os corpora estudados são os contos sobre a família Glass, de J. D. Salinger, e o roteiro do filme The Royal Tenenbaums, escrito por Wes Anderson e Owen Wilson. O enfoque comparatista aqui desenvolvido é duplo: de um lado, o diálogo temático entre a obra dos diferentes autores, de outro lado, a investigação sobre os modos em que os contos de Salinger e o filme dialogam com as demais artes. Desta forma, a leitura crítica aqui efetuada rastreia as estratégias intertextuais e inter-artísticas presentes nos corpora. A análise temática é desenvolvida a partir da definição de um conceito de desajuste. A inadaptação pode ser vista como uma inadequação ou reação do indivíduo ao grupo ou comunidade a que pertence, aos pensamentos, valores e modos de agir desta. Tanto os Glass quanto os Tenenbaums são irmãos que, quando crianças, foram destacadamente brilhantes em atividades comumente desempenhadas por adultos. Ao amadurecer tornaram-se pessoas problemáticas com dificuldades de relacionamento pessoal. Para chegar à síntese da leitura comparativa visualizamos três elementos comuns em ambos os corpora: o conflito do indivíduo com o mundo; a dificuldade da comunicação pessoal (além de discorrermos sobre as estratégias da comunicação ficcional) e a dificuldade em lidar com a instabilidade. Ao final, examino como tais problemas são superados pelos personagens. Além disso, também tentamos descrever como tais obras inserem-se na tradição ficcional norte-americana de produção obras cujo tema principal são as problemáticas relações familiares. / The present work analyses the theme of maladjusted families in the American fictional system. The corpora consists of the short stories about the Glass family, by J. D. Salinger, and the screenplay for The Royal Tenenbaums, written by Wes Anderson and Owen Wilson. The comparative approach here developed is twofold: on the one hand, a thematic dialogue between the different authors' works, on the other hand, a research about the ways in which Salinger's stories and the film dialogue with another arts. Thus, the critical reading searches the intertextual and interartistic strategies present in the corpora. The thematic analysis is developed from a definition of a concept of maladjustment. Maladjustment can be seen as an individual's inadequacy or reaction to the group or community to which he/she belongs, to the thoughts, to the values and ways of behaviour. Both Glass and Tenenbaums are siblings which, when children, were outstandingly brilliant in activities mainly fullfilled by adults. Coming of age they become problematical with difficulties in personal relationship. To summarize the comparative reading we highlight three elements in common to both corpora: the individual's conflict with the world; the difficult of the personal communication (besides the strategies of fictional communication) and the difficulty in deal with instability. Finally, I examine how such problems are overcome by the characters. Besides this, I also try to describe how such works are inserted in the American fictional tradition of producing works whose main theme is the problematic family relationship.

O presente trabalho analisa o tema das famílias desajustadas no sistema ficcional norte-americano. Os corpora estudados são os contos sobre a família Glass, de J. D. Salinger, e o roteiro do filme The Royal Tenenbaums, escrito por Wes Anderson e Owen Wilson. O enfoque comparatista aqui desenvolvido é duplo: de um lado, o diálogo temático entre a obra dos diferentes autores, de outro lado, a investigação sobre os modos em que os contos de Salinger e o filme dialogam com as demais artes. Desta forma, a leitura crítica aqui efetuada rastreia as estratégias intertextuais e inter-artísticas presentes nos corpora. A análise temática é desenvolvida a partir da definição de um conceito de desajuste. A inadaptação pode ser vista como uma inadequação ou reação do indivíduo ao grupo ou comunidade a que pertence, aos pensamentos, valores e modos de agir desta. Tanto os Glass quanto os Tenenbaums são irmãos que, quando crianças, foram destacadamente brilhantes em atividades comumente desempenhadas por adultos. Ao amadurecer tornaram-se pessoas problemáticas com dificuldades de relacionamento pessoal. Para chegar à síntese da leitura comparativa visualizamos três elementos comuns em ambos os corpora: o conflito do indivíduo com o mundo; a dificuldade da comunicação pessoal (além de discorrermos sobre as estratégias da comunicação ficcional) e a dificuldade em lidar com a instabilidade. Ao final, examino como tais problemas são superados pelos personagens. Além disso, também tentamos descrever como tais obras inserem-se na tradição ficcional norte-americana de produção obras cujo tema principal são as problemáticas relações familiares. / The present work analyses the theme of maladjusted families in the American fictional system. The corpora consists of the short stories about the Glass family, by J. D. Salinger, and the screenplay for The Royal Tenenbaums, written by Wes Anderson and Owen Wilson. The comparative approach here developed is twofold: on the one hand, a thematic dialogue between the different authors' works, on the other hand, a research about the ways in which Salinger's stories and the film dialogue with another arts. Thus, the critical reading searches the intertextual and interartistic strategies present in the corpora. The thematic analysis is developed from a definition of a concept of maladjustment. Maladjustment can be seen as an individual's inadequacy or reaction to the group or community to which he/she belongs, to the thoughts, to the values and ways of behaviour. Both Glass and Tenenbaums are siblings which, when children, were outstandingly brilliant in activities mainly fullfilled by adults. Coming of age they become problematical with difficulties in personal relationship. To summarize the comparative reading we highlight three elements in common to both corpora: the individual's conflict with the world; the difficult of the personal communication (besides the strategies of fictional communication) and the difficulty in deal with instability. Finally, I examine how such problems are overcome by the characters. Besides this, I also try to describe how such works are inserted in the American fictional tradition of producing works whose main theme is the problematic family relationship.

Many numeric models simulate the transport of sediment within rivers and streams. Engineers use such models to monitor the overall condition of a river or stream and to analyze the impact that the aggradation and degradation of sediment has on the stability of bridge piers and other features within a stretch of a river or stream. A model developed by the Federal Highway Administration, FST2DH, was recently modified to include the simulation of sediment movement within a channel. The tools for modeling sediment movement with FST2DH remain unproven. This thesis examines the sediment capabilities of FST2DH. It evaluates the sediment results for reasonableness and compares the results to those obtained from a sediment transport model developed by the Army Corps of Engineers, SED2D WES. Resulting concentrations from another program created by the Army Corps of Engineers, SAMwin, provide additional data comparison for FST2DH sediment solutions. Several test cases for laboratory flumes give additional insight into the model's functionality. Finally, this thesis suggests further enhancements for the sediment capabilities of the FST2DH model and provides direction for future research of the sediment transport capabilities of FST2DH. Results show that FST2DH appropriately models sediment movement in channels with clear-water and equilibrium transport rate inflow conditions. Transport formulas found to be functional include the Engelund—Hansen, Yang sand and gravel, and Meyer-Peter—Mueller equations. FST2DH has difficulty modeling channels with user-specified inflow concentrations or transport rates, models with very small particles, models containing hydraulic jumps, and models with small elements. The test cases that successfully run to completion provide appropriate patterns of scour and deposition. Other trends in the results further verify the functionality of many of the sediment transport options in FST2DH.