Cette thèse a pour objectif de caractériser les circulations de fluides en contexte d’effondrement d’un prisme d’accrétion crustal. Le Metamorphic Core Complex (MCC) de Naxos comprend un système de détachement/décollement caractérisé par mylonites, ultramylonites, cataclasites et failles normales dont les relations géométriques témoignent du litage rhéologique de la croûte continentale. La chimie des inclusions fluides déterminée par l’analyse microthermométrique, la spectroscopie RAMAN, l’ablation laser couplée à l’analyse spectroscopique (LA-ICP-MS), le « crush-leach », et les signatures isotopiques C et H des inclusions fluides permettent d’identifier trois grands types de fluides (1) des fluides salés riche en métaux, ii) des fluides aquo-carboniques en équilibre avec les encaissants métamorphiques, et iii) des fluides aqueux, probablement d’origine météorique. Ces données indiquent que la croûte est subdivisée en deux réservoirs séparés par la transition fragile-ductile. Les fluides météoriques circulent en association avec la déformation fragile de la croûte supérieure alors que les fluides salés et les fluides aquo-carboniques circulent en relation avec la déformation ductile. La géométrie de ces réservoirs évolue lors de la formation du MCC, conjointement avec l’exhumation et le refroidissement des roches métamorphiques. Le passage des roches du réservoir ductile au réservoir fragile est associée à un changement depuis un gradient géothermique élevé (60-100°C/km) vers un gradient géothermique plus faible (35-60°C/km). La transition fragile-ductile correspond ainsi à la fois à une limite rhéologique corrélée à une limite thermique et une limite de perméabilité. / The aim of this thesis is to characterize fluid circulations in the context of the collapse of a crustal accretionary belt. The Naxos Metamorphic Core Complex comprises a detachment/decollement system characterized by mylonites, ultramylonites, cataclasites and normal faults with structural relationships reflecting the rheological layering at the crustal scale. Fluid inclusion chemistry is determined by microthermometry, Raman spectroscopy; laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), crush-leach and stable isotopes (C and H) analyses. These data characterize three different types of fluids: (1) high salinity fluids with a high metal content and high Th, (2) aqueous-carbonic fluids in equilibrium with the wall rocks and (3) aqueous probably surface-derived fluids. These data indicate that the crust is subdivided into two crustal reservoirs separated by the brittle/ductile transition. Surface-derived aqueous fluids circulate in association with the brittle deformation within the upper crust whereas aqueous-carbonic and high salinity fluids circulate in relation with ductile deformation. The characteristics of the trapped fluids indicate that as rocks have passed through the ductile/brittle transition they undergo a drastic change in geothermal gradient from 60 to 100°C/km within a lithostatic pressure regime to 35-60°C/km within a hydrostatic pressure regime. This implies that the fluid circulations are closely related to the rheological layering within the crust and its evolution during crustal extension. The ductile/brittle transition corresponds to a rheological boundary correlated to a thermal boundary and impermeable cap.

<p>Intricate neural circuits underlie all brain functions. However, these neural circuits are highly dynamic. The ability to change, or the plasticity, of the brain has long been demonstrated at the level of isolated single synapses under artificial conditions. Circuit organization and brain function has been extensively studied by correlating neuronal activity with information input. The primary visual cortex has become an important model brain region for the study of sensory processing, in large part due to the ease of manipulating visual stimuli. Much has been learned from studies of visual cortex focused on understanding the signal-processing of visual inputs within neural circuits. Many of these findings are generalizable to other sensory systems and other regions of cortex. However, few studies have directly demonstrated the orchestrated neural-circuit plasticity occurring during behavioral experience. </p> <p>It is vital to measure the precise circuit connectivity and to quantitatively characterize experience-dependent circuit plasticity to understand the processes of learning and memory formation. Moreover, it is important to study how circuit connectivity and plasticity in neurological and psychiatric disease states deviates from that in healthy brains. By understanding the impact of disease on circuit plasticity, it may be possible to develop therapeutic interventions to alleviate significant neurological and psychiatric morbidity. In the case of neural trauma or ischemic injury, where neurons and their connections are lost, functional recovery relies on neural-circuit repair. Evaluating whether neurons are reconnected into the local circuitry to re-establish the lost connectivity is crucial for guiding therapeutic development.</p> <p>There are several major technical hurdles for studies aiming to quantify circuit connectivity. First, the lack of high-specificity circuit stimulation methods and second, the low throughput of the gold-standard patch-clamp technique for measuring synaptic events have limited progress in this area. To address these problems, we first engineered the patch-clamp experimental system to automate the patching process, increasing the throughput and consistency of patch-clamp electrophysiology while retaining compatibility of the system for experiments in <i>ex vivo </i>brain slices. We also took advantage of optogenetics, the technology that enables control of neural activity with light through ectopic expression of genetically encoded photo-sensitive channels in targeted neuronal populations. Combining optogenetic stimulation of pre-synaptic axonal terminals and whole-cell patch-clamp recording of post-synaptic currents, we mapped the distribution and strength of synaptic connections from a specific group of neurons onto a single cell. With the improved patch-clamp efficiency using our automated system, we efficiently mapped a significant number of neurons in different experimental conditions/treatments. This approach yielded large datasets, with sufficient power to make meaningful comparisons between groups.</p> <p>Using this method, we first studied visual experience-dependent circuit plasticity in the primary visual cortex. We measured the connectivity of local feedback and recurrent neural projections in a Fragile X syndrome mouse model and their healthy counterparts, with or without a specific visual experience. We found that repeated visual experience led to increased excitatory drive onto inhibitory interneurons and intrinsically bursting neurons in healthy animals. Potentiation at these synapses was absent or abnormal in Fragile X animals. Furthermore, recurrent excitatory input onto regular spiking neurons within the same layer remained stable in healthy animals but was depressed in Fragile X animals following repeated visual experience. These results support the hypothesis that visual experience leads to selective circuit plasticity which may underlie the mechanism of visual learning. This circuit plasticity process is impaired in a mouse model of Fragile X syndrome. </p> <p>In a separate study, in collaboration with the laboratory of Dr. Gong Chen, we applied the circuit-mapping method to measure the effect of a novel brain-repair therapy on functional circuit recovery following ischemic injury, which locally kills neurons and creates a glial scar. By directly reprogramming astrocytes into neurons within the region of the glial scar, this gene-therapy technology aims to restore the local circuit and thereby dramatically improve behavioral function after devastating neurological injury. We found that direct reprogramming converted astrocytes into neurons, and importantly, we found that these newly reprogrammed neurons integrated appropriately into the local circuit. The reprogramming also improved connections between surviving endogenous neurons at the injury site toward normal healthy levels of connectivity. Connections formed onto the newly reprogrammed neurons spontaneously remodeled, the process of which resembled neural development. By directly demonstrating functional connectivity of newly reprogrammed neurons, our results suggest that this direct reprogramming gene-therapy technology holds significant promise for future clinical application to restore circuit connectivity and neurological function following brain injury.</p>

Ce travail vise à améliorer la compréhension et la modélisation de la rupture des matériaux métalliques à gradient de propriétés. L'application se fait sur des pignons en acier 20MnB5 carbonitrurés insérés dans un "recliner", mécanisme de sécurité des siègesautomobiles. Le traitement de carbonitruration consisteà enrichir en carbone et azote une couche externe despièces en les chauffant dans le domaine austénitiquedans une atmosphère riche en ces deux éléments. Puisles pièces sont trempées afin de déclencher unetransformation martensitique. On obtient ainsi unmatériau à gradient de propriétés, intéressant pour despièces de transmission de puissance comme lesengrenages. Ce projet a commencé par l’analyse de larupture de mécanismes de sièges en test industriel. Celaa confirmé le double comportement à rupture binaire dumatériau : fragile sur une couche externe, ductile àl’intérieur. Un banc d’essai, spécialement conçu pour ceprojet, soumet une dent à un effort latéral jusqu’àrupture complète. Des observations in situ sonteffectuées et la courbe force-déplacement estenregistrée, montrant la diversité de comportement enfonction de la profondeur d'engagement des dents et dela présence ou non de la couche carbonitrurée. Desessais de traction, de flexion 4 points et de cisaillementsur éprouvettes papillons sont utilisés pour mesurer lespropriétés plastiques et calibrer les critères de rupturede la couche carbonitrurée comme de l'acier de base. Laplasticité de Von Mises avec une loi d'écrouissagesimple rend très bien compte de tous ces essaismécaniques. Différents critères de rupture ductile issusde la littérature sont calibrés; ils ne parviennent pas àreprésenter correctement tous les essais réalisés.Un critère plus adapté est donc proposé enconclusion de cette campagne expérimentale. Lasimulation de la rupture dans LS-Dyna est réaliséeavec une technique d'érosion d'éléments dont leslimitations sont discutées. La comparaison avec larupture de dent expérimentale permet d'évaluer lescritères numériques identifiés et d'analyser leslimites actuelles de la simulation, en particulier lanécessité de prendre en compte plus finement àl'avenir le gradient de propriétés mécaniques ainsique les contraintes résiduelles de compression dela couche carbonitrurée. / This work aims at a better understanding and modeling of the failure of gradient metallic materials. It is applied to carbonitrided pinions made out of 20MnB5 steel, inserted in a "recliner", a safety mechanism of automotive seats. Carbonitriding induces high surface hardness while preserving significant core ductility. The experimental analysis of the fracture behavior of seat recliners in an industrial test confirmed the dual failure behavior of the component : brittle external layer, ductile core material. A test bench has been specifically designed for the project: one tooth is submitted to a lateral force until complete failure. In situ observations are performed and the load-displacement curve recorded, showing a variety of behaviors as a function of the teeth engagement depth and of the presence or not of the carbonitrided layer. Experimental tests with various tress states were conducted to measure plastic properties as well as to calibrate fracture criteria, for the carbonitrided layer and for the core steel. Von Mises plasticity and a simple strain hardening curve fit very well all these experiments. As fracture criteria from the literature were unable to predict failure correctly for all the mechanical tests, an adapted criterion has therefore been proposed as an outcome of this extensive mechanical testing campaign. Fracture simulation in LS Dyna has been performed using the element erosion technique, the limitations of which are discussed. Comparison with the experimental tooth fracture measurements allows evaluation of the proposed failure criteria, and enables to stress out and discuss the present limits of the simulation, concluding that it will be necessary in future work to account more finely for the mechanical property gradient together with the compressive residual stresses in the carbonitrided layer.

Dans le cadre des opérations de perçage, les billettes en acier subissent un réchauffage de la température ambiante à une température d’environ 1250°C. Au cours de ce réchauffage, le gradient de température dans les billettes entraîne la détérioration de la santé axiale de celles-ci et est à l’origine de l’apparition de défauts sur le tube formé. Une méthodologie d’analyse des mécanismes à l’origine de ces défauts a été mise en place. Elle se base sur la caractérisation de la santé axiale par essais rhéologiques permettant d’établir des indicateurs de ductilité et par des examens métallurgiques identifiant les défauts internes.L'étude de la sollicitation thermomécanique induite par le réchauffage du produit est analysée à l’aide de simulations numériques par éléments finis et les zones de sollicitations critiques associées au procédé sont identifiées. La caractérisation des anomalies observées sur les billettes est ensuite faite à partir d’essais de fissuration et de simulations numériques X-FeM. L’implémentation d’un critère de rupture en contrainte dans la simulation du cycle de chauffe a permis de définir les valeurs de gradient thermique limite et les courbes de chauffe optimales. Les analyses montrent que les conditions de chauffe en début de cycle thermique ont une forte influence sur la santé axiale des billettes. Les résultats de ces travaux conduisent à des solutions concrètes pour l’amélioration de la productivité. / As part of the piercing operations, billets undergo a reheating process from room temperature to a temperature of about 1250°C. During this heating, the thermal gradient in the billet leads to a deterioration of the axial health and is responsible of the initiation ofdefects on the formed tube.A methodology for the analysis of the mechanisms at the origin of these defects has been established. It is based on first, the characterization of the axial health with hot rheological tests to establish some indicators of ductility and second, on metallurgical analyses to identify the internal defects.Then finite element simulations have been performed to study the thermo-mechanical loadings induced by heating. Critical solicitation zones of the product during the processes have been identified.Finally a characterization of the observed defects into the billets has been led coupling cracks growth tests and X-FeM numerical simulations. The implementation of the experimental stress failure criterion, in the simulation of the heating cycle allows to obtain good values of thermal gradient boundary curves and leads to optimal heating curves.The analysis shows that the conditions at the beginning of the reheating process have a strong influence on the axial health of the billets. The results of these studies lead to friendly industrial solutions for improving productivity.

Made available in DSpace on 2016-08-10T10:38:29Z (GMT). No. of bitstreams: 1 Fernanda Carla Stegani.pdf: 10431040 bytes, checksum: 2702ca1faeabb2d893b8f2971288b01e (MD5) Previous issue date: 2011-12-08 / The Intellectual Disability (ID) is defined as a disability characterized by significant limitations both in intellectual functioning and in the adaptive behavior and it is expressed in practical, social and conceptual skills, originating before the age of 18. It is one of the most common neuropsychiatric disorders in children and adolescents, with a 5% prevalence in our population. The Fragile X Syndrome (FXS) is the most frequent and best documented DI heritable in humans. The phenotype of FXS is associated with mutations in the gene FMR1 (Fragile X Mental Retardation-linked type 1) and it covers a broad spectrum of behavioral and physical involvement. It is caused by a CGG trinucleotide expansion in the first exon of the FMR1 gene located in the region Xq27.3 on the X chromosome Because of its phenotypic diversity, this disease has been under diagnosed in the pediatric population. Among the techniques used for molecular diagnosis of FXS, the MLPA (Multiplex Ligation-dependent Probe Amplification) has been considered promising. In this context, this study aimed to validate the molecular diagnosis of patients suspected of FXS in the Laboratory of Cytogenetics and Molecular Genetics (Lagene) by the MLPA technique. We selected 33 patients referred by medical from public health to Lagene with clinical of FXS. To perform the analysis by MLPA the Salsa MLPA P106-B1 MRX kit was used. The amplificons were obtained only for 15% of the patients. The MLPA kit used did not detect changes in the copy number of the FMR1 gene in any examined patient, being useful the need of other molecular methods to confirm the diagnosis of FXS. Thus, we concluded that such MLPA kit was not useful to detect specific changes in the copy numbers of the FMR1 gene. So the Salsa MLPA Kit P106-B1 MRX should not be used to the trial of patients with FXS. / A Deficiência Intelectual (DI) é definida como uma incapacidade caracterizada por limitações significativas, tanto no funcionamento intelectual quanto no comportamento adaptativo e está expressa nas habilidades práticas, sociais e conceituais, originando-se antes dos 18 anos de idade. É um dos transtornos neuropsiquiátricos mais comuns em crianças e adolescentes, com taxa de prevalência de 5% na população brasileira. A Síndrome do X-Frágil (SXF) é a forma mais frequente, mais pesquisada e melhor documentada de DI herdável em seres humanos. O fenótipo da SXF está associado a mutações no gene FMR1 (Fragile Xlinked Mental Retardation type 1) e abrange um amplo espectro de envolvimento físico e comportamental. É causada por uma expansão de trinucleotídeos CGG no primeiro éxon do gene FMR1 localizado na região Xq27.3 no cromossomo X. Em função de sua diversidade fenotípica, esta doença tem sido subdiagnosticada na população pediátrica. A importância do reconhecimento clínico e diagnóstico específico da SXF vem do fato de que teoricamente todos os casos são hereditários e familiais. Entre as técnicas moleculares utilizadas para o diagnóstico da SXF, a MLPA (Multiplex Ligation-dependent Probe Amplification) tem sido considerada promissora. Nesse contexto, este estudo teve como objetivo validar o diagnóstico genético-molecular de pacientes com suspeita da SXF no Laboratório de Citogenética e Genética Molecular (LaGene) da Secretaria Estadual de Saúde do Estado de Goiás, na cidade de Goiânia, pela técnica de MLPA. Foram selecionados 33 pacientes encaminhados pelo serviço médico da rede pública de saúde ao LaGene com indicação clínica de diagnóstico da SXF. Para realização da análise por MLPA foi utilizado o Kit: Salsa MLPA P106-B1 MRX. Foram obtidas amplificações de apenas 15% dos pacientes. O Kit utilizado não detectou alterações no número de cópias do gene FMR1 em nenhum paciente analisado, sendo necessário a utilização de outros métodos moleculares para confirmação do diagnóstico da SXF. Dessa forma, concluímos que o Kit utilizado não foi específico para detectar alterações no número de cópias do gene FMR1, não se mostrou sensível e específico na detecção de portadores da SXF, sendo considerado oneroso. Assim a técnica de MLPA, com o uso do Kit Salsa MLPA P106-B1 MRX , não deverá ser utilizada para se triar pacientes com suspeita da SXF.

A Síndrome do X frágil (SXF) é a forma mais comum de deficiência intelectual herdada. É causada por uma mutação no gene FMR1; (Fragile X Mental Retardation 1;), que resulta na deficiência da proteína FMRP (Fragile X Mental Retardation Protein;). O gene FMR1;, localizado no braço longo do cromossomo X, em Xq27.3, possui uma repetição de trinucleotídeos (CGG)n em sua região 5\' não traduzida (região reguladora). Na população geral, o tamanho dessa repetição varia entre 5 a 44 trincas de bases. Uma expansão superior a 200 trinucleotídeos leva à hipermetilação e consequente silenciamento da transcrição do gene. Quando isso ocorre, tem-se uma mutação completa, a causa da SXF. Se a repetição expandida tem de 55 a 200 trincas de bases, chamada de pré-mutação, não ocorre hipermetilação e a proteína FMRP é produzida; portanto, a pré-mutação não está associada à SXF, porém está relacionada a outros quadros clínicos, particularmente à síndrome de tremor/ataxia associada ao X frágil (FXTAS; Fragile-X associated Tremor Ataxia Syndrome;) e à insuficiência ovariana primária associada ao X frágil (FXPOI; Fragile-X associated Primary Ovarian Insufficiency;). O objetivo deste trabalho foi investigar duas famílias cujos casos-índice foram encaminhados para o Centro de Pesquisa sobre o Genoma Humano e Células-Tronco para investigar ataxia espinocerebelar e nos quais a avaliação clínica e a história familial sugeriram a possibilidade de FXTAS; em ambos os pacientes, pré-mutação do gene FMR1; foi detectada. Na Família 1, foi feito o diagnóstico de SXF em um neto da propósita e foi identificada a mutação completa em várias filhas e netas, todas com dificuldade de aprendizado. Na Família 2 não foram identificadas mutações completas e em um dos netos do propósito detectou-se mosaicismo de alelo intermediário e pré-mutação. Assim, diante da variada apresentação fenotípica, a possibilidade de condição associada ao gene FMR1; deve ser considerada frente aos fenótipos de deficiência intelectual, dificuldade de aprendizado, falência ovariana prematura e síndrome de tremor-ataxia. O diagnóstico de FXTAS em famílias em que não há registro de SXF não é frequente, provavelmente diante do desconhecimento dessa possibilidade, mas tem importância fundamental para o aconselhamento genético, particularmente quanto à ocorrência de deficiência intelectual / RIBEIRO, M. D. O. From top to bottom: genetic counseling in families ascertained through fragile X-associated tremor/ataxia syndrome (FXTAS) 2017. 64 f. Dissertação (Mestrado em Aconselhamento Genético e Genômica Humana) - Instituto de Biociências, Universidade de São Paulo, São Paulo, 2017. Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. It is caused by a mutation in the Fragile X Mental Retardation 1 (FMR1;) gene located on the long arm of the X chromosome at Xq27.3 that results in FMRP (Fragile X Mental Retardation Protein) deficiency. The FMR1; gene has a trinucleotide repeat (CGG)n at the 5\' untranslated region (regulatory region); in the general population, this repeat varies in size from 5 to 44 CGG triplets. An expanded repeat of more than 200 trinucleotides leads to hypermethylation and consequent silencing of the gene transcription - the full mutation that causes FXS. The repeat containing 55 to 200 triplets characterizes a premutation; there is no hypermethylation, the gene is transcribed, and the FMRP is produced; then premutations are not associated with FXS, but are related to other clinical conditions: Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) and Fragile X-associated Primary Ovarian Insufficiency (FXPOI). The objective of this study was to investigate two families whose index cases were referred to the Centro de Pesquisa sobre o Genoma Humano e Células-Tronco to investigate spinocerebellar ataxia, whose clinical evaluation and family history suggested the possibility of FXTAS. Both probands were found to carry FMR1; premutations. In Family 1, the diagnosis of FXS was established in a grandson of the proband, and the full mutation was also identified in several of her daughters and granddaughters, all presenting with learning difficulties. In Family 2, no full mutations were detected; a proband\'s grandson had size mosaicism for FMR1; ; alleles, carrying an intermediate allele and a premutation. Although uncommon, possibly due to lack of knowledge about the syndrome, the diagnosis of FXTAS in families without FXS is important for genetic counseling, particularly regarding the occurrence of intellectual disability

Made available in DSpace on 2016-04-27T18:12:37Z (GMT). No. of bitstreams: 1 Hedilamar Bortolotto.pdf: 842924 bytes, checksum: 44274588e35ebd044ff891e082281374 (MD5) Previous issue date: 2008-10-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The present clinical-qualitative research deals with a case study based on the symptomatic speech of a male child affected by the Fragile X Syndrome, diagnosed at the age of four and a half year. This paper follows on the therapeutical process from the age of four years up to six years old, with the purpose of identifying, in a more specific way, how the language functioning laws emerge in the child s speech. The elected approach privileges a view on the relative autonomy of the speech and language, moving away from the notion of lineal causality of the genetic syndrome and the language symptoms. There were elected, for analysis, enigmatic episodes extracted from the therapeutical sessions. Based on the Linguistics, more specifically, the Brazilian Interacionism, on the Lacanian Psychoanalyses and on the Speech-Language Clinic Therapy focused on the subject relation with the Other/other, a clinical practice that lays on the subjectivity was aimed. The analyses allowed to outline the child s trajectory in the singular interlacement of his speech to the functioning laws of the language, pointing out the therapist s language interpretations and scansions, meaning cuts and variations of intonation, rhythm and melody in the therapist s speech that leaded to displacements in the child s position as a speaker of the language. It was concluded that interpretative actions resting on the verbal stereotype and echolalia generate changes in the child s position and that the therapist s silence can open spaces for the child to establish his speaker position, which represent promising paths to the pathological Speech-Language Clinic Therapy / A presente pesquisa clínico-qualitativa aborda um estudo de caso por meio da fala sintomática de um menino afetado pela Síndrome de X Frágil, diagnosticada aos quatro anos e meio de idade. O trabalho acompanha o processo terapêutico dos quatro aos seis anos de idade, visando identificar, de forma mais específica, como as leis de funcionamento da Língua se manifestam na fala da criança. O foco escolhido privilegia o olhar sobre o funcionamento relativamente autônomo da Língua, afastando-se da noção de causalidade linear entre a síndrome genética e os sintomas na linguagem. Elegeram-se, para análise, episódios enigmáticos extraídos de gravações de sessões fonoaudiológicas. Fundamentando-se na Lingüística, mais especificamente no Interacionismo, na Psicanálise Lacaniana e na Clínica Fonoaudiológica que mira a relação do sujeito com o Outro/outro, buscou-se uma prática clínica assentada sobre a subjetividade. As análises permitiram delinear o percurso da criança no enlaçamento singular de sua fala ao modo de funcionamento da Língua, pontuando interpretações e escansões, isto é, cortes e alterações de entonação, ritmo e melodia da fala da fonoaudióloga que provocaram deslocamentos na posição de falante da criança pesquisada. Conclui-se que ações interpretativas sobre as ecolalias e estereotipias geram mudanças na posição da criança e que o silenciamento do terapeuta pode abrir espaços para que a criança ocupe sua posição de falante, caminhos promissores para a Clínica Fonoaudiológica que atua com falas patológicas

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-09-21T12:28:44Z No. of bitstreams: 1 Cristiane Tenani Pomeranz.pdf: 4211902 bytes, checksum: 0b7dcfbb031038106d44f262f87d9076 (MD5) / Made available in DSpace on 2017-09-21T12:28:44Z (GMT). No. of bitstreams: 1 Cristiane Tenani Pomeranz.pdf: 4211902 bytes, checksum: 0b7dcfbb031038106d44f262f87d9076 (MD5) Previous issue date: 2017-09-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / To approach Art and Old Age, with the interdisciplinary view of Gerontology, is the working method used in this documental research The research is also retrospective, descriptive and qualitative in character and has its main axis in the story of a ballerina named Elisa, whose stage name was Zuzima. After the stroke, and during rehabilitation, she is exposed to Art Therapy, where she finds ways to rescue the potential of life that was lost to the pathology. This research is based on authors from various fields of knowledge, such as Geertz, Tótora, Ciornai, Francisquetti, Carrière, Messy, Beauvoir, Foucault, Nietzsche among others, and features a method of art-therapeutic intervention named PREAMAR. The method consists of seven steps -perception, recognition, strategy, affection, hands-on, result analysis and refinement, and was developed during the professional involvement with Elisa. More than a methodology, Elisa revealed the imminent human frailty, as a condition that is able to stifle the potency of existing life in the elderly, and became what the sociologist Max Weber termed an “ideal type”, an instrument for researching sociological knowledge, a mental construction of the researcher which emphasizes the aspects to analyze in the object of study. Elisa allowed the selection of a series of interventions, building in this manner an “ideal type” that can be perceived in the practical cases of Art Therapy. These interventions were made with elderly people in a large institution of Long-permanence in the city of São Paulo, with elders from the Atelier of Art & Inclusion and Dementia of the project Make Memories, with socially vulnerable elders who attended a public day-Center, and other elders that were attended individually by the researcher, pointing towards an internal movement that was developed in favor of those elders who perceive the possibilities of living the old age. It was observed that Art Therapy is a facilitating tool for the understanding of elderliness, as well as a practice favoring conducts of meaning–of-life for the elderly. By being involved in this method, the elderly can find ways of interpreting the world, to exist inserted in the present time, in which the understanding of facts, of life and of elderliness can be clarified in the midst of the current scenario. The PREAMAR method, learned and replicated, shows to be effective in the transformation of landscapes that, in many old-ages, are devoid of enchantments. For the fragile old-ages , this study proposes an Art Therapy that seeks, in the force of Art and in the PREAMAR method, the conditions to rescue the Zuzimas oppressed by the nihilism that is found in the most diverse forms of growing old / Aproximar a Arte da velhice, com o olhar interdisciplinar da Gerontologia é o método de trabalho utilizado nesta pesquisa documental. A pesquisa também tem um caráter retrospectivo, descritivo e qualitativo que tem como eixo principal a história de uma bailarina chamada Elisa, cujo nome artístico era Zuzima. Após o derrame, ao fazer reabilitação, ela é exposta à Arteterapia, onde encontra maneiras de resgatar a potência de vida perdida em meio à patologia. A pesquisa está fundamentada em autores de diversas áreas do saber, como Geertz, Tótora, Ciornai, Francisquetti, Carrière, Messy, Beauvoir, Foucault, Nietzsche entre outros, e apresenta um método de intervenção arteterapêutica nomeado PREAMAR. O método é composto de sete passos - percepção, reconhecimento, estratégia, afeto, mão na massa, análise de resultado e refinamento foi desenvolvido durante o envolvimento profissional com Elisa. Mais do que uma metodologia, Elisa revelou a fragilidade humana eminente, como condição, capaz de abafar a potência de vida existente nos velhos, e tornou-se o que o sociólogo Max Weber chamou de “tipo ideal”, instrumento de pesquisa do saber sociológico, uma construção mental do pesquisador, que enfatiza aspectos que deseja analisar do objeto de estudo. Elisa permitiu que selecionássemos uma série de observações construindo assim um “tipo ideal” que pode ser percebido em casos práticos de Arte-terapia. Estas intervenções foram feitas com idosos de uma Instituição de Longa Permanência e de grande porte na cidade de São Paulo, com idosos do Atelier de Arte&Inclusão e demenciados do projeto Faça Memórias, com idosos em situação de vulnerabilidade social que frequentam um Centro-dia público, e outros idosos atendidos individualmente pela pesquisadora, apontando um movimento interno desenvolvido a favor do sujeito velho que percebe possibilidades de viver a velhice.Observo u-se que a Arteterapia é uma ferramenta facilitadora para a compreensão das velhices, assim como uma prática a favor das condutas de significação da vida para os velhos. Ao serem envolvidos neste método, os idosos podem encontrar meios de interpretar o mundo, para existir inserido no tempo presente, em que a compreensão dos fatos, da vida e da velhice pode clarificar-se em meio ao cenário atual. O método PREAMAR, aprendido e replicado, mostra-se eficaz na transformação das paisagens que, em muitas velhices, são desprovidas de encantamento. Para as velhices fragilizadas, esta pesquisa propõe uma Arteterapia que busca, na força da Arte e no método PREAMAR as condições de resgatar as Zuzimas oprimidas pelo niilismo encontrado nas mais diversas maneiras de envelhecer

L’objectif de cette thèse a été d’utiliser une approche numérique pour étudier l’impact des dommages d'irradiation sur la microstructure du combustible nucléaire composé d'un mélange d’oxyde de plutonium et d’uranium (MOX). Cette approche, réalisée à l'échelle atomique, repose sur l'utilisation de potentiels empiriques développés dans la littérature pour l'oxyde mixte $(U,Pu)O_2$ dans l’approximation des interactions d’ions rigides.Une première étape a été une analyse critique des propriétés structurales, thermodynamiques et mécaniques prédites par 5 potentiels de la littérature. Les calculs de dynamique moléculaire ont été réalisés à l'aide du code LAMMPS, sur l'ensemble de la gamme de composition de $UO_2$ à $PuO_2$ et à des températures comprises entre 300 K et le point de fusion. Nous montrons que les potentiels les plus satisfaisants sont ceux développés par Cooper et Potashnikov. Ces deux potentiels reproduisent correctement la stabilité thermodynamique des phases ainsi que l'évolution en température des paramètres de maille et de la chaleur spécifique. Cependant le comportement mécanique des oxydes est différent selon le potentiel choisi. Tout d'abord, on note que les constantes élastiques et le facteur d'anisotropie obtenus par le potentiel Cooper sont plus fidèles aux recommandations de la littérature. Ensuite, nous montons que la propagation d'une fracture induit une transformation de phase en pointe de fissure avec le potentiel de Cooper alors qu'une fissuration fragile est observée avec le potentiel Potashnikov.Une seconde étape a été l'étude des dommages d'irradiation dans les oxydes mixtes en se limitant à l'utilisation des deux potentiels de Cooper et de Potashnikov. Des calculs de dynamique moléculaire de cascades de déplacement ont été réalisés à différentes énergies, température et compositions en plutonium. Ensuite, afin d'évaluer les dommages d'irradiation sur des temps plus longs que ceux accessibles en dynamique moléculaire, la méthode d’accumulation de défauts a été utilisée. Pour les deux potentiels, l’évolution des dommages primaires avec l’augmentation de la dose suit globalement les mêmes étapes que celles trouvées précédemment dans $UO_2$. Tout d’abord, les défauts ponctuels sont créés. Par la suite, ils se regroupent et forment de petites boucles de Frank, qui après se transforment en dislocations parfaites. Cependant, la cinétique de la recombinaison de défauts ponctuels est significativement plus lente avec le potentiel de Cooper ce qui conduit à la création de petites régions désordonnées pour les cascades d'énergie élevée. L’effet de la teneur en plutonium est analysé. Nous montrons en particulier que la densité de dislocations crée diminue lorsque la teneur en plutonium augmente.Bien que la dynamique moléculaire a été décrite comme un microscope moléculaire en raison de sa capacité à décrire avec précision des systèmes atomiques, elle présente un inconvénient majeur, celui lié aux temps de l’ordre de la femto-seconde nécessaires pour résoudre les vibrations atomiques. Cela limite le temps total de simulation approximativement quelques nanosecondes. Afin de stimuler les processus, tels que la diffusion de cations, un autre outil de calcul est nécessaire. Les techniques de Monte Carlo (KMC) atomiques peuvent simuler de plus longtemps que la dynamique moléculaire . Cependant, pour que KMC fonctionne avec précision, il est nécessaire de connaître a priori tous les mécanismes de transition entre les états possibles. Pour cette raison, la method de Monte Carlo cinétique adaptative (aKMC) est choisie pour surmonter ces limitations. Cette méthode détermine les états de transition disponibles pendant la simulation. De cette manière, elle entraîne le système dans des états imprévus via des mécanismes complexes. La puissance de cet outil s'est révélée efficace pour découvrir la recombinaison de cations sur de plus longues périodes de temps que la DM. / The objective of this doctoral research is to use a numerical approach to study the impact of irradiation damage on the microstructure of the mixed uranium-plutonium oxide fuel (MOX). This numerical approach comprises mainly the use of Molecular Dynamics (MD) using empirical potential. Several empirical potentials for $(U,Pu)O_2$ can be found in the literature. The results of these potentials can exhibit significant differences. For this reason an extensive assessment of the main empirical potential found in the literature had to be performed.Five empirical interatomic potentials were assessed in the approximation of rigid ions and pair interactions for the $(U_{1-y},Pu_y)O_2$ solid solution. Simulations were carried out on the structural, thermodynamics and mechanical properties over the full range of plutonium composition, meaning from pure $UO_2$ to pure $PuO_2$ and for temperatures ranging from 300 K up to the melting point. The best results are obtained by potentials referred as Cooper and Potashnikov. The first one reproduces more accurately recommendations for the thermodynamics and mechanical properties exhibiting ductile-like behaviour during crack propagation, whereas the second one gives brittle behaviour at low temperature.From our results from the empirical potentials assessment, we can move to the radiation damage using only two potentials (Cooper and Potashnikov). In order to know the main source of defect during irradiation, MD displacement cascades were simulated. This revealed the damage created due to varying projectile energies. In addition, the Frenkel pair accumulation method was chosen to investigate the dose effect. This method circumvents the highly computing time demanding accumulation of displacement cascade by directly creating their final states, i.e. mainly point defects. Overall, results obtained with both potentials show the same trend. However, kinetics of point defect recombination are significantly slower with Cooper potential implying creation of small disordered region with high energy displacement cascades. The evolution of the primary damage with increasing dose follows the same steps as those found previously in pure $UO_2$. First, point defects are created. Subsequently, they cluster and form small Frank loops, which in turn transform and grow into unfaulted loops. We demonstrate also that increasing temperatures accelerate the production of dislocations shifting their creation to lower doses. The effect of the plutonium content is also evidenced, especially with Cooper potential. It shows that the dislocation density decreases when the plutonium content increases.Although, MD has been described as a molecular microscope due to its ability to discribe accuratily systems of atoms, it has a large drawback that is the short time steps of the order of femto-seconds needed to resolve the atomic vibrations. This limits the time typically few microsecond. In order to invetigate processess, such as, cation diffusion and rare-event annihilation of defects after cascaces, another computational tool is required. Atomistic or object kinetic Monte Carlo (KMC) techniques can run for longer timescales than MD. However, for KMC to work accurately, all of the possible inter-state transition mechanisms and their associated rates need to be known a priori. For this reason, the adaptive kinetic Monte Carlo (AKMC) is chosen to overcome these limitations. This method determines the available transition states during simulation. In this way, it takes the system into unforeseen states via complex mechanisms. The power and range of this tool proved to be efficient to discover cation Frenkel pair recombination over a longer periods of time than MD.

Cette thèse a pour objectif d’éprouver la mise en actes du dispositif de prise en soins dans la relation d’aides ausujet fragile à domicile. Ce travail est envisagé par une étude multidimensionnelle des caractéristiquespsychologiques liées à l’acte d'aide à domicile et celles de leurs conséquences en termes de psychopathologies etde qualité de vie. Selon les données de notre étude, le profil du dispositif de prendre soin à domicile s’ancre dansun axe très médicalisé. Un axe qui va à l’encontre des besoins et attentes des sujets fragiles comme de leursaidants qui soulignent une nécessité fondamentale de lien social. Parallèlement, nous constatons que lesdispositifs de prendre soins à domicile, aujourd'hui mis en place, ne sont pas de « vraies réponses » et restentencore largement sous-utilisés. L’Aidant-Expert n’est pas soutenu dans la construction de ses proprescompétences à savoir-faire et savoir-être. Il est dans l’incapacité de venir dire quelque chose de sa réalité du vécude l’aide ou de souligner la complexité des situations de prise en soins investies. Les résultats de ces travauxsoulignent, par ailleurs, un risque élevé d’accidents à domicile renforçant un sentiment de vigilance extrême. Cesdonnées vont dans le sens de l’analyse plus fine des réels besoins et attentes des acteurs de l’aide. In fine, cettethèse permet de mettre en exergue des recommandations à envisager pour une prise en soins adaptée du sujetfragile et de son entourage à domicile. En effet, la prise en considération de l’expérience collective del’environnement d’exercice de l’aide permettra de venir contrebalancer les effets délétères de cette prise en soinspermettant alors une mise en actes au plus juste du dispositif à domicile. / Our work aims at enhancing the quality of home caregiving for vulnerable patients. This objective is assessedvia a multidimensional study evaluating psychological characteristics of home caregiving, and also theconsequences of these acts on mental health and quality of life.Our data show that the structure of home caregiving is mainly of medical significance. A significance thatresponds to expectations of patients and their caregivers, and also the social interactions between both caregivingactors. We hence conclude that the actual structure of home caregiving does not refers to “right answers” andstill widely underused. Furthermore, the expert caregivers are likely to lack structuring of their competencies, asrelated to their know-how and life skills. These professionals show great difficulties expressing 1) the nature oftheir professional experience and 2) the complexity of some of their tasks. Another finding of our work is relatedto a high risk of home accidents which induces an important level of alertness. This outcome fits with a detailedanalysis of caregivers’ needs. Finally, our work highlights some recommendations for a better home caregivingfor vulnerable populations and their families. It seems that taking into account the collective experience of thecaregiving environment would address the deleterious effects of home caregiving, which may enhance thequality and efficiency of such intervention.