Ce travail de thèse porte sur l’étude de nouveaux phénomènes vibratoires dans les systèmes Nano-électromécaniques (NEMS) conçus à partir de nanofils (NFs) SiC ou de nanotubes de carbone (NCs) résonants. La configuration encastré-libre permet d'effectuer l'émission de champ (EC) pour caractériser nos échantillons et notamment mesurer le module de Young et le facteur de qualité (Q) de nos NEMS. Le chauffage du résonateur permet d'accroître fortement la valeur de Q des nanofils SiC (Qmax = 159 000). Les auto-oscillations observées sous EC sont obtenues seulement par l'application d'une tension continue et permettent un taux de conversion AC/DC de l'ordre de 50%. L'utilisation de NFs très résistifs couplée au courant d'EC est indispensable pour engendrer ces oscillations spontanées. La réalisation d'une nanoradio sous EC permet la démodulation d'un signal AM ou FM grâce à la résonance d'un NC. Nous décrivons une méthode originale pour exciter les vibrations d'un NF à partir du faisceau d'électrons d'un microscope électronique. L'évolution de la charge au bout du NF est la principale cause de ces auto-oscillations. La configuration encastré-encastré consiste à obtenir un transistor à base de NCs suspendus. Les composants sont caractérisés électriquement et mécaniquement dans un testeur sous pointe sous ultra vide à partir de techniques dites de mixing. La fréquence de résonance de ces échantillons est de l'ordre de 100 MHz et la démodulation d'un signal FM est réalisée pour la première fois dans cette configuration de NEMS. Pour l'ensemble des phénomènes découverts et traités dans ce manuscrit, un modèle et les simulations qui en découlent sont présentés et commentés / This thesis focuses on new phenomena in the mechanical resonances of SiC nanowires (NWs) and carbon nanotubes (CNs) of interest for the emerging field of nano-electro-mechanical systems (NEMS). The clamped-free confiuration allowed the study of our nanowire and nanotube samples by field emission (FE), including measuring the Young's modulus and the quality factor (Q). Heating NW resonators significantly increased their Q factor (Qmax = 159 000). Self-oscillations were observed during FE where only a DC voltage was applied, thus allowing DC/AC conversion with a rate of up to » 50%. Using highly resistive NWs coupled with FE current was required to generate these spontaneous oscillations. Achieving a nanoradio under FE allowed the demodulation of AM or FM signals through the mechanical resonance of CNs. We describe a new method to excite vibrations of a NW from the electron beam of an electron microscope. The evolution of the charge at the end of NW is the main source of these self-oscillations. The clamped-clamped configuration consists of a transistor based on suspended CNs. The devices are characterized electrically and mechanically in a probe station under ultrahigh vacuum with mixing techniques. The resonance frequencies of these samples was around 100 MHz. The demodulation of an FM signal was achieved for the first time in this NEMS configuration. For all the phenomena discovered and treated in this manuscript, a model and derived simulations are described and discussed

Résumé : L'interaction entre la β-Lactoglobuline (β-Lg) et le rétinol ou entre les micelles de phosphocaséines (PC) et le rétinol à un pH proche de la neutralité, a été étudiée à pression atmosphérique et sous pression isostatique jusqu'à 400 MPa. Les constantes de dissociation et le nombre de sites de liaison ont été calculés indiquant des différences d'affinité en fonction de la structure protéique. A 25°C, des pressions inférieures à 150 MPa favorisent l'association β-Lgrétinol (rapport molaire β-Lg/rétinol : 1/1). A ≥ 150 MPa le complexe se dissocie. A 350 MPa, la β-Lg est dénaturée et le complexe irréversiblement dissocié. Le complexe PCrétinol (rapport molaire PC/rétinol : 1/1) reste au contraire formé après un traitement à 400 MPa et 25°C, bien que la pression induise des phénomènes de dissociation/réassociation des assemblages micellaires à ≥ 100 MPa. L'interaction PCrétinol stabiliserait plutôt les micelles de PC vis-à-vis de la pression, de même qu'une température de pressurisation modérée (35°C) comparativement à une température plus basse (15°C). Un isolat protéique de lactosérum (IPL) en dispersion dans l'eau à 10% (p/p) de protéines (pH 6,5) et en présence d'acétate de rétinol (AcRet) (rapport molaire β-Lg/AcRet : 10/1) a été traité par (i) haute-pression isostatique (HP) (350 MPa, 25°C, 15 min), (ii) traitement thermique de courte durée (TTCD) (75°C, 4 s) ou (iii) homogénéisation à ultra-haute pression (UHPH) (300 MPa, Tin = 24°C). Les trois traitements permettent de former des agrégats de β-Lg capables de retenir l'acétate de rétinol, mais avec une efficacité différente dépendant probablement des mécanismes d'agrégation induit par le chauffage (TTCD), la pression isostatique (HP) ou dynamique (UHPH). Des dispersions à 2,38% (p/p) en phosphocaséines (pH 6,6) en présence d'acétate de rétinol (rapport molaire PC/AcRet : 5/1) ont été traitées par (i) HP (300 MPa, 14°C ou 34°C, 15 min), ou (ii) UHPH (300 MPa, Tin = 14°C). Ces deux traitements favorisent la rétention de l'acétate de rétinol par les micelles de PC pouvant ainsi servir de cargo pour véhiculer des molécules bioactives. Mots clefs : haute pression isostatique, haute pression dynamique, homogénéisation à ultra-haute pression, fluorescence, β-Lactoglobuline, micelles de phosphocaséines, rétinol, acétate de rétinol, agrégats protéiques, interaction protéine-ligand. / Abstract: The binding of retinol to native β-Lactoglobulin (β-Lg) or phosphocasein (PC) micelles at pH close to neutral was studied at atmospheric pressure or under isostatic high-pressure. The dissociation constants and number of binding sites were calculated indicating that difference in retinol affinity depended on protein structure. At 25°C, pressure level < 150 MPa promoted β-Lgretinol association (β-Lg/retinol molar ratio: 1/1). At ≥ 150 MPa, the complex dissociated. At 350 MPa, β-Lg was denatured and the complex irreversibly dissociated. PC and retinol (PC/retinol molar ratio: 1/1) remained associated after pressurisation at 400 MPa and 25°C, while pressure induced dissociation/reassociation phenomena of micelle assemblies. The binding of retinol to PC stabilised micelles towards pressure, as well as moderate temperature of pressurisation (35°C) compared to lower temperature (15°C).A whey protein isolate (WPI) dispersed in water at 10% (w/w) proteins (pH 6.5) in the presence of retinyl acetate (RetAc) (β-Lg/RetAc molar ratio: 10/1) was processed by (i) isostatic high-pressure (HP) (350 MPa, 25°C, 15 min), (ii) short-time thermal treatment (STTT) (75°C, 4 s) or (iii) ultra-high pressure homogenisation (UHPH) (300 MPa, Tin = 24°C). All processing produced β-Lg aggregates able to retain RetAc, but with different efficiency depending on aggregation mechanisms induced by heating (STTT), isostatic high-pressure (HP) or dynamic high-pressure (UHPH). Phosphocaseins dispersed at 2.38% (w/w) proteins (pH 6.6) in the presence of RetAc (PC/RetAc molar ratio: 5/1) were processed by (i) HP (300 MPa, 14°C or 34°C, 15 min), or (ii) UHPH (300 MPa, Tin = 14°C). Both treatments promoted RetAc retention by phosphocasein micelles that can be used as cargoes to transport bioactive molecules.Keywords: isostatic high-pressure, dynamic high-pressure, ultra-high pressure homogenisation, fluorescence, β-Lactoglobulin, phosphocasein micelles, retinol, retinyl acetate, protein aggregates, protein-ligand binding.Discipline: Biochimie, Chimie et Technologie des Aliments.Thèse préparée à : Université Montpellier 2 – Equipe de Biochimie et Technologie Alimentaire – UMR IATE 1208 – Pôle EVAP – Place E. Bataillon, 34095 Montpellier, France.

L’imagerie par résonance magnétique (IRM) est un outil d’investigation majeur donnant accès de manière non invasive à des nombreuses informations quantitatives et fonctionnelles. La qualité des images obtenues (rapport-signal-sur-bruit, RSB) est cependant limitée dans certaines applications nécessitant des résolutions spatiales et/ou temporelles poussées. Afin d’améliorer la sensibilité de détection des équipements d’IRM, diverses orientations peuvent être suivies telles qu’augmenter l’intensité du champ magnétique des imageurs, améliorer les performances des systèmes de détection radiofréquence (RF), ou encore développer des séquences d’acquisition et des techniques de reconstruction d’images plus efficaces. La thématique globale dans laquelle s’inscrit cette thèse concerne le développement des systèmes de détection RF à haute sensibilité pour l’IRM à haut champ chez l’homme. En particulier, des antennes auto-résonantes basées sur le principe des lignes de transmission sont utilisées parce qu’elles peuvent être réalisée sur substrat souple. Cette adaptabilité géométrique du résonateur permet d’ajuster précisément sa forme aux spécificités morphologiques de la zone anatomique observée, et ainsi d’augmenter le RSB. La première visée technologique de ce projet concerne le développement, de la conception jusqu’à la mise en œuvre dans un appareil 7 T corps entier, d’un système de détection RF flexible à haute sensibilité, utilisant des antennes miniatures associées en réseau. L’utilisation d’un réseau d’antennes miniatures permet d’obtenir des images sur un champ de vue élargi tout en conservant la haute sensibilité inhérente à chaque antenne miniature. De plus, la technologie de l’imagerie parallèle devient accessible, ce qui permet d’accélérer l’acquisition des images. De surcroît, un nouveau schéma de résonateur de ligne transmission avec un degré de liberté supplémentaire est introduit, ce qui permet de réaliser de grands résonateurs multi-tours pour l’IRM à haut champ. Cette thèse décrit le développement, la mise en œuvre et l’évaluation des nouveaux systèmes de détection RF au moyen de simulations analytiques et numériques, et des études expérimentales. / Magnetic resonance imaging (MRI), among other imaging techniques, has become a major backbone of modern medical diagnostics. MRI enables the non-invasive combined, identification of anatomical structures, functional and chemical properties, especially in soft tissues. Nonetheless, applications requiring very high spatial and/or temporal resolution are often limited by the available signal-to-noise ratio (SNR) in MR experiments. Since first clinical applications, image quality in MRI has been constantly improved by applying one or several of the following strategies: increasing the static magnetic field strength, improvement of the radiofrequency (RF) detection system, development of specialized acquisition sequences and optimization of image reconstruction techniques. This work is concerned with the development of highly sensitive RF detection systems for biomedical ultra-high field MRI. In particular, auto-resonant RF coils based on transmission line technology are investigated. These resonators may be fabricated on flexible substrate which enables form-fitting of the RF detector to the target anatomy, leading to a significant SNR gain. The main objective of this work is the development of a flexible RF coil array for high-resolution MRI on a human whole-body 7 T MR scanner. With coil arrays, the intrinsically high SNR of small surface coils may be exploited for an extended field of view. Further, parallel imaging techniques are accessible with RF array technology, allowing acceleration of the image acquisition. Secondly, in this PhD project a novel design for transmission line resonators is developed, that brings an additional degree of freedom in geometric design and enables the fabrication of large multi-turn resonators for high field MR applications. This thesis describes the development, successful implementation and evaluation of novel, mechanically flexible RF devices by analytical and 3D electromagnetic simulations, in bench measurements and in MRI experiments.

Ultra-High Energy Cosmic Rays (UHECR) can only be measured by the detection of Extensive Air Showers (EAS) created by the interaction of the cosmic ray particle with an atmospheric nuclei. The inference of some of the properties of UHECR, like their mass composition, is only possible by the comparison of measurements of EAS observables to predictions from Monte Carlo simulations. The most important source of uncertainties on the description of EAS by the simulations is the modeling of hadronic interactions. For many years it has been known that the hadronic interaction models fail on predicting the EAS observables related to their muonic component. The most evident manifestation of that is called muon deficit problem due to the fact that the number of muons in EAS with energies above 1018 eV predicted by simulations is smaller than the observed ones. The aim of this thesis is to approach this problem in three distinct fronts. First, a method is developed to interpret measurements of number of muons in terms of cosmic rays composition in despite of the muon deficit problem. Second, an EAS observable which is sensitive to the muon energy spectrum at ground and, consequently, can be used to constrain hadronic interaction models is proposed and tested. Third and final, the muon production in air showers is studied through measurements of hadron production spectra in pion-carbon interactions. / Raios Cósmicos Ultra Energéticos (Ultra-High Energy Cosmic Rays, UHECR) somente podem ser medidos através da detecção dos Chuveiros Atmosféricos Extensos (Extensive Air Showers, EAS) criados pela interação do raio cósmico primário com núcleos atmoféricos. A inferência de algumas propriedados dos UHECRs, como a composição de massa, é possível somente através da comparação entre medidas de observáveis dos EASs com predições geradas por simulações de Monte Carlo. A fonte de incerteza mais importante na descrição de EAS por simulações é a modelagem das interações hadrônicas. Por muitos anos é sabido que os modelos de interação hadrônica falham na predição de observáveis dos EASs relacionados a sua componente muônica. A manifestação mais evidente disso é chamada problema do déficit de múons devido ao fato que o número de múons em chuveiros com energias acima de 1018 eV predito por simulações é menor que os observados. O objetivo desta tese é abordar este problema através de três frentes. Primeiramente, um método é desenvolvido para interpretar as medidas do número de múons em termos de composição de raios cósmicos considerando o problema do déficit de múons. Segundo, a proposta e o teste de um observável que é sensível ao espectro de energia dos múons na superfície e, consequentemente, pode ser usado para discriminar entre os modelos de interação hadrônica. Por último, a produção de múons em chuveiros é estudada através de medidas do espectro de produção de hádrons em interações do tipo píon-carbono.

Ultradiluição (UHD) é o efeito de uma solução, diluída acima do número de Avogrado, que na dependência da sua dinamização (diluição com sucussão) induz um efeito celular supressivo ou estimulante, com conseqüente obtenção de uma curva dose-efeito oscilatória. Por outro lado, a 3,3,5 Triiodo-L-Tironina (T3) é o hormônio mais importante na indução e manutenção das mudanças metamórficas dos girinos, nelas incluídas a absorção da cauda. O presente estudo, cego e randomizado, tem como objetivo comprovar que o T3 5.10-24M (10ª cH) altera a apoptose induzida pelo T3 100 nM na cauda de girinos de Rana catesbeiana, in vitro. Foram distribuídos 60 explantes em três grupos: Grupo A: sem o estímulo do T3 em dose farmacológica e em UHD; Grupo B (teste): sob a ação de T3 100 nM e T3 10ª cH (5.10-24 M); Grupo C (controle): sob a ação do T3 100 nM e etanol 70% sem sucussão. A análise estatística da área dos explantes, no primeiro e ultimo dia do experimento, e do índice apoptótico foi realizado através do teste t Student e foi considerado estatisticamente significante quando p<0,05. Embora sem diferenças significativas na área dos explantes do grupo teste e no grupo controle, um maior e significante índice apoptótico foi identificado nos explantes do grupo teste. Este resultado confirma que o T3 na 10ª cH altera a ação do T3 em dose farmacológica. Futuros experimentos serão realizados, com diferentes dinamizações, com o objetivo da parametrização da curva dose-efeito / Ultra High Dilution (UHD) is the effect of a solution, beyond the Avogadro limits, that in the dependence of the applied dinamization (dilution with succussion) elicits a suppressive or a stimulant effect on a living cell, with a consequent generation of an oscillatory dose-effect curve. The entire process of anuran amphibian metamorphosis is under thyroid hormones control, included the complete resorption of the tadpole tail. A random and blind study was performed, with the intent to prove that T3 5.10-24 M (10ª cH) modifies the apoptosis induction of T3 100 nM in Rana catesbeiana tadpoles tail tips, in vitro. 60 Explants were distributed in three ways: Group A: without T3 action, at pharmacological and UHD dose; Group B (test): under the action of T3 100 nM and treated with T3 10ª cH (UHD); Group C (control): under the action of T3 100 nM and treated with ethanol 70% unsuccussed. In order to identify significant differences in the area of the remainder explants, at the first and final day of the experiment, and in the apoptotic index we used a student t-test. Although we didnt find statistical difference in macroscopic tadpoles tail tips area from test and control groups, a high and significant (p<0,05) index of apoptosis in histology was found in explants of test group. This data confirms that T3 10 cH modifies the effect of T3 at pharmacological dose. More studies will be necessary, using different dinamizations, to the parameterization of the dose-effect curve proceeding from these experiments

The development of advanced fiber reinforced cement-based materials to provide higher strength, ductility, and durability, as ultra-high performance fiber-reinforced concrete (UHPFRC), enables the design of precast beams with thin sections and reduced self-weight to meet the required flexural performance. However, such slender elements when subjected to transitory phases, and possibly also in permanent stages, are prone to instability failure. So, the present study aims to provide experimental data and analytical solution for UHPFRC beams during the lifting phase, and studies about the other stages. This type of test is rare and was not reported for UHPFRC beams. For testing, the beams were lifted by inclined cables and subjected to a transversal load applied at midspan to induce lateral instability. The displacements of the beams were monitored with total station equipment. Also, a new analytical solution was proposed to predict the failure load of lifted beams and closed-form analytical solutions to predict the rollover load of beams supported by bearing pads and subjected to different loading conditions. Furthermore, there are limited data that characterizes the constitutive behavior of this material. In this context, the present research also focused on providing such laboratory results for UHPFRC with different fiber contents. Besides, analytical models for damage evolution and stress-strain relationship are proposed and applied in numerical simulations. From the results, the UHPFRC beams failed by instability with a load capacity 3.7 times smaller than the flexural load capacity. Furthermore, the analytical solution for lifting predicted the peak load of the experiment with great accuracy. Also, the proposed equations for beams on bearing pads accurately predicted the experimental results available in the literature. The analytical and experimental rollover loads differed by 4.37% and 13.6% for the two studied cases. From material, the stiffness degradation occurred rapidly in UHPFRC under tensile loading while occurred gradually in compression. Also, fiber content influenced toughness and degradation evolution significantly over the loading cycles. Proposed equations were utilized in the Plastic-Damage model of Abaqus that predicted accurately damage growth and cyclic envelopes during all the phases of the tension, compression, and bending tests. The calibrated numerical model also predicted the experimental results with the UHPFRC beams. / O desenvolvimento de materiais avançados à base de cimento reforçado com fibra para fornecer maior resistência, ductilidade e durabilidade, como o concreto de ultra-alto desempenho reforçado com fibras (UHPFRC), permite o projeto de vigas pré-moldadas com seções esbeltas e peso próprio reduzido que atendem desempenho estrutural requerido. No entanto, esses elementos delgados quando submetidos a fases transitórias e também em serviço são propensos a falhar por instabilidade. Então, o presente estudo tem por objetivo apresentar resultados experimentais e soluções analíticas para vigas de UHPFRC durante a fase de içamento e estudos sobre as outras fases. Este tipo de teste é raro e não foi reportado para vigas de UHPFRC. Para o teste, as vigas foram levantadas por cabos inclinados e submetidas a uma carga concentrada transversal aplicada no meio do vão para induzir a instabilidade lateral. Os deslocamentos das vigas foram monitorados com estação total. Além disso, uma nova solução analítica foi proposta para prever a carga de instabilidade das vigas içadas e soluções analíticas para prever a carga de tombamento de vigas suportadas por aparelho de apoio e submetidas a diferentes condições de carregamento. Além disso, existem poucos resultados experimentais que caracterizam o comportamento constitutivo deste material. Neste contexto, a presente pesquisa também se concentrou em fornecer tais resultados experimentais para UHPFRC com diferentes teores de fibras. Além disso, modelos analíticos para evolução de dano e relação tensão-deformação são propostos e aplicados em simulações numéricas. A partir dos resultados, as vigas em içamento falharam por instabilidade com uma capacidade de carga 3,7 vezes menor que a capacidade à flexão. Além disso, a solução analítica para içamento previu carga máxima do experimento com grande precisão. As equações propostas para vigas sobre aparelhos de apoio previram com precisão os resultados experimentais disponíveis na literatura. As cargas de tombamento analíticas e experimental diferiram em 4,37% e 13,6% para os dois casos estudados. Dos resultados do material, a degradação da rigidez ocorreu de maneira rápida no UHPFRC submetido à tração enquanto ocorreu gradualmente na compressão. O teor de fibras influenciou significativamente a tenacidade e a degradação nos ciclos de carregamento. As equações propostas foram utilizadas em um modelo de Dano acoplado à plasticidade que previu com precisão a evolução do dano e as envoltórias cíclicas durante todas as fases dos testes de tração, compressão e flexão. O modelo numérico calibrado também previu os resultados experimentais das vigas de UHPFRC.

Relativity is one of the most important and well tested theories and Lorentz invariance is one of its pillars. Lorentz invariance violation (LIV), however, has been discussed in several quantum gravity and high energy models. For this reason, it is crucial to test it. Several tests, both terrestrial and astrophysical, have been performed in the last years and provide limits on the violation. This work takes part in these efforts and discuss the possibility of testing LIV with ultra-high energy cosmic rays (UHECRs). The effects of LIV in their propagation and the resulting changes in the spectrum of UHECRs are obtained and compared to the experimental data from the Pierre Auger Observatory. An analytical calculation for the inelasticity in the laboratory frame with LIV of any a + b &rarr; c + d interaction is presented and used to obtain the phase space and the energy losses of the pion production for protons, the photodisintegration for nuclei and the pair production for photons with LIV. A parametrization for the threshold energy of the photodisintegration with LIV is also proposed. The main effect seen is a decrease in the phase space and a resulting decrease in the energy loss. These changes have been implemented in Monte Carlo propagation codes and the resulting spectra of protons, nuclei and photons on Earth have been obtained and fitted to the data from the Pierre Auger Observatory. It is shown that upper limits on the photon LIV coefficient can be derived from the upper limits on the photon flux from the Pierre Auger Observatory. / Relatividade é uma das mais importantes e bem testadas teorias e a invariância de Lorentz é um de seus pilares. A violação da invariância de Lorentz (VIL), todavia, tem sido discutida em diversos modelos de gravidade quântica e altas energias. Por tal motivo, é crucial testá-la. Diversos testes, tanto terrestres quanto astrofísicos, foram realizados nos últimos anos e fornecem limites na violação. Este trabalho se insere nesses esforços e discute a possibilidade de testar VIL com raios cósmicos de altíssima energia. Os efeitos da VIL em sua propagação e as consequentes mudanças no espectro de raios cósmicos de altíssima energia são obtidos e comparados com os dados experimentais do Observatório Pierre Auger. Um cálculo analítico para a inelasticidade no referencial do laboratório com VIL para qualquer interação da forma a + b &rarr; c + d é apresentado e usado para obter o espaço de fase e as perdas de energia para a produção de píons para prótons, a fotodesintegração para núcleos e a produção de pares para fótons com VIL. Uma parametrização para o limiar de energia da fotodesintegração com VIL também é proposta. O principal efeito observado é uma diminuição no espaço de fase e uma consequente diminuição nas perdas de energia. Tais mudanças foram implementadas em códigos de Monte Carlo para a propagação e os espectros resultantes para prótons, núcleos e fótons na Terra foram obtidos e ajustados aos dados do Observatório Pierre Auger. É mostrado que limites superiores nos coeficientes de VIL para o fóton podem ser deduzidos dos limites superiores para o fluxo de fótons do Observatório Pierre Auger.

La psychose est un syndrome apparaissant progressivement à l’adolescence chez des individus à risque selon un processus dynamique appelé transition psychotique. Ces individus à risque sont repérables cliniquement mais les données biologiques actuelles sont insuffisantes pour expliquer l’apparition de la psychose. Au cours de cette thèse, nous avons cherché à identifier les facteurs biologiques responsables de ce processus. Les hypothèses permettant d’expliquer la transition psychotique privilégient l’interaction gène x environnement, sous-tendue par des mécanismes épigénétiques. Nous avons mené une étude des modifications de la méthylation de l’ADN et de la transcription à l’aide de techniques de biologie moléculaire et de bio-informatique à l’échelle pan-génomique. La transition psychotique semble être liée à des modifications de méthylation et de transcription de gènes impliqués dans des mécanismes comme le guidage axonal ou la régulation du stress oxydatif. Ces modifications longitudinales pourraient refléter l’influence de l’environnement. Les facteurs environnementaux pourraient déréguler l’axe biologique du stress dès les phases précoces de la maladie, comme le suggère l’augmentation de la sécrétion de cortisol basal que nous avons montré chez les individus à risque. En outre, il est probable que des spécificités au niveau des gènes et des processus régulant l’épigénome soient également impliquées dans cette réponse individuelle à l’environnement. Nous avons montré l’importance du métabolisme mono-carboné au moins dans un sous-groupe spécifique de patients. Ces résultats doivent être répliqués et étendus dans d’autres paradigmes pour valider l’implication de ces processus dans la transition psychotique. En cas de confirmation, ces voies biologiques pourraient s’avérer être des pistes intéressantes pour développer des thérapeutiques ciblées et relever le défi de la prévention de la psychose chez des individus à risque. / Psychosis is a progressive mental disorder which normally occurs during adolescence in at-risk subjects following a dynamic process termed “psychotic transition”. These at-risk subjects are clinically identifiable but biological data are still insufficient in explaining the onset of psychosis. Throughout this thesis, we aim to identify biological factors implicated in this pathophysiological process. Current hypotheses explaining the psychotic transition favor the interaction between genes and the environment mediated by epigenetic mechanisms. We conducted studies examining methylomic and transcriptomic changes during psychotic transition using molecular biology and bioinformatics techniques at a whole genome scale. Our results suggest that psychotic transition may be linked to methylomic and transcriptomic changes in genes implicated in axon guidance or oxidative stress. These longitudinal changes could be related to environmental factors. Some of these factors could deregulate the hormonal stress response at the earliest phases of psychosis. Indeed, our results show that secretion of basal cortisol is increased in prodromal individuals. Moreover, it is likely that genes and processes regulating epigenetic modifications are also implicated in the individual response to the environment. We have shown the importance of the one-carbon metabolism for at least one sub-group of patients affected by psychosis. Our results should be replicated using other paradigms in order to definitively validate the implication of these various actors in the psychotic transition. If confirmed, knowledge of these biological mechanisms could lead to the development of targeted therapeutics to prevent psychosis in at-risk individuals.

The development of advanced fiber reinforced cement-based materials to provide higher strength, ductility, and durability, as ultra-high performance fiber-reinforced concrete (UHPFRC), enables the design of precast beams with thin sections and reduced self-weight to meet the required flexural performance. However, such slender elements when subjected to transitory phases, and possibly also in permanent stages, are prone to instability failure. So, the present study aims to provide experimental data and analytical solution for UHPFRC beams during the lifting phase, and studies about the other stages. This type of test is rare and was not reported for UHPFRC beams. For testing, the beams were lifted by inclined cables and subjected to a transversal load applied at midspan to induce lateral instability. The displacements of the beams were monitored with total station equipment. Also, a new analytical solution was proposed to predict the failure load of lifted beams and closed-form analytical solutions to predict the rollover load of beams supported by bearing pads and subjected to different loading conditions. Furthermore, there are limited data that characterizes the constitutive behavior of this material. In this context, the present research also focused on providing such laboratory results for UHPFRC with different fiber contents. Besides, analytical models for damage evolution and stress-strain relationship are proposed and applied in numerical simulations. From the results, the UHPFRC beams failed by instability with a load capacity 3.7 times smaller than the flexural load capacity. Furthermore, the analytical solution for lifting predicted the peak load of the experiment with great accuracy. Also, the proposed equations for beams on bearing pads accurately predicted the experimental results available in the literature. The analytical and experimental rollover loads differed by 4.37% and 13.6% for the two studied cases. From material, the stiffness degradation occurred rapidly in UHPFRC under tensile loading while occurred gradually in compression. Also, fiber content influenced toughness and degradation evolution significantly over the loading cycles. Proposed equations were utilized in the Plastic-Damage model of Abaqus that predicted accurately damage growth and cyclic envelopes during all the phases of the tension, compression, and bending tests. The calibrated numerical model also predicted the experimental results with the UHPFRC beams. / O desenvolvimento de materiais avançados à base de cimento reforçado com fibra para fornecer maior resistência, ductilidade e durabilidade, como o concreto de ultra-alto desempenho reforçado com fibras (UHPFRC), permite o projeto de vigas pré-moldadas com seções esbeltas e peso próprio reduzido que atendem desempenho estrutural requerido. No entanto, esses elementos delgados quando submetidos a fases transitórias e também em serviço são propensos a falhar por instabilidade. Então, o presente estudo tem por objetivo apresentar resultados experimentais e soluções analíticas para vigas de UHPFRC durante a fase de içamento e estudos sobre as outras fases. Este tipo de teste é raro e não foi reportado para vigas de UHPFRC. Para o teste, as vigas foram levantadas por cabos inclinados e submetidas a uma carga concentrada transversal aplicada no meio do vão para induzir a instabilidade lateral. Os deslocamentos das vigas foram monitorados com estação total. Além disso, uma nova solução analítica foi proposta para prever a carga de instabilidade das vigas içadas e soluções analíticas para prever a carga de tombamento de vigas suportadas por aparelho de apoio e submetidas a diferentes condições de carregamento. Além disso, existem poucos resultados experimentais que caracterizam o comportamento constitutivo deste material. Neste contexto, a presente pesquisa também se concentrou em fornecer tais resultados experimentais para UHPFRC com diferentes teores de fibras. Além disso, modelos analíticos para evolução de dano e relação tensão-deformação são propostos e aplicados em simulações numéricas. A partir dos resultados, as vigas em içamento falharam por instabilidade com uma capacidade de carga 3,7 vezes menor que a capacidade à flexão. Além disso, a solução analítica para içamento previu carga máxima do experimento com grande precisão. As equações propostas para vigas sobre aparelhos de apoio previram com precisão os resultados experimentais disponíveis na literatura. As cargas de tombamento analíticas e experimental diferiram em 4,37% e 13,6% para os dois casos estudados. Dos resultados do material, a degradação da rigidez ocorreu de maneira rápida no UHPFRC submetido à tração enquanto ocorreu gradualmente na compressão. O teor de fibras influenciou significativamente a tenacidade e a degradação nos ciclos de carregamento. As equações propostas foram utilizadas em um modelo de Dano acoplado à plasticidade que previu com precisão a evolução do dano e as envoltórias cíclicas durante todas as fases dos testes de tração, compressão e flexão. O modelo numérico calibrado também previu os resultados experimentais das vigas de UHPFRC.

Made available in DSpace on 2017-07-21T20:42:32Z (GMT). No. of bitstreams: 1 Melina Correa Gabriel.pdf: 5915390 bytes, checksum: bae67fca28fd7999823fa6ec6ac98844 (MD5) Previous issue date: 2010-03-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The intention of this exploratory research is to study the modifications provided by high-energy mechanical milling in ultra-high molecular weight polyethylene (UHMWPE) and mixtures of this polymer with polyethylene glycol (PEG). These modifications can be of interest for future processing of UHMWPE. The mechanical milling was performed in an attritor mill, a type of mill that can be used in laboratory as well as in industry. The millings of UHMWPE were performed in different rotation speeds. For mixtures of UHMWPE and PEG, the amounts of PEG were also different. The samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The mechanical milling modified the UHMWPE particles morphology: with milling, the almost rounded shape became flat-like shape. This caused the reduction of apparent density of polymer after milling. The mechanical milling also provided structural changes. With the increasing of the rotation speed,there was the increasing of the monoclinic phase and the decreasing of the orthorhombic, up to 500 rpm. For 600 rpm, the amount of monoclinic phase decreased. In this rotation, the deformation rate probably increased the process temperature, allowing the monoclinic phase to return to its initial structural orthorhombic form. In mixtures of UHMWPE and PEG, after mechanical milling, the particles of PEG were probably reduced and better dispersed in the UHMWPE matrix. Changes in thermal characteristics of polymers also could be noted. The kinetics of UHMWPE crystal growth changed, as well as the behavior of PEG crystallization. Feasibly, dispersed particles of PEG acted as physical barriers against the crystalline phase growth of UHMWPE and the crystallization temperature of PEG decreased, when the UHMWPE and PEG mixtures were milled. / Este trabalho exploratório teve por objetivo estudar as modificações promovidas por moagem de alta energia no de polietileno de ultra-alta massa molar (PEUAMM) e sua mistura com polietileno glicol (PEG), que podem ser de interesse para auxiliar um posterior processamento do PEUAMM. As moagens foram realizadas em um moinho do tipo attritor, um tipo de moinho que pode ser usado tanto em laboratório quanto em escala industrial. Foram variadas as velocidades de rotação na moagem do PEUAMM, além das concentrações de PEG, quando feita a mistura. As amostras foram caracterizadas por microscopia eletrônica de varredura (MEV), microscopia de força atômica (MFA), calorimetria exploratória diferencial (DSC) e difração de raios X. A moagem de alta energia do material modificou a forma das partículas de PEUAMM, passando de arredondadas a flakes, com a evolução do processo de moagem, fazendo com que a densidade aparente do polímero diminuísse muito comparado ao polímero não moído. A moagem também proporcionou mudança estrutural, permitindo a formação de fase monoclínica em detrimento da ortorrômbica. A medida que se aumentou a rotação do moinho até 500 rpm, houve um crescimento da fase monoclínica. Apenas para 600 rpm, a quantidade dessa fase sofreu decréscimo, devido possivelmente ao aumento da frequência de choques e da temperatura de processamento, fazendo com que a estrutura monoclínica retornasse à estrutura ortorrômbica original. Na mistura de PEUAMM com PEG, a moagem provavelmente permitiu redução das partículas e a melhor dispersão de PEG na matriz de PEUAMM. Também se observaram mudanças nas características térmicas dos polímeros na mistura após moagem. Ocorreu mudança na cinética de crescimento dos cristais de PEUAMM e mudança no comportamento de cristalização do PEG, comportamento este que não ocorreu para o PEUAMM moído ou para a mistura de PEUAMM com PEG antes da moagem. Possivelmente, as partículas dispersas de PEG atuaram como barreiras ao crescimento da fase cristalina do PEUAMM e houve diminuição da temperatura de cristalização do PEG, na mistura com PEUAMM após moagem.