A Plataforma Continental Sul Brasileira (PCSB) é considerada uma importante região do litoral do Brasil, suas massas d’água e os processos dinâmicos apresentam um comportamento sazonal que imprime fortes efeitos no ecossistema costeiro. Com objetivo de caracterizar a Frente Subtropical de Plataforma (FSTP) e seu impacto na atmosfera, o presente trabalho utilizou o modelo acoplado oceano-atmosfera COAWST (Coupled Ocean-Atmosphere-Wave-Sediment Transport) para estudar, na região da PCSB, a distribuição das massas d’água e a variabilidade oceânica durante o ano de 2012. Assim como, o acoplamento oceano-atmosfera durante 10 dias do mês de junho de 2012, coincidentes com a realização do cruzeiro oceanográfico ACEx/SIMTECO. Os resultados de ambos os períodos de estudo foram comparados com observações históricas, com dados coletados in situ pelo cruzeiro ACEx/SIMTECO e com dados de satélite. Os resultados indicam que essa componente foi capaz de reproduzir as principais características termohalinas e a sazonalidade das águas que dominam a PCSB. A mistura entre as águas de plataforma subtropicais e subantárticas que ocorre na FSTP, apresentou uma clara mudança sazonal em seu volume. Como consequência da mistura e da oscilação sazonal de posição da FSTP, a estabilidade da coluna d´água dentro da PCSB também muda sazonalmente. Os valores de temperatura da superfície do mar (TSM) e altura da superfície do mar mostraram valores sazonais de REQM inferiores a 2°C e um skill médio superior a 0,75. Valores de velocidade sobre a plataforma para a Corrente Costeira do Brasil (CCB) chegam 0,6 (m.s-1), enquanto o transporte para a Corrente do Brasil (CB) e CCB foram de -7 a -44 Sv e -0,3 a 0,3 Sv, respectivamente. Os mapas sazonais de energia cinética média e energia cinética turbulenta representam o comportamento já conhecido da CB e ressaltam a importância do fluxo costeiro médio ao largo da costa da Argentina ao longo do ano. A comparação dos dados do modelo atmosférico, rodado no modo acoplado do COAWST, com dados observacionais indicam um satisfatório desempenho do modelo em representar as variáveis temperatura potencial, umidade relativa e específica, assim como os campos de vento na superfície do mar. O módulo atmosférico do COAWST foi também capaz de representar as variações da camada limite atmosférica marinha (CLAM), mesmo em condições sinóticas pré e pós-frontais como as observadas durante a realização do cruzeiro ACEx/SIMTECO. O presente trabalho apresenta, pela primeira vez para a região de estudo, resultados que demonstram a robustez do modelo regional COAWST em descrever o comportamento sinótico da atmosfera frente aos gradientes de TSM na região da PCSB. E oferece novos subsídios para o estudo do comportamento do sistema acoplado oceano-atmosfera nesta importante região da costa brasileira. / The South Brazilian Continental Shelf (SBCS) is considered an important region of Brazilian coast, their water masses and the dynamic processes present a seasonal behavior that has strong effects on the coastal ecosystem. In order to characterize the Subtropical Shelf Front (STSF) and its impact on the atmosphere, this work used the ocean-atmosphere coupled model COAWST (Coupled Ocean-Atmosphere-Wave-Sediment Transport) to study, in the SBCS region, the distribution of water massas and ocean variability during the year 2012. As well, the ocean-atmosphere coupling during 10 days of June 2012, coinciding with the ACEx/SIMTECO oceanographic cruise. The results of both study periods were compared with historical observations, data collected in situ by the ACEx/SIMTECO cruise and satellite data. The results indicate that this component was capable of reproducing the main thermohaline characteristics and the seasonality of dominant waters of the SBCS. The mixture between subtropical and subantarctic shelf waters that occurs in the STSF, showed a clear seasonal change in its volume. As consequence of mixing and seasonal STSF oscillation, the stability of the water column within the SBCS also changes seasonally. The values of sea surface temperature (SST) and sea surface height showed seasonal RMSE values below 2 °C and an average skill greater than 0,75. Velocity values on the shef for Brazilian Coastal Current (BCC) reach 0,6 (ms-1), while transport to Brazil Current (BC) and BCC were -7 to -44 Sv and -0, 3 to 0.3 Sv, respectively. The seasonal maps of medium kinetic energy and turbulent kinetic energy represent the behavior of the BC and highlight the importance of the average coastal flow off the coast of Argentina during the year. The comparison of data from the atmospheric model, run in coupled mode of COAWST, with observational data indicates a satisfactory performance of the model in representing the variables potential temperature, relative and specific humidity, as well as the wind fields at the surface of the sea. The atmospheric module of COAWST was able to represent the variations of marine atmospheric boundary layer (MABL), even in pré and post-frontal synoptic conditions such as those observed during the ACEx/SIMTECO cruise. The present work presents, for the first time in this region, results that demonstrate the robustness of the COAWST regional model in describing the synoptic behavior of the atmosphere in front of SST gradients in the SBCS region. And offers new subsidies for the study of the behavior of the ocean-atmosphere coupled system in this important region of the Brazilian coast.

L'importance croissante de l'évaluation de la performance des structures soumis au chargement sismique souligne la nécessité d'estimer le risque de liquéfaction. Dans ce scénario extrême de la liquéfaction du sol, des conséquences dévastatrices sont observées, par exemple des tassements excessifs et des instabilités de pentes. Dans le cadre de cette thèse, la réponse dynamique et l'interaction d'un système ouvrage en terre-fondation sont étudiées, afin de déterminer quantitativement le mécanisme de ruine dû à la liquéfaction du sol de la fondation. Par ailleurs, les chargements sismiques peuvent induire dans les ouvrages en terre un mode de rupture générant des bandes de cisaillement. Une étude de sensibilité aux maillages a donc été engagée pour quantifier la dépendance des résultats de l'analyse dynamique. Par conséquent, l'utilisation d'une méthode de régularisation est évaluée au cours des analyses dynamiques. Le logiciel open-source Code_Aster, basé sur la méthode des Eléments Finis et développé par EDF R&D, est utilisé pour les simulations numériques, tandis que le comportement du sol est représenté par le modèle de comportement de l'ECP, développé à CentraleSupélec. En premier lieu, un modèle simplifié de propagation 1D des ondes SH dans une colonne de sol avec comportement hydromécanique couplé non linéaire a été simulé. L'effet des caractéristiques du signal sismique et de la perméabilité du sol sur la liquéfaction est évalué. Le signal sismique d'entrée est un élément important pour l'apparition de la liquéfaction, puisque la durée du choc principal peut conduire à de fortes non linéarités et à un état de liquéfaction étendu. En outre, quand une variation de perméabilité en fonction de l'état de liquéfaction est considérée, des changements significatifs sont observés pendant la phase de dissipation de la surpression interstitielle de l'eau et au comportement du matériau. En revanche, ces changements ne suivent pas une tendance unique. Puis, l'effet d'une méthode de régularisation avec cinématique enrichie, appelée premier gradient de dilatation, sur la propagation des ondes SH est étudié au travers d'une solution analytique. Des problèmes à la réponse dynamique du sol sont observés et discutés quand cette méthode de régularisation est appliquée. Ensuite, un modèle 2D d'un déblai est simulé et sa réponse dynamique est évaluée en conditions sèches, complètement drainées et hydromécanique couplées. Deux critères sont utilisés pour définir le début de la rupture de la structure. Le travail du second ordre est utilisé pour décrire l'instabilité locale à des instants spécifiques du mouvement sismique, tandis que l'estimation d'un facteur de sécurité locale est proposée prenant en compte la résistance résiduelle du sol. En ce qui concerne le mode de ruine, l'effet de la surpression interstitielle de l'eau est de grande importance, puisqu'un déblai stable en conditions sèches et complètement drainées, devient instable lors de l'analyse couplée à cause de la liquéfaction de la fondation. Enfin, un système digue-fondation est simulé et l'influence de la perméabilité du sol, la profondeur de la couche liquéfiable, ainsi que, les caractéristiques du séisme sur la ruine induite par la liquéfaction du sol est évaluée. Pour ce modèle de digue, le niveau de dommages est fortement lié à la fois à l'apparition de la liquéfaction dans la fondation et la dissipation de la surpression d'eau. Une surface d'effondrement circulaire est générée à l'intérieur de la couche du sol liquéfié et se propage vers la crête dans les deux côtés de la digue. Pourtant, lorsque la couche liquéfiée est située en profondeur, la digue n'est pas affectée par la liquéfaction de la fondation pour ce cas particulier de chargement. Ce travail de recherche se concentre sur une étude de cas de référence pour l'évaluation sismique des ouvrages en terre soumis à un séisme et fournit des méthodes et outils de calculs numériques performants accessibles aux ingénieurs. / The increasing importance of performance-based earthquake engineering analysis points out the necessity to assess quantitatively the risk of liquefaction. In this extreme scenario of soil liquefaction, devastating consequences are observed, e.g. excessive settlements, lateral spreading and slope instability. The present PhD thesis discusses the global dynamic response and interaction of an earth structure-foundation system, so as to determine quantitatively the collapse mechanism due to foundation’s soil liquefaction. As shear band generation is a potential earthquake-induced failure mode in such structures, the FE mesh dependency of results of dynamic analyses is thoroughly investigated and an existing regularization method is evaluated. The open-source FE software developed by EDF R&D, called Code_Aster is used for the numerical simulations, while soil behavior is represented by the ECP constitutive model, developed at CentraleSupélec. Starting from a simplified model of 1D SH wave propagation in a soil column with coupled hydromechanical nonlinear behavior, the effect of seismic hazard and soil’s permeability on liquefaction is assessed. Input ground motion is a key component for soil liquefaction apparition, as long duration of mainshock can lead to important nonlinearity and extended soil liquefaction. Moreover, when a variation of permeability as function of liquefaction state is considered, changes in the dissipation phase of excess pore water pressure and material behavior are observed, which do not follow a single trend. The effect of a regularization method with enhanced kinematics approach, called first gradient of dilation model, on 1D SH wave propagation is studied through an analytical solution. Deficiencies of the use of this regularization method are observed and discussed, e.g. spurious waves apparition in the soil’s seismic response. Next, a 2D embankment-type model is simulated and its dynamic response is evaluated in dry, fully drained and coupled hydromechanical conditions. Two criteria are used to define the onset of the structure’s collapse. The second order work is used to describe the local instability at specific instants of the ground motion, while the estimation of a local safety factor is proposed by calculating soil’s residual strength. Concerning the failure mode, the effect of excess pore water pressure is of great importance, as an otherwise stable structure-foundation system in dry and fully drained conditions becomes unstable during coupled analysis. Finally, a levee- foundation system is simulated and the influence of soil’s permeability, depth of the liquefiable layer, as well as, characteristics of input ground motion on the liquefaction-induced failure is evaluated. For the current levee model, its induced damage level (i.e. settlements and deformations) is strongly related to both liquefaction apparition and dissipation of excess pore water pressure on the foundation. A circular collapse surface is generated inside the liquefied region and extends towards the crest in both sides of the levee. Even so, when the liquefied layer is situated in depth, no effect on the levee response is found. This research work can be considered as a reference case study for seismic assessment of embankment-type structures subjected to earthquake and provides a high-performance computational framework accessible to engineers.

Les travaux de cette thèse portent sur la navigation des véhicules autonomes, notamment la planification de trajectoires et le contrôle du véhicule. En premier lieu, un modèle véhicule plan est développé en utilisant une technique de modélisation qui assimile le véhicule à un robot constitué de plusieurs corps articulés. La description géométrique du véhicule est basée sur la convention de Denavit-Hartenberg modifiée. Le modèle dynamique du véhicule est ensuite calculé en utilisant la méthode récursive de Newton-Euler, qui est souvent utilisée dans le domaine de robotique. La validation du modèle a été conduite sur le simulateur Scaner-Studio développé par Oktal pour les applications automobiles. Le modèle du véhicule développé est ensuite utilisé pour la synthèse de lois de commande couplées pour les dynamiques longitudinale et latérale du véhicule. Deux correcteurs sont proposés dans ce travail : le premier est basé sur les techniques de commande par Lyapunov, le second utilise une approche ”Immersion et Invariance”. Ces deux contrôleurs ont pour objectifs de suivre une trajectoire de référence donnée avec un profil de vitesse désirée, tout en tenant compte du couplage existant entre les dynamiques longitudinale et latérale du véhicule. En effet, le contrôle couplé est nécessaire pour garantir la sécurité du véhicule autonome surtout lors de l’exécution des manœuvres couplées comme les manœuvres de changement de voie, les manœuvres d’évitement d’obstacles et les manœuvres exécutées dans les situations de conduite critiques. Les contrôleurs développés ont été validés en simulation sous Matlab/Simulink en utilisant des données expérimentales. Par la suite, ces contrôleurs ont été validés expérimentalement en utilisant le véhicule démonstrateur robotisé (Renault-Zoé) du laboratoire Heudiasyc financé par l’Equipex Robotex. En ce qui concerne la planification de trajectoires, une méthode de planification basée sur la méthode des tentacules sous forme de clothoides a été développée. En outre, une méthode de planification de manœuvres qui s’intéresse essentiellement à la manœuvre de dépassement a été mise en place, afin d’améliorer et de compléter la méthode locale des tentacules. Le planificateur local et le planificateur de manœuvres ont été ensuite combinés pour établir une stratégie de navigation complète. Cette stratégie a été validée par la suite sous Matlab/Simulink en utilisant le modèle de véhicule développé et le contrôleur basé sur Lyapunov. / In this thesis, the trajectory planning and the control of autonomous vehicles are addressed. As a first step, a multi-body modeling technique is used to develop a four wheeled vehicle planar model. This technique considers the vehicle as a robot consisting of articulated bodies. The geometric description of the vehicle system is derived using the modified Denavit Hartenberg parameterization and then the dynamic model of the vehicle is computed by applying a recursive method used in robotics, namely Newton-Euler based Algorithm. The validation of the developed vehicle model was then conducted using an automotive simulator developed by Oktal, the Scaner-Studio simulator. The developed vehicle model is then used to derive coupled control laws for the lateral and the longitudinal vehicle dynamics. Two coupled controllers are proposed in this thesis: In the first controller, the control is designed using Lyapunov control techniques while in the second one an Immersion and Invariance approach is used. Both of the controllers aim to ensure a robust tracking of the reference trajectory and the desired speed while taking into account the strong coupling between the lateral and the longitudinal vehicle dynamics. In fact, the coupled controller is a key step for the vehicle safety handling, especially in coupled maneuvers such as lane-change maneuvers, obstacle avoidance maneuvers and combined maneuvers in critical driving situations. The developed controllers were validated in simulation under Matlab/Simulink using experimental data. Subsequently, an experimental validation of the proposed controllers was conducted using a robotized vehicle (Renault-ZOE) present in the Heudiasyc laboratory within the Equipex Robotex project. Concerning the trajectory planning, a local planning method based on the clothoid tentacles method is developed. Moreover, a maneuver planning strategy focusing on the overtaking maneuver is developed to improve and complete the local planning approach. The local and the maneuver planners are then combined in order to establish a complete navigation strategy. This strategy is then validated using the developed robotics vehicle model and the Lyapunov based controller under Matlab/Simulink.

Le phénomène de suffusion correspond à la migration des particules fines érodées dans un milieu poreux sous l'action d’un flux hydraulique. Ce mécanisme pourrait être la cause principale des ruptures des remblais et des barrages en terre. De nombreuses études expérimentales ont été menées pour comprendre la suffusion et mettre en évidence les phénomènes couplés associés. Au niveau numérique, on trouve beaucoup de modèles analytiques et numériques mais rares sont ceux qui prennent en compte l’arrachement des particules, leur transport et leur dépôt éventuel (par un processus de colmatage ou pour des vitesses d’écoulement suffisamment faibles).En se basant sur une loi d’écoulement de type Darcy, sur la loi d’érosion de Papamichos et al (2001) modifiée par Bendahmane (2005)et sur une loi d’évolution de la viscosité de fluide (relation d’Einstein), nous développons une nouvelle approche hydromécanique de la suffusion. La résolution numérique du problème est réalisée par la méthode des éléments finis. Deux aspects sont présentés: le cadre général du modèle proposé (réalisé en 2D) avec une étude paramétrique et la validation du modèle avec une modélisation 3D réalisée avec le modèle géométrique de l’essai (Cross Erosion Test) (CET), ce qui permet de décrire à la fois les phénomènes d’érosion, de transport et de dépôt des particules érodées dans un milieu poreux saturé.Pour cela, nous avons choisi un outil de modélisation approprié à la représentation de phénomènes couplés tels que ceux mobilisés par l’érosion interne. Le logiciel Comsol-Multiphysics 3.4b, basé sur la méthode des éléments finis, a été retenu car il permet d’implanter relativement facilement de nouvelles équations constitutives des phénomènes. Dans un deuxième temps, le modèle a été validé sur des expériences de référence reflétant les phénomènes étudiés. Nous avons utilisé les résultats expérimentaux de Nguyen (2013) qui a mis au point un nouveau dispositif expérimental au laboratoire 3SR appelé " l'Essai d’Érosion Transverse " ou Cross Érosion Test. Deux types de sol ont été considérés : un sol gravelo-sableux(noté S3) et un sol limoneux de l’Isère (noté S4 et S4-a).Afin de discuter des aspects transitoire et dynamique du phénomène de suffusion, les vitesses d’écoulement, les gradients hydrauliques, la distribution de la porosité et de la perméabilité, la distribution de la concentration des particules érodées en suspension, et enfin la masse érodée sortantes ont mesurés au cours du temps et comparés aux résultats du modèle physique. / The phenomenon of Suffusion corresponds to the migration of fine eroded particles in a porous medium under the action of an internal water flow. This mechanism could be the main origin of damage in embankments and earth dams. Many experimental studies have been done to analyse the suffusion but actually understanding this phenomenon appears as a major scientific challenge. On the other hand, numerically, only a few studies were found which associate the mechanisms of detachment, transport and deposition of eroded particles.Based on the Darcy’s law model, the erosion model of Papamichos et al (2001) modified by Bendahmane (2005) and the fluid viscosity evolution law (Einstein relation), we developed a new hydro-mechanical approach of suffusion. The numerical solution of the problem is carried out by using a finite element method. Two aspects are presented: first, the general framework of the proposed model (implemented in 2D) with a parametric study and then the validation of the numerical model realized with a 3D study of the geometric model of the experimental study of Cross Erosion Test (CET). This model describes the three phenomena of suffusion: erosion, transport and deposition of eroded particles in a saturated soil.Furthermore, the numerical modeling of coupled phenomena of internal erosion is performed using the commercial software "Comsol Multiphysics-3.4b". However, to validate the model, experimental results on two types of soil: sandy gravel soil (S3) and the silt of Isère (S4 and S4-a) are used. These results are found in the PhD thesis of Nguyen(2013) who has developed a new apparatus called Cross Erosion Test (CET).Moreover, to discuss the transient and dynamic aspects of the phenomenon, the evaluation of the mass conservation with different figures of flow velocity, hydraulic gradient, hydraulic head, porosity and permeability distribution, concentration distribution, and of outgoing eroded particles, are measured over time and compared with experimental results.

A microextração líquido-líquido dispersiva baseada no uso de solventes orgânicos (OS-DLLME) vem recebendo grande destaque devido a facilidade de operação, baixo custo, rapidez e um consumo mínimo de solventes. Previamente a OS-DLLME um pré-tratamento do plasma se faz necessário a fim de propiciar a formação de uma adequada fase sedimentada. O levetiracetam (LEV) é um dos fármacos mais prescritos para o tratamento de crises epilépticas parciais e com generalizações secundárias. Assim, foi desenvolvido e validado um método bioanalítico para a quantificação do LEV em amostras de plasma por cromatografia em fase gasosa acoplada à espectrometria de massas (GC/MS). O pré-tratamento das amostras de plasma empregou ultrafiltros Amicon® (poros com tamanho de 10 kDa) que formavam um permeado adequado para a realização da OS-DLLME. A adição de 130 ?L de clorofórmio (solvente extrator) e 400 ?L de isopropanol (solvente dispersor), sem alteração na força iônica e agitação da amostra, proporcionaram 33 % de recuperação do LEV nas amostras de plasma. Tal análise foi realizada usando uma coluna de sílica fundida recoberta com Rtx-5MS (30 m × 0,25 mm x 0,25 ?m) empregando uma rampa de aquecimento. O tempo total de corrida cromatográfica foi de 9 minutos. O método apresentou-se linear no intervalo de concentração de 2 - 80 ?g mL-1 (r >= 0,99), onde os resultados foram ponderados (peso =1/x). A validade da regressão foi confirmada aplicando o teste da falta de ajuste linear. O limite inferior de quantificação (LIQ) foi de 2 ?g mL-1. Os parâmetros de precisão, exatidão, efeito matriz, efeito carry-over e estabilidade demonstraram-se em conformidade com o European Medicines Agency. Outro método foi desenvolvido e validado para a quantificação da risperidona (RSP) e seu metabólito 9-hidroxi-risperidona (9-OH-RSP) em amostras de plasma. A RSP e 9-OH-RSP correspondem a \"fração ativa\" do medicamento responsável pela atividade anticonvulsivante. As amostras de plasma foram pré-tratadas com ácido tricloroacético (TCA 30 %). O sobrenadante límpido foi diluído com solução de NaCl (10 %) e ajustado para o valor de pH 12, no qual foi desenvolvido a OS-DLLME. Foi adicionado um volume de 500 ?L de acetona (solvente dispersor) e 80 ?L de clorobenzeno (solvente extrator). Após otimização da extração, foi alcançado 89 % e 42 % de recuperação da RSP e 9-OH-RSP, respectivamente. Para tais análises foi empregada a cromatografia líquida acoplada à espectrometria de massas sequencial com ionização por eletrospray (LC-MS/MS). Uma coluna Ascentis® C18 (10 cm x 4,6 mm x 2,7 ?m), fase móvel composta por tampão acetato de amônio e acetonitrila, em modo de eluição gradiente, vazão de 500 ?L min-1 e temperatura da coluna de 40 ºC foram empregados. O tempo total da corrida cromatográfica foi de 8 minutos. O método foi linear na faixa de concentração de 5 - 80 ng mL-1 (r >= 0,99), para ambos os analitos. O LIQ foi de 5 ng mL-1. Todos os demais parâmetros estavam em conformidade com a agência regulatória. Ambos os métodos foram aplicados com sucesso em amostras de plasma de paciente em tratamento com LEV ou RSP. Desta forma foi possível demonstrar aplicabilidade dos métodos bioanalíticos desenvolvidos e averiguar a concentração plasmática dos devidos fármacos no paciente / Dispersive liquid-liquid microextraction technique based on the use of organic solvents (OS-DLLME) has received highlighted due to the easily, rapidity, low cost and low consumption of organic solvent. Prior to OS-DLLME, plasma pretreatment is necessary to provide the formation of a suitable settled phase. Levetiracetam (LEV) is one of the most prescribed drugs for the treatment-refractory partial onset seizures with or without secondary generalization. So, it was developed and validated a bioanalytical method for the quantification of LEV in plasma samples by Gas Chromatography Mass Spectrometry (GC/MS). The pretreatment of the plasma samples employed tubes of ultrafiltration Amicon® (pore size 10 kDa) in order to form a suitable permeated to carry out the OS-DLLME. The addition of 130 ?L of chloroform (extraction solvent) and 400 ?L of isopropanol (disperser solvent), without ionic strength and agitation of samples, have reached 33 % of recovery of LEV from plasma samples. This analysis was carried out using a fused silica coated Rtx-5MS column (30 m × 0.25 mm × 0.25 ?m) and a heating ramp. The run time was 9 minutes. The method was linear in the concentration range of 2 - 80 ?g mL-1 (r >= 0.99) and the results were weighted (1/x). The linear regression was confirmed by applying the lack of fit test. The lower limit of quantitation (LLOQ) was 2 ?g mL-1. The precision, accuracy, matrix effect, carry-over and stability were in agreement with European Medicines Agency. Another method was developed and validated for the quantification of risperidone (RSP) and its 9-hydroxy-risperidone metabolite (9-OH-RSP) from plasma samples. The RSP and 9-OH-RSP constitutes the total active moiety responsible for the anticonvulsant activity. Plasma samples were pretreated with trichloroacetic acid (TCA 30%). The clear supernatant was diluted with NaCl solution (10%) and adjusted to pH 12, where was developed the OS-DLLME. It was added 500 ?L of acetone (dispersing solvent) and 80 ?L of chlorobenzene (extraction solvent). After the parameters optimization, the recovery was 89% and 42% for RSP and 9-OH-RSP, respectively. It was employed liquid chromatography-electrospray-tandem-mass spectrometry (LC/ MS/MS). Ascentis® C18 column (10 cm x 4.6 mm x 2.7 ?M), ammonium acetate buffer and acetonitrile as mobile phase in gradient elution mode, at flow rate 500 ?L min-1 and column temperature of 40 °C for this analysis. The run time was 8 minutes. The method was linear in the concentration range 5 - 80 ng mL-1 (r >= 0.99) for both analytes. The LLOQ was 5 ng mL-1. All other parameters were in agreement with the regulatory agency. Both methods have been successfully applied in plasma samples from patient that receive diary doses of LEV or RSP. In this way, it was possible to present the applicability of developed bioanalytical methods and the quantitation of plasmatic concentration of these studied drugs.

A cetamina é uma droga amplamente utilizada e o seu uso inadequado tem sido associado à graves consequências para a saúde humana. Embora as propriedades farmacológicas deste agente em doses terapêuticas sejam bem conhecidas, existem poucos estudos sobre os efeitos secundários induzidos por doses não-terapêuticas, incluindo os efeitos nos estados de ansiedade e agressividade. Neste contexto, os modelos animais são uma etapa importante na investigação e elucidação do mecanismo de ação a nível comportamental. O zebrafish (Danio rerio) é um novo organismo-modelo, interessante e promissor, uma vez que apresenta alta similaridade fisiológica, genética e neuroquímica com seres humanos, respostas comportamentais bem definidas e rápida absorção de compostos de interesse em meio aquoso além de apresentar uma série de vantagens em relação aos modelos mamíferos tais como manutenção de baixo custo, prática e executável em espaços reduzidos. Nesse sentido, faz-se necessário a execução de ensaios comportamentais em conjunto com análises estatísticas robustas e rápidas tais como ANOVA e Métodos Multivariados; e também o desenvolvimento de métodos analíticos sensíveis, precisos e rápidos para determinação de compostos de interesse em matrizes biológicas provenientes do animal. Os objetivos do presente trabalho foram a investigação dos efeitos da cetamina sobre a ansiedade e a agressividade em zebrafish adulto empregando Testes de Claro-Escuro e Testes do Espelho e métodos estatísticos univariados (ANOVA) e multivariados (PCA, HCA e SIMCA) assim como o desenvolvimento de método analítico para determinação da cetamina em matriz biológica proveniente do animal, empregando Extração Líquido-Líquido e Cromatografia em Fase Gasosa acoplada ao Detector de Nitrogênio-Fósforo (GC-NPD). Os resultados comportamentais indicaram que a cetamina produziu um efeito significativo dose-dependente em zebrafish adulto na latência à área clara, no número de cruzamentos entre as áreas e no tempo de exploração da área clara. Os resultados das análises SIMCA e PCA mostraram uma maior similaridade entre o grupo controle e os grupos de tratamento expostos às doses mais baixas (5 e 20 mg L-1) e entre os grupos expostos às doses de 40 e 60 mg L-1. Na análise por PCA, dois componentes principais responderam por 88,74% de toda a informação do sistema, sendo que 62,59% da informação cumulativa do sistema foi descrito pela primeira componente principal. As classificações HCA e SIMCA seguiram uma evolução lógica na distribuição das amostras por classes. As doses mais altas de cetamina induziram uma distribuição mais homogênea das amostras enquanto as doses mais baixas e o controle resultaram em distribuições mais dispersas. No Teste do Espelho, a cetamina não induziu efeitos significativos no comportamento dos animais. Estes resultados sugerem que a cetamina é modulador de comportamentos ansiosos, sem efeitos indutores de agressividade. Os resultados da validação do método cromatográfico indicaram uma extração com valores de recuperação entre 33,65% e 70,89%. A curva de calibração foi linear com valor de R2 superior a 0,99. O limite de detecção (LOD) foi de 1 ng e o limite de quantificação (LOQ) foi de 5 ng. A exatidão do método cromatográfico manteve-se entre - 24,83% e - 1,258%, a precisão intra-ensaio entre 2,67 e 14,5% e a precisão inter-ensaio entre 1,93 e 13,9%. / Ketamine is a widely used drug and its inappropriate use has been associated with serious consequences for human health. Although the pharmacological properties of this agent in therapeutic doses are well known, there are few studies about the side effects induced at non-therapeutic doses, including the effects on states of anxiety and aggression. In this context, animal models are an important step in the investigation and elucidation of the mechanism of action at the behavioral level. The zebrafish (Danio rerio) is a new organism model, interesting and promising, since it presents high physiological, genetics and neurochemistry similarity in relation to humans, well-defined behavioral responses and rapid absorption of interesting compounds in an aqueous medium, apart from presents several advantages over mammalian models such as practical, low cost maintenance and executable in reduced spaces. In this sense, it is necessary to perform behavioral tests in conjunction with robust and rapid statistical analysis such as ANOVA and multivariate methods; and also the development of sensitive, accurate and rapid analytical methods to determination of compounds of interest in biological matrices from the animal. The objectives of this study were to investigate the effects of ketamine on anxiety and aggression in adult zebrafish using Light-Dark and Mirror Biting tests and univariate (ANOVA) and multivariate (PCA, HCA and SIMCA) statistical methods and to develop an analytical method for determination of ketamine in biological animal matrices using Liquid-Liquid Extraction and Gas Chromatography coupled with Nitrogen-Phosphorus Detector (GC-NPD). The behavioral results of Light-Dark Test indicated that ketamine produced a significant dose-dependent response in the latency to light area, in the number of midline crossings and in the time spent in light area. Results of SIMCA and PCA analysis showed a greater similarity between the control group and treatment groups exposed to lower doses (5 and 20 mg L-1) and between the treatment groups at doses of 40 and 60 mg L-1. In the analysis PCA, two principal components accounted for 88,74% of all the system information and 62,59% of the cumulative information of the system were described for the first principal component. The HCA and SIMCA results showed a logical evolution in the distribution of samples per class. The higher dose of ketamine induced a more homogeneous distribution of the samples while the lower doses and control resulted in more dispersed distribution. In the Mirror Test, ketamine induced no significant effect on the behavior of animals. These results suggest that ketamine is a modulator of anxious behavior without inducing aggressive effects. The results of the validation of chromatographic method indicated an extraction with recovery ranged between 33,65% to 70,89%. Calibration curve was linear with R2 value higher than 0,99. The limit of detection (LOD) was 1 ng and the limit of quantification (LOQ) was 5 ng. The accuracy of gas chromatographic method ranged between - 24,83% and - 1,258%, intra-assay precision between 2,67 and 14,5% and inter-assay precision between 1,93 and 13,9%.

Investigamos algumas capacidades computacionais de sistemas constituídos de mapas acoplados. Particularmente, exploramos o uso desses sistemas no tratamento de três problemas: a identificação de simetria de reflexão em imagens planas; a formação de clusters de elementos síncronos em redes com topologias do tipo small-worlds; e a construção de figuras que obedecem a uma regra de composição. Para a identificação de simetria, motivados por modelos biológicos construímos uma rede de mapas em que, acoplamentos locais e globais permitem verificar a simetria de reflexão de uma imagem plana através do sincronismo dos elementos do sistema. Em particular, esse sistema apresenta a habilidade de não requerer sua reinicialização para novas identificações e permite, assim, a identificação de simetrias em cenas que se modificam no tempo. Sistemas estendidos de mapas acoplados são, em geral, construídos conectando-se todos os elementos ou pela formação de uma malha uniforme de conexões. A dinâmica desses sistemas pode apresentar a formação de grupos de elementos síncronos. Esse comportamento de auto-organização pode ser encontrado em diversos sistemas complexos reais que, entretanto e mais comumente, exibem topologias de conexões não uniformes entre seus elementos. Mostramos aqui, a capacidade de mapas acoplados, em diferentes topologias de small-worlds, exibirem a formação de grupos de elementos síncronos com um número de conexões próximo ao das malhas com acoplamento local mas com uma significativa redução da distância média entre os elementos da rede. Por último consideramos o uso de sistemas de mapas como sistemas programáveis. Normalmente, para formação de padrões e figuras no plano, sistemas de funções iteradas são empregados com um conjunto fixo de contrações lineares no plano. Aqui, mostramos a possibilidade do uso de mapas mais gerais na produção de tais padrões e figuras, incluindo estruturas biológicas e fractais. Funções de troca são empregadas para alterar a dinâmica do sistema segundo ou o contexto ou o estado, e fornecem, desse modo, uma forma de programação. / We investigated some computational abilities of systems composed by coupled maps. Here, we explored the use of those systems in dealing with three problems: the identification of reflection symmetry in bidimensional images; the appearing of clusters of synchronous elements in networks with small-worlds topologies; and in constructing figures obeying a composition rule. For the symmetry identification problem, we were motivated by biological models to built a network of coupled maps, with local and global couplings, that verify reflection symmetry of plane images through the synchronism of the elements from the system. In matter, this system presents the ability to perform a new identification without re-initializing the system. This feature allows the identification of symmetries in scenes that can change during the time. In general extended coupled map systems have all elements connected, or the connections lying over a uniform lattice. The dynamics of these systems can present the formation of clusters with synchronous elements. Such auto-organization behavior can be found in several actual complex systems. However, more commonly, these systems do not exhibit uniform connections among their elements. Here, we investigated the capacity of coupled map systems, in different topologies of small-worlds, exhibiting the formation of clusters with synchronous elements, by using a number of connections close to the number in regular lattices but with a significant reduction of the mean distance among their elements. Last we considered the use of systems of maps as programmable systems. Usually, for formation of patterns and geometric figures in the plan, iterated function systems work with a fixed set of linear contractions in the plan. Here, we showed that is possible to use more general maps to the production of patterns and geometric figures, and biological patterns and fractals are generated. Shift functions are used to change the dynamics of the map system due to either the context or the state, giving a way of programming the system.

L’hydrodynamique et la probabilité de minéralisation (R²AI) autour des intrusions magmatiques ont été étudiées par modélisation numérique couplant transfert de chaleur et circulation de fluide. L’objectif principal de ce travail est de tester la nature du lien génétique entre l’intrusion et le processus de minéralisation. La première série de résultats s’appuie sur une comparaison avec des exemples naturels de gisements bien connus : i) L’hydrodynamique et la localisation des zones probables de minéralisation sont fortement dépendantes de la profondeur de mise en place du pluton. Au-dessus de 4.5km de profondeur de mise en place, le seuil de perméabilité de 10-16 m² est atteint et les cellules convectives peuvent créer des zones de décharge additionnelles où des minéralisations peuvent avoir lieu ; ii) Pour toutes les profondeurs d’emplacement, la zone en dessous du pluton n'est pas favorable à la précipitation minérale ; iii) Les apophyses focalisent les fluides convectifs et les zones de minéralisation autour d’elles ; iv) La phase de refroidissement n'est pas la phase majeure de convection. La zone advective principale et celle de haute favorabilité peuvent se produire avant et pendant la phase la plus chaude d’emplacement, avant que le magma ne cristallise complètement; v) Les détachements sont capables de fortement modifier et de re-localiser les flux convectifs déclenchés par une intrusion syn-tectonique; vi) Les conditions physiques favorables à la minéraliser sont produites pendant une durée courte autour de la phase la plus chaude de l'intrusion. Même si les arguments chimiques sont absents, la circulation de fluide (induite par la mise en place de magma) joue un rôle principal dans la genèse des gisements d'or associés aux intrusions. De plus, la formation de ce type de gisement est favorisée par l'occurrence d'une auréole thermique fracturée autour de l'intrusion. La seconde série de résultats concerne l’étude du cas naturel de la minéralisation W-Au de Tighza (Jebel Aouam) au Maroc Central. Une campagne d’acquisition de données gravimétriques, l’inversion données et l’utilisation de logiciel 3D, ont permis d’obtenir la géométrie 3D complexe du pluton de Tighza. Les résultats sont les suivants : i) la zone probable de la minéralisation apparaît au début de la mise en place du magma dans la zone perméable (veine W1) et s'étend pour remplir W1 et couvrir la région autour du pluton pendant la phase la plus chaude de mise en place; ii) lors du refroidissement, la zone probable est réduite et limitée à la zone perméable (W1) pendant 0,6 Ma; iii) L’application de la température de fermeture isotopique de la muscovite et de la biotite avec la distribution du R²AI montre que les âges de refroidissement entre la minéralisation au niveau de la veine W1 et l'intrusion ne sont pas séparés de plus de 0,10 Ma. Ceci est confirmé par la datation absolue de la minéralisation de Tighza et permet de discuter la fiabilité des âges obtenus pour la minéralisation dans la veine W1. / Coupled hydro-thermal numerical modeling has been used to simulate the hydrothermal fluid flow regime and the mineralization probability (R²AI) around plutons. The main objective behind this work is to test the nature of the genetic link between mineralization and intrusions. The first series of results comes from comparison with well-constrained mineral deposits: i) Fluid circulation and mineralization patterns are strongly dependent of the emplacement depth of the pluton. Deep seated plutons emplaced below 10 km do not induce an advective heat dissipation. For emplacement depth less than 4.5 km, the permeability threshold of 10-16 m2 is reached and second order convection cells may create additional discharge zones where mineralization are expected; ii) For all emplacement depths, the pluton floor zone is not favorable for mineral deposition; iii) The apexes strongly modified the fluid flow patterns by focusing convective fluids and mineralization zones around them; iv) The cooling phase is not the main phase of convection for large pluton often associated with long-lived magma emplacement. Major advective heat dissipation and mineral deposition zone may also occur sometime before and during the hottest phase of emplacement; v) Extensional detachments faults are able to delocalize and strongly modify classical fluid flow patterns induced by coeval intrusion; vi) Favorable physical conditions for mineral deposition are encountered around middle crust pluton, during a short time span bracketing the hottest phase of intrusion. We conclude that, even if chemical arguments are absent, fluid circulation induced by granite emplacement plays a key role in the genesis of granite-related Au deposits. Moreover, formation of this type of deposit is promoted and controlled by the occurrence of a fractured thermal aureole around the intrusion. The second series of results deals with the W-Au granite related Tighza deposits (Jebel Aouam, Morocco). Based on gravimetric data, inversion, and 3D modeling software, we were able to construct the most probable complex geometry of the Tighza pluton. The 3D geometries of the pluton and major fractures (W1 vein) were injected in the hydro-thermal modeling procedure. The results are: i) the probable zone of mineralization appears at the beginning of magma emplacement within the permeable zone (W1 vein) and extends to fill up W1 and covers the area around pluton at the hottest phase; ii) During the cooling phase, the story was reversed; the probable zone was reduced and restricted in the permeable zone (W1) during 0.6 Myr of cooling; iii) Application of isotopic closure temperature of muscovite and biotite coupled with R²AI distribution shows that the cooling ages between mineralization in W1 veins and the intrusion are not separated by more than 0.10 Myr. This is confirmed by the absolute dating obtained for Tighza Au mineralization and allows discussing the significance of older ages obtained for the mineralization in W1 veins.

Parmi les systèmes dédiés à l’analyse directe des solides, la vaporisation électrothermique occupe une place de choix. Elle offre plusieurs avantages. Le temps de préparation des échantillons est considérablement réduit. Il n’y a pas de dilution induite par la minéralisation et les risques de pertes ou de contaminations durant cette étape sont éliminés. Son principe de fonctionnement consiste à transformer, par chauffage, quelques milligrammes d’échantillon en un aérosol, qui est ensuite transporté dans un spectromètre d’émission atomique par plasma à couplage inductif, où la composition élémentaire est mesurée. Une première étude fondamentale a permis de mieux comprendre la dynamique de l’aérosol formé et de définir les meilleures conditions opératoires. L’utilisation de cette technique pour la détermination élémentaire dans les végétaux a présenté cependant des difficultés supplémentaires : difficulté d’étalonnage, effets de matrice et grandes variabilités sur les concentrations mesurées. L’utilisation d’un support de cellulose pour les solutions étalons a permis d’harmoniser les conditions de formation de l’aérosol pour l’échantillon et pour l’étalon, et d’obtenir ainsi des résultats justes. Les effets de matrices ont pu être considérablement réduits par une calcination préalable des échantillons. Le manque de précision des mesures, causée par le manque d’homogénéité des échantillons, a pu être limitée en de réduisant significativement la taille des particules solides. Ces résultats obtenus sur des poudres ont permis d’autres applications comme l’analyse d’échantillons entiers ou la cartographie de la composition chimique d’organes végétaux. / Among the systems dedicated to the direct analysis of the solids, electrothermal vaporization takes up a place of choice. It offers several advantages. The preparation time of the samples is considerably reduced. There is no dilution induced by the digestion and the risks of losses or contaminations during this stage are eliminated. Its functioning consists to convert, by heating, a few milligrams of sample into an aerosol which is then transported in an inductively coupled plasma atomic emission spectrometer, where the elemental composition of the sample is determinate. A first fundamental study allowed to better understand the dynamics of the formed aerosol and to define the best operating conditions. However, the use of this technique to determine the elemental composition of solid plant samples presented additional difficulties: difficulty of calibration, matrix effects and important imprecision on the measured concentrations. The use of a cellulose support for the standard solutions allowed to harmonize the formation of the aerosol between the sample and the standard, and to obtain accurate results. The matrix effects can be considerably reduced by a preliminary dry-ashing of the samples. The variability of measurements, caused by the lack of homogeneity of the samples, was limited by reducing significantly the size of the solid particles. These results, obtained on powders, allowed other applications as the analysis of whole plant samples or the imaging of the chemical composition of plant organs.

No description available.