Made available in DSpace on 2014-06-11T19:32:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-11Bitstream added on 2014-06-13T19:22:41Z : No. of bitstreams: 1 pavan_fr_dr_arafcf.pdf: 966119 bytes, checksum: c9d048c219b0b202a52cb7f70f5d5846 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Universidade Estadual Paulista (UNESP) / Tuberculose (TB) é uma doença infecciosa e curável transmitida pelo ar. A taxa de mortalidade reduziu globalmente em 2007, entretanto, TB-MDR, XDR e a coinfecção TB/HIV têm sufocado as tentativas de controle da TB, causando sofrimento e morte em todo o mundo. Adicionalmente, um terço da população mundial está infectada com o Mycobacterium tuberculosis (MTB) em estado de latência, o qual serve como reservatório para TB ativa. A rifampicina (RMP), descoberta há mais de 40 anos, representa a última classe de antibióticos introduzida como fármaco de primeira-linha no tratamento da TB. No esforço de sanar esta falha, é crescente a importância da Química Medicinal Inorgânica como um aliado na pesquisa de novos fármacos contra TB. É bem conhecido que alguns elementos metálicos desempenham papel fundamental nos seres vivos. Tem sido relatado desde 1970 que compostos de rutênio (Ru) exibem atividade anti-tumoral. Inclusive, alguns destes compostos se encontram na fase clínica de avaliação. Compostos de Ru foram avaliados também em nosso laboratório demonstrando atividade contra MTB. Os complexos com Ru(II) demonstraram ser mais ativos contra o MTB em relação a forma do ligante livre, em até 150 vezes, com baixa citotoxicidade e alta seletividade. Os resultados promissores inspiraram a procura de uma melhor abordagem para explorar o perfil pré-clínico in vitro e in vivo desses compostos. Assim, o objetivo deste trabalho foi desenvolver uma linha de pesquisa (pipeline) com ensaios fenotípicos rápidos, sensíveis, específicos e de baixo custo na pesquisa de um novo fármaco contra TB. Paralelamente, avaliou-se os melhores complexos heterolépticos de Ru(II) com fosfinas, diiminas e picolinato como ligantes, pré-selecionados, frente a esse pipeline. Os resultados obtidos com os complexos... (Resumo completo, clicar acesso eletrônico abaixo / Tuberculosis (TB) is a preventable and curable infectious disease transmitted through the air. The mortality rates decreased globally in 2007, however, MDR and XDR TB, and co-infection TB/HIV have stifled attempts to control TB causing suffering and death worldwide. Additionally, a third of the world population is infected with Mycobacterium tuberculosis (MTB) in state of latency, which serves as a reservoir for active TB. Rifampicin (RMP), discovered more than 40 years ago, represents the last class of antibiotics introduced as first-line drug to treat TB. In an effort to correct this failure is an increasingly importance of Inorganic Medicinal Chemistry as an ally in the search for new drugs against TB. It is well known that some metallic elements play a fundamental role in living organisms. It has been reported since 1970 that compounds of ruthenium (Ru) exhibit anti-tumor activity. Even some of these compounds are in clinical phase of evaluation. Ru compounds were evaluated in our laboratory showing activity against MTB. Complexes with Ru(II) showed activity against MTB in relation to the free ligand up to 150 higher, with low cytotoxicity and high selectivity. The promising results inspired the search for a better approach to explore the pre-clinical in vitro and in vivo profile of these compounds. So, the objective of this study was to develop a research line (pipeline) fast, sensitive, specific and low-cost phenotypic testing in the search for a new drug against TB. At the same time the best complexes of heteroleptic Ru(II) phosphine/diimines/picolinate, pre-selected, against several biological in vitro and in vivo assays. Those evaluated assays were inserted into the pipeline developed at our laboratory. The in vitro results obtained with the Ru(II) (compounds SCAR) complexes are comparable and/or better than the first choice... (Complete abstract click electronic access below)

Orientador: Clarice Queico Fujimura Leite / Banca: Sylvia Luisa Pincherle Cardoso Leão / Banca: Sergio Akira Uyemura / Banca: Victor Marcelo Deflon / Banca: Alzir Azevedo Batista / Resumo: Tuberculose (TB) é uma doença infecciosa e curável transmitida pelo ar. A taxa de mortalidade reduziu globalmente em 2007, entretanto, TB-MDR, XDR e a coinfecção TB/HIV têm sufocado as tentativas de controle da TB, causando sofrimento e morte em todo o mundo. Adicionalmente, um terço da população mundial está infectada com o Mycobacterium tuberculosis (MTB) em estado de latência, o qual serve como reservatório para TB ativa. A rifampicina (RMP), descoberta há mais de 40 anos, representa a última classe de antibióticos introduzida como fármaco de primeira-linha no tratamento da TB. No esforço de sanar esta falha, é crescente a importância da Química Medicinal Inorgânica como um aliado na pesquisa de novos fármacos contra TB. É bem conhecido que alguns elementos metálicos desempenham papel fundamental nos seres vivos. Tem sido relatado desde 1970 que compostos de rutênio (Ru) exibem atividade anti-tumoral. Inclusive, alguns destes compostos se encontram na fase clínica de avaliação. Compostos de Ru foram avaliados também em nosso laboratório demonstrando atividade contra MTB. Os complexos com Ru(II) demonstraram ser mais ativos contra o MTB em relação a forma do ligante livre, em até 150 vezes, com baixa citotoxicidade e alta seletividade. Os resultados promissores inspiraram a procura de uma melhor abordagem para explorar o perfil pré-clínico in vitro e in vivo desses compostos. Assim, o objetivo deste trabalho foi desenvolver uma linha de pesquisa (pipeline) com ensaios fenotípicos rápidos, sensíveis, específicos e de baixo custo na pesquisa de um novo fármaco contra TB. Paralelamente, avaliou-se os melhores complexos heterolépticos de Ru(II) com fosfinas, diiminas e picolinato como ligantes, pré-selecionados, frente a esse pipeline. Os resultados obtidos com os complexos... (Resumo completo, clicar acesso eletrônico abaixo / Abstract: Tuberculosis (TB) is a preventable and curable infectious disease transmitted through the air. The mortality rates decreased globally in 2007, however, MDR and XDR TB, and co-infection TB/HIV have stifled attempts to control TB causing suffering and death worldwide. Additionally, a third of the world population is infected with Mycobacterium tuberculosis (MTB) in state of latency, which serves as a reservoir for active TB. Rifampicin (RMP), discovered more than 40 years ago, represents the last class of antibiotics introduced as first-line drug to treat TB. In an effort to correct this failure is an increasingly importance of Inorganic Medicinal Chemistry as an ally in the search for new drugs against TB. It is well known that some metallic elements play a fundamental role in living organisms. It has been reported since 1970 that compounds of ruthenium (Ru) exhibit anti-tumor activity. Even some of these compounds are in clinical phase of evaluation. Ru compounds were evaluated in our laboratory showing activity against MTB. Complexes with Ru(II) showed activity against MTB in relation to the free ligand up to 150 higher, with low cytotoxicity and high selectivity. The promising results inspired the search for a better approach to explore the pre-clinical in vitro and in vivo profile of these compounds. So, the objective of this study was to develop a research line (pipeline) fast, sensitive, specific and low-cost phenotypic testing in the search for a new drug against TB. At the same time the best complexes of heteroleptic Ru(II) phosphine/diimines/picolinate, pre-selected, against several biological in vitro and in vivo assays. Those evaluated assays were inserted into the pipeline developed at our laboratory. The in vitro results obtained with the Ru(II) (compounds SCAR) complexes are comparable and/or better than the first choice... (Complete abstract click electronic access below) / Doutor

The imposed commission ban to Finnish insurance intermediaries has generated some controversy and the intermediary market has experienced consolidation in the few last years. The thesis examines the relationship between market structure and profitability among Finnish life insurance intermediaries and tests for the applicability of two market power hypotheses. The panel data analysis shows that there is support for the Relative Market Power hypothesis while the Structure-Conduct-Performance hypothesis is not applicable for Finnish life insurance intermediaries. The implication of this research is that competition authorities should be concerned with market structure effects when discussing changes to the regulatory environment which surrounds life insurance intermediaries.

<p>Den svenska marinen likväl som världens handels sjöfart nyttjar alltmer satellitnavigering för sin positionering. Enligt totalförsvarets forskningsinstitut kan sådana system störas med förhållandevis enkla medel. Nu när den svenska marinen alltmer engagerar sig i insatser utomlands mot irreguljära motståndare väcks frågan om hur en irreguljär motståndare kan påverka den svenska marinen och den svenska marinens taktik. I denna uppsats kommer frågor kring en irreguljär motståndares förmåga att påverka GNSS att ställas. Samt frågan om vilken påverkan detta har för såväl den svenska marinens fartyg som handelssjöfarten. Uppsatsen kommer även att behandla möjligheterna till skydd mot störning samt hur den svenska marinens taktik kommer påverkas om en irreguljär motståndare försöker störa ut GNSS-system.</p> / <p>The Swedish Navy as well as the worlds shipping industries use more and more satellite navigation for positioning purposes. According to the Swedish Defence Research Agency, those types of systems can relatively easily and at a low cost be jammed. With the Swedish Navy becoming more and more involved in missions overseas against insurgents, the question is whether an insurgent can affect the Swedish Navy and its tactics. This paper investigates the questions about what opportunities an insurgent have to affect the GNSS-system and how that can affect the Swedish Navyas well as the shipping industries. This paper is also about how the tactics of the Swedish Navy will be affected if an insurgent attempts to jam the GNSS-systems and the possibility of protection against jamming.</p>

Den svenska marinen likväl som världens handels sjöfart nyttjar alltmer satellitnavigering för sin positionering. Enligt totalförsvarets forskningsinstitut kan sådana system störas med förhållandevis enkla medel. Nu när den svenska marinen alltmer engagerar sig i insatser utomlands mot irreguljära motståndare väcks frågan om hur en irreguljär motståndare kan påverka den svenska marinen och den svenska marinens taktik. I denna uppsats kommer frågor kring en irreguljär motståndares förmåga att påverka GNSS att ställas. Samt frågan om vilken påverkan detta har för såväl den svenska marinens fartyg som handelssjöfarten. Uppsatsen kommer även att behandla möjligheterna till skydd mot störning samt hur den svenska marinens taktik kommer påverkas om en irreguljär motståndare försöker störa ut GNSS-system. / The Swedish Navy as well as the worlds shipping industries use more and more satellite navigation for positioning purposes. According to the Swedish Defence Research Agency, those types of systems can relatively easily and at a low cost be jammed. With the Swedish Navy becoming more and more involved in missions overseas against insurgents, the question is whether an insurgent can affect the Swedish Navy and its tactics. This paper investigates the questions about what opportunities an insurgent have to affect the GNSS-system and how that can affect the Swedish Navyas well as the shipping industries. This paper is also about how the tactics of the Swedish Navy will be affected if an insurgent attempts to jam the GNSS-systems and the possibility of protection against jamming.

Les exploitants des Installations de Stockage de Déchets Non Dangereux (ISDND) sont confrontés à la nécessité d'assurer une biodégradation homogène et rapide des déchets, pour ne pas prolonger la durée coûteuse de post-exploitation. Pour cela, il est nécessaire d'injecter des lixiviats (liquides résultant de la biodégradation) dans les déchets, tout en contrôlant les volumes injectés pour maintenir une bonne humidité assurant une meilleure biodégradation et limiter à 50 cm le niveau piézométrique en fond de casier (pour respecter la réglementation). Pour gérer ces contraintes, les industriels doivent disposer d'outils permettant de caractériser et de simuler les injections des lixiviats. Ce travail vise à étudier les injections des lixiviats et a pour but de contribuer à établir un modèle conceptuel de la circulation des lixiviats à l'échelle du site industriel par une approche combinée de la simulation et de l'hydrogéophysique. Deux méthodes géophysiques ont été utilisées, la Tomographie de Résistivité Electrique (ERT), employée en mode de « suivi temporel » et la Résonance Magnétique des Protons (RMP).La première étape consiste en un développement méthodologique des outils géophysiques ERT et RMP afin de faciliter leurs applications à la caractérisation des injections des lixiviats dans les massifs de déchets. La seconde étape de ce travail consiste en une analyse et une interprétation des résultats géophysiques des suivis temporels de résistivité lors d'injection des lixiviats dans les déchets. Ensuite les mesures RMP sont réalisées sur des échantillons saturés de déchets en laboratoire, puis sur le terrain dans une ISDND où les déchets étaient saturés. L'analyse des résultats ERT a permis de caractériser la structure et les propriétés hydrodynamiques du milieu. Les résultats RMP ont permis d'obtenir des informations sur les gammes de conductivité hydraulique dans le massif de déchets étudié.La troisième étape consiste en une combinaison entre les résultats géophysiques et une simulation hydrodynamique (réalisée avec HYDRUS-2D). Cela permet d'établir un modèle conceptuel des circulations des lixiviats dans les déchets. Les résultats de la simulation hydrodynamique montrent que les déchets ne peuvent-être comparés en aucun cas à un milieu poreux homogène à l'échelle du site industriel. De plus, le milieu s'apparente à un milieu composé d'une matrice poreuse de faible conductivité hydraulique, recoupée par des drains dont la conductivité est très forte.En résumé, les résultats de ce travail ouvrent de nouvelles perspectives dans l'application d'outils de simulation à l'échelle du site industriel pour l'étude de la circulation des lixiviats dans les déchets. Cette approche et les améliorations méthodologiques proposées dans ce travail, permettent d'entrevoir une application élargie pour d'autres types de problèmes hydrologiques, comme l'infiltration dans les premiers décimètres des sols, et l'identification des systèmes de recharge des aquifères, entre autres.

La présentation porte sur les deux principaux domaines de recherche dans lequel je me suis investi, depuis 2003, au BRGM, celui du développement de la prospection par Résonance Magnétique Protonique (RMP), et l'utilisation des méthodes Electro-Magnétique à Source Contrôlée (CSEM). Une brève introduction rappellera le principe de la mesure RMP. La première partie, présentera les travaux réalisés pour raffiner les modèles utilisés, pour prendre en compte la variation du signal liée aux conditions de mesures (champ géomagnétique, topographie) et à l'environnement géologique (zone non-saturée dans la craie, forte conductivité sur le bord de la mer Morte). Afin d'appréhender la nature 2D/3D des objets étudiés, j'ai développé un modèle 3D de la réponse RMP et mis au point une approche permettant d'évaluer la position et le volume de cavités remplies d'eau (imagerie d'un conduit karstique près de Rocamadour et cartographie de la dissolution d'une couche de sel générant des effondrements « sinkholes »). Enfin j'ai développé un programme d'inversion qui permet de réaliser une tomographie en 2D/3D de la teneur en eau et des temps de relaxation (illustrée dans le cas d'un aquifère sédimentaire interrompu par un système de failles). La deuxième partie concernera la mesure de la résistivité électrique par de grands dispositifs appliquée à l'imagerie d'aquifères complexes (biseaux salés et milieu volcanique) et la mise au point d'un dispositif CSEM dédié au suivi temporel de la résistivité dans un aquifère. L'originalité réside dans l'utilisation du tubage métallique des forages pour injecter le courant électrique en profondeur et permettant par la mesure en surface du champ électrique et magnétique, de mesurer les variations de résistivité au sein d'un réservoir profond. Ces travaux ont été réalisés dans le cadre du suivi de l'injection de CO2 (résistant) dans des réservoirs salins. La performance du dispositif sera illustrée par une étude numérique et sa mise en œuvre sur le site pilote de Ketzin en Allemagne. Je conclurai cet exposé par un aperçu des orientations vers lesquelles je propose de faire porter l'effort de recherche dans ces deux domaines, aujourd'hui en pleine évolution.

Edge localized modes (ELMs) are a concern for future magnetic fusion devices, such as ITER, due to the large transient heat loads they generate on the plasma facing components. A very promising method of ELM suppression is an application of resonant magnetic perturbations (RMP); however, such application leads to localized places of higher heat fluxes called footprints. Both ELMs and RMP could limit the operational lifetime of the device. In this thesis, we analyze the temporal and spatial distribution of footprints using the tangle distance method in the aim to prevent a transient overheating. We also analyze quasi-double-null configuration of the ITER plasma which can be expected to be the most susceptible to overheating of the upper wall. Based on the modelling, the potentially dangerous configurations of the RMP have been shown. Using the ELM filament model included in the LOCUST GPU code, we study temporal and spatial distribution of the heat fluxes caused by ELMs in the axially symmetric and the asymmetric magnetic field. The results are compared with published experimental observations. Powered by TCPDF (www.tcpdf.org)

(Hamiltonian chaos and its application to anomalous dynamics in turbulent environment) RMP-induced ELM control has been tested on several tokamaks. It is believed that increase of electron transport across the magnetic field plays an important role. Edge plasma turbulence also affects dynamics in the edge region of tokamak. We study the simultaneous effect of plasma turbulence and RMP-induced stochastic magnetic field within the single-particle framework. We find out that the plasma turbulence is an important element of dynamics that should be taken into account in further (especially single-particle) studies.

Resonant Magnetic Perturbation (RMP) fields produced by external control coils are considered a viable option for the suppression of Edge Localized Modes (ELMs) in present and future tokamaks. Repeated reversals of the toroidal phase of the I-coil magnetic field in RMP shot 147170 on DIII-D has generated uniquely different edge pedestal profiles, implying different edge transport phenomena. The causes, trends, and implications of RMP toroidal phase reversal on edge transport is analyzed by comparing various parameters at 0 and 60 degree toroidal phases, with an I-coil mode number of n=3. An analysis of diffusive and non-diffusive transport effects of these magnetic perturbations it the plasma edge pedestal for this RMP shot is characterized by interpreting the ion and electron heat diffusivities, angular momentum transport frequencies, ion diffusion coefficients, and pinch velocities for both phases.