Nanobelts are a new class of semiconducting metal oxide nanowires with great potential for nanoscale devices. The present research focuses on the manipulation of SnO₂ nanobelts suspended in ethanol using microfluidics and electric fields. Dielectrophoresis (DEP) was demonstrated for the first time on semiconducting metal oxide nanobelts, which also resulted in the fabrication of a multiple nanobelt device. Detailed and direct real-time observations of the wide variety of nanobelt motions induced by DEP forces were conducted using an innovative setup and an inverted optical microscope. High AC electric fields were generated on a gold microelectrode (~ 20 µm gap) array, patterned on glass substrate, and covered by a ~ 10 µm tall PDMS (polydimethylsiloxane) channel, into which the nanobelt suspension was introduced for performing the DEP experiments. Negative DEP (repulsion) of the nanobelts was observed in the low frequency range (< 100 kHz) of the applied voltage, which caused rigid body motion as well as deformation of the nanobelts. In the high frequency range (~ 1 MHz - 10 MHz), positive DEP (attraction) of the nanobelts was observed. Using a parallel plate electrode arrangement, evidence of electrophoresis was also found for DC and low frequency (Hz) voltages. The existence of negative DEP effect is unusual considering the fact that if bulk SnO₂ conductivity and permittivity values are used in combination with ethanol properties to calculate the Clausius Mossotti factor using the simple dipole approximation theory; it predicts positive DEP for most of the frequency range experimentally studied. A fluidic nanobelt alignment technique was studied and used in the fabrication of single nanobelt devices with small electrode gaps. These devices were primarily used for conducting impedance spectroscopy measurements to obtain an estimate of the nanobelt electrical conductivity. Parametric numerical studies were conducted using COMSOL Multiphysics software package to understand the different aspects of the DEP phenomenon in nanobelts. The DEP induced forces and torques were computed using the Maxwell Stress Tensor (MST) approach. The DEP force on the nanobelt was calculated for a range of nanobelt conductivity values. The simulation results indicate that the experimentally observed behavior can be explained if the nanobelt is modeled as having two components: an electrically conductive interior and a nonconductive outer layer surrounding it. This forms the basis for an explanation of the negative DEP observed in SnO₂ nanobelts suspended in ethanol. It is thought that the nonconductive layer is due to depletion of the charge carriers from the nanobelt surface regions. This is consistent with the fact that surface depletion is a commonly observed phenomenon in SnO₂ and other semiconducting metal oxide materials. The major research contribution of this work is that, since nanostructures have large surface areas, surface dominant properties are important. Considering only bulk electrical properties can predict misleading DEP characteristics.

The energy-planning involves finding a set of sources and conversion devices so as to meet the energy requirements/demands of all the activities in an optimal manner. This could occur at centralized or decentralized level. The current pattern of commercial energy oriented development, particularly focused on fossil fuels and centralized electricity, has resulted in inequities, external debt and environmental degradation. The current status is largely a result of adoption of centralized energy planning (CEP), which ignores the energy needs of rural areas and the poor and has further contributed to environmental degradation due to fossil fuel consumption and forest degradation. CEP does not pay attention to the variations in socio-economic and ecological factors of a region, which influence success of any intervention. Decentralized energy planning (DEP) provides an opportunity to address the energy needs of poor as well as promote efficient utilization of resources. The DEP mechanism takes into account various available resources and demands in a region. DEP, in the Indian context, could be at several scales namely district, block, panchayats (cluster of villages) and village level. Energy planning at the village level is the lowest level of the application of decentralized planning principle. A village constitutes a cluster of households with distinct geographic boundary consisting of settlement, agricultural land, water bodies and any other land category, in most parts of India. Further, the village level plans must be prepared within the limits set by a panchayat, a block or a district level plans, for the sum total of various village plans must correspond to a panchayat (local council), block (or taluka), or district level plan. A panchayat is the lowest administrative unit consisting of a cluster of villages and an elected body to administer developmental activities. A block (or taluka) consists of a cluster of panchayats and a district consists of a cluster of blocks. The main hypothesis for this study is that centralized energy planning has lead to excessive dependence on fossil fuels and import of petroleum, leading to concerns on environment and energy security and finally neglect of the energy needs of the rural communities and poor in particular. DEP could meet the local energy needs particularly in rural areas, protect environment and promote a self reliant and sustainable energy path. In this study, methodology for adopting energy planning from grassroot or village to district level is explored. The study adopts and compares the DEP approach of moving from village (Ungra), to panchayat (Yedavani), to block (Kunigal) and finally to district (Tumkur) level. Aims and objectives of research . • To review energy planning approaches adopted in India . • To evaluate models and methods for DEP at different scales; Village, Panchayat, District and State levels . • To develop a sustainable and decentralized energy planning approach . • To analyze the sustainable decentralized planning approach using multiple objective goal programming model and develop sustainable energy mix for meeting energy needs at village, panchayat, block and district level . • To assess the implications of sustainable and decentralized energy planning from the context of socio-economic and environmental concerns. The central theme of the research work is to prepare an optimized area-based decentralized energy plan to meet the energy needs, incorporating all potential alternate energy sources and end-use devices at least-cost to the economy and environment. One of the environmental goals addressed is to minimize or avoid CO2 emissions to address climate change. Study area selected for DEP is Tumkur district of Karnataka state, India and the DEP is carried out for the year 2005 and 2020. Advanced operation research technique, goal programming, is used to solve the large and complicated energy system problem having multiple conflicting goals.

Made available in DSpace on 2015-03-13T17:08:17Z (GMT). No. of bitstreams: 1 EduardoVQ.pdf: 3502040 bytes, checksum: cedac0b69deb4f4ec6d96c08f23f3160 (MD5) Previous issue date: 2008-12-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The study carried out in the environment of Maracaja? reef an S?o Roque channel, had as main objective to analyze the characteristics of sediments active locally expressed in the grains, through collections of sediments in the field, technical processing and data analyzes of sediments. Data processing were made on three main aspects: biotic composition, concentration of calcium carbonate and particle size of the sediment. Differences between the sediments of the reefs and channel were observed. It was emphasized the contribution of algae limestone in the production of carbonate, with some influence of foraminifera near the coast. The particle size distribution presented significant results for the understanding of locally sedimentary deposits. The results showed an environment of carbonate, with predominance of algae limestone, associated to unconsolidated sediments with gross granularity, besides the presence of rhodoliths in all samples.The fragmentation of biotic components and the prevalence of elliptical rhodoliths with little or no branch, indicate an environment of high energy hydrodynamics. This work is a further contribution to the understanding of sedimentology active locally in reef environments, in particular the of Maracaja? reef, by virtue of their complex ecosystem composed of a diversity of wild fauna and flora that still little studied in Brazil comparing to accelerated growth of teeth extractions and usufructs of natural resources causing often irreversible impacts to the environment / O estudo realizado teve como principal objetivo analisar as caracter?sticas dos sedimentos superficiais de fundo, atuantes localmente, no complexo recifal de Maracaja? e no canal de S?o R?que, sob diferentes aspectos: composi??o biog?nica, concentra??o de carbonato de c?lcio e granulometria do sedimento. Os resultados apresentaram as varia??es no sedimento superf?cial do fundo marinho quanto ? Biof?cies, An?lise Granulom?trica, Classifica??o Faciol?gica e Classifica??o de Rod?litos. Observou-se claramente diferentes padr?es sedimentol?gicos existentes nos recifes e no canal localizado entre os recifes e a costa, refletido em todos os par?metros levantados, revelando um ambiente carbon?tico, com predom?nio de algas calc?rias, associadas a um substrato inconsolidado com granula??o grossa. Enfatiza-se a contribui??o das algas calc?rias na produ??o de sedimentos carbon?ticos, com alguma influ?ncia de foramin?feros pr?ximos ? costa. A distribui??o granulom?trica apresentou resultados importantes na classifica??o dos sedimentos. Os sedimentos de tamanho m?dio se restringiram no canal numa ?rea protegida pelos recifes, enquanto que o sedimento com granula??o grossa se distribuiu no restante da ?rea, cobrindo parte da crista e toda regi?o frontal do recife, al?m de uma regi?o mais ao sul do canal. Rod?litos el?pticos se distribuiram em quase toda ?rea, excluindo apenas uma regi?o ao sul do canal e protegido pelos recifes com predom?nio de rod?litos discoidais. O predom?nio de rod?litos el?pticos com pouca ou nenhuma ramifica??o permite inferir um ambiente de alta energia hidrodin?mica, e a presen?a de rod?litos discoidais exclusivamente nos pontos ao norte do canal de S?o Roque e protegidos pelos Recifes possivelmente delimita uma ?rea de menor hidrodin?mica. O presente trabalho constitui mais uma contribui??o para o entendimento das caracter?sticas sedimentol?gicas atuantes localmente nos ambientes recifais, em especial os Parrachos de Maracaja?, em virtude de seu complexo ecossistema composto por uma diversidade de fauna e flora, ainda pouco estudadas no Brasil, contrapondo ao crescimento acelerado de extra??es e usufrutos dos recursos naturais causando impactos muitas vezes irrevers?veis ao meio ambiente

Made available in DSpace on 2015-03-13T17:08:22Z (GMT). No. of bitstreams: 1 SoraiaMCM.pdf: 2688997 bytes, checksum: ffeed0530642e4bf68011c85e553a11b (MD5) Previous issue date: 2004-09-24 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The main purpose of the present study is to integrate a geological and technological investigation of ornamental rocks of the Flores and Jacarand? granites, which are located near the Afonso Bezerra city, in the north central part of the Rio Grande do Norte State. The study area encompasses four litho-stratigrafic units: a Gneiss-Migmatitic Complex(cristalline basement), which is mainly composed of banded gneisses, usually deformed as mylonitic rocks and with several migmatic features, an Augen Gneiss, which occurs as an elongated body that constitutes the Jacarand? granite, a small granite stock, which presents a semi-circular form, named Flores granite, composed of pink, fine to medium coarse rocks, and fine to coarse alluvial sediments, which form extensive areas of large fluvial deposits. The technological characterization of the Flores and Jacarand? granites, carried out through several tests, has as the main purpose the determination of petrographic, physical, and mechanic parameters that allowed the characterization of these rocks. The test followed procedures recommended by Brazilian (ABNT Associa??o Brasileira de Normas T?cnicas) and foreigner institutions (ASTM American Society for Testing and Materials). The petrografhic analysis indicated that the rocks investigated are granite sensu estrictu, summing an average 85-90% modal. The Flores granite is the more felsic rock, which presents mafic content &#8764; 10% and monzonitic composition. The Jacarand? granite is an Augen Gneiss rock that presents sienogranitic composition and mafic modal content &#8764; 15%. Several technological tests carried out (alterability, physical indices, velocity of ultrasonic wave propagation, uniaxial compression, flection resistence, Amsler desgaste, and resistence to freezing and heating) indicated that parameters and values were identical for both granites investigated. These parameters and values are consistent with the Brazilian and international standards for siliciclastic rocks of ornamental use, as well as other Brazilian ornamental granites. The analysis of all results indicates that both the Flores and Jacarand? granites present good quality, and that they are indicated for ornamental use of revetment interior and exterior of buildings / Este trabalho tem como obejetivo um estudo integrado geol?gico e tecnol?gico de rochas ornamentais nas ?reas de ocorr?ncia dos granitos Flores e Jacarand?, localizados pr?ximo ao Munic?pio de Afonso Bezerra, na por??o centro norte do Estado do Rio Grande do Norte. Geologicamente, a ?rea compreende quatro unidades litoestraligr?ficas: um complexo Gn?issico Migm?tico (embasamento), formado essencialmente por gnaisses bandados, usualmente milonitizados e com fei??es migmat?ticas diversas; um augen Gnaisse que ocorrecomo um corpo alongado e constitui o "Granito Jacarand?"; um pequeno estock gran?tico que apresenta-se de forma subcircular (Granito Flores) onde dominam rochas de textura fina a fina-m?dia de colora??o rosa; por fim, sedimentos aluvionares finos a grossos, formando extensas ?reas de plan?ies aluviais. A caracteriza??o tecnol?gica dos granitos ornamentais Flores e Jacarand?, realizada por meio de ensaios diversos, teve como objetivo a obten??o de par?metros petrogr?ficos, f?sicos e me?nicos que permitiram a qualifica??o dessas rochas. Estes ensaios foram executados segundo procedimentos normatizados por entidades brasileiras (ABNT - Associa??o Brasileira de Normas T?cnicas) e estrangeiras (ASTM - American Society for Testing andMaterials). A an?lise petrogr?fica mostrou que as rochas estudadas s?o granitos senso estrito, somando em m?dia 85 - 90% modal. O Granito Flores ? a rocha mais f?lsica, com teor de m?ficos em torno de 10%, e de composi??o monzogran?tica. O Granito Jacarand? ? um augen gnaisse de composi??o sienogran?tica com m?ficos em torno de 15% modal. Os v?rios ensaios tecnol?gicos realizados (alterabilidade, ?dices f?sicos, velociodade de propaga??o de ondas ultra-s?nicas, compress?o uniaxial, resist?ncia a reflex?o, desgaste Amsler e resist?ncia ao congelamento e degelo) mostram par?metros e valores similares para ambos os granitos estudados e encontram-se dentro dos especificados em normas nacionais internacionais para rochas silic?ticas de uso ornamental. Da mesma forma, quando comparados com os granitos ornamentais estudados no Brasil, os par?metros e valores aqui encontrados mostram-se similares. A an?lise do conjunto de resultados dos ensaios realizados mostra que tanto o Granito Flores quanto o Jacarand? s?o rochas de boa qualidade tecnol?gica, er que se prestam muito bem para uso como material de revestimento interno e externo em edifica??es

Made available in DSpace on 2015-03-13T17:08:40Z (GMT). No. of bitstreams: 1 VeronicaDA.pdf: 5709097 bytes, checksum: 4074580aee5ec2b7d354ddab1d446e43 (MD5) Previous issue date: 2006-05-19 / This work presents geophysical and geological results obtained in a dunefield located in the east coast of Rio Grande do Norte State, with the aim to recognize the aeolian body depositional geometries to a future geologic modeling of the aeolian petroliferous reservoirs. The research, which was done in blowouts region situated at Nisia Floresta Municipally, included the characterization of external geometries with GPS and internal geometry analysis by GPR. Data was integrated in GoCAD software, where it was possible the three-dimensional characterization and interpretation of the studied deposits. The interpretation of GPR profiling allowed identifying: First-order bounding surfaces that separated the aeolian deposits of the Barreiras Formation rocks; Second-order bounding surfaces, which limit dune generations and Third-order bounding surfaces, a reactivation surface. This classification was based and adapted by the Brookfield (1977) and Kocurek (1996) propose. Four radarfacies was recognized: Radarfacies 1, progradational reflectors correlated to foresets of the dunes, Radarfacies 2, plain parallels reflectors related to sand sheets, Radarfacies 3, plain parallels reflectors associated to reworking of the blowout dune crest and Radarfacies 4, mounded reflectors associated to vegetated mound of sand or objects buried in subsurface. The GPR and GPS methods was also employed to the monitoring of dunefields susceptible to human activities in Buzios Beach, where the constructions along the blowout region and the tourism are changing the natural evolution of the deposits. This fact possibly to cause negative impacts to the coastal zone. Data obtained in Dunas Park, a unit environmental conservation, was compared with information of the Buzios Beach. There is a major tendency of erosion in Buzios, specifically in blowout corridor and blowout dune / Este trabalho apresenta os resultados geol?gicos e geof?sicos obtidos em um campo de dunas situados no litoral oriental do Rio Grande do Norte e teve como objetivo definir as geometrias deposicionais dos corpos e?licos para posterior aplica??o na modelagem geol?gica de campos produtores de ?leo e g?s de origem e?lica. A pesquisa foi realizada em uma regi?o de blowouts, situada no munic?pio de N?sia Floresta - RN, onde foi poss?vel definir a superf?cie externa com o uso do GPS geod?sico e a estrutura??o interna utilizando o GPR (Ground Penetrating Radar). Estes dados foram integrados no software de modelagem geol?gica Gocad, permitindo a visualiza??o tridimensional e interpreta??o dos dep?sitos estudados. O levantamento de perfis geof?sicos permitiu a investiga??o da geometria interna dos dep?sitos, nos quais foi poss?vel reconhecer superf?cies limitantes de 1? ordem (superf?cie deposicional que separa os dep?sitos e?licos de rochas da Forma??o Barreiras), 2? ordem (superf?cie que separa diferentes pulsos de sedimenta??o e?lica) e 3? ordem (superf?cies de reativa??o). A classifica??o destas superf?cies acima descritas foi baseada e modificada das propostas de Brookfield (1977) e Kocurek (1996). Foram ainda definidas quatro radarf?cies, com base na forma e termina??o dos refletores: Radarf?cies 1, representada por refletores progradantes, os quais se relacionam aos foresets das acumula??es e?licas; Radarf?cies 2, que ? constitu?da por refletores suscept?veis ? a??o antr?pica na praia de B?zios, onde constru??es ao longo da regi?o de blowouts e a pr?tica intensiva de turismo est?o modificando o desenvolvimento natural destas acumula??es e?licas, podendo gerar impactos ambientais negativos para a zona costeira. Dados obtidos numa ?rea situada no Parque das Dunas (unidade de conserva??o ambiental) foram utilizados para compara??o com as informa??es adquiridas em B?zios. H? uma tend?ncia maior de eros?o na ?rea de B?zios, notadamente no corredor do blowout e na duna de blowout

A MUC1 (MUC1) e a osteopontina (SPP1) são glicoproteínas expressas na superfície luminal uterina com funções na proteção e adesão celular. A MUC1 possui função antiadesiva, enquanto a osteopontina desempenha função adesiva. A expressão de ambas é regulada pelo hormônio esteróide progesterona. Durante a fase receptiva do útero, a MUC1 é inibida por este hormônio, enquanto a osteopontina é estimulada. O objetivo deste trabalho é caracterizar o polimorfismo genético destas moléculas e analisar a associação entre o polimorfismo, o diagnóstico de gestação e as diferenças esperadas na progênie (DEP) de várias características em novilhas da raça Nelore (Bos taurus indicus). A amostra foi constituída por 309 novilhas procedentes de duas fazendas participantes do Programa de Melhoramento Genético da Raça Nelore (PMGRN). A amostra da primeira fazenda incluiu 56 novilhas prenhas e foi utilizada para caracterização do polimorfismo e da estrutura do número variável de repetições em tandem (VNTR) MUC1 na raça Nelore. A segunda amostra foi constituída por 76 novilhas com resultado positivo de gestação e 156 com resultado negativo de gestação e foi utilizada para caracterização do polimorfismo dos genes MUC1 e SPP1 na raça Nelore, assim como para análise da associação entre os polimorfismos e os fenótipos. O gene MUC1 apresentou 5 alelos constituídos por um VNTR formado por uma seqüência de 60 nucleotídeos. A seqüência da repetição consensus foi idêntica às seqüências descritas em caprinos e em Bos taurus taurus. Descrevemos a seqüência de uma terceira repetição consensu na raça Nelore. O alelo 1 apresentou 10 repetições, o alelo 2 apresentou 12 repetições, o alelo 3 apresentou 15 repetições, o alelo 4 foi formado por 18 repetições, e o alelo 5 apresentou 24 repetições. O alelo com menor número de repetições apresentou a maior freqüência, sendo 0,70 na amostra do 1º grupo e 0,80 na amostra do 2º grupo. Os alelos 2, e 3 tiveram a segunda e terceira maior freqüência, sendo seguidos pelos alelos 4 e 5. A análise estatística não evidenciou associação entre o polimorfismo do gene MUC1 e o diagnóstico de gestação e entre o polimorfismo e os valores das diferenças esperadas na progênie das características consideradas economicamente importantes. Na amostra referente às novilhas da segunda fazenda, não identificamos o polimorfismo de nucleotídeo simples no íntron 4 (T/C) do gene SPP1 da osteopontina, como descrito na raça Holandesa. Sugerimos que a ausência deste polimorfismo possa constituir uma característica específica em Bos taurus indicus. Porém, dada a associação já descrita entre polimorfismo do gene SPP1 e características de crescimento, não descartamos a hipótese de que, assim como o MUC1, tenha ocorrido uma seleção indireta devido aos critérios aplicados pelo Programa de Melhoramento Genético da Raça Nelore. / MUC1 (MUC1) and osteopontin (SPP1) are glycoproteins expressed in the uterine luminal surface with predict functions in protection and cell adhesion. MUC1 has anti-adhesive role and osteopontin has adhesive role. The expression of both molecules is regulated by the steroid hormone, progesterone. During the receptive period for embryo implantation in the uterus, MUC1 is inhibited by progesterone and the osteopontin is stimulated. The objective of this work is to characterize the genetic polymorphism of these molecules, and to characterize associations between the polymorphisms, gestation rate and the expected progeny difference (EPD) in the Nelore breed (Bos taurus indicus). The study group comprised 309 heifers derived from two participating farms of the Nelore Cattle Breeding Program (PMGRN). The first farm provided 56 fertile female for the study for the characterization of the MUC1 polymorphism and the variable number of tandem repeats (VNTR) genomic structure in the Nelore breed. The second farm contributed 76 heifers with confirmed gestation and 156 no-pregnant female that were used to characterize both gene polymorphisms and to analyze the association between the MUC1 and SPP1 polymorphisms and the phenotypes. The MUC1 gene presented five alleles caused by length differences generated by a VNTR of 60 nucleotides. The consensus repeat sequence was identical to the caprine and Bos taurus taurus sequence. In this study we described the sequence of the third consensus repeat in the Nelore breed. Allele 1 presented with 10 repeats, allele 2 presented with 12 repeats, allele 3 presented with 15 repeats, allele 4 had 18 repeats and allele 5 had 24 repeats. Allele 1 had the smallest size and was the most frequent (0.70) in the group 1 and 0.80 in the group 2. Alleles 2 and 3 were the next most frequent followed by alleles 4 and 5. The ?2 test showed that the polymorphism was not significantly associated with the diagnostic of gestation and the EPD values. In this Nelore study group it was not possible to identify the single nucleotide polymorphism (T/C) of the SPP1 gene previously described in Holstein breed. The absence of this polymorphism could be specific to the Nelore cattle. However, considering the correlation between the SPP1 polymorphism and growth parameters, an indirect selection could happen due to the established criteria within the Nelore Cattle Breeding Program.

Cette thèse porte sur le développement d’un capteur plasmonique intégrant une fonction d’actuation des objets visés. L’objectif est de passer outre la limite de diffusion rencontrée à basse concentration en piégeant les particules sur la surface de détection. La stratégie adoptée est de structurer le film d’or servant à la détection de manière à pouvoir l’utiliser pour mettre en mouvement le fluide et les molécules par le biais de champs électriques. Le transfert de masse est réalisé par diélectrophorèse et électroosmose, deux effets électrocinétiques mis en oeuvre par des électrodes servant à la fois d’actuateur et de capteur plasmonique. Un état de l’art exhaustif et des simulations multiphysiques ont permis de concevoir un prototype de capteur intégré constitué d’électrodes interdigitées en or permettant la détection plasmonique. Le dispositif proposé a été obtenu par microfabrication en salle blanche puis caractérisé avant l’étude de ses performances. Une première phase de tests sur un système modèle, des billes de polystyrène dans de l’eau, a permis d’apporter la preuve de concept du fonctionnement du capteur, qui est effectivement capable de piéger rapidement les objets visés à sa surface afin de les détecter. Les mécanismes de transfert de masse ont été expliqués et la preuve de l’amélioration de la limite de détection par un facteur supérieur à 100 a été apportée. Dans un second temps, les performances du capteur appliqué à des objets biologiques ont été évaluées. Celui-ci piège efficacement des levures et des protéines, mais aucune amélioration n’a été observée dans le cas de la détection spécifique de l’hybridation entre deux brins d’acide désoxyribonucléique (ADN). Les causes de ce résultat ont été discutées et comprises et deux solutions différentes ont été explorées : l’adaptation de la fréquence d’opération et l’optimisation de la géométrie des électrodes. Ainsi, cette étude a permis de souligner la problématique de la mise en oeuvre d’effets électrocinétiques dans des milieux biologiques et de réfléchir aux pistes pertinentes pour sa résolution. / This thesis focuses on the development of an integrated plasmonic sensor capable to perform mass transport on targeted objects. The goal is to overcome the diffusion limit by trapping particules directly on the sensing surface. The adopted strategy was to structure the gold layer used for plasmonic detection in order to use the sofabricated structures to set the fluid and the molecules in motion by applying electric fields in the fluid. The mass transfer is realized through dielectrophoresis and electroosmosis, those two electrokinetic effects being operated by electrodes acting as sensor and actuator at the same time. An exhaustive state of the art as well as multiphysical simulations allowed us for designing a prototype for an integrated sensor consisting in gold interdigitated electrodes enabling plasmoninc sensing. The proposed device was obtained through microfabrication in clean room facilities and was characterized before the study of its performances. A first sequence of tests on a model system – polystyrene microbeads in water – brought the proof of concept we needed to validate the correct operation of the sensor, which is indeed capable of quickly trapping targeted objects on its surface and detecting them. The mass transfer mechanisms were explained and we showed the enhancement of the limit of detection by a factor greater than 100. In a second phase, performances of the sensor applied to biological objects were evaluated. It can effectively trap yeasts and proteins but no enhancement has been observed while detecting DNA hybridization events. Causes for this result were discussed and understood and two different solutions were explored: the adaptation of the operating frequency and the optimization of the electrodes geometry. Thus, this study highlighted the problematic of operating electrokinetic effects in biological media and suggested relevant leads towards its resolution.

L’angiogenèse et l’augmentation de la perméabilité vasculaire sont des éléments clés pour la croissance et la progression tumorale. Par conséquent, de nombreux efforts sont déployés à comprendre les mécanismes moléculaires impliqués dans la formation et le remodelage des vaisseaux sanguins de manière à identifier de nouvelles cibles thérapeutiques potentielles. De cette optique, les travaux de cette thèse se sont concentrés sur la protéine tyrosine phosphatase DEP-1, initialement identifiée comme un régulateur négatif de la prolifération et de la phosphorylation du VEGFR2 lorsque fortement exprimée dans les cellules endothéliales. Toutefois, en utilisant une approche d’ARNi, il a été démontré que via sa capacité à déphosphoryler la tyrosine inhibitrice de Src (Y529), DEP-1 était également un régulateur positif de l’activation de Src dans les cellules endothéliales stimulées au VEGF. Puisque Src joue un rôle central dans la promotion de l’angiogenèse et la perméabilité vasculaire, nous avons en plus démontré que DEP-1 était un promoteur de ces fonctions in vitro et que la tyrosine phosphorylation de sa queue C-terminale, permettant l’interaction et l’activation de Src, était requise. Les travaux de recherche présentés dans cette thèse démontrent dans un premier temps à partir d’une souris Dep1 KO, dont le développement ne présente aucun phénotype apparent, que la perte de l’expression de DEP-1 se traduit en une inhibition de l’activation de Src et de l’un de ses substrats, la VE-Cadherine, en réponse au VEGF chez la souris adulte. Nos résultats démontrent donc, pour la première fois, le rôle primordial de DEP-1 dans l’induction de la perméabilité vasculaire et de la formation de capillaires in vivo. Conséquemment, la croissance tumorale et la formation de métastases aux poumons sont réduites due à une inhibition de leur vascularisation ce qui se traduit par une diminution de la prolifération et une augmentation de l’apoptose des cellules cancéreuses. De façon intéressante, l’expression élevée de DEP-1 dans les vaisseaux sanguins tumoraux de patientes atteintes du cancer du sein corrèle avec une vascularisation accrue de la tumeur. En plus du rôle de DEP-1 dans la réponse angiogénqiue à l’âge adulte, nos travaux ont également démontré le rôle important de DEP-1 lors de la vascularisation de la rétine, un modèle in vivo d’angiogenèse développementale. Dans ce contexte, DEP-1 inhibe la prolifération des cellules endothéliales et limite leur bourgeonnement et la complexification du réseau vasculaire rétinien en permettant l’expression adéquate du Dll4, un régulateur crucial de l’organisation de la vascularisation développementale. Cette expression du Dll4 découlerait de la stabilisation de la β-caténine par l’inactivation de la GSK3β, un régulateur important de la dégradation de la β-caténine, en réponse au VEGF selon la voie de signalisation VEGFR2-Src-PI3K-Akt-GSK3β. Ainsi, ces travaux identifient DEP-1 comme un régulateur important de l’organisation vasculaire rétinienne. Les rôles positifs de DEP-1 dans les cellules endothéliales découlent principalement de sa capacité à lier et activer la kinase Src. En plus de contribuer à la réponse angiogénique, Src est également un oncogène bien caractérisé notamment pour sa contribution au programme invasif des cellules cancéreuses mammaires. Les travaux de cette thèse illustrent que DEP-1 est préférentiellement exprimée dans les cellules cancéreuses mammaires invasives et qu’il régule l’activation de Src, de voies de signalisation invasives et, par le fait même, de l’invasivité de ces cellules in vitro et in vivo. De façon intéressante, ces observations corrèlent avec des données cliniques où l’expression modérée de DEP-1 est associée à un mauvais pronostic de survie et de rechute. Ces résultats démontrent donc, pour la première fois, le rôle positif de DEP-1 dans l’activation de Src au niveau des cellules endothéliales et des cellules cancéreuses mammaires ce qui permet la régulation du bourgeonnement endothélial, de la perméabilité vasculaire, de l’angiogenèse normale et pathologique en plus de l’invasion tumorale. / Angiogenesis and increased vascular permeability are key component of tumor growth and progression. Consequently, numberous efforts are currently deployed to illucidate the molecular mecanisms contributing to the formation and remodelling of blood vessels in oder to identify new potential therapeutic targets. In that thought, the work of this thesis was focused on the protein tyrosine phosphatase DEP-1, initially identified as a negative regulator of proliferation and VEGFR2 phosphorylation when highly expressed in endothelial cells. However, using RNAi, it was shown that through its capacity to dephosphorylate the inhibitory tyrosine of Src (Y529), DEP-1 could also positively regulate Src activation in endothelial cells in response to VEGF. As Src is a central promoter of angiogenesis and vascular permeability, we showed that DEP-1 was a promoter of these vascular functions in vitro and that the tyrosine phosphorylation of its C-terminal tail, allowing interaction and activation of Src, was required. Interestingly, the catalytic inactivation of DEP-1 in mice resulted in increased proliferation in endothelial cells, but also in desorganization of vascular structures which contrast the absence of phenotype in DEP-1 complete knock-out mice (KO). The work of this thesis demonstrates for the first time that DEP-1 deletion causes inhibition of Src and one of its substrate, VE-Cadherin, activation in response to VEGF in Dep-1 KO mice, which develop normally. Our results show the crucial role of DEP-1 in VEGF-induced vascular permeability and capillary formation in vivo. Consequently, tumor growth and lung metastases formation were inhibited due to reduced tumor vascularisation causing reduced proliferation and increased apoptosis of tumor cells. Accordingly, high expression of DEP-1 in tumor-associated blood vessels of breast cancer patients correlates with greater tumor vascularisation. In addition to DEP-1 role in post-natal angiogenic response, our work also demonstrates the important role of DEP-1 during retinal vascularisation, an in vivo developmental angiogenesis model. In this context, DEP-1 inhibits proliferation of endothelial cells and limits their sprouting by allowing adequate β-catenin-dependant expression of Dll4, a Notch ligand regulating developmental vascularisation organisation. DEP-1 allows β-catenin stabilisation via inactivation of GSK3β, an important regulator of β-catenin degradation, in response to VEGF through VEGFR2-Src-PI3K-Akt-GSK3β signaling pathway. Thus, this work identifies DEP-1 as an important regulator of retinal vascular sprouting. The positive roles of DEP-1 in endothelial cells depend on it ability to bind and activate the kinase Src. In addition to its contribution to angiogenic response, Src is also a well-characterized oncogene notably for its contribution to invasive program of mammary cancer cells. This work illustrates that DEP-1 is preferentially expressed in invasive mammary cancer cells and that it regulates Src activation, pro-invasive signaling pathways and, consenquetly, cell invasiveness in vitro and in vivo. All these activities are dependant on DEP-1 catalytic activity and ability to bind Src. Interestingly, these results correlate with clinical data where moderate expression of DEP-1 is associated with poor pornostic of survival and relapse. Collectively, the results presented here demonstrate, for the first time, the crucial role of DEP-1 in Src activation in endothelial and breast cancer cells, leading to endothelial sprouting, vascular permeability, normal or pathological angiogenesis, and breast cancer invasiveness and metastases formation.

Erarbeitung eines Referenzprofils und der ersten kompletten Klimakurve für das kontinentale Perm Europas mit Hilfe sedimentologischer, petrologischer, geochemischer und mathematischer Analysen. Obwohl das Lodève Becken im gesamten Perm im Bereich der heutigen innertropischen Konvergenzzone lag, kam es zu häufigem Wechsel zwischen feuchteren und trockeneren Klimabedingungen.

Erarbeitung eines Referenzprofils und der ersten kompletten Klimakurve für das kontinentale Perm Europas mit Hilfe sedimentologischer, petrologischer, geochemischer und mathematischer Analysen. Obwohl das Lodève Becken im gesamten Perm im Bereich der heutigen innertropischen Konvergenzzone lag, kam es zu häufigem Wechsel zwischen feuchteren und trockeneren Klimabedingungen.