Les atomes sont des candidats intéressants pour l'information quantique, car leur neutralitée électrique devrait leur assurer un long temps de cohérence. Afin de pouvoir les manipuler un par un, nous avons choisi de les placer dans un piège dipolaire microscopique. Une analyse détaillée du nombre d'atomes piégés montre que celui-ci peut être compris entre 1 et 30, avec un réegime préférentiel de travail dans lequel les collisions inélastiques le limitent à un. Il est également possible de placer deux pièges dipolaires côte à côte, et donc de disposer de deux atomes, à quelques microns de distance. Dans le but d'intriquer ces deux atomes, il est important de connaître l'amplitude du mouvement des atomes piégés. Celle-ci se caractérise avec le paramètre de Lamb-Dicke, paramètre qui dépend des fréquences d'oscillation du potentiel dipolaire, mais aussi de la température des atomes. Ces deux grandeurs ont été mesurées expérimentalement, et montrent que le confinement est actuellement insuffisant. Il est donc nécessaire de refroidir les atomes davantage. Un autre champ d'investigation de cette expérience concerne le régime où le nombre d'atomes piégés est de l'ordre d'une trentaine. Nous avons alors démontré la possibilité d'évaporer le nuage atomique, et donc de le refroidir. Il devrait alors être possible d'obtenir des condensats de Bose-Einstein à très petit nombre d'atomes, et en régime de Lamb-Dicke.

Machine learning techniques have been widely used for classification problems in computational biology. They require that the input must be a collection of fixedlength feature vectors. Since proteins are of varying lengths, there is a need for a means of representing protein sequences by a fixed-number of features. This thesis introduces three novel methods for this purpose: n-peptide compositions with reduced alphabets, pairwise similarity scores by maximal unique matches, and pairwise similarity scores by probabilistic suffix trees. New sequence representations described in the thesis are applied on three challenging problems of computational biology: remote homology detection, subcellular localization prediction, and solvent accessibility prediction, with some problem-specific modifications. Rigorous experiments are conducted on common benchmarking datasets, and a comparative analysis is performed between the new methods and the existing ones for each problem. On remote homology detection tests, all three methods achieve competitive accuracies with the state-of-the-art methods, while being much more efficient. A combination of new representations are used to devise a hybrid system, called PredLOC, for predicting subcellular localization of proteins and it is tested on two distinct eukaryotic datasets. To the best of author&rsquo / s knowledge, the accuracy achieved by PredLOC is the highest one ever reported on those datasets. The maximal unique match method is resulted with only a slight improvement in solvent accessibility predictions.

Thesis (MScEng (Industrial Engineering))--University of Stellenbosch, 2009. / Traceability systems are capable of both tracking and tracing parts. They offer many benefits to an organisation from assisting with recall applications to monitoring the everyday workings of a production line or supply chain. There are numerous methods able to act as traceability systems but only a few can be regarded as automatic and unique identifiers. Automatic traceability of individual entities is the future. It is already widely used by a number of leading companies throughout different business sectors and wide mass adoption is imminent. At present, they are slightly more expensive than the simpler technologies but once mass produced, the cost will come down. To completely understand how traceability systems are implemented, practical experience is required. When starting a traceability project, there are a lot of different options. The different systems offer their own set of advantages and some don’t work in certain environments. It was for this reason that The Decision Making Model was developed to assist users through the difficult initial stages of traceability implementation (i.e. choosing the system most suitable to a particular environment). This model was programmed in Excel and supplies the user with a number of questions regarding the environment the system would work in as well as the user’s requirements. The answers to these questions help the user work through the different types of traceability options to eliminate unsuitable choices. The result is an easy to use program designed with the ability to be upgraded as the technologies evolve.

Made available in DSpace on 2014-12-17T14:46:40Z (GMT). No. of bitstreams: 1 RosangelaDC_DISSERT.pdf: 1849568 bytes, checksum: bb19fb5976dd5746dd1f52b5faa8a2f6 (MD5) Previous issue date: 2009-10-29 / This research aims to analyze, in the view of students, the pedagogic project of undergraduate nursing course, of UFRN, and its articulation with the SUS, in an attempt to understand the issues that permeate the teaching and learning of nursing. This is a qualitative study that used the focus group technique as a tool to collect empirical data. There were three meetings, where we had the collaboration of 23 graduating students from the eighth period of the semester 2009.1. For the analysis of information, we use a theoretical framework based on curriculum guidelines and basic principles of the SUS, making the analogy of the results with the metaphor of Greek mythology, Ariadne's thread, in dialogue with authors who discuss education as a transformative practice. Thus, the texture of the yarn was built of five thematic fields: joint the pedagogic project with the SUS; the teaching/service and theory/practice relation; interdisciplinarity or transdisciplinarity; didactic/methodological and relational approaches; and co-participation of students in the pedagogic project. According to the discussions, we find many difficulties in the teaching and learning process of undergraduate nursing in UFRN to strengthen the SUS, including: dislocation of educational institutions with services, professionals, managers and community; dichotomy between theory and practice; reality of services as a learning field and working process in health; posture adopted by professionals, teachers and other subjects included in the process of health education; decontextualization and fragmentation of teaching with the practice in health and nursing; excessive use of very illustrative methodologies, but little problem-solving; difficult and precarious situation in the relations between teachers and between teachers/students, regarding the acceptance of differences; absence of participation of students in the evaluation process and conduct of the educational project in progress. In this sense, we understand the need an auto-reflexive act of teaching and conducting collective pedagogical course with a view to achieving the SUS. Thus, it is necessary to support practices motivated by the polyphonic dialogue and the exercise of symbiosis and autopoiesis of subjects/actors jointly responsible for the ongoing process of learning for life. / A presente investiga??o tem como objetivo analisar, na vis?o de discentes, o projeto pedag?gico do curso de gradua??o de enfermagem, da UFRN, e sua articula??o com o SUS, na tentativa de compreender os desafios que permeiam o processo ensino/aprendizagem da enfermagem. Trata-se de um estudo com abordagem qualitativa que utilizou a t?cnica de grupo focal como instrumento para coleta do material emp?rico. Foram realizadas tr?s reuni?es, nas quais contamos com a colabora??o de 23 estudantes concluintes do oitavo per?odo do semestre letivo 2009.1. Para a an?lise das informa??es, utilizamos um aporte te?rico fundamentada nas diretrizes curriculares e princ?pios b?sicos do SUS, fazendo a analogia dos resultados encontrados com a met?fora da mitologia grega, o fio de Ariadne, mantendo o di?logo com autores que discutem a educa??o como pr?tica transformadora. Dessa forma, a tessitura do fio foi constitu?da por cinco teias tem?ticas: articula??o do projeto pedag?gico com o SUS; rela??o ensino/servi?o e teoria/pr?tica; transdisciplinaridade ou interdisciplinaridade; abordagens did?ticas/metodol?gicas e relacionais; e co-participa??o do discente no projeto pedag?gico. De acordo com as discuss?es, encontramos v?rias dificuldades no processo ensinar/aprender da gradua??o de enfermagem na UFRN para fortalecimento do SUS, entre elas: desarticula??o das institui??es de ensino com os servi?os, profissionais, gestores e comunidade; dicotomia persistente entre teoria/pr?tica; realidade dos servi?os como campo de aprendizagem e o processo de trabalho em sa?de; postura adotada por profissionais, docentes e outros sujeitos inseridos no processo de forma??o em sa?de; fragmenta??o e descontextualiza??o do ensino com as pr?ticas em sa?de e enfermagem; uso excessivo de metodologias muito ilustrativas e pouco problematizadoras; dificuldade e fragilidade na conviv?ncia entre professores e entre professores/alunos, no que diz respeito ? aceita??o das diferen?as; aus?ncia de participa??o de discentes no processo de avalia??o e condu??o do projeto pedag?gico em curso. Neste sentido, compreendemos a necessidade de autorreflex?o do agir pedag?gico e condu??o coletiva da proposta pedag?gica do curso, na perspectiva de concretiza??o do SUS. Desse modo, torna-se necess?rio o apoio em pr?ticas motivadas pelo di?logo polif?nico e no exerc?cio da simbiose e autopoiese dos sujeitos/atores co-respons?veis pelo processo permanente de aprendizagem para a vida

Orientador: Silmara Meneguin / Resumo: Introdução: A resolubilidade em saúde é a resposta satisfatória que o serviço fornece ao usuário quando busca atendimento para alguma necessidade. Frente ao exposto este estudo teve como objetivo principal avaliar a resolubilidade do cuidado oftalmológico em Centro Integrado de Saúde, sob a ótica dos usuários diabéticos e não diabéticos. E, como objetivos secundários: identificar as principais causas de solicitação de avaliação oftalmológica em ambos os grupos; identificar o tempo de espera para o atendimento oftalmológico; identificar os pacientes que tiveram indicação de cuidado oftalmológico para a rede de atenção à saúde, em ambos os grupos; conhecer os motivos que dificultam/atrasam a realização do cuidado, na rede de atenção à saúde, sob a ótica dos mesmos; propor estratégias para otimizar o cuidado aos pacientes que necessitam de cuidado oftalmológico. Método: estudo descritivo, exploratório, transversal e com abordagem mista. Uma amostra não probabilística foi constituída por todos os pacientes atendidos no Centro Integrado de Saúde do interior de São Paulo, no período de novembro de 2013 ao mesmo mês de 2015. Para responder os objetivos do estudo os participantes foram divididos em dois grupos: diabéticos e não diabéticos. A coleta de dados foi realizada em duas etapas: consulta a um banco de dados institucional para caracterização dos participantes e do atendimento médico; e entrevista com os pacientes que tiveram indicação de cuidado oftalmológico no Centro Integra... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Esta dissertação foca um processo de criação de imagens fotográficas a partir de manipulações químicas feitas sobre superfícies fotossensíveis, diretamente sobre o papel ou negativo, sem utilizar para isso o aparato tecnológico – a câmera. A partir dessa abordagem, a dissertação analisa os limites daquilo que conhecemos como fotografia. A pesquisa convergiu para a investigação das possibilidades fotográficas inerentes às superfícies sensíveis e fotossensíveis, às soluções fotoquímicas e para o cruzamento dessas possibilidades fotográficas com outras linguagens artísticas. O trabalho confrontou a fotografia com suas especificidades e buscou desvendar os domínios da fotograficidade, que se configurou como um lugar apropriado para vasculhar as certezas e incertezas do que é a fotografia. As reflexões teóricas foram instituídas pelo trabalho plástico. / This dissertation aims at a photographic images creation process from chemistry manipulations made over light sensitive surfaces, directly on the paper or negative, without the camera. From this point of view the dissertation analyses the limits of which we know as photograph. The research converged to an investigation of the inherent photographic possibilities to sensitive and light sensitive surfaces, to photochemical solutions and to an approaching of these photographic possibilities to other kinds of artistic languages. The creation process faced photograph and its unique features and, by dealing with them, tried to reveal the photographs unique characteristics, which showed a specific place to search the certainties and uncertainties of what photography is. The theoretic reflections were established by the artistic work.

L’optique quantique avec électron est un domaine de recherche en expansion depuis ses débuts au cours des années 90 prenant suite aux premières expériences d’interférence avec électrons réalisées dans les années 80. Ce domaine est dédié à la réalisation d’expérience d’optique quantique avec des électrons plutôt que des photons. Leur intérêt est double, d’une part les électrons étant des fermions de nouveaux phénomènes, en comparaison des photons qui sont des bosons, peuvent être observés. L’électron anti-bunching, en comparaison du bunching des photons obtenu dans des expériences de corrélations en est un exemple. Le deuxième avantage des électrons est le fait qu’ils peuvent être contrôlés et manipulés à l’aide de champ électrique, un tel contrôle n’est pas possible avec des photons. Alors que les composants de base pour la réalisation de ces expériences sont déjà existant comme la lame séparatrice, ou encore les sources cohérentes à électrons uniques, la détection immédiate d’un électron unique dans de telles expériences est toujours manquante. La difficulté étant le faible temps d’interaction entre l’électron en déplacement et le détecteur de charge qui est limité typiquement à moins de 1ns principalement à cause de la vitesse élevée de déplacement de l’électron qui est égale à la vitesse de Fermi soit 10-100km/s. Ce temps d’interaction est environ deux ordres de grandeurs plus petits que ce qui est nécessaire pour le meilleur détecteur de charge démontré jusqu’à présent.Dans ce manuscrit est présenté le développement d’un détecteur ultra-sensible pour la détection immédiate d’un électron se déplaçant à la vitesse de Fermi. Notre stratégie est de détecter un électron unique se déplaçant dans les canaux de bords (ECs) de l’effet Hall quantique à partir de la mesure d’une variation de phase d’un bit quantique singlet-triplet, appelé qubit détecteur par la suite. La détection immédiate de cet électron en déplacement n’étant possible que si l’interaction avec ce dernier induit une variation de phase de pi, avec une lecture immédiate de l’état de spin du qubit détecteur.Grâce au développement et à l’utilisation d’un RF-QPC, cette lecture immédiate de l’état de spin est tout d’abord démontrée. Par la suite le développement du qubit détecteur avec la réalisation d’oscillations cohérentes d’échange est décrit. Sa sensibilité en charge est démontrée avec l’observation d’une phase induite par l’interaction avec un courant d’électrons dans les ECs. Ce courant est imposé par l’application d’un biais de tension contrôlant le potentiel chimique de ces ECs.Après optimisation de ce qubit détecteur pour la détection d’un électron unique, il est calibré en utilisant le même procédé de courant imposé par application d’un biais de tension. Cette calibration nous fournie la variation de signal attendue pour l’interaction avec cette charge unique est indique que sa détection immédiate est impossible dans nos conditions expérimentales. Notre détecteur ayant une sensibilité de charge de l’ordre de 8.10-5 pour une bande passante allant de DC à 1THz. Cette sensibilité est environ deux ordres de grandeur trop petite que ce qui est nécessaire pour la détection immédiate de cette charge unique. Finalement, ce qubit détecteur est utilisé pour détecté, dans une expérience moyennée, ce qui est appelé un edge magneto plasmon composé par moins de 5 électrons. Néanmoins, atteindre la détection de la charge unique dans n’a pas été possible, la sensibilité en charge étant légèrement trop petite pour y arriver.Les différentes limites de notre détecteur sont listées et expliquées tout au long du manuscrit, avec une présentation de différents axes de développement qui devraient permettre de réussir cette détection d’un électron unique dans une nouvelle expérience. / The electron quantum optics field is a research topic with an interest growing over the years since the 80's and the first interference experiment with electrons. This field is dedicated to the implementation of quantum optics experiments with electrons instead of photon. The advantage is twofold, one is the fermion nature of the electrons which ensure the observation of phenomenon which cannot be observed with photon (boson), the anti-bunching of the electrons in correlation experiments contrary to the bunching for photons illustrates this point. The second advantage is the possibility to interact and control electrons with electric fields since they are charged particles. Such control does not exist with photon. In addition to these fundamental experiments, it has been recently demonstrated that this topic presents a possible candidate for quantum information with so called flying qubit. While the based components to mimic the quantum optics experiments are already demonstrated like the beam splitter, phase shifter or coherent single electron source, the single electron detection in a single shot manner in such system is still lacking. The difficulty being the short interaction time between the travelling charge and the charge detector, being of less than 1ns in such system where the electron propagate at the Fermi velocity 10-100km/s. This interaction is approximately two orders of magnitude shorter than what is required with the actual best on chip charge detector.In this thesis is presented the development of an ultra-sensitive detector for the single shot detection of an electron travelling at the Fermi velocity. Our strategy was to detect a single travelling electron propagating in the edge channels (ECs) of the quantum Hall effect by measuring the induced phase shift of a singlet-triplet qubit, referred as to the qubit detector. The single shot detection being only possible if the interaction with the travelling electron induces a complete π phase shift and the spin readout of the qubit detector being performed in a single shot manner.Thanks to the development and use of a RF-QPC the single shot spin readout of the qubit detector has been first demonstrated. Its development with the implementation of coherent exchange oscillations is then described. The charge sensitivity of the qubit detector is validated in an experiment consisting in recording a phase shift of these oscillations due to the interaction with an imposed flow of electrons in the ECs. This flow of electron was induced by a DC voltage bias applied on the ECs to tune their chemical potential.This qubit detector is then optimised for the single travelling charge detection. Its calibration has been implemented using the same imposed flow of electrons by application of a DC bias. This calibration provides the expected signal variation induced by the interaction with a single travelling electron, and indicates the impossibility to implement this detection in a single shot manner in our experimental conditions. Our detector exhibits a charge sensitivity estimated close to 8.10-5 e/Hz-1/2 for a detection bandwidth from DC to 1 THz. The sensitivity is close to two orders of magnitude smaller than required for a single shot detection. Finally this qubit detector has been employed to detect in average measurements an edge magneto plasmon composed by less than 5 electrons. However, the single electron level could not be reached in statistical measurement neither, the sensitivity of our qubit detector being too limited.The different limitations of our experiment are listed and explained with the presentation of different axes of development which could permit to succeed this detection in another experiment.

Le moteur flagellaire bactérien (BFM) est un complexe moléculaire qui permet aux bactéries de nager dans un milieu liquide. La rotation du moteur est générée à l’interface entre deux éléments clés: les protéines formant le stator (MotA and MoB) et l’anneau C “switching complex” à la base du rotor. Les stators sont des modules du moteur structurellement et fonctionnellement différentiables du reste du moteur, et leurs association et dissociation dynamique autour du rotor contrôle la génération du couple. Quand une protéine fluorescente (PF) est fusionnée à MotB, le moteur est en état de marche mais une réduction générale de la mobilité de la cellule a été observée. La raison précise d’une telle réduction de mobilité n’a pas été étudiée.Le but de cette étude est de comprendre comment la fusion PF de la protéine du stator modifie la génération du couple et le sens de rotation du moteur. C’est particulièrement important car le tag FP se trouve à l’interface entre le stator et le rotor, là où le couple et le changement du sens de rotation sont produits. Trois différentes PFs (eGFP, YPet, Dendra2) ont été fusionnées à la protéine MotB. Malgré la haute similarité de leurs structures, notre analyse a montré que les trois stators fusionnés génèrent des couples différents. Les stators marqués avec YPet produisent un couple moyen similaire au WT (stators sans tag PF), alors que les stators marqués avec eGFP et Dendra2 produisent respectivement 70% et 40% du couple moyen du WT. De plus, les moteurs utilisant les stators fusionnés ont montré des capacités de changement de sens de rotation réduites. Lors d’un changement de sens de rotation, la valeur absolue de la vitesse des moteurs WT ne change pas. Cette “symétrie” de vitesse lors du changement n’apparaît pas avec les moteurs à stators fusionnés et le changement peut être accompagné d’une importante diminution (~30%) de la vitesse absolue.En observant par microcopie TIRF avec détection de molécules uniques, des stators marqués dans un moteur en état de marche, les signaux de fluorescence sont détectés à la membrane comme prévu pour ces protéines, montrant une population de stators diffusant dans celle-ci. Les clusters fluorescents étaient visibles au centre des cellules en rotation, attachés au couvre-glace par une seule flagelle, confirmant que le tag de fluorescence peut être visualisé dans des moteurs en état de marche. Dans un second projet développé dans le laboratoire Bertus Beaumont à TU Delft, en prenant le BFM en tant que système modèle d’évolution expérimentale, sa modularité et son « évolubilité » ont été explorés pour apprendre les détails au niveau moléculaire de l’évolution de ce type de machine. Les stators de E.coli ont été échangés par un set de 21 stators étrangers homologues. L’expérience a révélé que les protéines du stator peuvent être échangées entre espèces de bactéries distantes et certains stators non compatibles peuvent être modifiés positivement par un procédé d’évolution pour devenir fonctionnels. Au cours de cette évolution, les bactéries ont accumulé des mutations avantageuses dans leurs gènes MotA et MotB étrangers, tout particulièrement dans leur domaine fonctionnel. Des mutations identiques dans des stators différents ont été observées, indiquant que l’évolution peut se reproduire. L’analyse fonctionnelle au niveau d’un seul moteur a révélé que ces mutations avantageuses amélioraient la génération du couple et/ou la capacité du moteur à changer de sens. Les investigations détaillées du génotype et du phénotype du BFM modifié par évolution apportés par cette étude, pourraient donner une idée sur la façon dont des machines moléculaires comme le BFM ont évolué, et les effets fonctionnels des mutations bénéfiques qui facilitent l'intégration fonctionnelle. / The bacterial flagellar motor (BFM) is the macromolecular complex which allows bacteria to swim in liquid media. Located at the base of the flagellum, anchored in the cell membrane, this remarkably small (~45nm) yet powerful rotary motor rotates each flagellum of the cell switching between counterclockwise (CCW) and clockwise (CW) direction. The motor rotation is generated at the interface between the two key components of the motor: the stator protein complexes (each composed of 4 MotA and 2 MotB proteins) and the C- ring protein complex at the base of the rotor. The stator complexes are structurally and functionally discernible modules of the motor, and their dynamical association and dissociation around the rotor controls the generation of torque.The first project of this study aims to investigate how the FP tag on the stator protein modifies the torque generation and switching of the motor. This is particularly important because the fluorescent protein tag lies at the interface between stator and rotor, where torque and switching are produced. Three different FPs (eGFP, YPet, Dendra2) were fused to MotB. Interestingly, despite the high similarity of their structures, our analysis revealed that the three fusion stators generate different torque. Furthermore, in the presence of fusion stators, the motor showed significantly impaired switching abilities. When switching direction of the rotation, the absolute value of the speed of WT motors does not change, whereas this symmetry of speed upon switching is not observed in the fusion stator motors, and switching can be accompanied with a significant (~30%) decrease in absolute speed. Both the impaired torque generation and the switching ability were improved by introducing a rigid linker between the stator and the FP tag. Taken together, this study provides a further insight into the dynamics of the stator and rotor interaction at its interface.When the cells carrying the fluorescently labeled stators were observed in a custom made TIRF-fluorescence microscope with single molecule capability, the fluorescence signals were detected as concentrated clusters in the membrane as expected for these membrane proteins around the motors, together with a population of stators diffusing in the membrane. Fluorescent clusters were visible at the center of rotating cells tethered to the glass slide by a single flagellum, confirming that the fluorescent tags can be visualized in functioning motors.In a second project developed in Bertus Beaumont lab at TU Delft, taking BFM as an experimental evolutionary model system, its modularity and evolvability have been explored to learn the molecular details of the evolution of molecular machines. The stators of E.coli have been exchanged by a set of 21 homologue foreign stators. The experiments revealed that the stator proteins can be exchanged between distant bacteria species, and some of the non-compatible stators can be positively modified by evolution to become functional. Those evolved strains accumulated beneficial mutations in their foreign motA and motB genes, especially on their functional domains. Identical mutations in different stators were common, indicating that evolution is repeatable. The functional investigation at the single motor level revealed that those beneficial mutations improved the torque generation and/or the switching ability of the motor. The detailed genotype and phenotype investigations of the evolutionary modified BFM may bring an insight into how molecular machines such as BFM have evolved as well as the functional effects of the beneficial mutations that facilitate functional integration.

Submitted by INES PAULA REGINA MAININI OLIVEIRA null (re.nini@bol.com.br) on 2017-09-27T20:30:37Z No. of bitstreams: 1 Dissertação.pdf: 4379014 bytes, checksum: a18ec2af2de2c337688c85edca5d8865 (MD5) / Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-09-28T14:44:39Z (GMT) No. of bitstreams: 1 oliveira_iprm_me_bot.pdf: 4379014 bytes, checksum: a18ec2af2de2c337688c85edca5d8865 (MD5) / Made available in DSpace on 2017-09-28T14:44:39Z (GMT). No. of bitstreams: 1 oliveira_iprm_me_bot.pdf: 4379014 bytes, checksum: a18ec2af2de2c337688c85edca5d8865 (MD5) Previous issue date: 2017-09-22 / Introdução: A resolubilidade em saúde é a resposta satisfatória que o serviço fornece ao usuário quando busca atendimento para alguma necessidade. Frente ao exposto este estudo teve como objetivo principal avaliar a resolubilidade do cuidado oftalmológico em Centro Integrado de Saúde, sob a ótica dos usuários diabéticos e não diabéticos. E, como objetivos secundários: identificar as principais causas de solicitação de avaliação oftalmológica em ambos os grupos; identificar o tempo de espera para o atendimento oftalmológico; identificar os pacientes que tiveram indicação de cuidado oftalmológico para a rede de atenção à saúde, em ambos os grupos; conhecer os motivos que dificultam/atrasam a realização do cuidado, na rede de atenção à saúde, sob a ótica dos mesmos; propor estratégias para otimizar o cuidado aos pacientes que necessitam de cuidado oftalmológico. Método: estudo descritivo, exploratório, transversal e com abordagem mista. Uma amostra não probabilística foi constituída por todos os pacientes atendidos no Centro Integrado de Saúde do interior de São Paulo, no período de novembro de 2013 ao mesmo mês de 2015. Para responder os objetivos do estudo os participantes foram divididos em dois grupos: diabéticos e não diabéticos. A coleta de dados foi realizada em duas etapas: consulta a um banco de dados institucional para caracterização dos participantes e do atendimento médico; e entrevista com os pacientes que tiveram indicação de cuidado oftalmológico no Centro Integrado de Saúde e na rede. Os dados qualitativos foram transcritos e analisados por meio da estratégia metodológica do Discurso do Sujeito Coletivo. Resultados: Na primeira fase foram identificados 816 pacientes, em 920 consultas. A maioria não diabéticos (76,2%), do sexo feminino (61,6%), com nível médio de ensino (65,1%), brancos (92%) e com companheiro (75,7%). A principal causa de solicitação de avaliação oftalmológica, em ambos os grupos, foi a consulta com o especialista, cujo tempo de espera foi menor para os não diabéticos, com diferença estatisticamente significante (p=0,0268). Do total de pacientes, 241 (29,5%) receberam indicação de cuidado oftalmológico, sendo o maior percentual de não diabéticos (69,2%). Na segunda fase do estudo foram entrevistados 208 pacientes cuja síntese das entrevistas contribuíram para elaboração do discurso do sujeito coletivo, agrupado em três temas: Resolubilidade do cuidado oftalmológico sob a ótica dos pacientes; Obstáculos para a realização do cuidado proposto na rede de atenção a saúde e Contribuições para a melhoria do cuidado oftalmológico. Conclusão: Os resultados apresentados evidenciaram que o Centro Integrado de Saúde onde a pesquisa foi realizada apresenta condição de resolubilidade para atender, em grande parte, as reais necessidades oftalmológicas dos usuários do Sistema Único de Saúde. Do total de pacientes atendidos no período do estudo praticamente 30% receberam indicação de cuidado oftalmológico na rede de atenção à saúde, e destes, 69% não eram diabéticos. O principal motivo de avaliação oftalmológica foi a consulta com o especialista, em ambos os grupos, cujo tempo de espera foi maior para os pacientes diabéticos, demonstrando que não há critérios que priorizem o atendimento. Os discursos apontaram que o município não tem controle sobre os desfechos dos cuidados oftalmológicos referenciados a outros serviços, e tão pouco, da contrarreferência. As dificuldades de resolução na rede, sob a ótica dos participantes, referem-se a problemas de gestão, burocráticos e a falta de recursos materiais que dificultam a realização de procedimentos diagnósticos e terapêuticos. Produto da dissertação: Desta forma, o estudo tem como produto a proposição de um protocolo para reorganização do cuidado oftalmológico no Centro Integrado de Saúde tendo como premissas ações regulatórias pautadas em classificação de risco e estabelecimento de fluxo de referência e contrarreferência na rede de atenção à saúde do interior de São Paulo. Outro produto foi o desenvolvimento de uma cartilha sobre as principais complicações oculares ocasionadas pelo diabetes para treinamento da equipe multiprofissional. / Introduction: Resolubility in health is the satisfactory answer that the service provides to the user when seeking care for some need. In view of the above, the main objective of this study was to evaluate the resolubility of ophthalmologic care in the Integrated Health Center, from the perspective of diabetic and non-diabetic users. And, as secondary objectives: to identify the main causes of request of ophthalmological evaluation in both groups; Identify the waiting time for ophthalmologic care; Identify the patients who had an indication of ophthalmologic care for the health care network in both groups; To know the reasons that hinder / delay the performance of care in the health care network, from the point of view of care; Propose strategies to optimize care for patients who need eye care. Method: descriptive, exploratory, transversal study with mixed approach. A non-probabilistic sample consisted of all patients attended at the Integrated Health Center from the interior of São Paulo, from November 2013 to the same month of 2015. In order to respond to the objectives of the study, participants were divided into two groups: diabetic and non-diabetic. Diabetics. Data collection was carried out in two stages: consultation of an institutional database to characterize participants and medical care; And interview with the patients who had indication of ophthalmologic care in the Integrated Health Center and in the network. The qualitative data were transcribed and analyzed through the methodological strategy of the Discourse of the Collective Subject. Results: In the first phase, 816 patients were identified, in 920 consultations. The majority were non-diabetic (76.2%), female (61.6%), with a mean level of education (65.1%), whites (92%) and partners (75.7%). The main cause of request for ophthalmologic evaluation in both groups was consultation with the specialist, whose waiting time was lower for non-diabetics, with a statistically significant difference (p = 0.0268). Of the total number of patients, 241 (29.5%) received an indication for ophthalmologic care, the highest percentage being non-diabetic (69.2%). In the second phase of the study, 208 patients were interviewed whose synthesis of the interviews contributed to the elaboration of Discourse of the Collective Subject, grouped into three themes: Resolubility of ophthalmological care from the perspective of the patients; Obstacles to the realization of the proposed care in the network of health care and Contributions for the improvement of ophthalmological care. Conclusion: The presented results showed that the Integrated Health Center where the research was performed presents a resolubility condition to meet, in large part, the real ophthalmological needs of Unique Health System users. Of the total number of patients seen in the study period, almost 30% received an indication of ophthalmological care in the health care network, of which 69% were non-diabetic. The main reason for ophthalmologic evaluation was consultation with the specialist, in both groups, whose waiting time was higher for diabetic patients, demonstrating that there are no criteria that prioritize the care. The speeches pointed out that the municipality has no control over the outcomes of ophthalmological care referenced to other services, and so little, of the counterreference. The difficulties of solving in the network, from the perspective of the participants, refer to problems of management, bureaucratic and the lack of material resources that make difficult the accomplishment of diagnostic and therapeutic procedures. Product of the dissertation: In this way, the study has as a product the proposal of a protocol for the reorganization of ophthalmologic care in Integrated Health Center, based on regulatory actions based on risk classification and establishment of referral flow and counter-referral in the health care network from the interior of São Paulo. Another product was the development of a playbook on the main ocular complications caused by diabetes for multiprofessional team training.

La synapse est une structure macromoléculaire dont les composants sont renouvelés en permanence alors que l’assemblage est quasi-stable. A l’échelle mésoscopique, les récepteurs aux neurotransmetteurs (RN) sont accumulés dans le compartiment post-synaptique (PSD). Cette accumulation résulte de la diffusion latérale des RNs dans la membrane neuronale et de leurs immobilisations transitoires dans la PSD. Les protéines d’échafaudage (PE) localisées sous la membrane post-synaptique constituent des sites de capture en interagissant avec les RNs. Mon travail de thèse s’inscrit dans le cadre d’une collaboration avec des chimistes et des physiciens afin de comprendre les paramètres impliqués dans le processus de diffusion-capture. Nous nous sommes intéressés au cas de la capture du récepteur de la glycine (RGly) par les agrégats de PEs des synapses inhibitrices, les géphyrines. Nous avons étudié l’impact de la liaison RGly-géphyrine sur le processus de diffusion-capture sous deux aspects. Le premier est lié à la nature bimodale de liaison du RGly. Le second aborde l’impact des phosphorylations de la boucle M3-M4 de la sous-unité β du RGly sur la liaison avec la géphyrine.Mon travail de thèse montre qu’il est maintenant possible, en utilisant des approches de microscopie super-résolutive, de quantifier les aspects thermodynamiques des interactions moléculaires dans les cellules vivantes. / The synapse is a macromolecular structure whose components are constantly renewed while the assembly remains quasi-stable. At the mesoscopic level, neurotransmitter receptors (RNs) accumulate in the post-synaptic compartment (PSD). This accumulation is the result of the lateral diffusion of RNs in the neuronal membrane and transient immobilization within the PSD. This mechanism, called diffusion-trapping has been highlighted by single-molecule-tracking techniques. Scaffold proteins (PE) are localized under the post-synaptic membrane. These proteins form trapping-sites by interacting with RNs. Through an interdisciplinary approach in collaboration with chemists and physicists, the aim of my doctoral research was to understand the parameters that are involved in diffusion-trapping mechanisms. We especially focused on glycine receptor (RGly) trapping by PE clusters at inhibitory synapses, namely the scaffold protein gephyrin. The gephyrin- interaction motif of the GlyR is located within the cytoplasmic domain of the β-subunit of the receptor, the so-called β-loop. Two aspects of the impact of RGly-gephyrin binding on diffusion-trapping were studied. The first was to identify the source of the RGly-gephyrin bimodal binding. The second one addressed the regulation of gephyrin binding by phosphorylation of the GlyR βLoop.My research thus shows that it is now possible to quantify thermodynamic aspects of molecular interactions in living cells using high-density single-molecule-tracking.