No description available.

Extracellular matrix (ECM) microfibrils are critical components of connective tissues with a wide range of mechanical and cellular signalling functions. The focus of this PhD thesis is the study of two microfibrillar assemblies, fibrillin-1 and collagen VI. Fibrillin is a large ECM glycoprotein which facilitates the deposition of elastin in elastic tissues such aorta, skin and lung and sequesters growth factors in the matrix. Collagen VI is a heteromeric network-forming collagen which is expressed in tissues such as skin, lung, blood vessels and articular cartilage where it anchors cells into the ECM allowing for the transduction of biochemical and mechanical signals. The structures of some individual domains and short fragments of both fibrillin and collagen VI have been solved, but it is not fully understood how they are arranged into microfibrils and how these microfibrils are arranged into tissues. Therefore the aim of this project has been to determine the hierarchical organisation of fibrillin and collagen VI across multiple length scales. The nanoscale structure of the fibrillin microfibril was determined using negative stain TEM and single particle reconstruction. Microfibrils had a hollow tube-like structure with well-defined bead, arm, interbead and shoulder regions. To overcome flexibility observed in the microfibril, separate sub-models of the different fibrillin regions were modelled. The bead region had a complex double layered structure with an interwoven core and ring structures. The arm region had four separate densities which are potentially formed from dimers of fibrillin molecules. Serial block face scanning electron microscopy (SBF-SEM) and electron tomography allowed for the in situ 3D imaging of individual fibrillin microfibrils in ciliary zonule tissue. Microfibrils in ciliary zonule fibres were held together by cross bridges between microfibrils. These ciliary zonule fibres were then organised into larger fascicle-like structures which were stabilised by circumferentially arranged ciliary zonule fibres. The frozen hydrated structure of the collagen VI half-bead was reconstructed using cryo-TEM. The half-bead region had a compact hollow head, and flexible tail regions, the tail regions were linked together by the collagenous interbead region. SBF-SEM and electron tomography of the pericellular matrix (PCM) of murine articular cartilage revealed that the PCM had a meshwork-like organisation formed from globular densities ~30 nm in diameter. Together a combinatorial approach to image ECM microfibrils from the sub-molecular level to intact tissue structures spanning nanometre to millimetre length scales is presented. This provides a better understanding of how fibrillin and collagen VI microfibrils are organised in tissues.

Submitted by Repositorio Tarefa (tarefarepositorio@gmail.com) on 2018-10-09T22:44:48Z No. of bitstreams: 2 Módulo VI_ Carmem Caroline Marques.pdf: 502534 bytes, checksum: 51f154d312f298b965045e70f2301717 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-10-09T22:44:48Z (GMT). No. of bitstreams: 2 Módulo VI_ Carmem Caroline Marques.pdf: 502534 bytes, checksum: 51f154d312f298b965045e70f2301717 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-10-01 / Atividade do Modulo VI da aluna Carmem Caroline do curso de repositórios institucionais. / Atividade do módulo VI

Thesis (M.A.)--Boston University / Since the discovery of VI antigen by Felix and Pitt in 1934 (The Lancet, 2:186, 1934), investigators have attempted to isolate, purify and characterize this antigen. Antisera against purified VI antigens would prove a valuable tool for studying the effects of purification on the antigenic molecule. Purified Vi antigen, however, has proven to be a hapten in rabbits with one exception. Landy and Webster's Vi preparation was immunogenic for rabbits as well as for mice (J. Immunol., 69:143, 1952) but the preparations of Ashida (Japan. J. Exper. Med., 20:181, 1949), and of Baker, et al (J. Immunol., 83:687, 1959) were non-immunogenic although Baker's preparation immunized mice and man. Landy and Webster, however, observed that more of their preparation than of whole organisms was necessary to immunize rabbits to an equal degree [TRUNCATED]

Cette thèse a été développé grâce à une Conventions Industrielles de Formation par la Recherche (CIFRE). Cette convention fait partie d’un programme de l’Association nationale de la recherche et de la technologie (ANRT), coordonné par le Centre nationale de la recherche scientifique (CNRS). L’accord CIFRE subventionne les entreprises françaises qui engagent un thésard pour conduire un projet scientifique dans l’entreprise, en partenariat avec un laboratoire publique de recherche. Pour cette thèse, l’accord CIFRE a été signé par Renault et les laboratoires GIPSA Lab de Grenoble et PRISME d’Orléans.Cette thèse se focalise sur la modélisation 0D, en particulier sur une description plus détaillé du processus de la combustion et l’estimation des masses enfermées dans la chambre de combustion d’un moteur à allumage commandé (Spark Ignited (SI) engine). Les principaux développements comportent des points suivants :- L’impact flamme parois pendant la combustion : un nouveau modèle pour prendre en compte ce phénomène dans le cadre d’un modèle de combustion 0D à deux zones a été développé. Ce modèle permet de prendre en compte la géométrie de la chambre de combustion et la proportion de flamme que brûle proche des parois du cylindre. Plusieurs études ont montré qu’une grand proportion (20% au 30%) du mélange frais brûle dans ce mode de combustion ce qui montre l’importance de prendre en compte ce phénomène. - L’estimation de la mass totale enfermée dans la chambre de combustion après la fermeture des soupapes est un phénomène très intéressant qui présente un Challenger pour les chercheurs motoristes. Une estimation plus précise de la mass enfermée dans la chambre de combustion permet d’avoir un meilleur contrôle de l’injection du carburant et une amélioration dans le traitement des polluants.- Le dernier point à traiter dans cette thèse est la commande d’un système d’injection “common rail”. Ce point a pour but de compléter la modélisation de la combustion en ajoutant une thématique liée à l’injection, lequel est un paramètre crucial dans le processus de la combustion. L’objectif d’un système d’injection common rail est de contrôler l’avance de l’injection, la durée et la pression, de façon indépendante dans chaque cylindre, pour avoir un meilleur contrôle de la combustion, en dépendant des conditions d’opération. Cette injection permet de réguler le carburant en quantités très petites, ce qu’aide à réduire la consommation, les émissions polluantes, et aussi à améliorer la performance du moteur. / This thesis has been developed thanks to a Conventions Industrielles de Formation par la Recherche (CIFRE)1 agreement, that is a program of the french agency Association nationale de la recherche et de la Technologie(ANRT), coordinated by the Centre nationale de la recherche scientifique (CNRS). The CIFRE program grants the Franch companies who engage a PhD student to carry out a research project of the company within a public research lab. For this thesis, a CIFRE agreement has been accorded between the automobile company Renault France and the scientific laboratories Gipsa Lab in Grenoble and PRISME in Orléans.This thesis is focused on the modeling of a detailed description of the 0D combustion process and the estimation of the enclosed mass in the combustion chamber for a Spark Ignited (SI) engine. The main developments are summarized as follows:- The combustion process is frequently modeled as growing flame inside of the combustion chamber. Many 0D thermodynamical Engine models mostly focus on the laminar characteristics of such a free developing ame, but they lack of a suitable approximation of the combustion when the ame reaches the cylinder walls. In this thesis, a flame-wall interaction model is proposed as a complement of a 0D two zones thermodynamical model.- The estimation of the total mass enclosed in the combustion chamber is an interesting and challenging task for the engine control community. In this thesis, two nonlinear observers are synthesized for the enclosed mass estimation: a classical nonlinear high gain observer and an extended linear parameter varying (LPV) high gain observer.- A controller for a common rail injection system is developed in this thesis. First, an input state linearization of a common rail model is performed, in order to overcome the strong nonlinearities and build a virtual linear model. Using the virtual model, two linear control strategies are implemented to regulate the common rail pressure: an optimal linear quadratic regulator LQR with integral action and an optimal LQR tracking (feedforward) with integral action strategy.

Idag ses skolan som en högriskmiljö när man talar om mobbning. Trots att stora satsningar genomförs både kring det förebyggande och åtgärdande arbetet visar inte statisktiken på någon märkbar skillnad vad gäller mobbningsfrekvensen. Brottsförebyggarna i Gävle (BIG) arbetar aktivt för att hjälpa kommunens skolor med att minska mobbningsfrekvensen. BIG har skapat en modell, Gävlemodellen, med syftet att genom personalutbildning samt ett aktivt arbete mot mobbning lyckas minska eller bibehålla en låg mobbningsfrekvens inom skolan. I den här studien har fyra intervjuer genomförts med informanter som alla arbetar på skolor med låg mobbningsfrekvens. Detta har gjorts då studiens syfte är att försöka finna några gemensamma framgångsfaktorer i arbetet mot mobbning. Studien syftar även till att undersöka hur personalen upplever Gävlemodellen och dess funktion. Resultatet visar bland annat att personalen upplever att de tar arbetet mot mobbning på största allvar. Det framkommer att det upplevs vara gynnsamt om eleverna får vara delaktiga i arbetet mot mobbning samt att arbetet bör genomsyra hela skolverksamheten. Informanterna talar även mycket om ”vi” vilket tyder på att de arbetar efter en så kallad ”hela-skolan-ansats”. Resultatet visar även att informanterna har en positiv inställning till Gävlemodellen och dess funktion och de upplever att modellen har varit till stor hjälp, framförallt när det kommer till att strukturera upp arbetet inom skolan.

Myosin VI, encoded by jaguar (jar) in Drosophila melanogaster, is the only member of the myosin superfamily of actin-based motor proteins known to move towards the minus ends of actin filaments. In vitro studies demonstrate that Myosin VI has the ability to perform distinct functions as a cargo transporter and anchor in the cell, however which of these roles Myosin VI plays in the nervous system has yet to be determined. A locomotor defect, observed as sluggish movement in severe jar mutant larvae, was confirmed by behavioural assays. As this can indicate problems at the neuromuscular synapse, microscopy and electrophysiology were used to investigate neuromuscular junction (NMJ) structure and function in jar loss of function mutants of varying severity. Confocal imaging studies revealed a decrease in NMJ length, a reduction in bouton number per NMJ, alterations to the microtubule cytoskeleton and mislocalization of the synaptic vesicle protein Synaptotagmin in jar mutant boutons. FM dye labeling was consistent with the immunostaining data revealing vesicles endocytosed following electrical stimulation occupy the bouton centre in jar mutants. The data is indicative of a function for Myosin VI in maintaining proper peripheral vesicle localization. Electrophysiological experiments revealed a role for Myosin VI in basal synaptic transmission, with a reduction in low frequency nerve-evoked responses and spontaneous release in severe jar mutants. Changes in short-term synaptic plasticity were also observed in Myosin VI mutants by using both paired-pulse experiments to examine release probability and high-frequency stimulation paradigms to recruit vesicles from different functional pools. Taken together, the data suggest that Myosin VI functions as an anchor to peripherally localize vesicles within the bouton enabling their efficient release during nerve stimulation. Synaptic vesicles are mobile at the Drosophila NMJ; thus if Myosin VI is acting as a vesicle tether, it would normally be expected to restrain vesicle mobility at the synapse. FRAP analysis revealed a significant increase in synaptic vesicle mobility in jar mutant boutons. This study elucidates novel roles for Myosin VI function in the nervous system via regulation of the synaptic microtubule architecture and localization of synaptic vesicles within the nerve terminal.

Myosin VI, encoded by jaguar (jar) in Drosophila melanogaster, is the only member of the myosin superfamily of actin-based motor proteins known to move towards the minus ends of actin filaments. In vitro studies demonstrate that Myosin VI has the ability to perform distinct functions as a cargo transporter and anchor in the cell, however which of these roles Myosin VI plays in the nervous system has yet to be determined. A locomotor defect, observed as sluggish movement in severe jar mutant larvae, was confirmed by behavioural assays. As this can indicate problems at the neuromuscular synapse, microscopy and electrophysiology were used to investigate neuromuscular junction (NMJ) structure and function in jar loss of function mutants of varying severity. Confocal imaging studies revealed a decrease in NMJ length, a reduction in bouton number per NMJ, alterations to the microtubule cytoskeleton and mislocalization of the synaptic vesicle protein Synaptotagmin in jar mutant boutons. FM dye labeling was consistent with the immunostaining data revealing vesicles endocytosed following electrical stimulation occupy the bouton centre in jar mutants. The data is indicative of a function for Myosin VI in maintaining proper peripheral vesicle localization. Electrophysiological experiments revealed a role for Myosin VI in basal synaptic transmission, with a reduction in low frequency nerve-evoked responses and spontaneous release in severe jar mutants. Changes in short-term synaptic plasticity were also observed in Myosin VI mutants by using both paired-pulse experiments to examine release probability and high-frequency stimulation paradigms to recruit vesicles from different functional pools. Taken together, the data suggest that Myosin VI functions as an anchor to peripherally localize vesicles within the bouton enabling their efficient release during nerve stimulation. Synaptic vesicles are mobile at the Drosophila NMJ; thus if Myosin VI is acting as a vesicle tether, it would normally be expected to restrain vesicle mobility at the synapse. FRAP analysis revealed a significant increase in synaptic vesicle mobility in jar mutant boutons. This study elucidates novel roles for Myosin VI function in the nervous system via regulation of the synaptic microtubule architecture and localization of synaptic vesicles within the nerve terminal.

No description available.

O ferrato(VI) de potássio, composto fortemente oxidante, foi testado em uma coluna de absorção de gases a fim de remover o NO presente em gases oriundos de fontes fixas de queima de combustíveis fósseis. O poder oxidativo do ferrato(VI) e seu comportamento através da cinética de decaimento do NO foram avaliados com o propósito de melhor entender a reação de oxidação. O sistema lavador de gases foi constituído por três subsistemas: o primeiro, um cilindro contendo uma mistura de NO/N2 com concentrações de NO de 50 e 98 ppm; o segundo, os lavadores de gases, constituído por dois reatores/lavadores com capacidade de 1.000 mL que foram completados com 600 mL de solução lavadora e com 400 mL de anéis de Rasching de vidro e um terceiro, reator/lavador que continha 400 mL da mesma solução dos demais, sem os anéis; o terceiro subsistema, constituído por equipamentos analisadores de NO e NO2. Os equipamentos de medição foram os da marca Oldham, modelo TX 2000, para NO, com escala de medida de 0-100 ppm NO e TX 2000, para NO2, com escala de medida de 0-30 ppm NO2. O ferrato(VI) de potássio foi obtido via úmida e analisado por volumetria de oxidaçãoredução. Os testes de oxidação foram realizados à temperatura de 25oC ± 0,5oC e pressão de uma atmosfera. Inicialmente, testou-se técnicas padrões de remoção de NO de gases a frio. Hidróxido de sódio e hidróxido de potássio tem sido empregados comercialmente na remoção de NOx. As soluções de hidróxido de potássio e de sódio apresentaram a mesma remoção de NO quando a concentração inicial do NO no gás foi de 50 ppm. A maior eficiência de remoção de NO deu-se para a razão molar de 5 OH  / 1 NO em cinco minutos de tempo de detenção, utilizando solução de ferrato(VI): 86% para a concentração inicial de 50 ppm e 85% para a concentração inicial de 98 ppm. Os resultados experimentais mostram que a solução de ferrato(VI) de potássio apresentou eficiência de remoção 25% superior à das outras soluções testadas. Apesar das reações de oxidação do NO serem bastante complexas, em função dos resultados analíticos realizados em termos de nitritos e nitratos, pode -se concluir que o NO é oxidado a NO2 e este passa a NO2 - e NO3 2- em solução, confirmando o mecanismo proposto por diversos autores. A abordagem cinética mostrou que a reação de oxidação pelo íon ferrato(VI) é de primeira ordem em relação ao NO e a constante média de velocidade de reação resultante dos dados experimentais foi de 9,80 x 10-4 s-1. A viabilidade técnica do uso do ferrato(VI) de potássio como oxidante do NOx em torres absorvedoras de gases foi comprovada, pois o composto mostrou-se um eficiente oxidante para o NO nas condições testadas.