Made available in DSpace on 2014-12-17T14:55:06Z (GMT). No. of bitstreams: 1 GutembergSS.pdf: 569123 bytes, checksum: 6f85b5ee47010d2d331986f17689304b (MD5) Previous issue date: 2008-05-30 / This work presents a cooperative navigation systemof a humanoid robot and a wheeled robot using visual information, aiming to navigate the non-instrumented humanoid robot using information obtained from the instrumented wheeled robot. Despite the humanoid not having sensors to its navigation, it can be remotely controlled by infra-red signals. Thus, the wheeled robot can control the humanoid positioning itself behind him and, through visual information, find it and navigate it. The location of the wheeled robot is obtained merging information from odometers and from landmarks detection, using the Extended Kalman Filter. The marks are visually detected, and their features are extracted by image processing. Parameters obtained by image processing are directly used in the Extended Kalman Filter. Thus, while the wheeled robot locates and navigates the humanoid, it also simultaneously calculates its own location and maps the environment (SLAM). The navigation is done through heuristic algorithms based on errors between the actual and desired pose for each robot. The main contribution of this work was the implementation of a cooperative navigation system for two robots based on visual information, which can be extended to other robotic applications, as the ability to control robots without interfering on its hardware, or attaching communication devices / Este trabalho apresenta um sistema de navega??o cooperativa de um rob? human?ide e um rob? com rodas usando informa??o visual, com o objetivo de efetuar a navega??o do rob? human?ide n?o instrumentado utilizando-se das informa??es obtidas do rob? com rodas instrumentado. Apesar do human?ide n?o possuir sensores para sua navega??o, pode ser remotamente controlado por sinal infravermelho. Assim, o rob? com rodas pode controlar o human?ide posicionando-se atr?s dele e, atrav?s de informa??o visual, localiz?-lo e naveg?-lo. A localiza??o do rob? com rodas ? obtida fundindo-se informa??es de odometria e detec??o de marcos utilizando o filtro de Kalman estendido. Os marcos s?o detectados visualmente, e suas caracter?sticas s?o extra?das pelo o processamento da imagem. As informa??es das caracter?sticas da imagem s?o utilizadas diretamente no filtro de Kalman estendido. Assim, enquanto o rob? com rodas localiza e navega o human?ide, realiza tamb?m sua localiza??o e o mapeamento do ambiente simultaneamente (SLAM). A navega??o ? realizada atrav?s de algoritmos heur?sticos baseados nos erros de pose entre a pose dos rob?s e a pose desejada para cada rob?. A principal contribui??o desse trabalho foi a implementa??o de um sistema de navega??o cooperativa entre dois rob?s baseados em informa??o visual, que pode ser estendido para outras aplica??es rob?ticas, dado a possibilidade de se controlar rob?s sem interferir em seu hardware, ou acoplar dispositivos de comunica??o

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No. of bitstreams: 1 IvanoscaAndradeDaSilva_TESE.pdf: 841267 bytes, checksum: 867ca6ea3d9afe5c4ff3619961095540 (MD5) Previous issue date: 2016-05-20 / L?gica fuzzy surge em 1965 com o trabalho de Lotfi Zadeh que tem por objetivo tratar de forma rigorosa a incerteza inerente na defini??o de no??es e propriedades imprecisas ou vagas presentes em diversas situa??es do cotidiano, como por exemplo, temperatura alta, pendente acentuada, etc. Para isto, Zadeh considerou um grau (um valor no intervalo [0,1]) com que um determinado elemento pertence a um conjunto ou satisfaz uma determinada propriedade. No entanto, algumas cr?ticas a esta teoria foram feitas, principalmente por causa desta teoria lidar com incertezas usando valores exatos, o que motivou a v?rios pesquisadores (entre eles o pr?prio Zadeh) em 1975, e de forma independente, a estender esta teoria relaxando o conjunto onde os graus tomam seus valores. Uma destas extens?es, a l?gica fuzzy intuicionista de Atanassov intervalarmente valorada, proposta em 1989 por Atanassov e Gargov, que usa um par de subintervalos de [0,1], um deles representa o quanto, considerando alguma imprecis?o, se acredita que o elemento satisfaz a propriedade enquanto o outro descreve o quanto se acredita que n?o satisfaz a propriedade. Este par de graus intervalares visam capturar a hesita??o e imprecis?o presente ao momento de se atribuir o grau com que o elemento satisfaz a propriedade. A l?gica fuzzy e suas diversas extens?es, tem sido aplicada com sucesso nas mais variadas ?reas, como por exemplo, medicina, engenharia, agricultura, econ?mia e em administra??o. Em particular, uma das principais aplica??es de l?gica fuzzy em administra??o diz respeito ao apoio na tomada de decis?o. Um problema t?pico de tomada de decis?o consiste em escolher a melhor alternativa entre um conjunto delas ou em ordenar as alternativas de melhor a pior, considerando alguns crit?rios a serem satisfeitos assi como a opini?o de um ou mais especialistas. Os m?todos fuzzy para problemas de tomada de decis?o usam graus fuzzy (ou de suas extens?es) para expressar o quanto uma alternativa satisfaz um determinado atributo ou crit?rio, e alguma forma de agregar a opini?o de todos os especialistas, para chegar no final a uma pontua??o (que pode ser um valor num?rico ou n?o) que permita decidir qual ? a potencialmente melhor alternativa.Nesta tese s?o apresentados avan?os te?ricos significativos na teoria dos conjuntos fuzzy intuicionistas de Atanassov intervalarmente valorados assim como, s?o proposto dois novos m?todos de tomada de decis?o, considerando m?ltiplos atributos (ou crit?rios) e um grupo de especialistas, aplica??o desses m?todos em problemas espec?ficos e ? realizada uma compara??o com resultados obtidos com outros m?todos de tomada de decis?o. Por outro lado, um dos grandes problemas com os m?todos ou processos de tomada de decis?o ? que, quando aplicado em problemas reais, em geral, n?o ? poss?vel determinar a qualidade da solu??o (ordena??o das alternativas) obtida pelo m?todo. De fato, diferentes m?todos de tomada de decis?o para um mesmo problema podem resultar em diferentes solu??es. Nesta tese, se prop?e considerar os resultados obtidos por diferentes m?todos (independente do tipo de extens?o fuzzy usada e tipo de problema de tomada de decis?o) como meras evid?ncias que podem ser usadas por um outro m?todo capaz de determinar uma ordena??o das alternativas que de alguma maneira represente a fus?o ou consenso desses ordenamentos de alternativas. / Fuzzy logic emerged in 1965 with the work of Lotfi Zadeh that aims rigorously deal with the uncertainty inherent in the definition of notions and inaccurate or vague properties in several everyday situations, such as high temperature, sharp drop, etc. For this, Zadeh considered a degree (a value in the range [0,1]) in order to express how much an element belongs to a set, i.e. satisfies a given property. However, some criticism of this theory have been made, mainly because that this theory deal with uncertainties using exact values, which led to several researchers (including himself Zadeh) in 1975 and independently, to extend this theory relaxing the set where the membership degrees take their values. One of these extensions, interval-valued Atanassov?s intuitionistic fuzzy logic, proposed in 1989 by Atanassov and Gargov, uses a pair of subintervals of [0,1], the first represent how much, considering some inaccuracy, it is believed that the element satisfies the property while the second describes how much it is believed that does not satisfy the property. This pair of interval degrees aim to capture the hesitation and inaccuracy present at the time of assigning the degree to which the element satisfies the property. Fuzzy logic and its various extensions, has been successfully applied in various areas, such as: medicine, engineering, agriculture, economics and management. In particular, one of the main applications of fuzzy logic in management concerns with the support to the decision making. A typical decision-making problem is the choice of the best alternative among a set of them or the obtention of a ranking of the alternatives, considering some criteria to be satisfied, as well as the opinion of one or more experts. The fuzzy methods for decision making problems based on decision matrices, use fuzzy degrees (or of their extensions) to express how much an alternative satisfies a particular attribute or criterion. On the other hand, the methods of fuzzy decision making problems based on preference relations, use fuzzy degrees (or of their extensions) to express how much an alternative is preferred to other alternative. In both cases, the opinion of all experts is aggregated to determine only a single decision matrix or preference relation, according be the case, and from them extract a score (which can be a numeric value or not) in order to decide which is the potentially best alternative. In this thesis are presents significant theoretical advances in the theory of intervalvalued Atanassov?s intuitionistic fuzzy sets as well as are proposed two new decisionmaking methods, considering multiple attributes (or criteria) and a group of experts, these methods are applyed on specific problems and made a comparison with the results obtained by others decision-making methods. On the other hand, one of the major problems with the methods or processes of decision-making is that, when applied to real problems, in general, can not determine the quality of the solution (ranking of the alternatives) obtained by the method. In fact, different decision making methods to the same problem may result in different solutions. In this thesis, it is proposed to consider the results obtained by different methods (independent of the fuzzy extension considered and of the type of decision-making problem) as information that can be used by another method capable of determining a ranking of the alternatives representing the fusion or consensus of these rankings.

This paper describes the design and implementation of an automated build system for the JAS39A simulator FUS39A at HiQ:s offices in Arboga. The assignment was to automate the process in which modules are built; the simulator is composed of a number of modules which are built manually at the end of each week, this process takes about a day of manual labor. The system can automatically build a module as either a scheduled service or by manual invocation. The system contains functionality for reporting the build results to any given recipient by e-mail. The purpose of the system is to free up the time put into manually building the modules for better suited tasks by automating the build of FUS39A. The assignment was split into two parts, an analysis part where information of the old system was gathered, tools and methods were chosen and the new system was designed. In the second part the system was implemented and tested. / Denna rapport beskriver designen och implementationen av ett system för automatiskt bygge av JAS39A simulatorn FUS39A vid HiQ:s kontor i Arboga. Målet var att automatisera bygget av modulerna som simulatorn består av då de i utgångsläget byggs manuellt mot en insats på en mandag i veckan. Systemet kan utan övervakning generera en modulutgåva genom en schemalagd tjänst eller en manuell invokering. Systemet innehåller även funktionalitet för att rapportera byggets resultat till avsedd mottagare via e-post. Syftet med systemet är att avlasta en persons arbetsbörda genom att automatisera bygget av mjukvaran i simulatorn FUS39A. Arbetet delades in i två delar, en analysfas där information om det nuvarande systemet samlas, verktyg väljs och designen av det nya systemet tas fram. I den andra delen implementeras och testas systemet.

Bakgrund   The Gugging Swallowing Screen - Intensive Care Unit (GUSS-ICU) är ett screeningtest med syfte att fånga upp indikationer på sväljsvårigheter efter långvarig intubering hos inneliggande patienter på intensivvårdsavdelningar (IVA). I dagsläget finns det inget svenskt översatt och validerat screeningtest för omvårdnadspersonalen att använda vid bedömning av sväljförmågan efter extubering på IVA. Syfte Syftet med studien var att översätta det internationella screeningtestet GUSS-ICU till svenska för användning i en svensk intensivvårdspopulation. Vidare syftade studien till att utföra en pilotstudie av den svenska versionen på extuberade patienter på IVA. Metod En framåt-bakåtöversättningsmetod användes vid översättningen av screeningtestet GUSS-ICU. Översättningsprocessen omfattade tre steg: framåtöversättning, granskning och kommentarer från en expertpanel och en bakåtöversättning. I översättningsprocessen deltog två logopedstudenter, två handledare, en expertgrupp och en översättare. Expertgruppen bestod av 10 deltagare med olika professioner inom hälso- och sjukvården. Fem inneliggande patienter från IVA planerades delta i en pilottestning av den svenska översättningsversionen. En innehållsanalys genomfördes för att kunna jämföra samtliga översättningar. Syftet med jämförelsen var att identifiera skillnader i ord och satser samt kulturella och kontextuella skillnader. Resultat       Studien resulterade i en svensk översättning (GUSS-IVA) av screeningtestet GUSS-ICU. Analysen visade på skillnader i val av ord, koncept och satser mellan de olika översättningarna. Flertalet skillnader var ej betydelseskiljande utan analyserades istället som resultat av skillnader i erfarenhet, kunskap och språkbruk. Översättningsmetoden bidrog till språklig, kontextuell och kulturell anpassning av översättningen. Slutsats Den svenska versionen av GUSS-ICU stämmer bra överens med originalversionen och enbart ett fåtal skillnader observerades mellan översättningarna. Skillnaderna mellan bakåtöversättningen och originalversionen var inte betydelseskiljande, vilket tyder på att den svenska versionen mäter det den avser att mäta. Framtida studier behöver pilottesta och validera den svenska versionen av GUSS-ICU, innan testet kan implementeras i en svensk intensivvårdspopulation. / Validering av screeningtest för sväljsvårigheter för användning inom svensk vårdkontext

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease is a fatal neurodegenerative disease. ALS is typically adult onset and is characterized by rapidly progressive loss of both upper and lower motor neurons that leads to death usually within 3-5 years. About 90% of all the cases are sporadic with no family history while the remaining 10% are familial cases with mutations in several genes including SOD1, FUS/TLS, TDP43 and C9ORF72. FUS/TLS (Fused in Sarcoma/Translocated in Liposarcoma or FUS) is an RNA/DNA binding protein that is involved in multiple cellular functions including DNA damage repair, transcription, mRNA splicing, RNA transport and stress response. More than 40 mutations have now been identified in FUS that account for about 5% of all the familial cases of ALS. However, the exact mechanism by which FUS causes ALS is unknown. While significant progress has been made in understanding the disease mechanism and identifying therapeutic strategies, several questions still remain largely unknown. The work presented here aims at understanding the normal functions of FUS as well as the pathogenic mechanisms by which it leads to disease. Several studies showed the association of mutant-FUS with structures made up of RNA and proteins, called stress granules that form under various stress conditions. However, little is known about the role of endogenous FUS under stress conditions. I have shown that under hyperosmolar conditions, the predominantly nuclear FUS translocates into the cytoplasm and incorporates into stress granules. The response is specific to hyperosmolar stress because FUS remains nuclear under other stress conditions tested, such as oxidative stress, ER stress and heat shock. The response of FUS is rapid, and cells with reduced FUS levels are susceptible to the hyperosmolar stress, indicating a pro-survival role for FUS. In addition to investigating the functions of endogenous wild-type (WT) FUS, the work presented also focuses on identifying the pathogenic mechanism(s) of FUS variants. Using various biochemical techniques, I have shown that ALS-causing FUS variants are misfolded compared to the WT protein. Furthermore, in a squid axoplasm based vesicle motility assay, the FUS variants inhibit fast axonal transport (FAT) in a p38 MAPK dependent manner, indicating a role for the kinase in mutant-FUS mediated disease pathogenesis. Analysis of human ALS patient samples indicates higher levels of total and phospho p38, supporting the notion that aberrant regulation of p38 MAPK is involved in ALS. The results presented in this dissertation 1) support a novel prosurvival role for FUS under hyperosmolar stress conditions and, 2) demonstrate that protein misfolding and aberrant kinase activation contribute to ALS pathogenesis by FUS variants.

Bakgrund Sväljning bedöms utifrån två aspekter - hur säker och hur effektiv den är. Tidigare studier har visat att vid stigande ålder blir sväljningen mindre effektiv och att förekomst av penetration ökar. Åldrande sväljning har i tidigare studier inte studerats specifikt utifrån säkerhet och effektivitet. Tidigare forskning med avseende på sväljning har enbart fokuserat på äldre individer respektive snävare åldersgrupper.  Syfte Aktuella studiens syfte är att undersöka om det ses en försämring i normal sväljförmåga vid stigande ålder. Studien syftar  även till att undersöka om det finns könsskillnader i hur sväljförmåga förändras vid ökande ålder, men även oavsett ålder. Bedömning av sväljfunktion, sväljningssäkerhet och sväljningseffektivitet genomfördes med Flexibel videoendoskopisk Undersökning av Sväljning (FUS).  Metod Totalt inkluderades 65 deltagare (33 st kvinnor och 32 st män), i åldrarna 21-91 år (median 44 år). FUS genomfördes för att undersöka sväljningen. Vid FUS sväljer deltagarna föda i olika konsistenser. Fynden från FUS bedömdes utifrån standardiserade skalor: The Dysphagia Outcome and Severity Scale (DOSS), Penetration-Aspiration Scale (PAS) och The Yale Pharyngeal Residue Severity Rating Scale (YPRSRS).  Resultat Majoriteten av alla deltagare bedömdes ha funktionell sväljning. Kvinnor uppvisade en bättre sväljfunktion överlag, men inga könsskillander kunde påvisas gällande säkerhet och effektivitet. Deltagare med en högre uppnådd ålder uppvisade en sämre sväljningssäkerhet och sväljningseffektivitet. Ålder kan således vara en påverkande faktor för sväljningssäkerhet och sväljningseffektivitet.   Slutsatser Denna studie visade att sväljfunktionen hos äldre deltagare var sämre än hos yngre deltagare. Sväljningens säkerhet och effektivitet var inte försämrad hos friska äldre deltagare, jämfört med friska yngre deltagare. Det fanns könsskillnader i sväljförmåga avseende sväljfunktion, kvinnor har en högre förekomst av normal sväljning än männen. Könsskillnader gällande sväljningssäkerhet kunde inte konstateras. Könsskillnad för sväljningseffektivitet kunde ses för sinus piriformis, men inte vallecula. Männen uppvisade genomgående en mindre effektiv sväljning, jämfört med kvinnorna.

La sclérose latérale amyotrophique (SLA) est une pathologie complexe multifactorielle dont les mécanismes de dégénérescence des motoneurones et de propagation rapide au sein du système nerveux sont encore incertains. Par l’utilisation du nématode Caenorhabditis elegans, nous avons pu investiguer génétiquement et pharmacologiquement certains facteurs entrant en jeu dans la toxicité de TDP-43 et FUS. Des mutations dominantes dans ces protéines liant l’ADN et l’ARN, structurellement et fonctionnellement proches, sont des causes de SLA familiales. Nous avons, par le passé, construit un modèle de ver transgénique possédant le gène TARDBP ou FUS codant respectivement pour les protéines humaines TDP-43 ou FUS, sous le contrôle d’un promoteur exprimé seulement dans les neurones GABAergiques. Uniquement lorsque les gènes TARDBP ou FUS sont mutés, des symptômes relatifs à la SLA apparaissent au cours du temps, à savoir une paralysie progressive et une neurodégénérescence des motoneurones GABAergiques. Nous avons voulu connaître le rôle que pouvait jouer le système immunitaire, dont des évidences croissantes montrent une implication dans la SLA, dans la protéotoxicité liée à ces protéines dans nos modèles de ver. Dans un premier temps, nous avons évalué la motricité des vers en milieu solide et en milieu liquide, et grâce à des vers transgéniques exprimant la GFP dans les neurones GABAergiques, nous avons pu quantifier la neurodégénérescence. Nos résultats soulignent un rôle prévalent de l’orthologue de la protéine du système immunitaire innée Sarm1 chez le ver, TIR-1, ainsi que les kinases en aval dans la pathologie. Nous avons pu, de surcroît, utiliser le marqueur NLP-29 dont le promoteur lié à la GFP nous indique l’activation de la voie Sarm1 dans l’ensemble du ver et non seulement dans les neurones. De manière intéressante, l’activation de ces protéines se produit entre autres dans des cellules non-neuronales de manière paracrine suggérant qu’un signal de danger opère extracellulairement et vraisemblablement à travers un récepteur membranaire. Ces dernières années, un nombre important d’études met en lumière le rôle proéminent des microARNs dans des maladies telle que la SLA. Classiquement vus comme des régulateurs de l’expression post-transcriptionnelle, ce qui en font notamment des outils antiviraux puissants, ils peuvent agir à d’autres niveaux et notamment comme ligands de récepteurs Toll-like (TLRs), eux aussi impliqués dans la SLA. iv Outre le potentiel biomarqueur de ces petites molécules, nous avons investigué leur rôle dans la neurodégénérescence observée dans la SLA. Ainsi, dans une deuxième partie d’étude, nous avons utilisé des mutants pour différentes protéines impliquées dans la biogénèse des microARNs et trouvé qu’elles étaient partie intégrante du processus de paralysie et de dégénérescence des vers TDP-43A315T. Plus encore, le microARN let-7 pourrait être une molécule signal transitant entre les neurones et les cellules avoisinantes. Enfin, des analyses bio-statistiques prédisent la possibilité que let-7 se lie au récepteur TOL-1, l’unique orthologue des TLRs chez C. elegans. Les propriétés des microARNs en font en effet des cibles de choix dans la recherche de nouveaux acteurs dans la SLA et de potentielles cibles thérapeutiques. / Amyotrophic lateral sclerosis is a complex multifactorial pathology characterized by the progressive spread of motor neuron degeneration. Unfortunalety, the underlying disease mechanisms remain unclear. By using the nematode Caenorhabditis elegans, we were able to investigate genetically and pharmacologically some factors involved in TDP-43 or FUS proteotoxicity. Dominant mutations in these structurally and functionally similar DNA/RNA binding proteins, are causative for familial ALS. We have constructed transgenic C. elegans models expressing human TARDBP or FUS genes - encoding respectively TDP-43 and FUS - only in GABAergic motor neurons. In these transgenics animals, the expression of mutant TARDBP or FUS alleles results in early the motor deficits leading to age-dependent paralysis accompanied by neuronal protein aggregation. Using transgenic strain expressing GFP in GABAeric neurons, we found an increased rate of neurodegeneration in TDP-43 and FUS mutants. With these models we investigated the potential role of the innate immune system as a modifier of these phenotypes. Our results highlight a prevalent role for the worm’s innate immune system, and specifically the TIR-1/Sarm1 pathway and associated downstream kinases in neurodegeneration. We used GFP fluorescence linked to NLP-29 promoter to indicate Sarm1 pathway activation in the entire worm. Interestingly, activation of the TIR-1/Sarm1 pathway occurs in a paracrine manner in non-neuronal cells, suggesting that a danger signal operates extracellularly likely through a membrane receptor. In a past few years, a number of studies have highlighted the prominent role of microRNAs in diseases such as ALS. Traditionally seen as post-transcriptional regulators, what makes them powerful antiviral tools is that they can act at other levels and in particular as Toll-like receptors (TLRs) ligands, also involved in ALS. In addition to the biomarker potential of these small molecules, we investigated their role in the neurodegeneration observed in ALS. As a result, in the a second section of this study, we used worms mutant for several proteins involved in the biogenesis of microRNAs and found that they were involved in the process of TDP-43A315T-independent paralysis and neurodegeneration. Moreover, the microRNA let-7 seems to be a signal molecule involved in the non-cell autonomous trans-neuronal and trans-cellular spread of motor neuron degeneration. Finally, bio-statistical analyzes predict the possibility that let-7 binds to the vi TOL-1 receptor, the single ortholog of TLRs in C. elegans. Thus microRNAs may be prime targets for ALS therapeutic intervention.

La sclérose latérale amyotrophique (SLA) est la maladie des neurones moteurs la plus fréquente, affectant 4-6 individus par 100,000 habitants à l’échelle mondiale. La maladie se caractérise par une faiblesse et une atrophie musculaire suite à la dégénérescence des neurones du cortex moteur, tronc cérébral et moelle épinière. Les personnes atteintes développent les premiers symptômes à l’âge adulte et la maladie progresse sur une période de trois à cinq ans. Il a été répertorié qu’environ 10% des patients ont une histoire familiale de SLA; 90% des gens affectés le sont donc de façon sporadique. La découverte il y a 19 ans de mutations dans le gène zinc/copper superoxide dismutase (SOD1), présentes dans 15-20% des cas familiaux de SLA et environ 2% du total des individus affectés, a été l’événement déclencheur pour la découverte de variations génétiques responsables de la maladie. La recherche sur la génétique de la SLA a connu une progression rapide ces quatre dernières années avec l’identification de mutations dans de nouveaux gènes. Toutefois, même si certains de ces gènes ont été démontrés comme réellement liés à la maladie, la contribution d’autres gènes demeure incertaine puisque les résultats publiés de ceux-ci n’ont pas, à ce jour, été répliqués. Une portion substantielle de cas reste cependant à être génétiquement expliquée, et aucun traitement à ce jour n’a été démontré comme étant efficace pour remédier, atténuer ou prévenir la maladie. Le but du projet de recherche de doctorat était d’identifier de nouveaux gènes mutés dans la SLA, tout en évaluant la contribution de gènes nouvellement identifiés chez une importante cohorte multiethnique de cas familiaux et sporadiques. Les résultats présentés sont organisés en trois sections différentes. Dans un premier temps, la contribution de mutations présentes dans le gène FUS est évaluée chez les patients familiaux, sporadiques et juvéniles de SLA. Précisément, de nouvelles mutations sont rapportées et la proportion de mutations retrouvées chez les cas familiaux et sporadiques de SLA est évaluée. De plus, une nouvelle mutation est rapportée dans un cas juvénile de SLA; cette étude de cas est discutée. Dans un deuxième temps, de nouvelles avenues génétiques sont explorées concernant le gène SOD1. En effet, une nouvelle mutation complexe est rapportée chez une famille française de SLA. De plus, la possibilité qu’une mutation présente dans un autre gène impliqué dans la SLA ait un impact sur l’épissage du gène SOD1 est évaluée. Finalement, la dernière section explique la contribution de nouveaux gènes candidats chez les patients atteints de SLA. Spécifiquement, le rôle des gènes OPTN, SIGMAR1 et SORT1 dans le phénotype de SLA est évalué. Il est souhaité que nos résultats combinés avec les récents développements en génétique et biologie moléculaire permettent une meilleure compréhension du mécanisme pathologique responsable de cette terrible maladie tout en guidant le déploiement de thérapies suite à l’identification des cibles appropriées. / Amyotrophic lateral sclerosis (ALS) is the most common of motor neuron diseases, affecting 4-6 individuals per 100,000 individuals worldwide. ALS is characterized by muscle weakness and atrophy caused by the degeneration of neurons located in the motor cortex, brain stem and spinal cord. This fatal disease generally has an adult onset and progresses over a three to five year period. While 10% of patients affected have a family history of the disease, 90% of cases do not and are considered sporadic. The finding of mutations in the zinc/copper superoxide dismutase gene (SOD1) gene 19 years ago in about 15-20% of familial ALS (FALS) patients and approximately 2% of overall cases developed the interest of identifying rare genetics variants causing the disease. The ALS research field experienced a rapid progression during the last four years as mutations in new genes have been identified. While mutations in some of those new genes have been clearly linked to ALS, the role of others is still questionable and so far has not been positively replicated in other populations. Importantly, a significant portion of cases still need to be genetically explained and, unfortunately, there is still no effective treatment to cure, attenuate or prevent the disease. The aim of this Ph.D research project was to identify new ALS mutated genes while analysing the causative role of other newly identified genes in a large familial and sporadic ALS cohort of different origins. The results presented here are categorized into three different sections. First, the contribution of FUS mutations to familial, sporadic and juvenile ALS is analysed. Specifically, new FUS mutations are reported in ALS cases and the proportions of variants present in the tested familial and sporadic ALS cohorts are assessed. In addition, a new mutation is reported in a juvenile ALS patient, and this interesting case is discussed. Second, new genetic avenues are explored for the SOD1 gene. Precisely, a new and complex SOD1 mutation is reported in a French ALS family. Moreover, the possibility that other ALS mutated genes influence SOD1 splicing events is evaluated. Third, the contribution of new candidate genes is evaluated. Precisely, the contribution of OPTN, SIGMAR1 and SORT1 genes to the ALS phenotype is assessed. Hopefully, our different findings combined with recent developments in genetics and molecular biology will permit a better understanding of the pathological mechanisms involved in the disease and will lead to the identification of the right targets in order to develop appropriate therapeutics for ALS patients.

Made available in DSpace on 2015-12-03T18:35:12Z (GMT). No. of bitstreams: 1 Adriano_da_Costa_Andrade.pdf: 1175815 bytes, checksum: 16b9a0577766cebffff52abbc3248678 (MD5) Previous issue date: 2010-03-29 / This thesis has the objective of highlighting the differences between the accounting aspects and the tax impacts under the circunstance of the negotiation of one company through the institute of the incorporation and / or division to replace the institut of the acquisition - purchase and sale. The granting of some fiscal concessions by the Federal Government was what initially motivated the use of these operations, in 1971 it was created the Commission of Fusion and Incorporation of Companies - COFIE - linked to the Ministry of Finance, in order to provide, coordinate and analyze such benefits. The reorganizations are operations of incorporation and / or division known by Americans as a business combination, which since the 90's, with the constant changes that are occurring in Brazil and in the world, has its contribution and importance increased by the benefits brought throught the operations, beyond being extremely relevant values. This research seeks to demonstrate that business organizations are using the incorporation of institutes and divisions to acquire other business endeavors, ie, using the legitimacy of the institution of reorganization for tax advantages, because in essence the operation is an acquisition - buying and selling - replaced by a corporate reorganization. Therefore, the methodology adopted will be the bibliographic research, which as collected through documental and empirical research, tried to highlight the legal aspects, legal doctrine, corporate, tax and accounting schools of merger, demerger and acquisition. The interpretation and analysis were based on the theoretical framework, based on the review of the literature relevant to the study, that was done through a case in a Brazilian petrochemical sector, in which was reorganized through the institute of incorporation, initiated in late 2007 and completed in mid-2009. The purpose was to demonstrate the economy tax through the not taxable income tax and contribution social over net proft through capital gains to shareholders of the merged company, to highlight, in the accounting theory, the question of the essence regarding the form and to make evident the different ways to account for each institute. / Esta disserta????o tem por objetivo evidenciar as diferen??as entre os aspectos cont??beis e os impactos tribut??rios quando a negocia????o de uma empresa se realiza atrav??s da reorganiza????o societ??ria por meio do instituto da incorpora????o - e/ou cis??o em substitui????o ao instituto da aquisi????o - compra e venda. A concess??o de alguns benef??cios fiscais pelo Governo Federal foi o que motivou, inicialmente, o emprego dessas opera????es; no ano de 1971 foi criada a Comiss??o de Fus??o e Incorpora????o de Empresas - COFIE, ligada ao Minist??rio da Fazenda, com a finalidade de conceder, coordenar e analisar tais benef??cios. As reorganiza????es societ??rias s??o opera????es de incorpora????o e/ou cis??o denominadas pelos norte-americanos como business combinations, que, a partir da d??cada de 90, com as constantes modifica????es que est??o ocorrendo no cen??rio brasileiro e mundial, vem tendo sua participa????o e import??ncia ampliadas pelos benef??cios trazidos ??s respectivas opera????es, al??m de serem valores relevantes. Nesta pesquisa, procura-se evidenciar que as organiza????es empresariais est??o utilizando os institutos da incorpora????o e cis??o para adquirir outros empreendimentos empresariais, ou seja, utilizando-se da licitude da instituto da reorganiza????o societ??ria para obter vantagens tribut??rias, por que na ess??ncia a opera????o ?? uma aquisi????o - compra e venda - substitu??da por uma reorganiza????o societ??ria. Para tanto, a metodologia adotada ser?? pesquisa bibliogr??fica; os dados da pesquisa ser??o coletados por meio de pesquisa documental e emp??rica, em que se procurou evidenciar os aspectos legais, jur??dicos doutrin??rios, societ??rios, tribut??rios e cont??beis dos institutos de incorpora????o, cis??o e aquisi????o. A interpreta????o e an??lise dos dados embasou-se no referencial te??rico, fundamentado na revis??o da literatura pertinente ?? ??rea de estudo, sendo a pesquisa feita mediante um estudo de caso em uma empresa brasileira do setor petroqu??mico, que se reorganizou por interm??dio do instituto da incorpora????o, iniciada no final de 2007 e conclu??da em meados de 2009. O prop??sito foi de demonstrar a economia tribut??ria por meio da n??o tributa????o do imposto de renda da pessoa jur??dica e a contribui????o social sobre o lucro l??quido atrav??s da tributa????o do ganho de capital aos acionistas da empresa incorporada, trazer ?? luz da Teoria Cont??bil a quest??o da ess??ncia sobre a forma e evidenciar as diferentes formas de se contabilizar cada instituto.

Made available in DSpace on 2014-12-17T15:42:01Z (GMT). No. of bitstreams: 1 IedaNSM.pdf: 5948604 bytes, checksum: dbf245a349dd04cff535e8ba2e89601d (MD5) Previous issue date: 2007-07-06 / The aim of this work was to study a series of 11 different compositions of Ti-Zr binary alloys resistance to aggressive environment, i. e., their ability to keep their surface properties and mass when exposed to them as a way to evaluate their performance as biomaterials. The first stage was devoted to the fabrication of tablets from these alloys by Plasma-Skull casting method using a Discovery Plasma machine from EDG Equipamentos, Brazil. In a second stage, the chemical composition of each produced tablet was verified. In a third stage, the specimen were submitted to: as-cast microstructure analysis via optical and scanning electron microscopy (OM and SEM), x-ray dispersive system (EDS) chemical analysis via SEM, Vickers hardness tests for mechanical evaluation and corrosion resistence tests in a 0.9% NaCl solution to simulate exposition to human saliva monitored by open circuit potential and polarization curves. From the obtained results, it was possible to infer that specimens A1 (94,07 wt% Ti and 5,93% wt% Zr), A4 (77,81 wt % Ti and 22,19 wt % Zr) and A8 (27,83 wt% Ti and 72,17 wt% Zr), presented best performance regarding to corrosion resistance, homogeneity and hardness which are necessary issues for biomaterials to be applied as orthopedic and odontological prosthesis / Este trabalho teve como finalidade estudar uma s?rie de onze ligas met?licas bin?rias, tit?nio zirc?nio, quanto ? capacidade de resistirem ?s deteriora??es sem sofrerem modifica??es de suas propriedades iniciais de massa e superf?cie quando expostas a meios agressivos, como condi??o fundamental para que as mesmas sejam aplicadas como biomateriais. A primeira etapa tratou da confec??o das amostras das ligas em forma de pastilhas, empregando-se o processo de fundi??o Plasma Skull realizado na m?quina Discovery Plasma, produzida no Brasil pela EDG Equipamentos. Na segunda etapa, as amostras confeccionadas foram submetidas aos ensaios para a determina??o da composi??o qu?mica resultante de cada liga da s?rie ap?s a fus?o. E durante a terceira etapa foram feitos os procedimentos de avalia??es das amostras quanto ? homogeneidade e apresenta??o da microestrutura de cada uma das ligas no estado bruto de fus?o, como resultados dos ensaios metalogr?ficos por microscopia ?ptica e microscopia eletr?nica de varredura acoplada a espectroscopia por energia dispersiva de raios-x; quanto ? propriedade mec?nica de dureza medida em escala Vickers (HV); e quanto ?s propriedades qu?micas de resist?ncia ? corros?o, quando expostas em solu??o de cloreto de s?dio 0,9 %, para simular a saliva, empregando-se o monitoramento do potencial de circuito aberto e as curvas de polariza??o. A partir dos resultados obtidos foi poss?vel identificar as pastilhas de composi??es qu?micas A1 (94,07% de Ti e 5,93% de Zr), A4 (77,81% de Ti e 22,19% de Zr) e A8 (27,83% de Ti e 72,17% de Zr) que resultaram como maiores detentoras do conjunto de propriedades de resist?ncia ? corros?o, homogeneidade e dureza, as quais s?o mais necess?rias em biomateriais tipo pr?teses ortop?dicas ou odontol?gicas