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The bidirectional influence of parenchymal cells and cells of the immune system, especially of antigen-presenting and CD8\(^+\) T cells, in situations of putative auto- immune pathogenicity and degeneration was the main topic of this thesis. In the first part, the influence of human muscle cells on antigen-presenting cells was investigated. In inflammatory myopathies prominent infiltrates of immune cells containing T cells and antigen-presenting cells like macrophages and dendritic cells are present. The hypothesis was that human myoblasts have an inhibiting influence on these antigen-presenting cells under homeostatic conditions. A dysfunction or impairment under inflammatory circumstances might contribute to the development of myopathic conditions. The surface analysis of dendritic cells cocultured with myoblasts showed that immature dendritic cells could be driven into a reversible semi- mature state with significantly elevated levels of CD80. These dendritic cells were additionally characterized by their inhibiting function on T-cell proliferation. It was also shown that the lysates of healthy myoblasts could strongly enhance the phagocytic ability of macrophages, which could help with muscle regeneration and which might be disturbed in myositis patients. The second part of this thesis was about the clonal specificity of CD8\(^+\) T cells in a mouse model with genetically induced over-expression of PLP in oligodendrocytes. Here, we could show that the cytotoxic T lymphocytes, which had previously been shown to be pathogenic, were clonally expanded in the CNS of the transgenic mice. The amino acid sequences of the corresponding receptor chains were not identical, yet showed some similarities, which could mean that these clones recognize similar antigens (or epitopes of the same antigen). The knockout of PD-1 in this setting allowed for an analysis of the importance of tissue immune regulation. It became evident that the absence of PD-1 induced a larger number of clonal expansions in the CNS, hinting towards a reduced threshold for clonal disturbance and activation in these T cells. The expansions were, however, not pathogenic by themselves. Only in the presence of tissue damage and an antigenic stimulus (in our case the overexpression of PLP), the PD-1 limitation exacerbated the immune pathogenicity. Therefore, only in the presence of a “tissue damage signal”, the dyshomeostasis of T cells lacking PD-1 achieved high pathogenetic relevance. Finally, we investigated the pathogenetic role of CD8 T cells in Rasmussen encephalitis, a rare and chronic neurological disease mainly affecting children. The analysis of the T-cell receptor repertoire in Rasmussen encephalitis patients in the peripheral CD4\(^+\) and CD8\(^+\) T-cell compartments as well as the brain revealed the involvement of T cells in the pathogenicity of this disease. Many clonal expansions in the brain matched CD8\(^+\) T-cell expansions in the periphery on the sequence level. These putatively pathogenic clones could be visualized by immunohistochemistry in the brain and were found in close proximity to astrocytes and neurons. Additionally, the expanded clones could be found in the periphery of patients for at least one year. / Der Einfluss von Parenchymzellen auf Immunzellen und umgekehrt, im Besonderen von Antigen-präsentierenden Zellen und CD8\(^+\) T-Zellen, im Zusammenhang von auto- immuner Pathogenese und Degeneration war das Hauptthema dieser Dissertation. Im ersten Teil wurde der Einfluss menschlicher Muskelzellen auf Antigen- präsentierende Zellen untersucht. In entzündlichen Myopathien kommt es zu massiven Infiltraten von Immunzellen, die T-Zellen und auch Antigen-präsentierende Zellen wie Makrophagen und dendritische Zellen enthalten. Die Hypothese war, dass menschliche Myoblasten einen hemmenden Einfluss auf die Antigen-präsentierenden Zellen unter homöostatischen Bedingungen haben. Eine Störung dieses Einflusses oder eine Beeinträchtigung unter entzündlichen Rahmenbedingungen könnte eventuell zur Entwicklung eines myopathischen Zustands beitragen. In der Oberflächenanalyse der dendritischen Zellen, die mit Myoblasten kultiviert wurden, zeigte sich, dass unreife dendritische Zellen in einen halb-reifen Zustand versetzt werden konnten, der sich beispielsweise durch stark erhöhte CD80 Expression kennzeichnet. Diese dendritischen Zellen wurden weiterhin charakterisiert über ihre hemmende Funktion auf die T-Zell Proliferation. Außerdem wurde gezeigt, dass Zelllysate gesunder Myoblasten die Phagozytoserate von Makrophagen enorm verstärken, was die Regeneration des Muskelgewebes erhöhen und möglicherweise in Myositispatienten gestört sein könnte. Im zweiten Teil der Dissertation ging es um die klonale Spezifität von CD8\(^+\) T-Zellen in einem Mausmodell mit genetisch induzierter Überexpression von PLP in Oligodendrozyten. Hier konnte gezeigt werden, dass die zytotoxischen T-Zellen, deren Pathogenität Gegenstand früherer Arbeiten war, im ZNS der transgenen Mäuse klonal expandiert waren. Die Aminosäuresequenzen der TCRβ Kette der expandierten Klone waren nicht identisch, zeigten jedoch einige Ähnlichkeiten, die darauf hinweisen könnten, dass diese Klone ähnliche Antigene (oder Epitope des gleichen Antigens) erkennen. Die genetisch induzierte Abwesenheit von PD-1 ermöglichte es, in diesem Zusammenhang den Einfluss von spezifischer Immunregulation im Gewebe zu untersuchen. Es zeigte sich, dass die Deletion von PD-1 eine erhöhte Anzahl von klonalen Expansionen im ZNS der Mäuse erzeugte, was auf eine herabgesetzte Schwelle für klonale Störungen und Aktivierung schließen lässt. Diese Expansionen 
 waren jedoch für sich genommen nicht pathogen. Nur in der Anwesenheit eines Gewebeschadens und eines zusätzlicher Antigenstimulus (in unserem Fall in Form der PLP Überexpression) konnte man die erhöhte Pathogenität durch die PD-1 Deletion erkennen. Deswegen erreichten die PD-1 deletierten T-Zellen nur in der Gegenwart eines „Gewebeschaden-Signals“ hohe pathogenetische Relevanz. Schließlich untersuchten wir die pathogenetische Rolle von CD8\(^+\) T-Zellen in der Rasmussen Enzephalitis, einer seltenen, chronischen Erkrankung des Gehirns, die hauptsächlich in Kindern vorkommt. Die Analyse des T-Zell-Rezeptor Repertoires in Rasmussen Enzephalitis Patienten in peripheren CD4\(^+\) und CD8\(^+\) T-Zell Populationen und im Gehirn zeigte die Beteiligung von T-Zellen in der Pathogenese dieser Krankheit auf. Viele klonale Expansionen waren zwischen Gehirn und der peripheren CD8\(^+\) Population bis hin zur Aminosäuresequenz identisch. Diese vermutlich pathogenen Klone konnten in Gehirnbiopsien von Rasmussenpatienten histochemisch nachgewiesen werden und wurden in enger Nachbarschaft zu Astrozyten und Neuronen gefunden. Zusätzlich konnten diese expandierten Kone in der Peripherie von Patienten für die beobachteten Zeiträume (mindestens ein Jahr) nachgewiesen werden.

Würzburg, Univ., Diss., 2009. / Zsfassung in dt. Sprache.

Submitted by Marco Antônio de Ramos Chagas (mchagas@ufv.br) on 2016-11-17T14:37:39Z No. of bitstreams: 1 texto completo.pdf: 635324 bytes, checksum: 44b8b4d255b4364f077baa4e3c3565ab (MD5) / Made available in DSpace on 2016-11-17T14:37:39Z (GMT). No. of bitstreams: 1 texto completo.pdf: 635324 bytes, checksum: 44b8b4d255b4364f077baa4e3c3565ab (MD5) Previous issue date: 2005-12-06 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Objetivou-se, neste trabalho, analisar os setores de produção e de processamento de café na estrutura econômica de Minas Gerais, determinando a importância destes e seus encadeamentos na estrutura do Estado. O referencial teórico utilizado foi o modelo insumo-produto, bem como o de desenvolvimento regional. Foram calculados os índices de Rasmussen-Hirschaman, o campo de influência, os índices puros de ligações e 03 multiplicadores de produção, renda e emprego. Para tanto, utilizou-se a matriz regional de insumo-produto de 1995, para Minas Gerais. Os resultados decorrentes desta análise permitem caracterizar a estrutura produtiva de Minas Gerais, os seus setores-chave e o efeito multiplicador de cada setor econômico em termos de produção, renda e emprego. De acordo com os resultados, os setores considerados como chaves pelas abordagens adotadas (índice de Rasmussen-Hirschman e índice puro de ligação) e que apresentaram grande campo de influência foram: (4) Produtos não metálicos, siderurgia e metalurgia, (5) Mecânica, material elétrico e material de transportes e (10) Outras lndustrias de Produtos Alimentares. Quando se consideram apenas o índice de Rasmussen-Hirschman e o campo de influência, inclui-se entre os setores-chave o setor (1) Café em coco, (6) Produtos de madeira, papel, borracha e plástico e (9) Indústria do café. Com relação a análise dos multiplicadores, observou-se que os setores: (4) Produtos não metálicos, siderurgia e metalurgia, (9) Indústria do Café e (10) Outras Indústrias de Produtos Alimentares foram os que apresentaram os maiores valores em termos de geração de produto; os setores (13) Comércio, (2) Agropecuária e (3) Café em coco, em termos de geração de renda; e 03 setores (16) Serviços, (1) Café em coco e (2) Agropecuária em termos de geração de emprego. Por meio desses resultados, pode-se inferir que a indústria de café apresenta fortes Iigações para trás; já o setor de produção de café é importante em termos de encadeamentos para trás e para frente. O setor de produção do café também apresentou poder de contribuir para a geração de renda e emprego na economia mineira e a indústria de café, para a geração de produto. Em face dos resultados, conclui-se que políticas que incentivam o aumento no consumo de café podem, de maneira indireta, produzir o crescimento no próprio setor e nos outros setores da economia. Tendo em vista que a indústria de café torrado e moido tem capacidade para crescer e modernizar-se para ampliar a sua competitividade, é também um setor com potencial para receber investimentos. / The objective of this work was to analyze the coffee production and processing sectors in Minas Gerais’s economic structure, determining their importance and linkages in the structure of the State. The theoretical referential used in this research were the input-output model and the regional development. The indexes Rasmussen-Hirschman, fields of influence, pure linkages and production, income and employment multipliers were calculated using the regional input-output matrix of Minas Gerais for the year 1995. The analysis results allowed the characterization of Minas Gerais’ productive structure, its key-sectors and the multiplying effect of each economic sector in terms of production, income and employment. According to the results, the sectors that were considered keys by the used approaches (Rasmussen-Hirschman and pure linkage indexes) and presented great field of influence, were: (4) non-metallic products, siderurgy and metallurgy, (5) mechanical, electric material, and transport material and (10) other industries of food products. When only the indexes Rasmussen-Hirschman and field of influence were considered, the key-sectors (1) coffee bean, (6) wooden, paper, rubber and plastic products and (9) coffee industry were included. In relation to the multiplier analysis, the sectors (4) non-metallic products, siderurgy and metallurgy, (9) coffee industry and (10) other industries of food products gave the highest values for product generation; the sectors (13) commerce, (2) farming and (3) coffee beans for income generation; and the sectors (16) services, (1) coffee beans and (2) farming for employment generation. Through these results one can infer that the coffee industry has strong backward linkages; however the coffee production sector is important in terms of backward and fonNard linkages. The sector of coffee production also showed capacity to contribute to income and employment generation in the State’s economy, and the coffee industry for product generation. In agreement with results, the work concluded that politics that stimulate the increase of the coffee consumption can, in indirect way, result in the growth in all sectors of the economy. The coffee processing industry is a potential sector to receive investments because it has the capacity to grow and to modernize, increasing its competitiveness. / Dissertação importada do Alexandria

Rasmussen's encephalitis is a rare neurological disease first described in 1958 that is characterized by medico-refractory seizures, focal unilateral cerebral inflammation, and deficits such as hemiparesis. While we still do not have a full understanding of this disease, proposed theories behind its etiology include auto-immune manifestations, immune attack by T cells, and malfunctional alterations in genetic expression. It is classically considered a rare childhood malady with a median age of onset of six years, and cases in adolescents and adults are even rarer, representing up to 10% of all cases to date. In this report, we would like to share a rare case of Rasmussen's encephalitis that occurred in an adolescent. Our 17-year-old male patient presented with signs and symptoms beginning at age 14 and was initially diagnosed with cerebral palsy only to later present with additional symptoms and characteristic EEG and MRI findings that ultimately led to a diagnosis of Rasmussen's encephalitis. Thus, with this case report, our intent is twofold: to shed light on an atypical presentation of an already rare disease, even rarer in adolescents and adults, and to underscore the importance of keeping a broad differential when it comes to evaluating a patient with seizures.

INTRODUÇÃO: A encefalite de Rasmussen (ER) é uma doença rara e esporádica, apresentando-se como uma síndrome com disfunção cerebral multifocal e convulsões focais refratárias ao tratamento medicamentoso, por vezes se manifestando com epilepsia parcial contínua. O início das crises focais predomina na infância e afeta crianças previamente hígidas, com curso progressivo. Na maioria das vezes envolve apenas um hemisfério cerebral, que se torna atrófico. O diagnóstico é feito através da análise do eletroencefalograma, características clínicas, achados de ressonância magnética (RM) e/ou achados histopatológicos. A RM encefálica é particularmente útil no estudo destes doentes, fornecendo dados que podem contribuir para o diagnóstico, ajudar na seleção do local para biópsia, assim como no acompanhamento da evolução progressiva da doença. MATERIAIS E MÉTODOS: Foram coletados os dados demográficos, avaliações neuropsicológicas, dados cirúrgicos e achados de imagem de todos os pacientes diagnosticados com ER no HCFMRP, de 1997-2016. RESULTADOS: Foram incluídos 35 pacientes com média de idade de 5,8 anos. Setenta por cento destes apresentaram-se com epilepsia parcial contínua e 29 tiveram também a confirmação histopatológica. Não houve nenhum caso de acometimento bilateral confirmado nesta amostra. Os achados de imagem mais comuns foram alteração de sinal, atrofia focal ou hemisférica e dilatação ventricular, em graus variados. Trinta e três pacientes foram submetidos ao tratamento cirúrgico. CONCLUSÕES: A definição da conduta e tratamento dos pacientes com ER deve ser discutida por equipe multidisciplinar, levando em consideração os achados clínicos, EEG e de exames de imagem, com objetivo de controlar as crises a fim de minimizar os déficits cognitivos, motores e de linguagem destes pacientes. / INTRODUCTION: Rasmussen encephalitis (RE) is a rare and sporadic disease, presenting as a multifocal brain dysfunction and focal seizures, refractory to drug treatment, sometimes manifesting with continuous partial epilepsy. The onset of seizures predominates in childhood, and affects previously healthy children with progressive course. Most often involves one cerebral hemisphere, which becomes atrophic. Diagnosis is made through EEG analysis, clinical, magnetic resonance imaging (MRI) findings and/or histopathological findings. Brain MRI is particularly useful, and provides data that can contribute to the diagnosis, help in site selection for biopsy, as well as in monitoring the progressive course of the disease. MATERIALS AND METHODS: We collected demographic data, neuropsychological evaluations, surgical and imaging findings of all patients diagnosed with RE in HCFMRP, from 1997-2016. RESULTS: It included 35 patients with a mean age of 5.8 years. Seventy percent of these presented with continuous partial epilepsy and 29 also had histopathologic confirmation. There were no cases of confirmed bilateral involvement in this sample. The most common imaging findings were signal change , focal or hemispheric atrophy and ventricular dilatation , in varying degrees. Thirtythree patients underwent surgical treatment. CONCLUSIONS: The definition of management and treatment of patients with ER should be discussed by a multidisciplinary team, taking into account the clinical, EEG and imaging findings, in order to control seizures and minimize cognitive, motor and language deficits of these patients.

INTRODUÇÃO: A encefalite de Rasmussen (ER) é uma doença rara e esporádica, apresentando-se como uma síndrome com disfunção cerebral multifocal e convulsões focais refratárias ao tratamento medicamentoso, por vezes se manifestando com epilepsia parcial contínua. O início das crises focais predomina na infância e afeta crianças previamente hígidas, com curso progressivo. Na maioria das vezes envolve apenas um hemisfério cerebral, que se torna atrófico. O diagnóstico é feito através da análise do eletroencefalograma, características clínicas, achados de ressonância magnética (RM) e/ou achados histopatológicos. A RM encefálica é particularmente útil no estudo destes doentes, fornecendo dados que podem contribuir para o diagnóstico, ajudar na seleção do local para biópsia, assim como no acompanhamento da evolução progressiva da doença. MATERIAIS E MÉTODOS: Foram coletados os dados demográficos, avaliações neuropsicológicas, dados cirúrgicos e achados de imagem de todos os pacientes diagnosticados com ER no HCFMRP, de 1997-2016. RESULTADOS: Foram incluídos 35 pacientes com média de idade de 5,8 anos. Setenta por cento destes apresentaram-se com epilepsia parcial contínua e 29 tiveram também a confirmação histopatológica. Não houve nenhum caso de acometimento bilateral confirmado nesta amostra. Os achados de imagem mais comuns foram alteração de sinal, atrofia focal ou hemisférica e dilatação ventricular, em graus variados. Trinta e três pacientes foram submetidos ao tratamento cirúrgico. CONCLUSÕES: A definição da conduta e tratamento dos pacientes com ER deve ser discutida por equipe multidisciplinar, levando em consideração os achados clínicos, EEG e de exames de imagem, com objetivo de controlar as crises a fim de minimizar os déficits cognitivos, motores e de linguagem destes pacientes. / INTRODUCTION: Rasmussen encephalitis (RE) is a rare and sporadic disease, presenting as a multifocal brain dysfunction and focal seizures, refractory to drug treatment, sometimes manifesting with continuous partial epilepsy. The onset of seizures predominates in childhood, and affects previously healthy children with progressive course. Most often involves one cerebral hemisphere, which becomes atrophic. Diagnosis is made through EEG analysis, clinical, magnetic resonance imaging (MRI) findings and/or histopathological findings. Brain MRI is particularly useful, and provides data that can contribute to the diagnosis, help in site selection for biopsy, as well as in monitoring the progressive course of the disease. MATERIALS AND METHODS: We collected demographic data, neuropsychological evaluations, surgical and imaging findings of all patients diagnosed with RE in HCFMRP, from 1997-2016. RESULTS: It included 35 patients with a mean age of 5.8 years. Seventy percent of these presented with continuous partial epilepsy and 29 also had histopathologic confirmation. There were no cases of confirmed bilateral involvement in this sample. The most common imaging findings were signal change , focal or hemispheric atrophy and ventricular dilatation , in varying degrees. Thirtythree patients underwent surgical treatment. CONCLUSIONS: The definition of management and treatment of patients with ER should be discussed by a multidisciplinary team, taking into account the clinical, EEG and imaging findings, in order to control seizures and minimize cognitive, motor and language deficits of these patients.

The main purpose of this Bachelor´s thesis is to investigate the visions chief librarians have for their public libraries. The world around us and our way of living is changing as the society is changing ever more rapidly. This evolvement also influences the public library, its role for society and individuals, its activities and its design. The question is how the public library can face these changes and what function and role it can get and make for itself in the future. Through qualitative interviews with five chief librarians our aim is to answer the main question of this thesis: What are the visions that chief librarians on public libraries have for the public library´s future? This study also contain the role the chief librarians give the public library of today and what they mean is necessary for their visions to be achieved. Our theoretical choice fell upon Hvenegaard Rasmussen, Jochumsen and Skot-Hansens at this time new scientific model that reflect the library in relation to the concepts place, relations and space. The results showed that the chief librarians have a lot of visions. They’re not particularly revolutionary but more like a further development of the activities and role of the public library of today. The library must continue to be a meeting-place, a common ground for democracy and a central place in the local society with wide ranging activities for all citizens. Greater collaboration and integration plus being a creative platform for the users are also part of their visions. / Program: Bibliotekarie

The aim of this Master thesis is to describe why and how public librariesuse the social networks Facebook and Twitter. The focus is to study whatbrought about their use, how the work is carried out, ideas and objectivesbehind the use and what libraries actually convey on the networks. Themethodology is twofold: semi-structured interviews with responsiblepersonnel at four Swedish public libraries, and an ethnographic contentanalysis of four months of the libraries' status updates and tweets onFacebook and Twitter. The theoretical framework consists of a model forthe roles of the public library in society, and of discourses about thepublic library in media.Results indicate that social networks are used to market, make accessibleand inform of the library's resources and services. Furthermore, networksare used to communicate/interact with followers and to inspire people toread. We also detect a tutoring trait. Libraries also view social networksas a meeting place. What libraries do on the networks can be seen as anonline interpretation of traditional library goals. All four spaces from themodel for the new library – Inspiration, Learning, Meeting andPerformative – were represented in the objectives expressed in theinterviews. In what is conveyed on the networks focus lay on Inspirationand Meeting. Social networks also act as a place to market the physicallibrary. From a discourse perspective the study suggests that librariesexpress disidentification and demonstrate ability to remain open both todifferent media formats and different methods for library servicesdelivery. / Program: Bibliotekarie

Knowledge of a species habitat-use patterns, as well as an understanding of the distribution and spatial arrangement of preferred habitat, is essential for developing comprehensive management or conservation plans. This information is absent for many species, especially so for those living or breeding in remote areas. Habitat-use models can assist in delineating specific habitat requirements or preferences of a species. When coupled with geographic information system (GIS) technology, such models are now frequently used to identify important habitats and to better define species distributions.<p> Recent and persistent warming, widespread contaminant accumulation, and intensifying land use in the arctic heighten the urgent need for better information about spatial distributions and key habitats for northern wildlife. Here, I used aerial survey and corresponding digital land cover data to investigate breeding-ground distributions and landscape-level habitat associations of greater white-fronted geese (Anser albifrons frontalis), small Canada geese (Branta canadensis hutchinsii), tundra swans (Cygnus columbianus), king eiders (Somateria spectabilis), and long-tailed ducks (Clangula hyemalis) in the Queen Maud Gulf Migratory Bird Sanctuary and the Rasmussen Lowlands, Nunavut, Canada.<p> First, I addressed the sensitivity of inferences about predicting waterfowl presence on the basis of the amounts and configurations of arctic habitat sampled at four scales. Detection and direction of relationships of focal species with land cover covariates often varied when land cover data were analysed at different scales. For instance, patterns of habitat use for a given species at one spatial scale may not necessarily be predicted from patterns arising from measurements taken at other scales. Thus, inference based on species-habitat patterns from some scales may lead to inaccurate depictions of how habitat influences species. Potential variation in species-environment relationships relative to spatial scale needs to be acknowledged by wildlife managers to avoid inappropriate management decisions.<p> Second, I used bird presence determined during aerial surveys and classified satellite imagery to develop species-habitat models for describing breeding-ground distributions and habitat associations of each focal species. Logistic regression models identified lowland land cover types to be particularly important for the species considered. I used the Receiver Operating Characteristic (ROC) technique and the area under the curve (AUC) metric to evaluate the precision of models, where the AUC is equal to the probability that two randomly selected encounter and non-encounter survey segments will be discriminated as such by the model. In the Queen Maud Gulf, AUC values indicated reasonable model discrimination for white-fronted geese, Canada geese, and tundra swans (i.e, AUC > 0.7). Precision of species-habitat models for king eiders and long-tailed ducks was lower than other species considered, but predict encounters and non-encounters significantly better than the null model. For all species, precision of species-habitat models was lower in the Rasmussen Lowlands than in the Queen Maud Gulf, although discrimination ability remained significantly better than the null model for three of five species (king eider and long-tailed duck models performed no better than the null model here).<p> Finally, I simulated anticipated environmental change (i.e., climate warming) in the arctic by applying species-habitat models to manipulated land cover data, and then predicted distributional responses of focal species. All species considered in this research exhibited some association to lowland cover types; white-fronted geese, Canada geese, and tundra swans in particular demonstrated strong affinity toward these habitats. Others authors predict lowland cover types to be most affected by warming. Reductions of wet sedge, hummock, and tussock graminoid cover predicted in this simulation, predominantly along the coast of the Queen Maud Gulf study area and in central areas of the Rasmussen Lowlands, suggest that distributions of species dependant on these lowland habitats will be significantly reduced, if predictions about warming and habitat loss prove to be correct. Research presented here provides evidence that modeling of species distributions using landscape-level habitat data is a tractable method to identify habitat associations, to determine key habitats and regions, and to forecast species responses to environmental changes.