11 resultados para NK-landscapes
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This article argues that the study of literary representations of landscapes can be aided and enriched by the application of digital geographic technologies. As an example, the article focuses on the methods and preliminary findings of LITESCAPE.PT—Atlas of Literary Landscapes of Mainland Portugal, an on-going project that aims to study literary representations of mainland Portugal and to explore their connections with social and environmental realities both in the past and in the present. LITESCAPE.PT integrates traditional reading practices and ‘distant reading’ approaches, along with collaborative work, relational databases, and geographic information systems (GIS) in order to classify and analyse excerpts from 350 works of Portuguese literature according to a set of ecological, socioeconomic, temporal and cultural themes. As we argue herein this combination of qualitative and quantitative methods—itself a response to the difficulty of obtaining external funding—can lead to (a) increased productivity, (b) the pursuit of new research goals, and (c) the creation of new knowledge about natural and cultural history. As proof of concept, the article presents two initial outcomes of the LITESCAPE.PT project: a case study documenting the evolving literary geography of Lisbon and a case study exploring the representation of wolves in Portuguese literature.
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RESUMO A Esclerose Múltipla (EM) é uma doença desmielinizante crónica do Sistema Nervoso Central (SNC), provocada, em grande parte, por um ataque imuno-mediado contra diversos elementos da bainha de mielina. Dentro dos alvos antigénicos desta resposta autoimune, vários componentes proteicos e lipídicos da mielina têm vindo a ser identificados ao longo dos anos, entre os quais se destacam a proteína básica de mielina(MBP), glicoproteína ligodendrocitária da mielina (MOG), proteína proteolipídica (PLP) e glicoproteína associada à mielina (MAG). Com o desenvolvimento do modelo animal de Encefalomielite Autoimune Experimental (EAE), diversas terapias antigénio-específicas foram desenhadas, baseadas na modificação benéfica da resposta autoimune contra a mielina, tais como a administração de mielina ou seus componentes, os copolímeros terapêuticos, os ligandos peptídeos alterados e, recentemente, a vacinação com ácido desoxirribonucleico (ADN) codificador de proteínas de mielina, integrado em plasmídeos e purificado para administração parentérica. Neste trabalho, apresentamos os resultados de um extenso conjunto de experiências, subordinadas a dois temas fundamentais: 1) avaliação do potencial terapêutico, e dos mecanismos de acção, da vacinação tolerizadora com ADN codificador de proteínas de mielina (MBP, MOG, PLP, MAG) na EAE, e da associação desta vacinação com a administração de ADN de citocinas Th2, ou de oligonucleótidos imunomoduladores; 2) identificação e caracterização da resposta imune contra um novo componente da mielina com potencial antigénico, a proteína inibidora do recrescimento axonal, Nogo-A. No que respeita à vacinação com ADN, os nossos resultados comprovam a eficácia desta terapêutica antigénio-específica na prevenção e tratamento da EAE. Os seus mecanismos de acção incluem, entre outros, a supressão anérgica da proliferação antigénioespecífica dos linfócitos T anti-mielina (no modo de prevenção da doença), o enviesamento Th2 da resposta imune (quando co-administrada com a vacina de ADN codificadora da citocina IL-4, funcionando como terapia génica local), e a redução da diversificação de epítopos da resposta humoral anti-mielina, avaliada através de myelin spotted arrays. A associação das vacinas de ADN com oligonucleótidos imunomoduladores GpG, desenvolvidos para contrariar as sequências CpG imunoestimuladoras presentes no vector de vacinação, levou à melhoria da sua eficácia terapêutica, devida, provavelmente, ao efeito estimulador preferencial dos oligonucleótidos GpG sobre linfócitos Th2 e sobre células reguladoras NK-T. Com base nestes resultados a vacinação com ADN foi desenvolvida para o tratamento da EM em humanos, com ensaios clínicos a decorrerem neste momento. Em relação à proteína Nogo-A, estudos de estrutura primária e de previsão de antigenicidade identificaram a região Nogo-66 como alvo antigénico potencial para a EAE. Nas estirpes de ratinho SJL/J e C57BL/6, fomos capazes de induzir sinais clínicos e histológicos de EAE após imunização com os epítopos encefalitogénicos Nogo1-22, Nogo23- 44 e Nogo45-66, utilizando protocolos de quebra de tolerância imune. Ao mesmo tempo, identificámos e caracterizámos uma resposta linfocitária T específica contra os antigénios contidos na região Nogo-66, e uma resposta linfocitária B com diversificação intra e intermolecular a vários determinantes presentes noutras proteínas da mielina. A transferência adoptiva de linhas celulares Th2 anti-Nogo45-66, levou à melhoria clínica e histológica da EAE em animais recipientes induzidos com outros antigénios de mielina, após migração destas células para o SNC. Estes dados comprovam a importância da Nogo-66 como antigénio na EAE, e a eficácia de terapias antigénio-específicas nela baseadas. No seu conjunto, os nossos resultados confirmam o potencial terapêutico das vacinas de ADN codificadoras de proteínas de mielina, bem como a importância dos encefalitogénios contidos na proteína Nogo-A para a fisiopatologia da EAE e da EM, com eventual relevância para o desenvolvimento de novas terapias antigénio-específicas. O aperfeiçoamento futuro destas terapias poderá levar, eventualmente, a uma capacidade de manipulação da resposta imune que permita o tratamento eficaz das doenças inflamatórias desmielinizantes, como a Esclerose Múltipla. ABSTRACT Multiple Sclerosis (MS) is a chronic demyelinating disease of the Central Nervous System (CNS), caused, mainly, by an immune-mediated attack against several elements of the myelin sheath. Among the antigenic targets for this autoimmune response, several proteic and lipidic myelin components have been identified throughout the years, of which myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), proteolipidic protein (PLP), and myelin associated glycoprotein (MAG) are the best characterized. With the development of the animal model for MS, Experimental Autoimmune Encephalomyelitis (EAE), several antigen-specific therapies have been designed, based on beneficial modifications of the autoimmune response against myelin. These have included myelin and myelin component administration, therapeutic copolymers, altered peptide ligands and, more recently, vaccination with myelin-protein encoding deoxyribonucleic acid (DNA), integrated into plasmids and purified for parenteral administration. In this work we present the results of an extensive series of experiments, subordinate to two fundamental areas: 1) evaluating the therapeutic potential, and mechanisms of action, of tolerizing myelin protein (MBP, MOG, PLP, MAG) DNA vaccination in EAE, alone and in association with Th2 cytokine DNA administration, or immunomodulatory oligonucleotides; 2) identifying and characterizing the immuneresponse against a new myelin component with antigenic potential, the axonal regrowth inhibitor Nogo-A. Regarding DNA vaccination, our results prove the efficacy of this antigen-specific therapy for the prevention and treatment of EAE. Its mechanisms of action include, among others, anergic suppression of antigen-specific T-cell proliferation against myelin (in prevention mode), Th2 biasing of the immune response (when co-administered with the IL- 4 codifying DNA vaccine, acting as local gene therapy), and reduction of epitope spreading of the anti-myelin antibody response, assessed by myelin spotted arrays. The combination of myelin DNA vaccination with the administration of GpG immunomodulatory oligonucleotides, designed to counteract immunostimulatory CpG motifs present in the vaccination vector, led to an improvement in therapeutic efficacy, probably due to the preferential stimulatory effect of GpG oligonucleotides on Th2 lymphocytes and on regulatory NK-T cells. Based on these results, tolerizing DNA vaccination is being developed for human use, with ongoing clinical trials. As concerns the Nogo-A protein, based on studies of primary structure and prediction of antigenicity, we identified the Nogo-66 region (responsible for the most of the inhibitory capacity of this protein) as a potential antigenic target for EAE. In the SJL/Jand C57BL/6 mouse strains, we were able to induce clinical and histological signs of EAE,after immunization with the encefalitogenic epitopes Nogo1-22, Nogo23-44 and Nogo45-66,using a tolerance breakdown protocol. Concomitantly, we identified and characterized a specific T cell response against these antigens, together with a B cell response which showed extensive intra and intermolecular epitope spread to several determinants present in other myelin proteins. Adoptive transfer of nti-Nogo45-66 Th2 cell lines resulted in clinical and histological improvement of EAE in recipient animals induced with other myelin antigens, after intraparenchymal CNS migration of anti-Nogo cells. These data confirm the relevance of Nogo-66 as an antigen in EAE, as well as the efficacy of antigenspecific therapies based on the response against this protein.In conclusion, our results substantiate the therapeutic potential of myelin-encoding DNA vaccination, as well as the importance of encefalitogenic epitopes present in the Nogo-A protein for the pathophysiology of EAE and MS, with potential relevance for the creation of new antigen specific-therapies. The future development of these therapies may eventually lead to a degree of manipulation of the immune response that allows the effective treatment of autoimmune, inflammatory, demyelinating diseases, such as Multiple Sclerosis.
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Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies.
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Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.
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Sabbatical Studies Report
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A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics
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Os espaços públicos das cidades, sobretudo os daquelas para onde converge o turismo mundial, são sujeitos a múltiplos mecanismos de representação que os fragmentam e, em última análise, os reduzem a imagens idealizadas. Os autores dessas imagens, e dos seus sentidos, são muito diversificados, mas os profissionais ligados ao turismo (agências de viagem, revistas turísticas, documentaristas, etc.) e as instâncias públicas interessadas na divulgação turística das cidades (câmaras municipais, governos regionais, etc.) são, sem dúvida, duas das instâncias que mais operam no interior desses processos complexos de representação (e de mercadorização) do espaço das cidades. E se esses processos se associam hoje à relação feliz que milhões de pessoas estabelecem com as cidades no mundo inteiro, é no entanto necessário não esquecer que parte dessas paisagens são cuidadosamente construídas de forma, por um lado, a obliterar a lamentável realidade do urbanismo envolvente e, por outro, a delas excluir todos aqueles que inviabilizam a dinâmica cultural de construção de paisagens. We consider that the public spaces of cities, especially those which converge to the global tourism, are subject to multiple mechanisms of representation that fragment and, ultimately, reduce its idealized images. The authors of these images, and their senses are very diverse, but the professionals linked to tourism (travel agencies, tourist magazines, documentaries, etc.) and the government stakeholders interested in the dissemination of tourist cities (municipalities, regional governments, etc.) are undoubtedly two of the actors that operate within these more complex processes of representation of all urban space. And if these processes are associated today with the happy relationship that millions of people have with cities worldwide, it is however necessary not to forget that part of these landscapes are carefully constructed in a way, on one hand, to obliterate the unfortunate reality of the urban environment and, secondly, to delete all those that prevent the construction of dynamic cultural landscapes.
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Tese apresentada para cumprimento dos requisitos necessários à obtenção do grau de Doutor em Geografia e Planeamento Territorial - Especialidade: Geografia Humana
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In a world that has moved away from narratives based on the idea of progress, the past has established itself as a place of reference: confirming to ourselves that what we were is indispensible for sustaining what we think we are. The recovery of the past is thus one of the most common symbolic instruments used in negotiating identities. The cultural practices that have recourse to representation mechanisms that call on the past in order to consider the present always end up translating themselves, insofar as they fragment, reorganize and interpret it in their transformation, or, to use a formula that has become unavoidable, in their “invention”. Patrimonialization is one such practice. It associates the notion of heritage – which is not a given fact, but rather a socially constructed classification, and therefore one that is constantly being negotiated – with specific objects that come to serve as cultural representations of the groups who consider themselves to be their rightful owners. In the Lisbon Metropolitan Area, as in other ethnographic contexts, patrimonialization encompasses things as diverse as landscapes, monuments, popular architecture, handicrafts, local feast days/processions/pilgrimages and people; all things that can, once transformed into material representations of the past, serve as arguments for the identity fictions of the people who inhabit them.
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Due to the global acceptance of the reality of global warming, ever more countries are in the process of implementing alternative energies such as wind power. In this article, we focus on the transformation of space as a consequence of these newly established alternative energy policies. Landscapes are the level at which political visions and policy decisions endorse (or not) their very materiality. We analyze the deployment of wind power in three European countries, France, Germany and Portugal through the lens of ethnographic landscape studies. We argue that the successful implementation of low carbon futures is highly dependent on the respective national cultures of administration as well as on local practices, initiatives and perceptions of space at the local level. In each of the countries under scrutiny, we analyze the way in which wind power and landscape issues are framed, we point at potential tensions and explore how these are overcome (or not) at the local level so as to give way for the emergence of (new) wind power landscapes. We compare the role played by landscape cultures, institutions or practices in the development and resolution of tensions over the deployment of wind energy.
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Contém resumo