Th. 3e cycle--Math. pures--Grenoble 1, 1982. N°: 5.

Les persones amb discapacitat intel·lectual no practiquen els nivells suficients d’activitat física per que aquesta impliqui una millora de la seva qualitat de vida. Estudiar la relació entre ambdós constructes és clau per afavorir-la en cas de que no es doni. L’objectiu d’aquesta tesi és, per tant, identificar quin impacte produeix la pràctica d’activitat física en la qualitat de vida de persones amb discapacitat intel·lectual avaluant cadascuna de les vuit dimensions que la defineixen segons el criteri internacionalment acceptat. Per a fer-ho s’han validat dos instruments per avaluar, per una banda, la qualitat de vida en termes de resultats personals i, per l’altra, les necessitats i estratègies de suport en l’àmbit de l’activitat física. El primer instrument l’hem obtingut de la traducció i adaptació de la Personal Outcomes Scale i el segon s’ha elaborat ex-novo degut que en la bibliografia consultada no disposàvem de cap eina que s’ajustés a la nostra finalitat. La mostra ha estat formada per persones adultes amb discapacitat intel·lectual (n=529), els seus professionals de referència (n=522) i un membre de la família (n= 462). A tots ells se’ls va administrar els dos instruments per entrevistadors prèviament formats. A partir de les dades obtingudes en cada instruments s’han examinat tant la fiabilitat i la validesa; i posteriorment s’han estimat els paràmetres estructurals que ens han permès confirmar que l’activitat física té un impacte significatiu en la millora de la qualitat de vida de les persones amb discapacitat intel·lectual. Cadascuna de les fases realitzades i els resultats corresponents obtinguts han donat lloc als quatre articles que es presenten en aquesta tesi. / Las personas con discapacidad intelectual no practican suficiente actividad física para que ello represente una mejora de su calidad de vida. Estudiar la relación entre ambos constructos es clave para favorecerla en caso de que no se dé. El objetivo de esta tesis es, por tanto, identificar qué impacto produce la práctica de actividad física en la calidad de vida de personas con discapacidad intelectual evaluando cada una de las ocho dimensiones que la definen según el criterio internacionalmente aceptado. Para ello se validaron dos instrumentos para evaluar, por una parte, la calidad de vida en términos de resultados personales y, por otra, las necesidades y estrategias de ayuda en el ámbito de la actividad física. El primer instrumento se obtuvo a partir de la traducción y adaptación de la Personal Outcome Scale y el segundo se elaboró ex-novo debido que en la bibliografía consultada no se dispuso de ninguna prueba que se ajustara a nuestra finalidad. La muestra estuvo compuesta por personas adultas con discapacidad intelectual (n=529), sus profesionales de referencia (n=522) y un miembro de la familia (n=462). A todos ellos se les administró los dos instrumentos mediante entrevistadores previamente formados. A partir de los datos obtenidos en cada instrumento se examinaron tanto la fiabilidad como la validez y, posteriormente se estimaron los parámetros estructurales que nos ha permitido confirmar que la actividad física tiene un impacto significativo en la mejora de la calidad de vida en las personas con discapacidad intelectual. Cada una de las fases realizadas y resultados correspondientes ha dado lugar a los cuatro trabajos que se presentan en esta tesis. / People with intellectual disabilities do not get enough physical activity so that it represents an improvement in their quality of life. To study the relationship between both constructs is important to favor it if you do not give. The aim of this thesis is therefore to identify what impact does the practice of physical activity on the quality of life of people with intellectual disabilities evaluating each of the eight dimensions that define it according to internationally accepted criteria. For this, two questionnaires for assessing, on the one hand, the quality of life in terms of personal outcomes and, on the other, needs and assistance strategies in the area of physical activity were validated. The first instrument was obtained from the translation and adaptation of the Personal Outcome Scale and the second was drawn up ex-novo because in the literature were not available no evidence that suited our purpose. The sample consisted of adults with intellectual disability (n = 529), their professional reference (n = 522) and a member of the family (n = 462). All of them were given the two instruments by interviewers previously trained. From the data obtained in each instrument both reliability and validity were examined, then the structural parameters estimation enabled us to confirm that physical activity has a significant impact on improving the quality of life in people with estimated intellectual disability. Each of the phases made and corresponding results has led to the four works presented in this thesis.

La resistencia a la minería no es una novedad y sin embargo, la extracción de recursos se ha ido expandiendo material y geográficamente durante los últimos 150 años, llegando a nuevas fronteras, moviendo cantidades más grandes de tierra y agua e impactando a más comunidades. Las resistencias que han surgido contribuyen cada vez más a la forma de la frontera de extracción siendo a su vez un factor importante en la política económica de la expansión minera. Así pues, es cada vez más crucial entender porque surge resistencia social a la minería y como está evolucionando. Esta tesis focaliza la atención en el uranio, la fuente de la energía nuclear, estudiando las dinámicas industriales de la minería de uranio, los impactos e implicaciones a la salud, y la resistencia en la frontera de extracción del uranio en África. Namibia y Níger, los principales productores de uranio en África, están a la cabeza de lo que ha sido una fuerte demanda global de uranio parcialmente ralentizada por el accidente Tepco-Fukushima. Esta tesis propone tres factores que pueden ayudar a explicar el surgimiento e intensidad de la resistencia de comunidades locales a la minería de uranio: la ecología y la geografía del recurso, el grado y tipo de marginalización política y económica de la comunidad, y crucialmente, la creación de alianzas externas que conecten e integren las inquietudes locales con movimientos sociales más amplios y demandas globales. Muestro como estos tres elementos juegan un papel diferente en cinco comunidades en Namibia que están o estarán afectadas por la minería de uranio, y explico como las ecologías locales de resistencia dan forman, o no, a la frontera global del uranio. Los casos presentados tratan sobre radiación de bajo nivel causada por la minería de uranio que afecta la salud de los trabajadores y la de las comunidades cercanas a la mina. Con personas impactadas reclamando relaciones causales que no están probadas científicamente, el peso de probar su impacto queda relegado a las comunidades. A través de contactos, grupos de organización de base en Níger y Namibia están aliándose con científicos y produciendo nuevo conocimiento para protegerse de los impactos de la minería y confrontar la manufacturación de incertidumbre producida por las compañías mineras. Impulsado localmente, este proceso de ‘Activismo Movilizando Ciencia’ (AMS en inglés) da a los activistas visibilidad y legitimidad para transformarse en nuevos actores políticos y formar parte de una “comunidad extendida de iguales” (siguiendo el lenguaje de la ciencia post normal). Un segundo objetivo de esta tesis es descubrir como la resistencia a la minería ha evolucionado. Mientras huelgas, protestas y demandas relacionadas con temas laborales han dominado conflictos mineros a través de la historia, estamos viendo como en las últimas dos décadas comunidades que viven en las zonas aledañas a los proyectos mineros están oponiéndose cada vez más a los proyectos mineros por temas ambientales y objetando su falta de representación y participación en las decisiones que conciernen su desarrollo. Estos grupos están innovando con una combinación de narrativas locales y alternativas con discursos globales de derechos y justicia ambiental. Las alianzas entre escalas han permitido a grupos locales incrementar su conocimiento y visibilidad, actuar en contra de su débil posición en la cadena de producción y a la emergencia de diversas estrategias como juicios legales y consultas comunales. La respuesta del estado y de las compañías mineras a esta resistencia también se explora. La tesis concluye, que si bien los recursos y la geografía de un proyecto minero son factores determinantes en un conflicto socio-ambiental, el esfuerzo de una comunidad por adquirir reconocimiento y participar conduce a la conexión e integración de preocupaciones locales con exigencias políticas más amplias o a la producción de nuevo conocimiento, trayectos clave para la formación y éxito de movimientos de resistencia a la minería. / Resistance to mining is not new and nonetheless, resource extraction has been expanding materially and geographically during the last 50 years, reaching new frontiers, moving bigger quantities of soil and water and impacting more communities. The resistances that are emerging are becoming more relevant in shaping the commodity frontier and are an important factor in the political economy of mineral expansion. Thus, it has become crucial to understand why is resistance to mining emerging and how is it evolving. Bringing attention to uranium, the often forgotten source of nuclear power, this thesis studies the industrial dynamics of uranium mining, its impacts and health implications, and the resistance at the uranium mining frontier in Africa. Namibia and Niger, the main producers of uranium in Africa, stand at the forefront of what was a global uranium rush partially slowed down by the Tepco-Fukushima accident. This thesis proposes three enabling factors that help to explain the emergence and intensity of resistance by local communities to uranium mining: the ecology and geography of the resource; the degree and type of political and economic marginalisation of the community; and crucially, the creation of extra-local alliances that connect and integrate local concerns with broader social movements and global demands. I show how these three attributes play out differently in five Namibian communities that have been, or stand to be, affected by uranium mining, and explain how local ecologies of resistance shape, or fail to shape, the global uranium frontier. The cases presented deal with Low Level Radiation caused by uranium mining affecting workers' health and those of people living in nearby communities. With people impacted claiming causal links that are still not scientifically sustained, the burden of proof is left to the communities. Through extra-local contacts local grassroots organisations in Niger and Namibia are engaging with scientists to produce new knowledge to learn how to protect themselves from the impacts and confront the manufactured uncertainty and other information produced by the mining companies. Locally driven, this ‘Activism Mobilizing Science’ process gives activists visibility and legitimacy to become new political actors and form part of an ‘extended peer review’ community (in Post Normal science language). A second objective of this thesis aims at uncovering how resistance to mining has evolved. Whilst strikes, protest and demands linked to labour issues have dominated mining conflicts through history, we have seen how in the last two decades communities living in the surrounding areas of mining projects are increasingly opposing them on environmental grounds and objecting their lack of representation and participation in decisions concerning their development path. These groups are innovatively combining local narratives and alternatives with global discourses on rights (to clean water, to take decisions, indigenous rights) and environmental justice. Cross-scalar alliances have allowed local groups to increase their knowledge about the projects, give them visibility and comprehend and act against their weak position in the global commodity chain. These alliances have also contributed to the emergence of a diverse set of resistance strategies such as legal court cases, activist-scientist collaborations or "consultas" at community level to reject mining projects. The response of the state and the mining companies to resistance is also explored. The thesis concludes that whilst the resource and geography of a mining project are key determinants in a socio-environmental conflict, the community’s strive for participation and recognition drive the connection and integration of local concerns with broader political demands and the control or production of new knowledge, key paths in the formation and success of resistance movements to mining.

Dans ce travail de thèse, nous nous sommes intéressés à mieux comprendre le rôle du métabolisme du tryptophane (TRP), et en particulier de la voie de la kynurénine (KYN), dans la physiopathologie des troubles dépressifs en utilisant un modèle murin de dépression - le stress chronique imprédictible modéré (Unpredictable Chronic Mild Stress = UCMS). Nous avons montré que 1) l'UCMS affecte de façon différentielle le métabolisme de la KYN selon qu'il se déroule en périphérie ou dans le SNC 2) l'UCMS induit l'accumulation de certains métabolites toxiques de la KYN en périphérie alors que dans le cerveau, l'effet est structure-dépendant 3) la concentration en KYN est inversement proportionnelle à la concentration en 5-HT dans le SNC 4) que l'activation de la voie KYN périphérique est positivement corrélée à l'expression de comportements anxio-dépressifs 5) que l'inhibition pharmacologique de la voie KYN a des effets antidépresseurs. / During this thesis, we were interested in better understand the role of the kynurenine pathway (KP) in the pathophysiology of depressive disorders by using a murine model of depression - the Unpredictable Chronic Mils StressProcedure = UCMS). We have shown that 1) UCMS has different effects on peripheral and cerebral tissues 2) UCMS induces accumulation of some toxic KP metabolites in the periphery and the CNS 3) the cerebral level of KYN innegatively correlated to the level of 5-HT 4) activation of the peripheral KP is positively correlated to the expression of anxiety-like and depressive-like behaviors, only in UCMS mice 5) pharmacological inhibition of the KP have antidepressant properties.

We discuss how to realize simple Smale Flows on 3-manifolds. We focus on three questions: (1) What are the topological conjugate classes of Lorenz Smale flows that can be realized on S3? (2) Which 3-manifolds can also admit a Lorenz Smale flow? (3) What are the topological conjugate classes of simple Smale flows whose saddle set can be modeled by &nu(0+,0+,0,0) can be realized on S3? This dissertation extends the work of M. Sullivan and B. Yu.

Glioblastoma multiforme (GBM) is the most malignant form of brain cancer. Therapies targeting glioblastoma have not consistently been able to give those diagnosed the best prognosis. Treatments that directly infiltrate into the tumor are highly sought after. Indirubins have been used to treat various types of cancers and are a promising avenue for future glioma research. In the current study, we further researched several key GSK-3 inhibitors, BIO (an indirubin) and CHIR99021, in addition to LiCl, to see their effects on the translocation of β-catenin to the nucleus, and the invasion and migration of cells in both a sphere assay and an aortic ring assay. Here we studied anti-invasive therapies that may have a future role in GBM treatment. It is thought that combining conventional treatments with anti-invasive therapies will create cytotoxicity in and reduce migration of the tumor. Three types of cells were used throughout the experiments: HBMEC, HUVEC, and U251 glioma cells. We reported that GSK-3 inhibitors might have a valuable role in the treatment of GBM. The selected inhibitors (BIO, CHIR99021, and LiCl) all were shown to lessen cell migration and invasion in vitro in a range of assays and in all cell lines tested. All inhibitors tested cause a dose-dependent, reversible inhibition of glioma cell invasion in spheroid assays. BIO was shown to cause a rapid upregulation of total and nuclear β-catenin. BIO, at higher concentrations, also created a toxic environment for cells, sometimes killing them. This shows that a more in-depth experiment involving different BIO concentrations is needed to test the optimal concentration for treatment. Each of the experimented GSK-3 inhibitors also showed a change in the junctions between cells. NaCl as a control showed normal, spikey, junctions, while CHIR99021 and BIO caused the junctions to become more smooth. This suggests that GSK-3 inhibition has a role in either maintaining the ECM and/or in communication between cells. Also in this assay, there was a heterogeneity between cells treated with the same inhibitor and in the same dish, indicating that not all cells respond to each drug the same way. The reasons for this are not known and further investigation is required. A new construct was also made to report β-catenin transcriptional coactivation using luciferase expression as the reporter in response to these selected GSK-3 inhibitors.With the combined results of these experiments, we concluded that GSK-3 inhibitors may be a promising approach to the treatment of GBM. Further investigation is required before any treatments can be administered to those diagnosed.

BARROS, A.S. Efeitos comportamentais e neuroquímicos da suplementação de ácidos graxos ômega-3 em ratos submetidos à lesão estriatal com 6-OHDA. 2013. 61f. Dissertação (Mestrado em Biotecnologia) – Campus de Sobral, Universidade Federal do Ceará, Sobral, 2013. / Submitted by Mestrado Biotecnologia (biotecnologiasobral@gmail.com) on 2017-03-28T13:20:16Z No. of bitstreams: 1 2013_dis_asbarros.pdf: 1062516 bytes, checksum: e86a5b09795c1b3641969dcb285150b3 (MD5) / Approved for entry into archive by Ana Márcia Sousa (marciasousa@ufc.br) on 2017-04-11T13:20:03Z (GMT) No. of bitstreams: 1 2013_dis_asbarros.pdf: 1062516 bytes, checksum: e86a5b09795c1b3641969dcb285150b3 (MD5) / Made available in DSpace on 2017-04-11T13:20:03Z (GMT). No. of bitstreams: 1 2013_dis_asbarros.pdf: 1062516 bytes, checksum: e86a5b09795c1b3641969dcb285150b3 (MD5) Previous issue date: 2013-02-28 / Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. The neuronal degeneration may result from the convergence of a number of different pathogenic factors, including apoptosis, excitotoxicity, oxidative stress and inflammation. Many studies emphasize the importance of omega-3 (w-3) in vital processes such as maintenance of the properties of cell membranes, participate in signal transduction and biodynamic activity of neuronal membranes. This study aimed to determine the effects of supplementation with w-3 in the brain of rats subjected to an experimental model of PD induced by 6-OHDA. Male Wistar rats (200-250g) received W-3 (1.5 and 3mg/kg, orally) for 28 days. On the 4th day of treatment was performed 6-OHDA injection into the striatum right (SR). The sham group received saline. On the 25th day of treatment was observed rotational behavior induced by apomorphine and by day 28 the animals were sacrificed. The results showed an increase in the number of apomorphine-induced rotations in the control animals (6-OHDA) compared to the sham group. A motor partial recovery was observed in animals treated with w-3, which reduced the number of rotations around 40 and 75% (1,5 and 3,0 g / kg, respectively). The control group showed a decline of about 70% on locomotor activity when compared to the sham group and treatment with n-3, increased the horizontal exploratory activity. The 6-OHDA promoted increase in MDA content in the prefrontal cortex (PFC), hippocampus (HC) and striatum (CE) (6-OHDA: 75%, 44% and 104%, respectively) compared to sham. The w-3 was capable of reducing the lipid peroxidation about 40%. The w-3 caused a reduction in the concentration of nitrite / nitrate in all areas tested. We observed a significant reduction in the concentration of dopamine (DA) on the ipsilateral controls (61%). However, in animals treated with n-3 this reduction was minor. The results of this study suggest that supplementation with n-3 reversed the behavioral and neurochemical changes of 6-OHDA, with effects potentially beneficial in the treatment of PD. / A doença de Parkinson (DP) é caracterizada por uma degeneração progressiva dos neurônios dopaminérgicos da substância negra. A degeneração neuronal pode resultar da convergência de um conjunto de diferentes fatores patogênicos, incluindo apoptose, excitotoxicidade, estresse oxidativo e inflamação. Muitos estudos ressaltam a importância dos ácidos graxos ômega-3 (w-3) em processos vitais, como a manutenção das propriedades das membranas celulares, participação na transdução de sinais e na atividade biodinâmica das membranas neuronais. O presente trabalho objetivou determinar os efeitos da suplementação com w-3 em cérebro de ratos submetidos ao modelo experimental da DP induzido por 6-OHDA. Ratos Wistar machos (200-250g) receberam w-3 (1,5 e 3mg/kg, por gavagem) durante 28 dias. No 4ºdia de tratamento foi realizada a injeção de 6-OHDA no estriado direito (ED). O grupo sham recebeu salina. No 25º dia de tratamento foi observado o comportamento rotacional induzido por apomorfina e no 28º dia os animais foram sacrificados. Os resultados mostraram aumento do número de rotações induzidas por apomorfina nos animais controles (6-OHDA), quando comparado ao grupo sham. Uma recuperação motora parcial foi observada nos animais tratados com w-3, que reduziu o número de rotações em torno de 40 e 75 % (1,5 e 3,0 g/kg, respectivamente). O grupo controle apresentou um declínio de cerca de 70 % sobre na atividade locomotora quando comparado ao grupo sham e o tratamento com w-3, promoveu aumento na atividade exploratória horizontal. A 6- OHDA aumentou o conteúdo de MDA no córtex pré-frontal (CPF), hipocampo (HC) e corpo estriado (CE) (6-OHDA: 75 %, 44 % e 104 %; respectivamente) quando comparado com o sham. O w-3 foi capaz de reduzir a peroxidação lipídica em torno de 40%. O w-3 promoveu redução na concentração de nitrito/nitrato em todas as áreas testadas. Observou uma redução significativa da concentração de dopamina (DA) no lado ipsilateral dos controles (61 %). No entanto, nos animais tratados com w-3 essa redução foi menor. Os resultados deste estudo sugerem que a suplementação com w-3 reverteu às alterações comportamentais e neuroquímicas da 6-OHDA, apresentando efeitos possivelmente benéficos no tratamento da DP.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-16T20:46:25Z No. of bitstreams: 1 Domingos Ramon Moreau da Cunha Lasp-HIV1-Restool Desenvolvimento de uma ferramenta de bionformática para análise de resistencia do HIV-1 aos antirretrovirais.pdf: 2043486 bytes, checksum: 1cd7e640420b0a4675e14d21f7f04c9d (MD5) / Made available in DSpace on 2012-07-16T20:46:25Z (GMT). No. of bitstreams: 1 Domingos Ramon Moreau da Cunha Lasp-HIV1-Restool Desenvolvimento de uma ferramenta de bionformática para análise de resistencia do HIV-1 aos antirretrovirais.pdf: 2043486 bytes, checksum: 1cd7e640420b0a4675e14d21f7f04c9d (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / As terapias antirretrovirais (TARV) trouxeram um grande benefício para os pacientes infectados pelo HIV, porém não conseguem impedir totalmente o surgimento de formas virais resistentes, causadas principalmente pela elevada taxa mutacional do vírus. O desenvolvimento de resistência do HIV aos antirretrovirais é um fator limitante para o sucesso da TARV. Os portadores de vírus resistentes, além de não responderem adequadamente ao tratamento, podem também transmitir estes vírus mutantes, representando grave problema de saúde pública. O acúmulo de mutações de resistência aos antirretrovirais representa um desafio importante na melhoria do tratamento de pacientes com vírus multirresistentes. Atualmente, dois tipos de métodos estão estabelecidos para avaliação da resistência ou sensibilidade do HIV aos antirretrovirais: os testes fenotípicos e genotípicos de resistência. As análises de resistência do HIV aos antirretrovirais, avançaram muito nos últimos anos com o desenvolvimento dos algoritmos para avaliação de resistência. Atualmente, uma série de sistemas de interpretação de resistência fenotípica e genotípica do HIV aos antirretrovirais estão disponíveis na Internet. Estes sistemas identificam respectivamente os níveis de sensibilidade in vitro aos antirretrovirais e mutações associadas à resistência em sequêcias virais, e retornam o perfil de resistência do HIV, funcionando portanto, como importantes ferramentas para utilização em análises de resistência. No presente trabalho, foi desenvolvida uma ferramenta de bioinformática para análise de resistência do HIV-1 aos antirretrovirais, chamada de LASP-HIV1-ResTool. A ferramenta LASP-HIV1-ResTool é capaz de otimizar a análise de dados genômicos do HIV-1, é de fácil manuseio e está disponível no site da unidade de bioinformática do LASP/CPqGM/FIOCRUZ, Bioafrica e IOC/FIOCRUZ para domínio público. Esta ferramenta pode acessar um banco de dados com seqüências gênicas previamente armazenadas, extrair informações relativas à resistência aos antirretrovirais, comparar sequências de HIV-1 dos bancos de dados públicos, identificando mutações nos genes que codificam a transcriptase reversa e a protease e associar esses dados a resistência a cada antirretroviral utilizado nas terapias anti-HIV/AIDS. Adicionalmente, a ferramenta possibilita localizar sítios pós-traducionais e traçar um perfil de distribuição das sequências armazenadas no banco de dados local, tanto por resistência, quanto por sítios pós-traducionais, para servirem de parâmetro de comparação com as sequências iv submetidas pelos usuários da ferramenta. A ferramenta LASP-HIV1-ResTool apresenta uma tabela de quantidade e percentual de sequências brasileiras do HIV-1, dispostas por subtipo e outra tabela apresentando a quantidade e o percentual de seqüências das regiões Protease e Trasncriptase Reversa do HIV-1 armazenadas no Banco de Dados. Os usuários da ferramenta podem analisar sequências do banco de dados que compõe a ferramenta ou submeter suas próprias sequências de HIV-1 no formato FASTA. Durante o processamento das sequências, o sistema identifica a sequência através do número de acesso e localiza a posição inicial da sequência dentro da região gênica escolhida. Em seguida identifica a fase de leitura correta e realiza a conversão da sequência de nucleotídeos em sequência de aminoácidos. Inicia-se então o processo de localização de todas as mutações ocorridas, tanto na sequência de ácido nucléico como na sequência de aminoácido. O sistema então apresenta uma tabela apenas com as mutações que conferem a resistência do HIV-1 contra o antirretroviral. Além disso, exibe o grau de resistência de cada mutação e indica, ao final da tabela, se a amostra de HIV-1 submetida na análise é susceptível, apresenta resistência intermediária ou se é resistente ao antirretroviral. O sistema exibe dois gráficos que relacionam: a quantidade de sítios pós-traducionais em função do total de sequências submetidas e os padrões de resistência aos antirretrovirais (susceptível, intermediária e resistente) em função do total de sequências. Além de apresentar um gráfico de barras mostrando a quantidade de ocorrências de cada mutação de resistência no conjunto de sequências analisadas. A ferramenta LASP-HIV1-ResTool também gera uma página em formato XML contendo os dados das análises do usuário, que podem ser salvas em um arquivo. Os arquivos XML podem ser importados de outras ferramentas tais como: planilhas eletrônicas, programas de análise estatística e sistemas gerenciadores de bancos de dados. Para validação da aplicabilidade da ferramenta LASP-HIV1-ResTool foram utilizadas 111 amostras correspondentes a região gênica da protease e da transcriptase reversa derivadas da genotipagem da resistência do HIV-1 provenientes de pacientes infectados, que apresentavam falha virológica a TARV. Quando comparados os dados obtidos na ferramenta LASP-HIV1-ResTool com os dados obtidos através das análises realizadas com a ferramenta de Stanford, pode-se observar a similaridade entre os resultado. Por outro lado, pode-se observar diferenças entre os resultados das análises realizadas com a ferramenta LASP-HIV1-ResTool quando comparados com a ferramenta o sistema RENAGENO. / The antiretroviral therapy (HAART) has brought a great benefit to HIV-infected patients, but can not completely prevent the emergence of resistant viral forms, mainly caused by the high mutation rate of the virus. The development of HIV resistance to antiretroviral drugs is a limiting factor for the success of HAART. The patients with resistant virus, that do not respond adequately to treatment, may also transmit this virus mutants, representing a serious public health problem. The accumulation of resistance mutations to antiretroviral drugs represents a major challenge in improving the treatment of multiresistant virus. Currently, two types of methods are established to assess resistance or susceptibility of HIV to antiretroviral drugs: the phenotypic and genotypic resistance. However, the analysis of HIV resistance to antiretrovirals, have advanced greatly in recent years with the development of algorithms for evaluation of resistance. Currently, a number of systems for interpretation of HIV resistance to antiretrovirals, using algorithms, are available on the Internet. These systems identify the mutations associated with resistance, in amino acids sequences and return the viral resistance profile of HIV, acting therefore as, important tools for use in resistance analysis. In this study, we developed a bioinformatics tool for analysis of HIV-1 resistance to antiretrovirals. This tool is easy to use, will be available at the bioinformatics unit of LASP / CPqGM / FIOCRUZ, Bioafrica and IOC / FIOCRUZ in public domain and is able to optimize the analysis of genomic data of HIV-1. This tool can access a database of gene sequences previously stored, extract information, compare HIV-1 sequences from public databases, identifying mutations in genes that encode reverse transcriptase and protease, and associate that data with resistance to the individual anti -retroviral therapies used in anti-HIV/AIDS. Additionally, the tool allows locate post-translational sites and establish a distribution profile of the sequences stored in local databases, both for resistance and by post-translational sites to serve as parameter for comparison with the sequences submitted by users of the tool.

Conceptions of geography and learning geography have been studied through recording the experiences of a group of secondary school pupils over a threeyear period. This group formed part of the first cohort to experience Key Stage 3 Geography in the National Curriculum. The study is set within the context of Geography in the National Curriculum and the formulation and issues arising from this are discussed. A review of recent research in geographical education is presented to indicate how this study adds to current thought and practice. The study sought evidence to answer two specific questions: 1. What is geography? 2. What is learning geography? The study is set in a secondary school in Kent where the researcher has taught for sixteen years. Evidence was obtained from two classes of pupils, these were taught geography by the researcher for the whole period of Key Stage 3 1991- 1994. Data was obtained through applying a range of methods. The study was conducted in the phenomenographic tradition, seeking qualitatively different ways in which pupils understood the phenomena of geography and learning geography, and describing the "structural" and "referential" aspects of each. Categories of description of the distinctly different ways in which the phenomena are understood have been identified, presented and discussed. The categories are illustrated by quotes from individual pupils. These form the results of the study. The results of the study shed light on the ways in which pupils understand aspects of geography and learning geography as developed in the context of Geography in the National Curriculum. The longitudinal perspective adopted illuminates how these understandings change over time. A discussion is presented which clarifies the main features of the conceptions discovered. This is followed by a consideration as to how the results of the research could be applied by teachers to their understanding of geography, the pupils they teach, and in planning learning experiences. The thesis concludes by drawing together the contextual setting of the research, methodology and key findings. It suggests reasons that may have influenced the findings before considering their utility and avenues for further research.

Made available in DSpace on 2014-06-11T19:23:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-05-04Bitstream added on 2014-06-13T20:30:10Z : No. of bitstreams: 1 camargo_la_me_arafcf.pdf: 458749 bytes, checksum: e566ad21072ed4474151776ec23f5806 (MD5) / Universidade Estadual Paulista (UNESP) / A presente dissertação permitiu quantificar a presença de glicerol-3-fosfato oxidase (GPO, sn-glicerol-3-fosfato: oxigênio 2-oxidorredutase, EC 1.1.3.21) em extratos de levedura seca de panificação por dois métodos: polarográfico e colorimétrico. A melhor metodologia de purificação da GPO foi obtida por rompimento celular com esferas de vidro, em homogenizador do tipo Bead Beater (Biospec products, USA), por 15 minutos, com 27,6% de eficiência de lise celular. O extrato celular bruto foi tratado com 1% de sulfato de estreptomicina antes da precipitação com igual volume de solução 30% (p/v) de polietilenoglicol 3350, dialisado e a sua atividade otimizada por método colorimétrico. A determinação das características da GPO foi possível em ensaios contendo: 250 mM de glicerol-3-fosfato em tampão 0,1 M Tris-HCl pH 8,0 contendo 0,1% Triton X-100; 0,0133% de 4-aminoantipirina; 0,0266% de fenol; cerca de 0,40 unidade de peroxidase (PO) e água destilada para completar o volume de ensaio. A reação foi iniciada pela adição de 15 æL de extrato enzimático diluído 10 vezes seguido de uma incubação de 2 horas a 60°C e interrompida pela adição de solução 10% de SDS e a coloração desenvolvida foi medida a 500 nm. A GPO apresentou alta estabilidade térmica, pH de estabilidade entre 7,0 - 8,0 e a presença de azida de sódio na concentração de 0,05% manteve a atividade da enzima por 21 dias a 40°C. Este método permitiu também quantificar glicerol-3- fosfato, importante metabólito intermediário da biossíntese lipídica e glicolítica, na faixa de 56 - 250 mM. / The present dissertation allowed to quantify the presence of glycerol-3- phosphate oxidase (GPO, sn-glycerol-3-phosphate: oxygen 2-oxidoreductase, EC 1.1.3.21) in baker s yeast extract by two methods: polarographic and colorimetric. The best methodology of purification of GPO was obtained by cell debris with glass beads, in a Bead Beater homogenizator (Biospec products, USA), for 15 minutes, with 27.6% of efficiency of cellular lysis. The crude cellular extract was treated with 1% of streptomycin sulfate before the precipitation, with equal volume of a solution of 30% (w/v) polyethylene glycol 3350, dialysed and its activity was optimized by colorimetric method. The determination of the characteristics of GPO was possible in assays containing: 250 mM of glycerol-3-phosphate in 0.1 M Tris-HCl buffer, pH 8.0 containing 0.1% Triton X-100; 0.0133% of 4-aminoantipyrine; 0.0266% of phenol; about 0.40 unit of peroxidase (PO) and water distilled to complete the volume. The reaction was started by the addition of 15 ìL of enzymatic extract diluted 10 times, followed by incubation of 2 hours at 60°C, interrupted by the addition of solution 10% of SDS, and the developed coloration was measured at 500 nm. GPO presented high thermal stability, pH of stability among 7.0 - 8.0, and the presence of sodium azide in the concentration of 0.05% maintained the activity of the enzyme for 21 days at 40°C. This method also allowed to quantify glicerol-3- phosphate, important intermediate metabolite of lipid biosynthesis and glycolysis, in the range 56 - 250 mM.