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Aplicacao da tecnica de fluorescencia de raios X na marcacao com Mn, Sr e Cu, do parasitoide e do hospedeiro: Muscidifurax uniraptor Kogan e Legner, 1970 (Hymenoptera: Pteromalidae) e Musca domestica L., 1758 (Diptera: Muscidae)ITEPAN, NATANAEL M. 09 October 2014 (has links)
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A 2'-alkynylnucleotide strategy for site-directed spin labelling of DNAHaugland, Marius Myreng January 2016 (has links)
This thesis describes the synthesis of derivatives of 2'-ethynyl-2'-deoxynucleosides, and their conversion into phosphoramidite building blocks for DNA synthesis. Herein is also outlined the preparation of azide-bearing nitroxyl radicals. After site-selective incorporation of 2'-alkynylnucleosides into DNA using a standard solid-supported phosphoramidite protocol, the modified oligonucleotides were spin labelled with the azide-bearing nitroxyl spin labels via the Cu(I)-catalysed azide-alkyne [3+2] Huisgen cycloaddition (CuAAC or 'click' reaction). The destabilising effect of the spin labelling was determined by UV denaturation studies and circular dichroism, and the spin labelled DNA was investigated by EPR spectroscopy. It was found that this novel site-directed spin labelling strategy afforded conformationally restricted systems, and that the structure of the spin label exerts a significant influence on the results.
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Etude structurale et fonctionnelle par RMN d'une chaperonine de 1 MDa en action / Structural and functional studies by NMR of a 1 MDa chaperonin in actionMas, Guillaume 03 December 2015 (has links)
Les chaperonines sont des chaperonnes moléculaires indispensables pour le repliement de certaines protéines dans les cellules. La taille et la complexité de ces machineries biologiques rendent complexes l'étude de leurs propriétés structurales et fonctionnelles. La spectroscopie RMN permet de suivre des changements structuraux et dynamiques en temps réel avec une résolution atomique. Cependant, l'étude par RMN de protéines ou de complexes de haut poids moléculaires a été un challenge pendant de nombreuses années. Dans la première partie de cette thèse, il a été montré que la combinaison de marquage spécifique des groupements méthyles, d'expériences RMN optimisées et de microscopie électronique peut être utilisée pour suivre différents états du cycle fonctionnel d'une chaperonine de 1 MDa. Pour étudier ce mécanisme, la chaperonine native a été reconstituée avec un marquage des groupements méthyles des méthionines et valines. Les résidus méthionines ont pu être utilisés comme des sondes pour identifier les spectres RMN correspondant aux états intermédiaires et aux espèces actives du cycle fonctionnel. Grâce à ces sondes il a été possible de suivre en temps réel les réarrangements structuraux correspondant aux différentes conformations de la chaperonine durant son cycle fonctionnel. La seconde partie traite de la caractérisation de l'interaction de la chaperonine avec une protéine cliente dépliée. L'observation de la stabilisation de l'état déplié de la protéine par la chaperonine a permis de mettre en évidence une activité de "holdase" de la chaperonine. En utilisant une combinaison astucieuse de différents marquages de groupements méthyles et d'expériences RMN optimisés pour des assemblages de haut poids moléculaire, il a été possible d'observer le repliement de cette protéine par la chaperonine et les effets de la présence d'une protéine dépliée sur le cycle fonctionnel de la chaperonine en action. / Chaperonins are essential molecular chaperons for the refolding of proteins in the cells. Size and complexity of these biological machineries make complex the study of their structural and functional properties. NMR spectroscopy offers an unique ability to monitor structural and dynamic changes in real-time and at atomic resolution. However, the NMR studies of large proteins and complexes has been a real challenge for a long time. In the first part of this thesis, it has been shown that the combination of methyl specific labeling, optimized NMR spectroscopy for large assemblies and electron microscopy can be used to monitor the different states of the functional cycle of a 1 MDa chaperonin. To study this mechanism, the native chaperonin was reconstituted with a labeling of the methionines and valines methyl groups. Methionines residues have been used as probes to identify the NMR spectra corresponding to intermediates states and active species of the functional cycle. Thanks to theses probes, it has been possible to follow in real time the structural rearrangements corresponding to the different conformations of the chaperonin during its functional cycle. The second part deals with the characterization of the interaction between the chaperonin and an unfolded protein. Observation of the stabilization of the unfolded protein by the chaperonin allowed to identify the holdase activity of the chaperonin. Using a clever combination of a differential methyl labeling and optimized NMR spectroscopy for large assemblies, it has been possible to follow the refolding of the unfolded protein by the chaperonin and the effects of the unfolded protein on the functional cycle of the chaperonin in action.
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Développement de méthodes systémiques pour l'amélioration de la connaissance et du traitement des gliomes / Development of systemic approaches to improving gliomas knowledge and treatmentNugue, Guillaume 04 September 2014 (has links)
Es gliomes sont des tumeurs cérébrales associées à une mortalité élevée. Le glioblastome multiforme (GBM) est la forme la plus fréquente des tumeurs cérébrales primaires. Malgré une prise en charge thérapeutique optimale constituée d'une chirurgie, d'une radiochimiothérapie concomitante et d'une chimiothérapie adjuvante, la survie médiane est de 15 mois. Ceci s'explique surtout par le potentiel infiltratif de ces tumeurs. Il est donc difficile de réaliser une exérèse chirurgicale totale, ce qui entraine une récidive quasi-systématique avec l'apparition de chimiorésistance. Ces phénomènes de résistances associés à une importante toxicité des molécules cytotoxiques mettent en évidence l'importance de rechercher de nouvelles stratégies thérapeutiques. Parmi ces dernières, les anticorps monoclonaux thérapeutiques sont très prometteurs, leurs actions ciblées limitent la toxicité au niveau du tissu sain. Cependant ces nouvelles thérapies manquent cruellement de suivi. L'apparition d'effets secondaires graves remet en cause leur intérêt. C'est pourquoi ces nouvelles thérapies, bien qu'efficaces, doivent être contrôlées par l'intermédiaire de biomarqueurs compagnons ce qui permettrait une meilleure efficience de la molécule. Le bevacizumab en est un bon exemple, de par une pharmacocinétique interindividuelle variable (de 11 à 50 jours) et une absence d'adaptation de la posologie on constate l'apparition d'effets secondaires (phlébite, hémorragie) qui entrainent l'arrêt du traitement. Or, ces effets secondaires pourraient être limités par un simple suivi de la concentration sérique de bevacizumab. De plus, dans le cas particulier des GBM, la présence de la barrière hémato-encéphalique (BHE) nécessite de développer de nouvelles stratégies pour favoriser une meilleure biodistrubution de molécules au niveau de la tumeur cérébrale. De ce fait, nous avons étudié l'efficacité d'un contournement de la BHE mécanique par une administration localisée directement dans la tumeur. Et dans cette étude préclinique, une amélioration significative de la médiane de survie des animaux ayant eu un traitement par CED (Convection Enhanced Delivery) par rapport à une administration intrapéritonéale. Enfin, dans le but de proposer une technique innovante de criblage de biomarqueurs compagnons, nous avons mis en place une stratégie innovante de marquage isotopique in vivo afin d'étudier la dynamique du protéome tumoral en réponse au traitement. Cette stratégie, déjà validée, est en cours de transfert chez l'homme dans l'étude du métabolisme des GBM. / Gliomas are brain tumors associated with important mortality. Glioblastoma multiforme (GBM) is the most frequent of primary brain tumors. Despite an optimal therapeutic management consists that includes surgery, radiotherapy plus concomitant and adjuvant chemotherapy, the median survival is 15 months. This, is mainly due to the presence of infiltrative tumor cells that hamper total surgical excision, and leads to relapse with the emergence of drug resistance. This highlights the importance of seeking new therapeutic strategies.Of these, therapeutic monoclonal antibodies are very promising. Their targeted actions limit the toxicity to healthy tissue. However, these new therapies are desperately short of monitoring. The appearance of serious side effects is a present challenge to their use. In consequences, these targeted therapies, even effective, have to be controlled via companion’s biomarkers that would provide better monitoring of the molecule. Bevacizumab is a good illustration for the existence of interindividual pharmacokinetic variability (11 to 50 days). In addition to its effect on the therapy efficiency, this inte variability must be also considered for side effects (phlebitis, hemorrhage) that lead to failure of treatment. However, these side effects could be limited by a simple monitoring of serum concentration of bevacizumab.Moreover, in the specific case of GBM, the action to the blood-brain barrier (BBB) requires the development of new strategies to promote a better bio-distribution of molecules in the brain tumor. Therefore, we investigated the effectiveness of a mechanical bypass of BBB in experimental brain tumors by a localized administration directly in the tumor. In this preclinical study, a significant improvement in median survival of animals treated with convection-enhanced delivery (CED) versus intraperitoneal administration was demonstrated.Finally, in order to offer an innovative technique of companion’s biomarkers screening, we have implemented an isotope labeling in vivo in order to study the dynamics of the proteome in tumor response to treatment. This strategy has already been released and is being transferred in humans in the study of the metabolism of GBM.
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Detecção não supervisionada de posicionamento em textos de tweets / Unsupervised stance detection in texts of tweetsDias, Marcelo dos Santos January 2017 (has links)
Detecção de posicionamento é a tarefa de automaticamente identificar se o autor de um texto é favorável, contrário, ou nem favorável e nem contrário a uma dada proposição ou alvo. Com o amplo uso do Twitter como plataforma para expressar opiniões e posicionamentos, a análise automatizada deste conteúdo torna-se de grande valia para empresas, organizações e figuras públicas. Em geral, os trabalhos que exploram tal tarefa adotam abordagens supervisionadas ou semi-supervisionadas. O presente trabalho propõe e avalia um processo não supervisionado de detecção de posicionamento em textos de tweets que tem como entrada apenas o alvo e um conjunto de tweets a rotular e é baseado em uma abordagem híbrida composta por 2 etapas: a) rotulação automática de tweets baseada em um conjunto de heurísticas e b) classificação complementar baseada em aprendizado supervisionado de máquina. A proposta tem êxito quando aplicada a figuras públicas, superando o estado-da-arte. Além disso, são avaliadas alternativas no intuito de melhorar seu desempenho quando aplicada a outros domínios, revelando a possibilidade de se empregar estratégias tais como o uso de alvos e perfis semente dependendo das características de cada domínio. / Stance Detection is the task of automatically identifying if the author of a text is in favor of the given target, against the given target, or whether neither inference is likely. With the wide use of Twitter as a platform to express opinions and stances, the automatic analysis of this content becomes of high regard for companies, organizations and public figures. In general, works that explore such task adopt supervised or semi-supervised approaches. The present work proposes and evaluates a non-supervised process to detect stance in texts of tweets that has as entry only the target and a set of tweets to classify and is based on a hybrid approach composed by 2 stages: a) automatic labelling of tweets based on a set of heuristics and b) complementary classification based on supervised machine learning. The proposal succeeds when applied to public figures, overcoming the state-of-the-art. Beyond that, some alternatives are evaluated with the intention of increasing the performance when applied to other domains, revealing the possibility of use of strategies such as using seed targets and profiles depending on each domain characteristics.
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Rotulagem ambiental: estudo de critérios para a concessão do selo verde para produtos manufaturados de couroBarra, Bruna Neri [UNESP] 14 July 2009 (has links) (PDF)
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Digital product labels and the mapping of consumer valuesDodan'Li, Nihal January 2013 (has links)
Current labels of consumer products provide some level of information to consumers but at the moment, this expanding labelling logic, and the multitude of requirements it generates, is often tricky to implement and difficult to translate into a clear and accessible form of communication for consumers to engage with. In the first part of the thesis, an analysis of current labels is carried out which examine a selection of widely used consumer products. This examination supports the objective to imagine the type of complementary information consumers may deem useful, and also highlights the difficulty there may be for consumers in accessing and verifying some key information that directly concerns the product they use and that may significantly influence the assessment they make of it. To improve the quality of the information provided to the public, a fourtiered architecture is proposed in the second section that can respond to the issues that have been identified during the analysis and also with reference to techno-sociological considerations presented in the Literature Review. The end result is an online database which generates real-time digital labels that uses collaborative logics and allows users to conveniently explore essential information about the products and services they use and make decisions more in accordance with their own requirements and values. The system also offers the possibility for the various label stakeholders to actively engage with the evolution of the product they manufacture, verify, legislate upon or consume depending on their relation to the product. In order to illustrate the potential of this architecture, the digital label is applied to informational situations commonly encountered by consumers. Conceptually, the digital label appears capable to meet consumer needs and is ready to be implemented into a prototype. The architecture is also considered against recent developments in terms of digital product labels, and appears to offer a solid foundation to catalogue, compare and analyse them critically. The third section of the dissertation is a reflection on the merits of the digital labelling system, this time from a sociological perspective. The discussion has two objectives (1) validating the digital label as an information arrangement capable of responding to current societal demands and (2) determining the label underlying principles in order to guide further development.
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O que não engorda, mata? estudos experimentais sobre os efeitos das alegações de saúde e alertas em rótulos de alimentosSilva, Josuéliton da Costa 24 June 2015 (has links)
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Previous issue date: 2015-06-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Though the labels are rich in information, studies suggest that these are not made in favor of
the consumer. This can make them vulnerable to advertising on food. One of the causes of
this is the lack of the ability to find and process information efficiently – literacy. Therefore,
this study aims at understanding how do the labels influence the consumer’s perception and
decision making. In addition, two categories of products have been analyzed, so it can be
verified if different product types are differently affected by the messages: a healthier product
(cereal bar) and a less healthy one (chocolate cookies). Also, positive messages
(advertisements) as well as negative messages (warnings) have been used. An online
experiment with 6 different treatments was performed. Data from each group were compared
with the non-parametric tests Mann-Whitney U and Kruskal-Wallis, with the Dunn’s
technique for paired comparisons. The t-test (parametric) was also used for the analysis. With
more than 300 respondents, it can be inferred that advertisements have a positive effect on
any product, but the warning had no effect on the cookies. Cereal bars can benefit from
advertisements, but not as much as the cookies. As for price, only the cookie with the
advertisement achieved a significantly higher result, indicating that people are more attracted,
and could pay more, for these kinds of products when they come with propaganda. To test this
assumption in a more realistic environment, cookies were sold for college students. Almost
half of the sample of 38 students preferred the more expensive cookies (carrying
advertisement), even though both products (with/without propaganda) had identical back-ofpackage
information and design. Only few individuals were able to find and interpret the
back-of-package information. Those who bought the most expensive product justified
themselves saying that the product was nutritionally better. It is suggested that further studies
on labeling seek to be more realistic, and that industries and governments should be more
concerned on how the consumer understands the labels. Especially for the companies, it
should not be the goal of its investigations solely which formats sell more, but which label
formats are more efficient to inform the consumer. / Apesar de os rótulos serem ricos em informações, estudos sugerem que estes não são feitos
para o benefício do consumidor. Isso pode torná-los vulneráveis às mensagens publicitárias
nos alimentos. Uma das causas é a falta de capacidade em encontrar e processar informações
eficientemente – a literacia. Por isso, este estudo busca entender como as informações dos
rótulos interferem na percepção e tomada de decisão dos consumidores. Ainda, duas
categorias de produtos são analisadas, para que possa verificar se diferentes tipos de produto
são diferentemente afetados pelas mensagens: um produto mais saudável (barra de cereal) e
um menos saudável (biscoito de chocolate). Ademais, tanto mensagens positivas
(propagandas) quanto negativas (alertas) foram usadas. Um experimento online com 6
diferentes tratamentos foi realizado. Os dados de cada grupo foram comparados com os testes
não-paramétricos de Mann-Whitney U e Kruskal-Wallis, com aplicação da técnica de Dunn
para comparações em pares. Paralelamente usou-se, ainda, o teste t (paramétrico) nas análises.
Com mais de 300 respondentes, pode-se inferir que as propagandas têm um efeito positivo em
qualquer produto, mas os alertas não tiveram nenhum efeito nos biscoitos. Barras de cereal se
beneficiam de propagandas, mas menos que os biscoitos. Quanto à estimativa de preço,
apenas o biscoito com propaganda conseguiu resultado significativamente maior, indicando
que as pessoas têm mais atração, e podem estar dispostas a pagar mais por esses produtos,
quando estes vêm propaganda. Para testar essa suposição num ambiente mais realista,
biscoitos foram colocados à venda para alunos universitários. Quase metade da amostra de 38
alunos preferiu os biscoitos mais caros (com propaganda), apesar de os rótulos traseiros serem
idênticos. Poucos foram capazes de acessar e decodificar as informações do rótulo traseiro.
Todos os que compraram o mais caro se justificaram dizendo que o produto seria melhor
nutricionalmente. Sugere-se que estudos futuros sobre rotulagem busquem sempre se
aproximar da realidade, e que indústrias e governos se preocupem mais em como o
consumidor compreende os rótulos. Para as empresas não deveria ser meta de suas
investigações apenas os formatos que vendem mais, mas sim, os formatos de rótulo que
informem melhor o consumidor.
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Avaliacao da radiomarcacao da enexina A5 com tecnecio-99m: influencia do metodo de marcacao nas propriedades fisico-quimicas e biologicas do composto / Evaluation of radiolabeling of annexing A5 with technetium-99m: influence of the labeling methods on physico-chemical and biological properties of the compoundsSANTOS, JOSEFINA da S. 09 October 2014 (has links)
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Marcacao do iomazenil com 123/131 iodo para uso como neurotracador em medicina nuclearPETRONI, MARIANE F. 09 October 2014 (has links)
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