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High grade astrocytomas are very progressive brain tumors. Glioblastoma multiforme is the most frequent and the most malignant type with very infiltrative phenotype of the tumor cells. Fibroblast activation protein FAP is a predominantly membrane bound prolyl peptidase bearing exo- and endopeptidase hydrolytic activities. FAP is known to play a role in wound healing, cell migration and invasion and its expression is linked to the pathogenesis of several malignancies. mRNA expression of FAP is upregulated in 48% of glioblastomas according to The Cancer Genome Atlas microarray data. The involvement of FAP in the pathogenesis of astrocytic tumors is largely unknown. The aims of this work are to analyse the expression of FAP in primary cell cultures derived from high grade gliomas and to analyse the influence of FAP on the growth, migration and invasion of glioma cells. Our ELISA and western blot results showed heterogenous expression of FAP in the studied glioma primary cell cultures and cell lines. Both enzymatic activities characteristic of FAP were detected in the primary glioma cell culture P11 with high expression of FAP. In these cells, FAP was present not only in the typical plasma membrane localization, but also in the cytoplasm as demonstrated by immunofluorescence staining. The P11 cells...

Amyloid diseases are a world-wide problem causing great human suffer and large economical costs. Although amyloid deposits, a common denominator in all amyloid disorders, are detrimental to the surrounding tissue, there is a poor correlation between total amyloid burden and clinical symptoms. Soluble oligomers are much more potent to exert a tissue damaging effect.  Alzheimer’s disease (AD) is strongly linked to self-assembly of the amyloid-β (Aβ) peptide. Antibodies selectively targeting cytotoxic Aβ-species are useful both for understanding oligomer formation and for their therapeutic abilities. We hypothesized that the effect of avidity would compensate for a low single site affinity and be enough to selectively target oligomers. To evaluate this hypothesis, we focused on the IgM isotype having ten antigen-binding sites. In accordance with the hypothesis, the IgM isotype effectively bound oligomeric Aβ also in presence of a vast excess of its monomeric counterpart, clearly illustrating the potentiating effect of avidity. As a continuation of this work, we have shown that the avidity effect from a bivalent binding is enough to induce oligomer specificity. This finding facilitates a direct application on the clinically more useful IgG isotype, where the binding properties now can be controlled in detail. The method is general and we have, using this technique, also designed oligomer specific antibodies targeting α-synuclein. Transthyretin (TTR) is an amyloidogenic protein involved in both hereditary and sporadic amyloidosis. The cytotoxicity of TTR is intriguing since studies have shown cytotoxic potential from oligomers, tetramers and even monomers. Elucidation of the molecular properties associated with TTR cytotoxicity is hence of interest. By preventing tetramer dissociation, TTR aggregation and TTR-induced cytotoxicity is abolished. Based on this rationale, a current therapeutic strategy is to stabilize the TTR tetramer with small molecules. The kinetic stability within the spectra of known TTR mutations spans more than three orders of magnitude. However, although the most stable mutants are inert, a poor correlation within the group of cytotoxic variants exists where the cytotoxic effect is not potentiated in proportion to their kinetic stability. Through analysis of a large spectra of TTR variants, our results indicate that TTR induced cytotoxicity requires an intermediate stability of the TTR molecule. The kinetic stability should be low enough to permit tetramer dissociation and the thermodynamic stability high enough to prevent instant aggregation and to allow formation of the cytotoxic fold.

Made available in DSpace on 2016-07-27T14:20:52Z (GMT). No. of bitstreams: 1 Maira Ribeiro Magri.pdf: 752733 bytes, checksum: af7ce31e8751e2549e6bc05bca14762c (MD5) Previous issue date: 2015-12-16 / This study aimed to compare the effects of FAP and THS interventions on behaviors related to social skills class (or social anxiety disorder) of an adult participant with social phobic, to assess the level of anxiety during the intervention and between sessions, and to compare the results of the SPIN and IHS before and after the intervention and compare. For that, it was used an AB1CB2 multiple baseline design between behaviors where A was the baseline phase, B1 and B2 were phases in which two classes of behavior (C1 and C2) were submitted to FAP interventions and other two (C3 and C4) were submitted to THS interventions, and C was intervention phase classes of behavior (C1 and C2) were submitted to THS interventions and other two (C3 and C4) were submitted to FAP interventions. The results showed an increase in the frequency of occurrence of classes throughout the sessions and the highest frequencies were in the sessions of FAP. The participant related a higher level of anxiety in THS sessions compared to FAP. The application of the instruments, showed no difference between aplications before and after interventions. The data indicated that FAP may be effective in the interventions for social skill behaviors. However, further studies should be performed either to evaluate the generalization and for provide more evidence of the effectiveness and provide the area of research and application the possibility of providing more effective treatments to behavior problems. / O presente estudo teve como objetivo comparar os efeitos das intervenções FAP e THS nas classes de comportamentos relacionados a habilidades sociais (ou ansiedade social) de um participante adulto fóbico social, comparar os resultados das aplicações do SPIN e do IHS antes e depois da intervenção; avaliar o nível de ansiedade ao longo da intervenção e entre as sessões. Para isso, foi utilizado um delineamento AB1CB2 de linha de base múltipla entre comportamentos sendo A a fase de linha de base, B1 e B2 as fases em que duas classes de comportamento (C1 e C2) passaram por intervenções FAP e outras duas (C3 e C4) por intervenção THS e C a fase em que as classes C1 e C2 passaram por THS e C3 e C4 foram submetidas a intervenção FAP. Os resultados apontaram um aumento na frequência de ocorrência das classes de comportamento sob intervenção ao longo das sessões, com maiores frequências nas sessões de FAP. O participante relatou maior nível de ansiedade nas sessões de THS comparado às de FAP. Em relação às aplicações dos instrumentos, não foi possível observar diferença entre as aplicações realizadas antes da linha de base e ao final das intervenções. Os dados indicaram que a FAP também pode ser eficaz no tratamento de comportamentos relacionados a habilidades sociais. Contudo, novos estudos devem ser realizados tanto para avaliar a generalização como para fornecer mais evidências da eficácia e prover à área de pesquisa e de aplicação a possibilidade de fornecer tratamentos mais eficazes aos comportamentos problemas.

Un processus de convergence des techniques algorithmiques de deux domaines autrefois disjoints, convergence facilité par l'émergence de normes telles que MPEG-4, s'est engagé au cours de ces dernières années. Grâce au concept de codage par objets, une scène peut être reconstituée par la composition de divers objets dans un ordre déterminé. <br />Cette thèse s'inscrit dans le cadre de la composition d'objets visuels qui peuvent être de natures différentes (séquences vidéo, images fixes, objets synthétiques 3D, etc.). Néanmoins, les puissances de calcul nécessaires afin d'effectuer cette composition demeurent prohibitives sans mise en place d'accélérateurs matériels spécialisés et deviennent critiques dans un contexte de terminal portable.<br />Une revue tant algorithmique qu'architecturale des différents domaines est effectuée afin de souligner à la fois les points de convergence et de différence. Ensuite, trois axes (interdépendants) de réflexions concernant les problématiques de représentation des données, d'accès aux données et d'organisation des traitements sont principalement discutés.<br />Ces réflexions sont alors appliquées au cas concret d'un terminal portable pour la labiophonie : application de téléphonie où le visage de l'interlocuteur est reconstruit à partir d'un maillage de triangles et d'un placage de texture. Une architecture unique d'un compositeur d'image capable de traiter indifféremment ces objets visuels est ensuite définie. Enfin, une synthèse sur une plateforme de prototypage de cet opérateur autorise une comparaison avec des solutions existantes, apparues pour la plupart au cours de cette thèse.

Un très grand nombre de problèmes combinatoires appartient à la famille des problèmes de satisfaction de contraintes (Constraint Satisfaction Problem ou CSP) : configuration, ordonnancement, affectation de ressources... Ces problèmes partagent une description commune qui autorise en général une modélisation claire et intuitive. Dans cette thèse, nous avons proposé et étudié une nouvelle méthode de résolution hybride pour les CSPs. Nous avons nommé cette méthode Tabu-NG pour Tabu Search based on NoGood. Le nom est un peu réducteur car il s'agit d'une hybridation d'algorithme de filtrage, de propagation de contraintes, de Recherche Tabou et de gestion de nogoods. La méthode a été appliquée sur deux types de problèmes. Le premier est l'affectation des fréquences (FAP) dans les réseaux de radiocommunications militaires, en particulier les problèmes proposés de 1993 (instances du projet européen CALMA) jusqu'à 2010 (instances d'un projet DGA). Le deuxième est le problème académique de k-coloration de graphes sur les instances DIMACS. La méthode a amélioré quelques meilleurs scores connus actuellement. Dans les deux problèmes nous avons traité des contraintes unaires et binaires, ainsi que des contraintes n-aires et de l'optimisation de fonction sous contraintes pour le FAP. Les principes de Tabu-NG sont généraux et elle peut s'appliquer sur d'autres CSP. Elle peut par ailleurs accueillir des heuristiques spécifiques aux problèmes, nous l'avons pratiqué sur les problèmes cités, et en ce sens nous pensons pouvoir qualifier la méthode de métaheuristique sans abuser de cette définition.

<p>This Master’s Thesis deals with a special problem that may be of importance when planning a frequency hopping mobile communication network. In normal cases the Frequency Assignment Problem is solved, in order to plan the use of frequencies in a network. The special case discussed in this thesis occurs when the network operator requires that the frequencies must be arranged into groups. In this case the Frequency Assignment Problem must be solved with respect to the groups, i.e. a Group assignment Problem. </p><p>The thesis constitutes the final part of the Master of Science in Communication and Transport Systems Engineering education, at Linköping University, Campus Norrköping. The Group Arrangement Problem was presented by ComOpt, a company that has specialized in solving the Frequency Assignment Problem for network operators. </p><p>This thesis does not deal with solutions for the Frequency Assignment Problem, with respect to the groups. The main issue in the thesis is to construct a computer based algorithm that solves the Group Arrangement Problem, i.e. creating the groups. The goal is to construct an algorithm that creates groups which imply a better solution for the Frequency Assignment Problem than manually created groups. </p><p>Two algorithms are presented and tested on two cases. Their respective results for both cases are compared with the results from a manual grouping. The two computer based algorithms creates better groups than the manual grouping strategy, according to an artificial quality measure. As of spring 2003 a variant of one of the presented algorithms was implemented in ComOpt’s product for solving the Frequency Assignment Problem.</p>

<p>The new mobile standard Long Term Evolution delivers high data rates, small delay and a more efficiently utilized RF spectrum. A solution to maintain this performance in user dense areas or areas with bad reception is the deployment of so-called femtocells. Femtocells are small base stations that are deployed indoors and share the RF spectrum with the whole mobile network. The idea is that femtocells will increase mobile operators network coverage and capacity while it at the same time increase users data throughput. There are several challenges with femtocells, both technical and economical ones. The most debated issues is how femtocells should schedule users while operating in an environment where other femtocells and base stations are interfering. In this work we developed a simulation tool to simulate the scheduling interaction between femtocells and base stationsin order to show the performance of radio resource schedulers. This rapport also aims to evaluate an approach to a femtocell scheduler to solve this issue in a satisfying way. The report gives a description of the structure of the implemented simulation tool together with some reflections on how future designs of similar or more complex simulation environments could be done.</p>

The new mobile standard Long Term Evolution delivers high data rates, small delay and a more efficiently utilized RF spectrum. A solution to maintain this performance in user dense areas or areas with bad reception is the deployment of so-called femtocells. Femtocells are small base stations that are deployed indoors and share the RF spectrum with the whole mobile network. The idea is that femtocells will increase mobile operators network coverage and capacity while it at the same time increase users data throughput. There are several challenges with femtocells, both technical and economical ones. The most debated issues is how femtocells should schedule users while operating in an environment where other femtocells and base stations are interfering. In this work we developed a simulation tool to simulate the scheduling interaction between femtocells and base stationsin order to show the performance of radio resource schedulers. This rapport also aims to evaluate an approach to a femtocell scheduler to solve this issue in a satisfying way. The report gives a description of the structure of the implemented simulation tool together with some reflections on how future designs of similar or more complex simulation environments could be done.

This Master’s Thesis deals with a special problem that may be of importance when planning a frequency hopping mobile communication network. In normal cases the Frequency Assignment Problem is solved, in order to plan the use of frequencies in a network. The special case discussed in this thesis occurs when the network operator requires that the frequencies must be arranged into groups. In this case the Frequency Assignment Problem must be solved with respect to the groups, i.e. a Group assignment Problem. The thesis constitutes the final part of the Master of Science in Communication and Transport Systems Engineering education, at Linköping University, Campus Norrköping. The Group Arrangement Problem was presented by ComOpt, a company that has specialized in solving the Frequency Assignment Problem for network operators. This thesis does not deal with solutions for the Frequency Assignment Problem, with respect to the groups. The main issue in the thesis is to construct a computer based algorithm that solves the Group Arrangement Problem, i.e. creating the groups. The goal is to construct an algorithm that creates groups which imply a better solution for the Frequency Assignment Problem than manually created groups. Two algorithms are presented and tested on two cases. Their respective results for both cases are compared with the results from a manual grouping. The two computer based algorithms creates better groups than the manual grouping strategy, according to an artificial quality measure. As of spring 2003 a variant of one of the presented algorithms was implemented in ComOpt’s product for solving the Frequency Assignment Problem.