Submitted by BRUNO RAFAEL PEREIRA LOPES null (brunorpl@hotmail.com) on 2016-05-11T19:53:59Z No. of bitstreams: 1 Dissertação versão repositório.pdf: 7264895 bytes, checksum: 0ac82b804ba7471cb20cb92afa6c4d3f (MD5) / Rejected by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: O arquivo submetido está sem a folha de aprovações providenciada pela Pós-graduação. Lembramos que a versão submetida por você é considerada a versão final da dissertação/tese, portanto não poderá ocorrer qualquer alteração em seu conteúdo após a aprovação. Corrija esta informação e realize uma nova submissão contendo o arquivo correto. Agradecemos a compreensão. on 2016-05-13T16:24:02Z (GMT) / Submitted by BRUNO RAFAEL PEREIRA LOPES null (brunorpl@hotmail.com) on 2016-05-16T19:16:16Z No. of bitstreams: 1 Dissertação numerado FINAL Capa Dura versão folha de aprovação.pdf: 7936969 bytes, checksum: b93b6e0c25c357b92f65cec6ffb9e789 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-05-18T13:48:58Z (GMT) No. of bitstreams: 1 lopes_brp_me_assis.pdf: 7936969 bytes, checksum: b93b6e0c25c357b92f65cec6ffb9e789 (MD5) / Made available in DSpace on 2016-05-18T13:48:58Z (GMT). No. of bitstreams: 1 lopes_brp_me_assis.pdf: 7936969 bytes, checksum: b93b6e0c25c357b92f65cec6ffb9e789 (MD5) Previous issue date: 2016-03-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / No mundo, estima-se que exista cerca de 12 milhões de casos graves e 3 milhões de casos muito graves de infecção do trato respiratório inferior em crianças anualmente. Dentre os agentes etiológicos destas infecções, o vírus sincicial respiratório humano (hRSV) é a principal causa de internações infantis em países desenvolvidos, agravando os casos de bronquiolite, pneumonia e infecções pulmonares obstrutivas crônicas em pessoas de todas as idades, principalmente crianças e idosos. Estudos preliminares demonstraram que a Quercetina possui ação virucida sobre hRSV, além de inibir sua replicação. Entretanto, não se tem conhecimento do quão promissora é a atividade antiviral de Quercetina sobre o vírus hRSV ou mesmo se esta atividade poderia ser melhorada através de mudanças químicas em sua estrutura molecular. Assim, o objetivo deste trabalho foi estabelecer o índice de seletividade (IS) para Quercetina e seus derivados acetilados durante a infeção por hRSV através de ensaios in vitro. A análise de viabilidade celular através da adição do sal de MTT determinou os valores de CC50 para Quercetina na presença/ausência do vermelho de fenol (85 e 11,4 µM, respectivamente). Dentre as condições testadas, Quercetina apresentou atividade virucida (16-30% de proteção celular) sem apresentar efeitos no pré ou pós-tratamentos. Os valores de CC50 dos compostos derivados Q1 e Q2 foram 37,1 µM e 53,15 µM, respectivamente. O composto Q1 apresentou atividade anti-hRSV nos protocolos virucida e pós-tratamento (60-90%; 4-8 µM). O composto Q2 não apresentou atividade anti-hRSV relevante em nenhuma das condições testadas. A proteção celular apresentada pela Quercetina não possibilitou o cálculo de IS (CC50/CE50) o que nos sugere que este composto não seja um promissor agente anti-hRSV. Os índices de Seletividade calculados para o composto Q1 nos protocolos virucida e pós-tratamento foi de 9,27. O conjunto de resultados obtidos neste trabalho apresenta menor citotoxicidade e melhor performance anti-hRSV do composto Q1 em relação à Quercetina comercial. Estes dados nos estimulam a dar continuidade aos estudos do composto Q1 com o intuito de melhorarmos sua atividade antiviral e assim propormos um novo composto que seja efetivos na prevenção e/ou tratamento das infecções por hRSV. / Worldwide, is estimated that there are about 12 million serious cases and 3 million severe cases of lower respiratory tract infection in children every year. Among the etiological agents of these infections, respiratory syncytial virus (hRSV) is the leading cause of children's hospitalizations in developed countries, aggravating cases of bronchiolitis, pneumonia and chronic obstructive pulmonary infections in people of all ages, especially children and the elderly. Preliminary studies demonstrated that Quercetin has virucidal action on hRSV, and inhibits replication. However, we do not know how promising is the antiviral activity of Quercetin on the hRSV. The objectives of this work is to understand the action of Quercetin and some of its derivatives acetylated on the steps of the replicative cycle of hRSV, determining the selectivity index for each compound. The development of this project will assist in the search for effective compounds in the prevention and/or treatment of hRSV infections. In the cytotoxicity assays, Quercetin showed CC50 values variable depending on the presence/absence of phenol red (11.4 and 85 μM respectively). Among the concentrations tested Quercetin only showed a slight virucidal activity (16-30% concentration 5-10 μM). The CC50 values were derived compounds 37.1 μM for Q1 and Q2 to 53.15 μM. Compound Q1 showed anti-hRSV activity in virucidal and post-treatment protocol (60-90% at 4-8 μM). The Q2 compound showed no anti-hRSV relevant activity. The presence or absence of phenol red had great influence in determining the CC50 values of Quercetin (11.4 μM and 85 μM with phenol red). In addition, Quercetin showed little (virucidal protocol without phenol) or no anti-hRSV activity. Thus it has not been possible to establish the EC50 of Quercetin and determine its selectivity index (SI). The Q1 compound showed a greater CC50 value (37.1 μM) and relevant anti-hRSV activity in post-treatment and virucidal protocols (SI 9.27). Among the compounds tested, Q2 showed the highest value of CC50 (53.15 μM without phenol) however, had little or no anti-hRSV activity, making it impossible to determine their SI.

Human adult mesenchymal stem cells (MSCs) derived from bone marrow have the capacity to self-renew and to differentiate into a variety of cells and tissues. They can leave their niche to migrate to remote tissues where they play a critical role in angiogenesis, wound repair and tissue regeneration. A major goal in adult stem cell research is to define how MSC fate is controlled by the pericellular extracellular matrix (ECM) and soluble factors that largely constitute their tissue-specific niches. Defining crucial regulatory signals that control the fate and function of MSCs in vitro will contribute to the development of therapeutic strategies to improve tissue regeneration. The objective of this study was to investigate the molecular relationships between cell-ECM integrin receptors and platelet-derived growth factor receptor (PDGFR) tyrosine kinases, which are crucial in modulating MSC expansion, recruitment, and differentiation towards a number of different cell lineages. This study reports that ECM-directed cross-talk between PDGFR-β and alpha5β1 integrin controls the migration of MSCs. Cell adhesion to fibronectin induced integrin alpha5β1-dependent phosphorylation of PDGFR-β in the absence of growth factor stimulation. Phosphorylated PDGFR-β co-immunoprecipitated with integrin alpha5 and co-localised with alpha5β1 in a transient tidemark of focal adhesions. Adhesion to fibronectin also strongly potentiated platelet-derived growth factor (PDGF)-BB-stimulated PDGFR-β phosphorylation, in an alpha5β1-dependent manner. PDGFR-β-activated phosphatidylinositol 3 ́-kinase (PI3-kinase) and Akt activity, actin reorganisation and cell migration were all regulated by fibronectin engagement of alpha5β1 integrin. This synergistic relationship between integrin alpha5β1 and PDGFR-β is a fundamental determinant of mesenchymal cell migration. Thus, fibronectin-rich matrices can prime PDGFR-β to recruit mesenchymal cells at sites of tissue remodelling.

The current research study examined the formation of derived stimulus relations consisting of course content material in an undergraduate rehabilitation class. Specifically, the study examined the degree to which the stimulus equivalence instructional paradigm could be effectively used to teach the relationships between the names, definitions, causes, and common treatments for disabilities using a paper-and-pencil training format. Twenty-two participants were pre and post-tested on definition-to-name, cause-to-name, and treatment-to-name relations by the experimenter in a flashcard-style fashion. Training was conducted using an instructional package consisting of multiple-choice questionnaires in which name-to-definition, name-to-cause, and cause-to-treatment relations were taught and feedback was delivered from the experimenter until mastery. Results suggest that the stimulus equivalence paradigm can be effectively trained in a paper-and-pencil training format with great ease.

La L-théorie classique d'un anneau commutatif est construite à partir des formes quadratiques sur cet anneau modulo une relation d'équivalence lagrangienne. Nous construisons la L-théorie dérivée, à partir des formes quadratiques $n$-décalées sur un anneau commutatif dérivé. Nous montrons que les formes $n$-décalées qui admettent un lagrangien possèdent une forme standard. Nous montrons des résultats de chirurgie pour la L-théorie dérivée, qui permettent de réduire une forme quadratique décalée en une forme plus simple équivalente. On compare la L-théorie dérivée avec la L-théorie classique.On définit un champ dérivé des formes quadratiques dérivées, et un champ dérivé des lagrangiens dans une forme, qui sont localement algébriques de présentation finie. On calcule les complexes tangents, et on trouve des points lisses. On montre un résultat de rigidité pour la L-théorie : la L-théorie d'un anneau commutatif est isomorphe à celle d'un voisinage hensélien de cet anneau. Enfin, on définit l'algèbre de Clifford d'une forme quadratique n-décalée, qui est une déformation d'une algèbre symétrique en tant qu'E_k-algèbre. On montre un affaiblissement de la propriété d'Azumaya pour ces algèbres, dans le cas d'un décalage nul n=0, qu'on appelle semi-Azumaya. Cette propriété exprime la trivialité de l'homologie de Hochschild du bimodule de Serre. / The classical L-theory of a commutative ring is built from the quadratic forms over this ring modulo a lagrangian equivalence relation.We build the derived L-theory from the n-shifted quadratic forms on a derived commutative ring. We show that forms which admit a lagrangian have a standard form. We prove surgery results for this derived L-theory, which allows to reduce shifted quadratic forms to equivalent simpler forms. We compare classical and derived L-theory.We define a derived stack of shifted quadratic forms and a derived stack of lagrangians in a form, which are locally algebraic of finite presentation. We compute tangent complexes and find smooth points. We prove a rigidity result for L-theory : the L-theory of a commutative ring is isomorphic to that of any henselian neighbourhood of this ring.Finally, we define the Clifford algebra of a n-shifted quadratic form, which is a deformation as E_k-algebra of a symmetric algebra. We prove a weakening of the Azumaya property for these algebras, in the case n=0, which we call semi-Azumaya. This property expresses the triviality of the Hochschild homology of the Serre bimodule.

The present study evaluated the effectiveness of stimulus equivalence procedures using the instructional protocols from the PEAK-E curriculum to develop the emergence of cause and effect relational responding in two children with autism. The procedures were taken from the PEAK-E program Transitivity: Multiple Actions & Outcomes-9p to aid in clinical replication. This study utilized a multiple baseline design across participants to evaluate the functional relationship between cause and effect relations. The results suggested that direct training of an action (A) to an outcome (B) (A-B) and direct training of an outcome (B) with an action that is produced by the outcome (C) (B-C) was effective for both participants. Following A-B and B-C training, the participants demonstrated emergent relations and untrained action (A) to action (C) relations which are consistent with transitivity. The results demonstrate efficacy of stimulus equivalence procedures for training cause and effect skills as well as the PEAK-E curriculum

In the present study, two children diagnosed with autism spectrum disorder were taught to identify reflexive relations across three varying stimuli using procedures outlined in the Promoting the Emergence of Advanced Knowledge Equivalence Module (PEAK-E). Two programs from the PEAK-E module were utilized, programs 2B and 3C, both of which incorporated reflexive relations utilizing two differing sensory modalities. Visual relations were directly trained to the participants while the tactile relations were derived and monitored through probes. The same three stimuli were utilized in both PEAK-E programs for each participant; however, those three stimuli varied across participants. All stimuli were retrieved from the participants’ environments and were familiar objects to the participants. The results indicate that only one sense mode, visual, required corrective feedback and praise in order for cross-modal transfer to occur for the second sense mode, tactile. Both participants demonstrated they acquired the reflexive skills for both visual and tactile stimuli. Participant 1 reached mastery criterion for both skills in 36 trials, and participant 2 reached mastery criterion within 20 trials. Limitations and future directions for implication of cross modal transfer are discussed.

This study sought to evaluate the efficiency of the methods outlined in the Promoting the Emergence of Advanced Knowledge Relational Training System Equivalence Module (PEAK-E) utilizing a single-subject design. Three participants from a Midwest town were recruited to participate in the study and were assessed and validity, reliability, and efficacy were evaluated to determine the assessments ability to identify three language skills that weren’t currently present in their repertoire. Baseline levels determined that the 3 skills for each participant (a total of 9 skills across the 3 participants) were not currently present in their repertoire prior to implementation of PEAK-E programs, as the participants demonstrated low levels of correct responding. Upon completion of program implementation across all three participants with autism, mastery criteria was obtained for all directly trained skills, and relations were derived for 9 out of 9 programs.

Individuals with autism are largely taught using direct contingency learning, limiting their already potentially limited relational repertoire. A multiple baseline design across skills with an embedded multiple probe design was implemented to demonstrate the efficacy of training procedures used to established nonarbitrary relations in the context of block design. The PEAK – Transformation module (PEAK-T) is a curriculum designed to develop the relational repertoire of individuals with and without developmental disabilities, from which procedures were adapted. Training phases were each preceded by test probes of each of the target relations. Transfers of stimulus function were tested by presenting a novel context in which the trained and derived relations were used in completion of a task. The entailment probes across each of the programs showed transfers of function across three relational stimulus classes. All three directly trained relations across three frames resulted in mastery level responding. The results support the efficacy of the PEAK-T curriculum such that complex relational responding can be taught to a child with intellectual disabilities.

vi, 85 p. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / We define and study a gluing procedure for Bridgeland stability conditions in the situation where a triangulated category has a semiorthogonal decomposition. As one application, we construct an open, contractible subset U in the stability manifold of the derived category [Special characters omitted.] of [Special characters omitted.] -equivariant coherent sheaves on a smooth curve X , associated with a degree 2 map X [arrow right] Y , where Y is another curve. In the case where X is an elliptic curve we construct an open, connected subset in the stability manifold using exceptional collections containing the subset U . We also give a new proof of the constructibility of exceptional collections on [Special characters omitted.] . This dissertation contains previously unpublished co-authored material. / Committee in charge: Alexander Polishchuk, Chairperson, Mathematics; Daniel Dugger, Member, Mathematics; Victor Ostrik, Member, Mathematics; Brad Shelton, Member, Mathematics; Michael Kellman, Outside Member, Chemistry

Submitted by Luciane Willcox (luwillcox@gmail.com) on 2016-09-01T16:51:25Z No. of bitstreams: 1 TESE AXEL.pdf: 13901759 bytes, checksum: 6f744b4d3c67d9fcc80db57c1c5944a7 (MD5) / Approved for entry into archive by Luciane Willcox (luwillcox@gmail.com) on 2016-09-01T17:02:42Z (GMT) No. of bitstreams: 1 TESE AXEL.pdf: 13901759 bytes, checksum: 6f744b4d3c67d9fcc80db57c1c5944a7 (MD5) / Made available in DSpace on 2016-09-01T17:02:42Z (GMT). No. of bitstreams: 1 TESE AXEL.pdf: 13901759 bytes, checksum: 6f744b4d3c67d9fcc80db57c1c5944a7 (MD5) / Messenger ribonucleoprotein particles (mRNPs) são complexos formados por RNA mensageiro (mRNA) e um pool de diferentes proteínas que se ligam diretamente ou indiretamente ao mRNA. Proteínas diferentes podem formar diferentes mRNPs com diferentes funções. Agregação de mRNPs formam grânulos que são visíveis ao microscópio. Dois desses grânulos comumente encontrados em células eucarióticas são os processing bodies (PB) e os grânulos de estresse (GE) possuem função fundamental na regulação pós-transcricional, mais especificamente, na degradação (PB) e na estocagem (PB e GE) do mRNA. Enquanto os PB são constitutivamente encontrados, GE são vistos somente em condições de estresse. TTP e RCK são componentes presentes em ambos os grânulos enquanto que TIA1 e TIAR são exclusivos de GE e DCP2 exclusivo de PB. Human Adipocyte Derived Stem Cells (ADSCs) são células-tronco adultas multipotentes com capacidade de autorrenovação e diferenciação em células de diversos tecidos. Desde que pouco se sabe sobre a função dos PB e dos GE durante a diferenciação das células-tronco, nosso objetivo é elucidar a dinâmica e função desses grânulos nestas celulas. Foram utilizadas ADSCs derivadas de cirurgia bariátrica e lipoaspiração. Diversos componentes de PB e de GE foram analisados por Imunofluorescência após 1, 4, 7 e 12 dias de diferenciação adipogênica. Oligos de RNA de interferência (siRNA) específicos para RCK, DCP2, TTP, TIAR e TIA1 foram transfectados concomitantemente com a indução à diferenciação adipogênica e as culturas mantidas por 1, 4, 7 e 14 dias de diferenciação. A diferenciação foi mensurada por intensidade de fluorescência após marcação com AdipoRed. GE são ausentes em ADSCs indiferenciadas e durante a diferenciação como determinado por imunomarcação com TIAR que se localiza predominantemente no núcleo. Interessantemente imunomarcação com TIA1/R mostrou que ADSCs possuem grande quantidade de grânulos contendo TIA1/R em células indiferenciadas e não estressadas. Sob estresse oxidativo há um aumento de PB em ADSCs e a formação de GE. Esses grânulos parecem variar de composição, uma vez que eIF4E é ausente e GE imunomarcados com eIF4B são mais perinucleares do que GE imunomarcados com TIAR. PB variam em número e tamanho em células diferenciadas. Notavelmente, em ADSCs possuem poucos PB e até mesmo ausente em algumas células, além disso, TIA1/R e PB significativamente aumentam após 24 horas de diferenciação e após 12 dias o número de PB é similar a células diferenciadas enquanto que os grânulos de TIA1/R praticamente desaparecem. siRNA de componentes essenciais de PB e GE em ADSCs indiferenciadas (tempo 0) mostrou que há um aumento significativo na diferenciação em adipócito após 4, 7 e 12 dias de diferenciação adipogênica. Interessantemente esse aumento se deu pela maturação do adipócito, i.e. tamanho da vesícula de lipídio e não pelo aumento da quantidade de células diferenciadas. Nossos dados mostram que PB estão em baixo número e que existem grânulos de TIA1/R citoplasmárico nunca antes mostrados em ADSCs indiferenciadas. Ainda, esses grânulos aumentam durante a diferenciação e parecem exercer um papel importante na maturação dos adipócitos uma vez que ensaios de siRNA de componentes de PB e GE levam a uma diferenciação mais acelerada. Também, os GE são formados após indução a estresse oxidativo e esses grânulos são praticamente ausentes de eIF4E mostrando que a composição desses grânulos varia em relação a células diferenciadas.