Submitted by Pedro Barros (pedro.silvabarros@ufpe.br) on 2018-07-27T19:05:47Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Valmir Joaquim da Silva Junior.pdf: 960136 bytes, checksum: 45ed78e652f34ca5f6167c4691220304 (MD5) / Approved for entry into archive by Alice Araujo (alice.caraujo@ufpe.br) on 2018-08-02T21:55:38Z (GMT) No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Valmir Joaquim da Silva Junior.pdf: 960136 bytes, checksum: 45ed78e652f34ca5f6167c4691220304 (MD5) / Made available in DSpace on 2018-08-02T21:55:38Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Valmir Joaquim da Silva Junior.pdf: 960136 bytes, checksum: 45ed78e652f34ca5f6167c4691220304 (MD5) Previous issue date: 2017-02-10 / Reconhecendo uma relação dialética entre sociedade e linguagem, que já vem sendo explorada por diversos autores e áreas de estudo, entendemos que é da fricção entre ambos que as identidades emergem e se moldam. Assim, este trabalho analisa a construção de identidades dos moradores de Tejucupapo, um povoado pertencente ao município de Goiana, em PE. Essa análise foi feita através das orações com verbos de cognição, tais orações são entendidas como Processos Mentais dentro do escopo da Linguística Sistêmico-Funcional (HALLIDAY 1999; HALLIDAY & MATHISSIESSEN 2014). Os autores propõem que nossas experiências são representadas através do Sistema de Transitividade, o qual é composto por seis tipos de Processos, entre eles, os Processos Mentais. Baseamo-nos, também, em Figueredo (2007; 2011), uma vez que esse autor apresenta aspectos do funcionamento dos Processos Mentais em seus estudos. Além dos Processo Mentais, guiamos nossa análise pelos Princípios de Identidade, formulados por Bucholzt e Hall (2005). O corpus da pesquisa é composto por dez entrevistas, em formato de áudio, realizadas por Cordeiro da Silva (2015) para sua tese de doutorado, em que o pesquisador investigou a construção da cláusula completiva nos dizeres dos moradores de Tejucupapo. Ainda trazemos uma breve discussão de como a entrevista se alinha aos conceitos de identidade e são bastante utilizadas em trabalhos sobre o tema. A análise das orações com Processos Mentais, feita basicamente através dos Processos Gostar, Ver, Achar, Saber e Querer, revelou variados traços identitários dos tejucupapenses, entre eles, a importância dada ao exercício de alguma atividade profissional e o apreço pelo trabalho de pesca na maré realizado por eles. Também pudemos visualizar como foram percebidas e sentidas diversas modificações pelas quais passaram Tejucupapo e seus habitantes ao longo dos anos. Como essas mudanças, tais como o aumento da violência, o aparecimento das drogas, algumas melhorias, ainda que poucas, nas condições de vida no lugar etc, foram capazes de transformar hábitos e comportamentos e, assim, alterar as identidades deles e as de seus conterrâneos. Por fim, foi unânime o desejo de, num futuro próximo, uma vida melhor, tanto para eles, quanto para seus filhos e netos. / Recognizing a dialectic relationship between society and language, that already has been explored by several authors and study areas, we believe it is the friction between both the identities emerge and shape. So, this research aims to analyse multiple identities of Tejucupapo residents, a village in Goiana, Pernambuco. This study will be done through cognitive mental verbs. These clauses are understood as Mental Processes within scope of the Systemic-functional Linguistics (HALLIDAY 1999; HALLIDAY & MATHISSIESSEN 2014). The author suggests our experiences are represented through Transitivity system, which is composed of six types of processes, among them, the Mental Processes. Theses processes are responsible to represent the world inside of our conscience. They are able to externalize what is thought, felt and desired etc, indicating, affection, feeling, cognition, desire, value and belief judgment, for example. Also based in Figueredo (2007;2011) once this author represents operational aspects of Mental Processes in his studies. In addition to the Mental Processes, we guide our analysis by the Principles of Identity formulated by Bucholzt and Hall (2005). Our corpus consists of ten audio interviews made by Cordeiro of Silva (2015) for his doctoral thesis which the researcher investigated the construction of the completive clause in the words said by the residents of Tejucupapo. We still present a brief discussion of how the interview is aligned with the concepts of identity and are widely used in research about this subject. The analysis of clauses with Mental Processes, basically done through the Processes to Like, to See, to Think, to Know and to Want revealed a variety of identitary traits among the tejucupapenses, among them the importance given to the exercise of some professional activity and appreciation for fishing work in the Tide performed by them. We have also been able to visualize how various modifications were perceived and felt by Tejucupapo and the inhabitants over the years. As these changes, such as violence increase, the emergence of drugs, some improvements, although few, in living conditions in the Village etc., were able to transform habits and behaviors and thus change their identities and those of their countrymen. Finally, there was a unanimous desire for a better life in the near future, both for them and for their children and grandchildren.

Late SV40 factor (LSF) is a CP2 family transcription factor involved in cell cycle regulation. In liver cancer, LSF is an oncogene, in part due to its role in upregulation of osteopontin leading to increase tumor size. As a result, LSF is a potential target for drug discovery. LSF binds the p65 subunit of the transcription factor NFkB and also the transcription factor ying yang 1 (YY1). In this thesis, I show that binding of both YY1 and p65 occurs at the ubiquitin-like domain of LSF in U2OS cell extracts. Interestingly, when phosphatase inhibitors are added during preparation of U2OS cell extracts, the binding of YY1 and p65 to LSF shifts from the ubiquitin-like domain of LSF to the DNA binding domain. The role of a yet unidentified docking protein may be responsible for this shift in binding. In an attempt to map the specific region of the LSF sequence that is involved in these interactions, I have developed a peptide identification assay which utilizes protease digestion, protein mediated peptide capture, and LC ESI-MS. Through the use of this assay, I'm confident that the sequence(s) involved in these LSF protein-protein interactions can be further defined.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Current treatments are subpar, with late stage diagnosis and poor prognosis contributing to limited treatment options. The evolutionarily conserved, ubiquitously expressed transcription factor LSF is overexpressed in HCC, and its expression is positively correlated with disease severity. Certain small molecules, known as Factor Quinolinone Inhibitors (FQIs), specifically inhibit LSF DNA-binding activity, inhibit HCC cell proliferation in vitro and prevent tumor growth in an endogenous mouse liver cancer model without apparent toxicity. The targeting of transcription factors by small molecule inhibitors has been historically difficult (Dunker and Uversky, 2010), warranting further molecular investigation into the requirement for LSF in HCC to confirm that the anti-tumor effects of FQIs are the consequence of LSF inhibition. This body of work investigates a dual approach for inhibiting LSF function in order to determine the molecular consequences for HCC cells. To identify the specific point of the cell cycle where LSF is required for HCC proliferation, synchronous HCC cells were treated with FQI or with short interfering RNA to reduce levels of LSF. The results indicate that LSF is required for proper mitotic progression in HCC cells. Specifically, these data show a reduction of key mitotic regulators Aurora Kinase B and Cdc20, at the level of mRNA and protein expression. Time-lapse microscopy also demonstrated an increase in the time for progression through mitosis, with a prometaphase/metaphase delay. Immunofluorescence analysis revealed a prometaphase delay plus aberrant cell division and generation of multi-nucleated cells. These findings were consistent with both FQI1 treatment and RNA interference. Additionally, shorter incubation with FQI1 surprisingly revealed a distinct, non-transcriptional regulation of mitosis in HCC cells, suggesting that mitotic regulation by LSF is multi-faceted. As a targeted therapy for use in the clinic, the in vivo toxicity of FQIs is critical to investigate. Whole blood provides populations of rapidly dividing normal cells that can test susceptibility to anti-mitotic compounds. When mice were treated with FQI1, the blood analysis showed no toxicity. Taken together, these findings indicate that LSF is a mitotic regulator in HCC, further supporting the therapeutic promise of molecular therapies targeting LSF. / 2019-03-04T00:00:00Z

Factor Quinolinone Inhibitor 1 (FQI1), discovered as a small molecule inhibitor of the transcription factor LSF, causes cell death in many cancer cell lines and inhibits tumor growth in tumor xenografts and an endogenous hepatocellular carcinoma model in mice. Significantly, multiple animal studies have shown minimal to no toxicity after FQI1 treatment, making it a promising potential lead chemotherapeutic for multiple cancer types. In determining how FQI1 causes cancer cell death, it was previously shown that FQI1 treatment, like knockdown of LSF expression by siRNA, produced a mitotic arrest with condensed but unaligned chromosomes, but with no clearly observable transcriptional dysregulation. In this thesis, I establish that introducing FQI1 to cells already in mitosis induces a mitotic arrest in colorectal cancer cells, demonstrating that FQI1 inhibits mitotic processes directly while these processes are occurring. This mitotic arrest is characterized by defects in the mitotic spindle and limited connections of mitotic spindles to the kinetochores, as indicated by a dramatic decrease cold-stable microtubules in mitosis. Additionally, in a dose-dependent manner, FQI1 treatment resulted in supernumerary γ-tubulin-containing mitotic centrosomes and γ-tubulin-deficient aster-like bodies, indicating a defect in centrosome stability. As FQI1 is known to be a specific inhibitor of LSF, with its dose dependence for LSF inhibition directly proportional to its ability to inhibit cell proliferation, these findings suggested the novel hypothesis that LSF regulates mitosis through non-transcriptional mechanisms by interacting with key mitotic proteins required for proper spindle formation and metaphase alignment. By mass spectrometry, multiple proteins were identified that interact with biotinylated LSF in mitosis in a FQI1-sensitive manner, with several related to the formation and stability of the mitotic spindle. Proximity ligation assays validated endogenous LSF interactions with CKAP5, a processive microtubule polymerase that protects kinetochore microtubules from depolymerization, and MISP, a requirement for proper mitotic spindle positioning. However, in this assay these interactions were not demonstrably FQI1-sensitive. In conclusion, FQI1 treatment results in defects in kinetochore-microtubule attachment and centrosome stability, triggering a mitotic arrest. Combined with the target specificity of FQI1, this suggests the hypothesis that LSF is required for proper mitotic spindle formation through its protein interactions in mitosis. / 2022-10-16T00:00:00Z

Epilepsy is a neurological disorder that causes recurrent and unprovoked seizures due to imbalances in synaptic transmission in distinct regions of the brain. In both human patients and animal models of epilepsy, there is a marked increase in brain-derived neurotrophic factor (BDNF), a critical signaling molecule in the brain that contributes to two divergent pathways important to disease pathology: 1) the regulation of type A receptors for the major inhibitory neurotransmitter GABA (GABAARs), and 2) aberrant neurogenesis with ectopic expression of new neurons from progenitor cells that disrupt neural network activity in the hippocampus. The first part of my thesis addresses how neurons regulate levels of α1-containing GABAARs through BDNF signaling at its receptors, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR). I hypothesized and showed that BDNF, working at TrkB, rapidly activates the Janus kinase and signal transducers and activators of transcription (JAK/STAT) pathway in neurons and identified a novel intracellular receptor signaling complex composed of p75NTR and JAK2 that is present in neuronal processes, cell body, and nucleus. Based on this finding, we suggest that an intracellular p75NTR/JAK2 signalsome recruits STAT3, a transcriptional activator of the gene coding for the cAMP inducible early repressor (ICER) that blocks synthesis of α1 subunits reducing synaptic GABAARs in response to status epilepticus. This model is consistent with our collaborative studies that show a JAK2 inhibitor, WP1066, inhibits development of spontaneous seizures in an epilepsy model and my observation that WP1066 degrades JAK2 protein in primary neurons. The second part of my thesis addresses BDNF regulation of the Late SV40 Factor (LSF), a ubiquitous transcription factor that regulates cell cycle progression and survival. I show that BDNF through the mitogen-activated protein kinase pathway selectively phosphorylates LSF at serine 291 (p291LSF) and that p291LSF is present throughout neurogenesis, increases with status epilepticus in the hippocampus, and is highest in structures associated with neurogenesis (such as olfactory bulb and hippocampus when compared to cortex). Taken together, these results suggest LSF may play an important role in neuronal development and potentially in epilepsy, providing an additional target for future therapeutic intervention. / 2016-12-15T00:00:00Z

[pt] Com o crescimento gigantesco da Internet e dos sistemas de comunicações móveis celulares, as aplicações de processamento de voz nessas redes têm despertado grande interesse . Um problema particularmente importante nessa área consiste no reconhecimento de voz em um sistema servidor, baseado nos parâmetros acústicos calculados e quantizados no terminal do usuário (Reconhecimento de Voz Distribuído). Como em geral estes parâmetros não são os mais indicados como atributos de voz para o sistema de reconhecimento remoto, é importante que sejam examinadas diferentes transformações dos parâmetros, que permitam um melhor desempenho do reconhecedor. Esta dissertação trata da extração de atributos de reconhecimento eficientes a partir dos parâmetros dos codificadores utilizados em redes móveis celulares e em redes IP. Além disso, como a taxa dos parâmetros fornecidos ao reconhecedor de voz é normalmente superior àquela com a qual os codificadores geram os parâmetros, é importante analisar o efeito da interpolação dos parâmetros sobre o desempenho do sistema de reconhecimento, bem como o melhor domínio sobre o qual esta interpolação deve ser realizada. Estes são outros tópicos apresentados nesta dissertação. / [en] The huge growth of the Internet and cellular mobile communication systems has stimulated a great interest in the applications of speech processing in these networks. An important problem in this field consists in speech recognition in a server system, based on the acoustic parameters calculated and quantized in the user terminal (Distributed Speech Recognition). Since these parameters are not the most indicated ones for the remote recognition system, it is important to examine different transformations of these parameters, in order to allow a better performance of the recogniser. This dissertation is concerned with the extraction of efficient recognition features from the coder parameters used in cellular mobile networks and IP networks. In addition, as the rate that parameters supplied for the speech recogniser must be usually higher than that generated by the codec, it is important to analyze the effect of the interpolation of the parameters over the performance of the recognition system. Moreover, it is paramount to establish the best domain over which this interpolation must be carried out. These are other topics presented in this dissertation.

No description available.

[pt] Este trabalho examina o impacto da quantização vetorial das LSFs sobre a qualidade de voz em codecs a baixas taxas operando em redes IP e em diversos ambientes ruidosos. São considerados diferentes esquemas de quantização vetorial (QV) multiestágio com busca em árvore envolvendo QV sem memória e QV preditiva chaveada com 2 e 4 classes. A distribuição de perda de quadros em redes IP foi modelada de acordo com o Modelo de Gilbert e a avaliação de desempenho foi realizada tanto em termos das distorções espectrais como da qualidade de voz resultante de codecs a baixas taxas. Ainda neste trabalho, foi avaliada a qualidade da voz codificada após a utilização de uma técnica de supressão de ruído baseada em transformadas wavelets (Wavelet Denoising). / [en] This work investigates the impact of LSF vector quantisation over the voice quality in low rate codecs operating in IP networks. Tree-structured multistage vector quantisation (VQ) schemes involving memoryless VQ and switched-predictive VQ with 2 and 4 classes are considered. The packet loss frame distribution in IP networks was modelled according to the Gilbert Model and the performance was carried out both in terms of spectral distortions and the speech quality at the out put of low rate codecs. In this work, we also evaluated the quality of the coded speech after employing Wavelet Denoising.

A motivação inicial deste trabalho foi o interesse pelo desenvolvimento de estratégias argumentativas mais eficazes de ensino de produção textual na escola básica, no âmbito dos gêneros organizados segundo modo argumentativo. Além disso, motivou-nos também a percepção de que um grande número de alunas leem, hoje, crônicas voltadas para o público feminino, tendo seu discurso altamente influenciado pelo conteúdo ideológico-comportamental por elas veiculado o que acaba se refletindo nos textos que escrevem nas aulas de redação. Esse fato chamou nossa atenção, o que nos levou a perceber, também, a vendagem em massa de livros de autoajuda para mulheres. Percebemos que, ao examinarmos as escolhas linguísticas de um discurso de autoajuda, poderíamos trazer à tona algumas crenças e alguns valores, subjacentes à mensagem relativa à experiência de ser mulher e invisíveis para quem aceita esse tipo de discurso como algo natural. Analisaremos então - tendo como suporte teórico a Linguística Sistêmico-Funcional proposta por Halliday, no escopo da transitividade cinco crônicas voltada para o público feminino, com características dos discursos de autoajuda, em cujos textos se vê um grande quantitativo de estratégias argumentativas (algumas clichês) para o convencimento do leitor, estratégias essas apoiadas nas escolhas linguísticas de seus autores, cujo objetivo claro é a produção de determinados sentidos / The initial motivation of this work was the interest by the development of the most efficient text productions strategies on elementary and high school. Furthermore prompted us, that a large number of female students read crhonichals directed to women audience, having their speech heavily influenced by behavioral- ideological content conveyed by them which is reflected in the texts they write in writing production classes. We realized that when we examine the grammatical choices of a self-help text could bring out some beliefs and some values that belongs to the message, and would say invisible to those who accept this type of speech as something natural. Thinking this way, we form our corpus from five chronics for the female audience, because we believe that this specimen contained a lot of characteristics that also appeared in texts belonging to what we call self-help and we will analyze them supported by Systemic Functional Linguistics proposed by Halliday. Our goal is therefore to characterize self-help women's texts chronics as argumentative structure very similar to argumentative structure of the proverbs, establishing the necessary links between the use of clichés phrases and their persuasive objectives facing to women in general and evaluate the argumentative strategies used by the authors of self-help books as exemplars for the production of argumentative texts in school. With this, we hope we contributed to form critical readers able to realize the common sense and the cliché in argumentative texts such as texts of self-help books and to form producers of argumentative clear objectives and effective texts in view of the communicative goal of its author

O presente projeto de pesquisa trata da investigação detalhada dos aspectos relacionados à \'\'Região Ótima\" do campo de radiação, particularmente voltada a sistemas mamográficos. Tal região foi definida em pesquisas anteriores como a faixa do campo onde o sistema apresenta sua melhor performance em termos de resolução espacial, produzindo, portanto, imagens mais nítidas. A investigação aqui proposta tomará por base a associação de dois métodos de avaliação de sistemas de imagem radiológica, que empregam simulação computacional para determinar as Funções de Transferência de Modulação (FTMs) - método de simulação a partir da FEL [SCHIABEL92] e método de simulação a partir da FEP [MARQUES92] - devidas ao ponto focal em diversas orientações e posições do campo. A finalidade é propor um método de prever a existência e extensão da Região Ótima, bem como seu significado prático para a nitidez da imagem e para a utilização de equipamentos mamográficos não isotrópicos, através de comparações entre os modelos de simulação. A comprovação prática dos resultados e das conclusões foi complementada com avaliações de imagens radiográficas feitas com \"phantoms\". / The propose of this work is to make a detailed investigation related with the optimum region aspects of x-rays radiation fields, specially in mammographic systems. Previous researches defined the optimum region as a field range where the system produces the best performance and best sharpened images.This investigation is based on the association of two analysis methods of radiological imaging systems which use computational simulation to determine the focal spot Modulation Transfer Function (MTF) - simulation method of Spread Line Function [SCHIABEL92] and simulation method of Spread Point Function [MARQUES94] - in severa! orientations and x-ray field positions. The intent is to propose a method to preview the existence of the optimum region, as well its practical meaning for the image sharpness and the utilization of a non-isotropic mammographic equipment, through comparison between both simulation models. The practical validation of the results and conclusions was complemented with the valuation of some radiographic images made with \"phantoms\".