Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 338-360).

Thesis (Ph.D.) Mississippi State University. Department of Chemistry. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 97-104).

How the linear protein chains fold into their three-dimensional active conformation is one of the remaining puzzles of modern science. Other than molecular chaperones, ribosome - the cellular protein synthesis machinery, has also been implicated in protein folding. The active site of protein folding activity of the ribosome (PFAR) is in the domain V of the main RNA component of the large ribosomal subunit, which also constitutes the peptidyl transferase center. We have characterized the mechanism of PFAR using ribosomes or ribosome-borne folding modulators (RFMs) and human carbonic anhydrase I (HCA) as a model system. RFMs from all three kingdoms of life showed PFAR.  By multiple addition of the denatured protein in the refolding assay we demonstrate that the RFMs can recycle efficiently to assist refolding of a new batch of denatured protein. The turnover of the RFMs, which includes release of the protein substrate, takes milliseconds. Furthermore, fast kinetics of HCA refolding suggests that an early folding intermediate is the substrate for PFAR. Our results demonstrate for the first time that PFAR is catalytic. It was shown that two anti-prion drugs 6AP and GA specifically inhibit PFAR by binding to the domain V of the 23S / 25S rRNA. Using UV-crosslinking followed by primer extension we have identified the interaction sites of 6AP on domain V of 23S rRNA, which overlap with the protein binding sites, and are sensitive to mutagenesis. We find that 6AP and GA inhibit PFAR by direct competition with the substrate protein for the binding sites. Also, 6AP derivatives inhibit PFAR in the same order as their antiprion activity, 6AP8CF3 > 6AP8Cl > 6AP > 6APi. These results suggest involvement of PFAR in prion processes. To clarify the role of PFAR in prion processes, we studied HET-s prion aggregation in the presence of domain V/ IV/II of rRNA. The rRNAs, especially domain V rRNA not only reduced HET-s aggregation, but also changed the morphology of the HET-s fibrils, which became shorter and less compact. These results show that PFAR actively prevents large amyloid aggregation and thus, possibly influence prion propagation.

Submitted by Antonio Bento de Oliveira Junior null (junioreif@hotmail.com) on 2018-01-23T13:42:06Z No. of bitstreams: 1 Tese-final.pdf: 43113195 bytes, checksum: 7cc85051e3a1420a2983ce716e0ae144 (MD5) / Rejected by Elza Mitiko Sato null (elzasato@ibilce.unesp.br), reason: Solicitamos que realize correções na submissão seguindo as orientações abaixo: Problema 01 : A data na capa deve conter somente o ano; Problema 02: A data na folha de aprovação deve ser a data da defesa; Problema 03: Se você teve financiamento da FAPESP é obrigatório constar também na folha de rosto e o numero do processo; Problema 04: As páginas viii, xvi, xviii, 10, 34, 38, 46 e 60 estão em branco; Problema 05: A numeração das páginas deve ser contínua. Caso ainda tenha dúvida consulte, por gentileza o modelo que consta na página da seção de pós-graduação, link Instruções para Qualificação e Defesas :http://www.ibilce.unesp.br/#!/pos-graduacao/instrucoes-para-aluno-que-vai-defender/ Agradecemos a compreensão. on 2018-01-23T17:41:25Z (GMT) / Submitted by Antonio Bento de Oliveira Junior null (junioreif@hotmail.com) on 2018-01-23T18:20:41Z No. of bitstreams: 1 Tese-final.pdf: 42848208 bytes, checksum: 26d4aab1e2a66d06ba87e4533f1cdd40 (MD5) / Approved for entry into archive by Elza Mitiko Sato null (elzasato@ibilce.unesp.br) on 2018-01-24T12:12:56Z (GMT) No. of bitstreams: 1 oliveirajunior_ab_dr_sjrp.pdf: 42589488 bytes, checksum: 6433ad3adeeb7e56b159e54ad745abe2 (MD5) / Made available in DSpace on 2018-01-24T12:12:56Z (GMT). No. of bitstreams: 1 oliveirajunior_ab_dr_sjrp.pdf: 42589488 bytes, checksum: 6433ad3adeeb7e56b159e54ad745abe2 (MD5) Previous issue date: 2017-12-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O enovelamento de proteínas acontece em um espaço de fase multidimensional, onde o número conformações possíveis é exponencialmente alta. Uma forma comum de representar essas conformações é utilizar uma coordenada de reação efetiva (por exemplo, fração de contatos nativos). Porém, como a informação de cada conformação não é representada neste tipo de aproximação estatistifica, alguns mecanismos do enovelamento de proteínas não são possíveis de ser descritos ou analisados. Neste trabalho, usou-se uma métrica para descrever a distancia entre quaisquer duas conformações, essa métrica é calculada levando em conta as distâncias internas dos aminoácidos presentes em cada estrutura. Utilizando-se um método de projeção efetiva é possível ir além da representação em uma dimensão e visualizar a superfície de enovelamento da proteína em duas ou três dimensões. Para aplicar essa metodologia realizou-se simulações computacionais do enovelamento de proteínas utilizando o modelo baseado em estrutura, com aproximação para Cα. Três proteínas foram analisadas: CI-2, o Domínio SH3 e a Proteína A. Dos resultados, foi possível observar que para cada tipo de "motifs"estrutural (folha-β e/ou α-hélice) projetou funis de enovelamento distintos. A partir da visualização foi possível analisar o processo de enovelamento em detalhes, sendo possível identificar a conectividade entre as conformações assim como, possíveis rotas de enovelamento (f olding pathsways). Analisou-se também as diferenças estruturais da rota dominante no domínio SH3 e a competitividade entre a estrutura do estado nativo e do estado espelhado que acontece em proteínas que possuem somente α-hélice, como é o caso da proteína A. / Protein folding occurs in a very high dimensional phase space, in which an exponentially large number of states is represented in terms of one effective reaction coordinate. Since the role of each local minimum is not considered in this statistical approach, the folding mechanism is unveiled by describing the local minima in an effective onedimensional representation. In this work, we used a metric to describe the distance between any two conformations, which is based on internal distances between amino acids in each conformation. A effective projection method allows to go beyond the one-dimensional representation and visualizing a 2D folding funnel representation. Computer simulations of protein folding were performed using Cα structure-based model. Three proteins have been studied: CI2, SH3 Domain and Protein-A. Distinct funnels have been generated according to the major motifs in each proteins, (β-sheet or/and α-helix). The visualization allows assessing the folding process in detail, e.g. by identifying the connectivity between conformations and establishing the paths that lead to the native state and we analyzed structural differences in the dominant route of SH3 and the competitiveness between the native and mirror structures in protein A.

No description available.

Decades have passed since the realisation that a protein’s amino acid sequence can contain all the information required to form a complex three-dimensional fold. Until recently, these encoded structures were thought to be crucial determinants of protein function. Much effort was directed to fully understand the mechanisms behind how and why proteins fold, with natively unfolded proteins thought to be experimental artefacts. Today, the field of natively unfolded – or so-called intrinsically disordered – proteins, is rapidly developing. Protein disorder content has been positively correlated with organismal complexity, with over thirty percent of eukaryotic proteins predicted to contain disordered regions. However, the biophysical consequences of disorder are yet to be fully determined. With the aim of addressing some of the outstanding questions, the work described in this thesis focuses on the relevance of structure within disordered proteins. Whilst populating a variety of conformations in isolation, a subset of disordered proteins can fold upon binding to a partner macromolecule. This folded state may be present within the ensemble of conformations sampled by the unbound protein, opening the question of what comes first: folding or binding? Protein engineering techniques were employed to alter the level of residual ‘bound-like’ structure within the free conformational ensemble, and the consequences on coupled folding and binding reactions were investigated. Resultant changes in the rate of association are easily imaginable; yet, this work demonstrates that the majority of the observed changes in binding affinity were due to alterations in the rate of dissociation, thus altering the lifetime of the bound complex. Promiscuous binding is a touted advantage of being disordered. If many disordered proteins, each with their own conformational ensemble, can bind and fold to the same partner, then where is the folding component encoded? Does the partner protein template the folding reaction? Or, is the folding information contained within the disordered protein sequence? Utilising phi-value analysis on the BCL-2 family of proteins, residues in the disordered sequence were probed to ascertain which form contacts at the transition state of the reaction. Comparison with phi-value analyses of alternative pairs – sharing either the ordered or disordered protein – provides insight into the encoding of these interactions. In the context of a bimolecular reaction, the amino acid sequence of the disordered protein was shown to determine the interactions within the transition state. Thus, analogous to the discovery from decades’ past, it is the sequence of the protein that folds which encodes its pathway, even when binding is a prerequisite.

A contribuição deste trabalho foi orientada principalmente ao desenvolvimento de alternativas de hardware para a execução nativa de bytecodes Java em sistemas embarcados que naturalmente possuem restrições quanto à potência consumida, ao desempenho e à área ocupada. Primeiramente, o desenvolvimento do Femtojava Low- Power demonstra que a utilização de um pipeline e de um banco de registradores interno em arquiteturas de pilha resultam em uma redução significativa no consumo de potência. Após, a técnica de folding, que basicamente transforma várias operações de pilha em uma operação tipo RISC, é avaliada. A análise de uma segunda solução arquitetural, baseada em VLIW (Very Long Instruction Word), também traz resultados satisfatórios na redução do consumo de potência, sendo que a paralelização do código, feita por um analisador desenvolvido, é facilitada devido à utilização de uma arquitetura de pilha. O desempenho e a potência consumida de todas as arquiteturas propostas neste trabalho foram validadas utilizando-se o simulador CACO-PS, também desenvolvido no contexto desta dissertação. Os estudos de caso adotados para a validação das alternativas arquiteturais compreenderam algoritmos matemáticos, de ordenação, busca e processamento de sinais, bastante utilizados no domínio de sistemas embarcados. Resultados promissores principalmente em termos de energia consumida são alcançados, assim como na disponibilização de diferentes arquiteturas para a execução nativa de Java, principal proposta deste trabalho. / The main contribution of this work was the development of hardware alternatives for native execution of Java bytecodes for embedded systems that have power, performance and area constraints. Firstly, the development of the Femtojava Low- Power shows that the use of a pipeline and an internal register bank in stack architectures brings a significant reduction in the power consumption. After that, the folding technique, that basically changes a set of stack operations into a simple RISC one, is evaluated. Then, the analysis of a second architectural solution, based on VLIW (Very Long Instruction Word), demonstrates also good results concerning power consumption. Moreover, it is shown that the parallelization of the code is facilitated due to the specific stack architecture. The power consumption and performance of all architectures here proposed were evaluated using the CACO-PS simulator, which was also developed in this work. The case studies adopted for the validation of the architectures were mathematic, sort, search and DSP algorithms, widely used in the embedded system domain. Promising results mainly in energy consumption were achieved, as well as the disponibilization of different architectures for native execution of Java, the main objective of this work.

Radioactive decay of nuclei via emission of ??-particles is studied using three different theoretical approaches, viz: the quasi-bound state wavefunction approach (QSWA), the superasymmetric ??ssion model (SAFM) and the semiclassical approximation (QCA). The half-lives of the radioactive nuclei, calculated using these methods, are compared with each other and with available experimental data. The resonance wavefunction is obtained by numerically integrating the Schrödinger equation with outgoing boundary conditions. The sensitivity of the calculated decay widths to two particular parameter sets of the Woods-Saxon (WS) optical potentials are studied. Double folding (DF) model calculations to obtain the bare ??-nucleus potential have been carried out with the Reid M3Y effective nucleon-nucleon (NN) interactions. The exchange part of the interaction was taken to be of zero-range pseudo-potential and the density dependence of the NN interaction is accounted for. The effectiveness of the method is demonstrated using both even-even and odd-mass spherical nuclei. / Physics / MSC (PHYSICS)

Korean calligraphy went through tremendous changes during the twentieth century, and Jung Hyun-bok (1909-1973), a gifted calligrapher, played an important role in bringing about these changes. This thesis focuses on one of Jung's most mature and refined works, "Using the Peak of the Five Elders as a Brush," owned by the Jordan Schnitzer Museum of Art. In addition to translating and explicating the poems on the screen, through a close examination of both the form and content of the work I explore how it reflects Jung's values, intentions, and background. This thesis also addresses the question of why some critics have classified Jung as a professional artist and considers some of the ways in which he actually cultivated and projected an image of himself as a traditional literatus.