Oligomers which have a tendency to form well-defined secondary structures are called foldamers. They offer an attractive opportunity for the design of novel molecules that mimic the structures and functions of proteins and enzymes including biocatalysis and biomolecular recognition. Herein a new class of non-natural γ-AApeptides and their derivatives are synthesized and studied in our lab. Previous studies of γ-AApeptides have revealed that they are highly resistant to proteolysis, and have virtually limitless potential in functional group diversity. However, to improve the bio-activity and explore new bio-applications, the understanding of the folding conformation of γ-AApeptides are necessary. Thus, NMR spectroscopy is used to interpret the 3D structures of these γ-AApeptides. The two-dimensional solution NMR spectroscopy data for those sequences demonstrate right-handed helical structures. Further development of γ-AApeptide may lead to new foldamers with discrete functions, enabling expanded application in chemical biology and biomedical sciences.

Theories of perception can broadly be divided into two groups: orthodox and heterodox theories (Noë & Thompson, 2002). Orthodox theories of perception consider perception as a neurological process, i.e. as a phenomenon which can be explained solely in terms of intracranial facts. Heterodox views expand this scope, maintaining that an understanding of perception must include extracranial facts, or facts about the environment in which a perceiver is situated (ibid.). This thesis will attempt to defend a particular exemplar of this heterodox approach, namely the enactive theory of perception proposed by Alva Noë. The thesis has two primary goals. First, I will attempt to offer an exegesis of Noë's theory, attempting to clarify the scope and strength of Noë's view. Secondly, I will consider the particular objections leveled against Noë, and heterodox theories more generally, by Ken Aizawa. I conclude that Noë's theory can better account for the nature of perception.

Thesis (M.A,)--Cincinnati Christian University, 2005. / Abstract and vita. Includes bibliographical references (leaves 106-108).

Thesis (M.A,)--Cincinnati Christian University, 2005. / Abstract and vita. Includes bibliographical references (leaves 106-108).

La presente tesis pretende establecer un puente entre el modelado, identificación y control de sistemas y la microelectrónica, aportando una herramienta con la capacidad de afrontar requerimientos de velocidad, precisión y tamaño de implementación. Así mismo pretende, implementar algoritmos de identificación que puedan ser desarrollados en un chip y proveer un análisis de los errores que se producen como consecuencia de la digitalización y operaciones de punto fijo. / This thesis aims to establish a bridge from modeling, identification and control systems to microelectronics, providing a tool with the ability to meet requirements of speed, accuracy and size of the implementation. Furthermore, implement an identification algorithm that can be implemented on the chip and provide, also, an analysis of the errors occurring as a result of digitization and fixed point operations.

<p>A molecular depiction of the assembly, interaction and regulation of protein complexes is essential to the understanding of biological functions of protein complexes. Structural analysis of protein complexes by Nuclear Magnetic Resonance (NMR) has relied heavily on the detection and assignment of intermolecular Nuclear Overhauser Effects (NOEs) that define the interactions of protons at the molecular interface. Intermolecular NOEs have traditionally been detected from 3-D half-filtered NOE experiments by suppressing intramolecular NOEs prior to NOE transfer. However, due to insufficient suppression of undesirable signals and a lack of dispersion in the H dimension, data analysis is complicated by the interference of residual intramolecular NOEs and assignment ambiguity, both of which can lead to distorted or even erroneously packed protein complex structures. Leveraging the recent development of fast NMR technology based on sparse sampling in our lab, we developed a strategy for reliable identification and assignment of intermolecular NOEs using high resolution 4-D NOE difference spectroscopy. Spectral subtraction of individually labeled components from a uniformly labeled protein complex yields an "omit" spectrum containing only intermolecular NOEs with little signal degeneracy. </p><p>The benefit of such a strategy is first demonstrated in structural analysis of a homooligomeric protein complexes, the foldon trimer. We show that intermolecular NOEs collected from the 4-D omit NOE spectrum can be directly utilized for automated structural analysis of the foldon trimer by CYANA, whereas intermolecular NOEs derived from 3-D half-filtered NOE experiments failed to generate a converged structure under the same condition. </p><p>Such a strategy was further demonstrated on a heterodimeric protein complex in translesion sysnthesis (TLS), a DNA damage tolerance pathway. The TLS machinery consists of several translesion DNA polymerases that are recruited to the stalled replication fork in response to monoubiquitinated proliferating cell nuclear antigen (PCNA) in order to bypass DNA lesions encountered during genomic replication. The recruitment and assembly of translesion machinery is heavily dependent on ubiquitin-binding domains, including ubiquitin-binding motifs (UBMs) and ubiquitin-binding zinc fingers (UBZs) that are found in translesion DNA polymerases. Two conserved ubiquitin-binding motifs (UBM1 and UBM2) are found in the Y-family polymerase (Pol) &iota, both of which contribute to ubiquitin-mediated accumulation of Pol &iota during TLS. Although the Pol&iota UBM2-ubiquitin complex has been previous reported by our lab and others, the Pol &iota UBM1-ubiquitin complex has remained a challenge due to significant signal overlap in conventional 3-D NOE spectroscopy. In order to determine the molecular basis for ubiquitin recognition of Pol &iota, we solved the structures of human Pol &iota UBM1 and its complex with ubiquitin by 4-D fast NMR, revealing a signature helix-turn-helix motif that recognizes ubiquitin through an unconventional surface centered at L8 of ubiquitin. Importantly, the use of 4-D omit NOE spectroscopy unambiguously revealed an augmented ubiquitin binding interface that encompasses the C-terminal tail of UBM1.</p><p>4-D omit NOE spectroscopy was also used to study the Fanconi anemia associated protein 20 (FAAP20)-ubiquitin complex within the Fanconi Anemia (FA) complexes required for efficient repair of DNA interstrand crosslinks (ICLs), a process that is mediated by the ubiquitin-binding zinc finger (UBZ) domain of FAAP20. Unexpectedly, we show that the FAAP20-ubiquitin interaction extends beyond the compact UBZ module and is accompanied by transforming the disordered C-terminal tail of FAAP20 into a rigid &beta-loop, with the invariant C-terminal tryptophan (W180 of human FAAP20) emanating toward I44 of ubiquitin for enhanced binding. Accordingly, alanine substitution of the absolutely conserved C-terminal tryptophan residue of FAAP20 abolishes ubiquitin binding and impairs FA core complex-mediated ICL repair <italic>in vivo<italic>.</p><p>Reliable detection and unambiguous assignment of intermolecular NOEs is essential to NMR-based structure determination of protein complexes. The development of 4-D omit NOE spectroscopy in this thesis overcomes many limitations of conventional 3-D half-filtered experiments to allow for reliable detection and unambiguous assignment of intermolecular NOEs of heterodimeric complexes and homooligomeric complexes. These advantages render such a strategy particularly attractive for structural studies of protein complexes by biomolecular NMR.</p> / Dissertation

Annotation: The seven Noahide laws represent a divine non-Jewish complementary to Jewish law. This thesis has been looking for an answer to the question about concept of those laws, their content, intentions and contemporary use. The main method is analysis of original sources and investigating their mutual relations. Comparison of contemporary guides is also included.

[pt] Leitura de traços convergentes que atualizam a questão da modernidade na obra de Miguel Torga. A escolha dos tópicos, centrada na análise de determinados marcadores textuais, objetiva evidenciar os elementos agenciadores do discurso, bem como estabelecer os mecanismos que levam à busca de um sentido de identidade e de um sentimento de universalidade, propiciadores da descoberta da unidade, que se fundamenta na redescoberta de si mesmo e da terra portuguesa. / [en] A reading of converging outlines that bring up to date the question of modernity in Miguel Torga work. The choice of themes, centered on the analisys of certain textual traits, has the purpose of turning clea the structural elements of the discourse, as well as establishing the mechanism that lead to the search of a sense of identy and a communal feeling, facts that favour the unveiling of unity, which is based in the rediscovery of self and of the portuguese land.

Les méthodes RMN standard appliquées à l'analyse structurale des protéines sont basées sur la mesure d'informations géométriques locales entre protons. Le manque de contraintes à longue portée est un facteur limitant pour l'étude des protéines modulaires, des complexes protéiques et des assemblages supramoléculaires. La deutération des échantillons est nécessaire pour l'étude de ces systèmes de grande taille. Néanmoins, le remplacement des protons par du deutérium limite le nombre de contraintes structurales détectables, en particulier des contraintes de distances de types NOEs. Pour résoudre ce problème, une stratégie basée sur la protonation de quelques sites discrets a été mise en place. La protonation spécifique des méthyles dans des protéines constitue un choix optimal pour l'obtention de contraintes à longue portée. Les protocoles de marquage spécifique des méthyles des Isoleucines, des Valines et des Leucines ont été implémentés et optimisés, et une nouvelle méthode de protonation spécifique des Alanines a été développée. Dans des systèmes de taille modérée, l'utilisation de ce type de marquage combiné aux développements d'expériences RMN adaptées permet la détection de contraintes (NOEs et RDCs) entre paire de méthyles séparés par plus de 12 Å. Une méthode robuste a été développée pour extraire des distances avec une très haute précision. Cette approche s'applique également à des protéines de grande taille, ainsi des NOEs entre méthyles distants par plus de 7 Å sont détecté dans un assemblage supramoléculaire de 468 kDa.

This thesis dedicates to implementation of the boys' orphanage in developing country. The project belongs to Little Noah Foundation, while significant partner for direct realization is non-government organization Njovu. This thesis is classically created by theoretical and practical parts. The theoretical part defines frequented concepts, informs about actual situation in the country, especially in west province of Zambia, and contains information about organizations participated into this project. The practical part continues to theoretical knowledge, defines goal and methodology of thesis and mainly presents results of its. The goal, which follows this thesis, is to map out the progress of boys' orphanage in Mongu. In the line with the thesis they are asked these research questions: Why was this boys' orphanage established in Mongu? How was the project progressing? What are the results of the project? I have chosen qualitative research to answer the research questions. During my residence there and active participating to realization of project (February December 2014) I have used methods of observation, questioning and analysis of the data. The results of this thesis are created by profound SWOT analysis of the project, approach of personal securing, describing of process of intake of children and case reports of adopted children, whose value is in demonstrating of local social reality. Numerous supplements illustrate presented information. Discussion summarizes and recapitulates results and their outputs are recommendations and notices for similar starting projects. Very important aspect for whole thesis is to implant it into the context of very different conditions. The contribution of the project is especially in promoting of family model of childcare in institution. Family character of this orphanage is specified by relatively low number of children and the caregivers are married couple with two own children. This thesis brings interrelated and concrete and detailed information about whole project and its progress. This thesis may be used like source of information about concrete project, like documentation of start of Little Noah Children's Home and as well it can be some kind of inspiration for similar projects in developing countries.