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      • Translation of DNA into a library of synthetic macrocycles for in vitro selection

        Tse, Brian Noel Harvard University 2008 해외박사(DDOD)

        RANK : 247343

        A central focus of chemical research is the discovery of functional molecules. Nature's strategy, which fundamentally differs from that of a synthetic chemist, relies on an iterative process of translation, selection, and amplification with diversification. Applying this approach to synthetic small molecules necessitates the translation of encoded sequences directly into synthetic structures. DNA-templated synthesis accomplishes this feat by linking chemical reactivity directly to the Watson-Crick pairing of complimentary DNA strands. The properties of DNA-templated synthesis are conducive to synthesizing small molecule libraries. These libraries serve as potential sources of novel biochemical probes and drug candidates. In this thesis, we take advantage of the unique features of DNA-templated synthesis to produce a library of synthetic macrocycles for in vitro selection. The study begins with the synthesis of a pilot library of 65 macrocycles to demonstrate the translation, selection, and amplification of a combinatorial library of synthetic compounds. This also serves to validate our macrocycle synthetic route. We then expand on this work by performing an intense study into the relationship between sequence content and DNA-templated reactivity. Here, we reveal that a regime of maximal reactivity exists between the extremes of too much and too little secondary structure. Since secondary structure can be computationally screened, this work enables us to generate effective codon sets for future DNA-templated library synthetic efforts. We also improve upon our pilot library scheme by adopting a capping strategy; this increases the robustness and yield of our synthetic approach. After a detailed study of building block compatibility, we construct a series of sublibraries to evaluate the reactive efficacy and sequence fidelity of our template/reagent pairs. The effort culminates in the DNA-templated synthesis of a library of >13,000 macrocycles. This library will be used for in vitro selection against a variety of interesting biological targets. The sufficient diversity, size, and quality of the library suggest a favorable outlook for probe discovery.

      • Quality Control Mechanisms of Molecular Chaperones in the Folding and Degradation of Client Proteins

        Tse, Eric ProQuest Dissertations & Theses University of Mich 2017 해외박사(DDOD)

        RANK : 247343

        Molecular chaperones are essential proteins that assist in the folding of substrate 'client' proteins to adopt their functionally active three-dimensional structures. The process of protein folding in the cell occurs in a highly concentrated cro.

      • Sequence and structure of influenza Hemagglutinin cleavage site modulate viral pathogenesis

        Tse, Long Ping Victor ProQuest Dissertations & Theses Cornell University 2014 해외박사(DDOD)

        RANK : 247343

        Viruses are obligatory intracellular pathogens requiring host machinery for survival and reproduction. Differing from living organisms, which can grow where nutrients are available, viruses absolutely require hijacking of host machineries to complete their life cycle. Enveloped viruses evolved to have dedicated strategies to passively sense environmental cues to ensure that initiation of infection occurs at the correct moment and place. One general strategy used by enveloped viruses is to precisely control activation of their envelope glycoprotein just prior entry into host cells. Influenza A virus (AIV) is the causative agent of influenza illness and causes both economical and public health problems globally and annually. As a successful pathogen infecting a wide range of animals, IAV excels in sensing the environment to ensure efficient infection by employing two sequential activating steps during viral entry: proteolytic cleavage for priming of the hemagglutinin (HA) and low-pH-triggered conformational changes allowing release of the fusion peptide. Proteolytic cleavage of influenza HA controls viral pathogenesis by influencing viral growth rate and viral tropism. The primary sequence and tertiary structure of the HA determine the overall properties of HA activation and hence, viral pathogenesis. Mutations on the primary sequence of the HA cleavage site affect viral activation in two dimensions, 1) HA activation efficiency and 2) alteration in protease repertoire for HA activation. The former modulates viral growth kinetics and the later is important for viral tropism. Mutations that modifies HA tertiary structure also play an important role in viral activation, in particular virus growth. In this thesis, I describe three interrelated studies of mutations on primary and tertiary structure of HA and their consequence on HA cleavage and viral pathogenesis. These mutations also allow influenza virus to interact with prokaryotic pathogens and open up another dimension in virus-bacteria-host interactions and synergy.

      • A Comparative Study of Four American Professional Wind Bands

        Tse, Mark University of Washington ProQuest Dissertations & 2020 해외박사(DDOD)

        RANK : 247343

        This study compares the repertoire, business models, and philosophies of four American professional wind bands; Dallas Winds, Lone Star Wind Orchestra, San Diego Winds, and the Royal Hawaiian Band. For the purposes of this study, “professional” is defined as generating sufficient income to pay the performers.The Royal Hawaiian Band is an outlier of professional wind bands because of its history and function. The other three bands perform two to nine concerts per season like the first American orchestras. For these young professional bands to achieve comparable success as current professional orchestras, they should make similar revolutionary leaps (not evolutionary steps) that early American orchestras made to guarantee their performers a full season of concerts, enough to provide a livable income.

      • Electrical properties of nanostructured carbons in aqueous and non-aqueous electrolytes

        Tse, Kiu-Yuen The University of Wisconsin - Madison 2007 해외박사(DDOD)

        RANK : 247343

        Nanostructured carbons have many interesting and useful properties such as high surface area and excellent chemical and electrochemical stability. Due to these properties, nanostructured carbons have potential in a wide variety of applications such as electroanalysis, chemical/biological sensing, energy storage, and catalysis/electrocatalysis. This work reports investigations of the electrical properties of as-grown and chemically modified nanostructured carbon interfaces in various electrolytes. Particular emphasis is placed on two materials: (1) polycrystalline diamond (PCD) and (2) vertically aligned carbon nanofibers (VACNFs). Using a combination of surface analysis and electrochemical methods, the chemical, electrical properties and their interplay were studied. The influence of the atomic structure on the interfacial capacitance and electron transfer processes was investigated. Using electrical impedance spectroscopy, contributions from the individual components of the complex interface such as carbon substrate, the molecular layer and the electrolytes were separated. The results have implications for using nanostructured carbons as ultra-stable, chemically tunable substrates.

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