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Thesis (M.S.) in Mechanical Engineering--University of Maine, 2008. / Includes vita. Includes bibliographical references (leaves 111-113).

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PhD, Faculty of Health Sciences, University of the Witwatersrand, 2009 / Chronic infection with the hepatitis B virus (HBV) is a major risk factor for cirrhosis and hepatocellular carcinoma, which is the sixth most common cancer worldwide. Available treatment for chronic HBV infection has limited efficacy in preventing associated complications. The compact and multifunctional nature of the viral genome limits its mutability making HBV an ideal candidate for therapy based on nucleic acid hybridisation. The potent and specific gene silencing that can be achieved with RNA interference (RNAi) has fueled interest in exploiting this pathway as a therapeutic modality. Synthetic and expressed RNA sequences have been used to activate RNAi. These engineered sequences mimic natural substrates of the RNAi pathway, which allows them to enter and reprogramme the pathway to effect silencing of intended targets. Tradionally expressed RNAi activators have been transcribed as short hairpin RNA (shRNA) sequences from RNA polymerase III (Pol III) promoters. These shRNA mimic precursor microRNA (pre-miRNA) and consequently enter the RNAi pathway at a relatively late stage. Overexpression of shRNA sequences from Pol III promoters, specifically the U6 promoter, has been associated with toxic side effects and has raised concerns about the use of expressed RNAi activators. Another concern of developing therapeutic RNAi expression cassettes is the emergence of HBV mutants that are resistant to silencing by a single expressed RNAi effecter. These points have highlighted the need for the development expressed RNAi activators that are effective at low concentrations and capable of combinatorial silencing. To address these issues the aim of this study was to assess the feasibility of anti HBV effecter sequences that mimic an early substrate (viz. primary miRNA or pri-miRNA) of the RNAi pathway. Pri-miRNA expression is typically under the transcriptional control of Pol II promoters. Consequently RNAi activators that Abstract - xi - mimic pri-miRNA, so-called pri-miR shuttles, may be expressed from Pol II promoters. Initially a panel of shRNA expression cassettes driven by a Pol III promoter was constructed and silencing of HBV replication assessed. Pri-miR shuttles were then designed by incorporating guide sequences of the most effective anti HBV U6 shRNA into naturally occurring pri-miR-122 and pri-miR-31. Potent inhibition of viral replication was observed with both Pol III and Pol II-driven pri-miR shuttle expression cassettes in vitro and in vivo. Subsequently liver-specific pri-miR-122 and multimeric pri-miR-31 shuttle expression cassettes were created. Pri-miR-122 shuttle sequences expressed from the alpha-1 antitrypsin promoter and HBV basic core promoter exhibited the best liver-specific silencing. Polycistronic pri-miR-31 shuttle sequences were shown to produce multiple RNAi activators capable of silencing multiple target sequences. Silencing by the pri-miR shuttle sequences was independent of toxic effects that arise from induction of the interferon response or saturation of the endogenous miRNA pathway. Pri-miR shuttles clearly represent an improved option for the use of expressed shRNA and brings therapeutic RNAi technology a step closer to clinical application.

This thesis reports the efforts towards the design and synthesis of a small molecule walker that would potentially move along the track directionally by exploiting the secondary interactions between the track and the walker. This thesis also reports the synthesis and operation of a light driven molecular shuttle featuring a novel acylpyridyl hydrazone station. Chapter One describes the biological walkers which are the source of inspiration towards the synthetic walkers, characteristics of a walker, previously described small molecule walkers and recent progress on the synthesis of molecular shuttles that operate under variety of different stimuli. Chapter Two describes the design and synthetic efforts towards a molecular walker that has the potential to operate directionally along the track by exploiting secondary interactions between the walker and the track namely the hydrogen bonding interactions introduced by subtle incorporation of excellent hydrogen bond donor/acceptor squaramides. This chapter briefly mentions the hydrogen bonding capabilities of squaramides on which the directional operation relies. Optimization of critical reactions and attempted strategies for the assembly of the whole machine is described as well. Chapter Three describes the synthesis and operation of 1- and 2- station [2]-rotaxanes that operate under light irradiation. 2- station [2]-rotaxane that function as a light driven molecular shuttle presents remarkable positional fidelity with high efficacy. The bistable acyl pyridyl station is incorporated as a photo active station upon which light irradiation alters the binding affinities towards the macrocycle. Series of rotaxanes featuring different amide based stations were synthesized to determine the best non-photo active station.

Thesis (M.S. in Space Systems Operations)--Naval Postgraduate School, September 2003. / Thesis advisor(s): Eric Christiansen, Rudy Panholzer, Dan Bursch. Includes bibliographical references (p. 75-76). Also available online.

"Shuttle" presents a text' with maps and color photographs, suitable for publication, to inform members of the news media uninformed with space shuttle flights. Because of the voluminous press materials for shuttle missions submitted by the National Aeronautics and Space Administration, this creative project attempted to compile information as to the most relevant topics of space shuttle flights obtained from official NASA publications, interviews, transcripts and from veteran space center reporters. Since the author has photographed and covered six Orbiter missions for newspapers and radio, personal observations in this creative project explain a "behind-the-scenes” of varying practical experience at the John F. Kennedy Space Center.NASA has four space shuttles--Columbia, Challenger, Discovery and Atlantis. From that combined "space pool" at least 400 manned missions are planned, some more ambitious than others. But each of the four Orbiters will require relevant information on the part of media representatives at Kennedy, especially those at the space center for the very first time. "Shuttle" is intended to help meet those news responsibilities.

Thesis (M.S.)--Ohio University, August, 1992. / Title from PDF t.p.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [213]-218).

The work described in this thesis is inspired by natural-occurring molecules that are used throughout biology to perform specific, highly-selective tasks. This thesis illustrates the design, synthesis and investigation of novel molecular devices based on acyl hydrazones for the synthesis of a small molecule walker and light-driven molecular shuttles. Chapter One outlines a general overview of the design and synthesis of molecular devices, including molecular walkers and molecular shuttles. Some of the most important examples of walking molecules (both natural and synthetic) are described in detail, along with a comprehensive introduction of molecular shuttles and their synthetic mimics. Examples of stimuli-responsive molecular shuttles that have been developed are highlighted throughout the chapter. Chapter Two describes the design and synthetic progress towards a molecular walker, as well as detailing the optimisation of the synthetic steps achieved thus far. In this chapter, most of the work presented is based on the design and optimisation of the synthesis of an acyl hydrazone-based molecular walker, which will be able to walk directionally and repetitively along its conjugate track when the conditions are changed. A novel acyl hydrazone pyridine moiety is introduced to the system to achieve a high directional bias during the walking process. First, the concept and basis of the design is explained and further, the synthesis of the walker system is discussed in detail. Chapter Three illustrates the synthesis and operation of 1- and 2- station [2]-rotaxanes which exhibit all the requirements for a light-driven molecular shuttle. The effect of a new photo switchable binding station, an acyl pyridyl hydrazone, on the shuttling process is investigated by comparing the positional distribution of the macrocycle between the acyl hydrazone station and the succinamide-ester station, while the acyl hydrazone undergoes photo- and thermal isomerisation. The successful synthesis of this molecular architecture is described along with its operation, demonstrating high positional integrity and efficiency during the shuttling process.