Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

published_or_final_version / Chemistry / Master / Master of Philosophy

Thesis (Ph.D.) -- McMaster University, 2001. / Includes bibliographical references. Also available via World Wide Web.

Thesis (Ph. D.)--University of Alberta, 2010. / Title from pdf file main screen (viewed on June 22, 2010). A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Chemistry, University of Alberta. Includes bibliographical references.

The most efficient and stereoselective total synthesis of (+/-) lausbine II to date has been achieved. The key steps in this are the copper-mediated conjugate addition reaction of the Grignard reagent of 1-bromo-4-chlorobutane to a dihydropyridone and a stereoselective reduction of a quinolizidinone. Methodology has been developed for the convenient synthesis of 1-acyl-2-substituted-1,2,5,6-tetrahydropyridines. This was accomplished by adding novel alkylzinc iodides to the 1-acyliminium ion derived from Nphenoxycarbonyl-4-methoxy-1, 2, 3, 4-tetrahydropyridine.

No / Beta-2-microglobulin (2m) has been shown to form amyloid fibrils with distinct morphologies under acidic conditions in vitro. Short, curved fibrils (<600 nm in length), form rapidly without a lag phase, with a maximum rate at pH 3.5. By contrast, fibrils with a long (~1 m), straight morphology are produced by incubation of the protein at pH=<3.0. Both fibril types display Congo red birefringence, bind Thioflavin-T and have X-ray fibre diffraction patterns consistent with a cross-beta structure. In order to investigate the role of different partially folded states in generating fibrils of each type, and to probe the effect of protein stability on amyloid formation, we have undertaken a detailed mutagenesis study of 2m. Thirteen variants containing point mutations in different regions of the native protein were created and their structure, stability and fibril forming propensities were investigated as a function of pH. By altering the stability of the native protein in this manner, we show that whilst destabilisation of the native state is important in the generation of amyloid fibrils, population of specific denatured states is a pre-requisite for amyloid formation from this protein. Moreover, we demonstrate that the formation of fibrils with different morphologies in vitro correlates with the relative population of different precursor states.

by Ching-hung Wong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 75-78). / Chapter i --- Biography / Chapter ii --- Abstract / Chapter iii --- Acknowledgments / Chapter iv --- Abberivations / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Review on the published syntheses of Zoapatanol --- p.1 / Chapter 1.2 --- Review on the construction of the oxepane ring --- p.7 / Chapter 1.3 --- "Review on the intramolecular nitrone and nitrile oxide 1,3-dipolar cycloaddition" --- p.15 / Chapter 1.3.a. --- Nitrone-olefin cycloaddition --- p.16 / Chapter 1.3.b. --- Nitrile-oxide-olefin cycloaddition --- p.17 / Chapter 1.4 --- Isoxazoline Transformation --- p.18 / Chapter Chapter 2 --- Results and Discussion / Chapter 2.1 --- General Aspect --- p.19 / Chapter 2.2 --- "Entries to 6 and 7-membered O-heterocycles via 1,3-dipolar nitrone cycloaddition" --- p.21 / Chapter 2.3 --- "Entries to 6 and 7-membered O-heterocycles via l,，3-diploar nitrile oxide cycloaddition" --- p.33 / Chapter 2.4 --- Conclusion --- p.47 / Chapter Chapter 3 --- Experimental / General --- p.49 / Experimental --- p.51 / References --- p.75

Antibiotic resistance represents a real threat in the modern world. The problem of resistance is brought about by the fast evolution of bacteria, accelerated by misuse and over-prescription of antibiotics and compounded by the decline in the discovery and development of new classes of antibiotics. Consequently, new targets for antibiotics are in high demand. Flavin-dependent thymidylate synthase (FDTS), which is not present in humans and is responsible for the biosynthesis of a DNA building block in several human pathogens (e.g., M. tuberculosis, B. anthracis, H. pylori), is one such novel target. FDTS catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) to produce 2'-deoxythymidine-5'-monophosphate (dTMP), with N⁵,N¹⁰-methylene-5,6,7,8-tetrahydrofolate (CH₂H₄fol) serving as the carbon source and a nicotinamide cofactor as the electron source. No efficient inhibitors of FDTS are known, despite high-throughput screening attempts to find them. Intermediate and transition-state mimics are likely to bind the enzyme with greater affinity and hence have a better chance at inhibiting FDTS. Therefore, the understanding of the chemical mechanism of FDTS is critical to the informed design of compounds capable of disrupting its function in bacteria. We utilized various techniques, including chemical trapping of reaction intermediates, substrate isotope exchange and stopped-flow, to investigate the FDTS mechanism and determine what sets it apart from other pyrimidine methylases. We found that at least two different intermediates kinetically accumulate in the FDTS-catalyzed reaction. Both of these intermediates are trapped in acid in the form of 5-hydroxymethyl-dUMP, which has never been isolated in other uracil-methylating enzymes. Under basic conditions, however, the earlier intermediate is converted to a species with an unusual flavin-derived adduct, while the later intermediate is converted to dTMP product. Our experiments also suggest that dUMP is activated for the reaction by the reduced flavin - a substrate activation mechanism distinct from the one employed by the classical pyrimidine-methylating enzymes.

This dissertation investigates the effects of foreign direct investment (FDI) and international trade on firm level decisions and examines the effect of policy changes on aggregate productivity and welfare in open economies. The first two chapters build an open economy model of FDI and trade where heterogeneous firms make simultaneous foreign investment and export decisions. The theoretical model is estimated using Indonesian manufacturing data. The estimated model is then used to perform a variety of counterfactual experiments to assess the positive and normative effects of international barriers to trade and FDI. I find that the impact of FDI on aggregate productivity is at least three times the impact of international trade on aggregate productivity. The third chapter, co-authored with Hiroyuki Kasahara, investigates whether importing intermediate goods improves plant performance. While addressing the issue of simultaneity between productivity shocks and the decision to import intermediates, we estimate the impact of the use of foreign intermediates on plants' productivity using plant-level Chilean manufacturing panel data. We find that by importing foreign intermediates, manufacturing plants can improve productivity. / Thesis (Ph.D, Economics) -- Queen's University, 2008-06-20 10:21:01.069

Thesis (Ph.D.) -- McMaster University, 1999. / Includes bibliographical references (leaves 260-271). Also available via World Wide Web.