Thesis (Ph. D.)--University of Wisconsin, 1967. / Typescript. Vita. Includes reprints of 3 articles from the Journal of chemical physics and the Journal of physical chemistry by the author and others. eContent provider-neutral record in process. Description based on print version record. Includes bibliographies.

Thesis (Ph.D.)--Kent State University, 2006. / Title from PDF t.p. (viewed Sept. 19, 2006). Advisor: R. S. Prosser. Keywords: membrane, NMR, protein, lovemonkey, lyotropic, liquid crystal, bicelle. Includes bibliographical references (p. 250-256).

Thesis (Ph. D.)--Florida State University, 2006. / Advisor: Timothy A. Cross, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed June 9, 2006). Document formatted into pages; contains xv, 98 pages. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (p. 135-151).

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 69-72).

Thesis (Ph. D.)--Miami University, Dept. of Chemistry and Biochemistry, 2007. / Title from second page of PDF document. Includes bibliographical references.

Throughout biological, chemical, and pharmaceutical research,conformational searches are used to explore the possiblethree-dimensional configurations of molecules. This thesis describesa new systematic method for conformational search, including anapplication of the method to determining the structure of a peptidevia solid-state NMR spectroscopy. A separate portion of the thesis isabout protein-DNA binding, with a three-dimensional macromolecularstructure determined by x-ray crystallography.The search method in this thesis enumerates all conformations of amolecule (at a given level of torsion angle resolution) that satisfy aset of local geometric constraints, such as constraints derived fromNMR experiments. Systematic searches, historically used for smallmolecules, generally now use some form of divide-and-conquer forapplication to larger molecules. Our method can achieve a significantimprovement in runtime by making some major and counter-intuitivemodifications to traditional divide-and-conquer:(1) OmniMerge divides a polymer into many alternative pairs ofsubchains and searches all the pairs, instead of simply cutting inhalf and searching two subchains. Although the extra searches mayappear wasteful, the bottleneck stage of the overall search, which isto re-connect the conformations of the largest subchains, can be greatlyaccelerated by the availability of alternative pairs of sidechains.(2) Propagation of disqualified conformations acrossoverlapping subchains can disqualify infeasible conformations veryrapidly, which further offsets the cost of searching the extrasubchains of OmniMerge.(3) The search may be run in two stages, once at low-resolutionusing a side-effect of OmniMerge to determine an optimalpartitioning of the molecule into efficient subchains; then again athigh-resolution while making use of the precomputed subchains.(4) An A* function prioritizes each subchain based onestimated future search costs. Subchains with sufficiently lowpriority can be omitted from the search, which improves efficiency.A common theme of these four ideas is to make good choices about howto break the large search problem into lower-dimensional subproblems.In addition, the search method uses heuristic local searches withinthe overall systematic framework, to maintain the systematic guaranteewhile providing the empirical efficiency of stochastic search.These novel algorithms were implemented and the effectiveness of eachinnovation is demonstrated on a highly constrained peptide with 40degrees of freedom.

The status of the myocardial 'high energy phosphate' metabolism is a sensitive marker of the occurrence and progression of heart failure. Magnetic resonance spectroscopy enables non-invasive, direct and potentially quantitative measurements of the phosphate containing metabolites present in the human myocardium. This thesis is primarily concerned with the creation of measurement techniques for cardiac phosphorus magnetic resonance spectroscopy (³¹P-MRS) at the 7 tesla field strength. Chapter 1 provides an overview of the physical basis of magnetic resonance spectroscopy, the myocardial high energy phosphate metabolism, and the clinical relevance of the technique. Chapter 2 describes the advantage of 7 tesla scanners over lower field strengths. The radio frequency coil hardware is characterised experimentally. The multivoxel spectroscopy methods used throughout the thesis are described. Chapter 3 details the implementation of an open source spectroscopy fitting program. It is validated against previous closed-source implementations. The program's use is demonstrated in several clinical studies of heart failure, and to improve a previously implemented ¹H spectroscopy coil combination method. In Chapter 4 the measurement of inorganic phosphate in the presence of overlapping peaks is attempted. Suppression of overlapping peaks, originating from the blood, is tried using B_o gradients, then saturation transfer. The myocardial pH of hypertrophic cardiomyopathy patients is measured. Chapter 5 describes the effect of creatine kinase catalysed chemical exchange on the ³¹P-MRS spectrum. A survey of methods suitable for measuring creatine kinase kinetics at 7 tesla is made. Multi-parametric fitting of variable repetition time saturation transfer data is explored in simulation and experiment. Chapter 6 describes the re-implementation and extension, for dynamic measurements, of the triple repetition time saturation transfer method for two clinical studies at 3 tesla. The creatine kinase forward rate constant is measured in heart failure and healthy cohorts, at rest, and during cardiac stress. In Chapter 7 a Bloch-Siegert B₁ mapping sequence is implemented for ³¹P-MRS. An optimal Bloch-Siegert method for X-nuclear spectroscopy is calculated. B₁maps are validated in skeletal muscle and collected in 5 volunteer's hearts. Chapter 8 uses the Bloch-Siegert B₁ mapping sequence and the four angle saturation transfer method to implement creatine kinase rate measurement at 7 tesla. The first 3D localised creatine kinase rate measurements in the human myocardium are achieved in 10 volunteers.

The pathophysiology of traumatic brain injury (TBI) includes perturbations to energy metabolism. Improving our understanding of cerebral energy metabolism will lead to strategies that improve clinical outcomes. For the studies in my thesis I used microdialysis to deliver carbon-13 labelled substrates to the human brain. I combined this with nuclear magnetic resonance (NMR) spectroscopy of interstitial fluid sampled from the brain to interrogate glucose, lactate and tricarboxylic acid (TCA) cycle metabolism. Study I: I defined the optimal parameters for quantitative proton and carbon-13 NMR of cerebral microdialysates. Study II: I measured baseline microdialysate metabolite concentrations for brain and muscle and investigated the influence of muscle activity and cerebral catheter placement in grey or white matter on metabolite concentrations. Study III: I used 1,2-13C2 glucose to measure glycolysis and pentose phosphate pathway activity. Glycolysis is the dominant lactate-producing pathway but the pentose phosphate pathway also contributes and is increased in some TBI patients. Study IV: I used arterio-venous gradients to measure glucose and lactate delivery to the brain. There are periods after injury when lactate is imported from the circulation despite relatively high brain lactate levels suggesting up-regulation of lactate transport. Study V: I followed the metabolism of 3-13C lactate and demonstrated that lactate is metabolised by the TCA cycle. This occurs in both normal and injured brain but not in muscle. Study VI: I used 2,3-13C2 succinate to investigate the role of the TCA cycle in producing metabolites that are exported into the interstitium. The TCA cycle is found to be a source of lactate. Succinate delivered to the brain improves redox and enhances glutamate uptake into cells. The implications of the findings in my thesis on existing knowledge of cerebral metabolism are discussed. Strategies that might potentiate cerebral metabolism and improve clinical outcomes are suggested.