No description available.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Additional advisors: Houston Boyd, Tracy Hamilton, Christopher Lawson, Charles Watkins. Description based on contents viewed Feb. 8, 2008; title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--Mississippi State University. Department of Chemistry. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Brent L. Iverson. Vita. Includes bibliographical references. Also available from UMI.

Thesis (M.S.)--Mississippi State University. Department of Computational Engineering. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Schuster, Gary; Committee Member: Barry, Bridgette; Committee Member: Collard, David; Committee Member: Tolbert, Laren; Committee Member: Wartell, Roger. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (M. S.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2006. / Fahrni, Christoph, Committee Member ; Collard, David, Committee Member ; Schuster, Gary, Committee Chair.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 102-112.

Accumulating evidence links oligomeric species of the protein alpha-synuclein to the neuronal death associated with Parkinson's disease. However, the direct detection of alpha-synuclein oligomers in post-mortem brain has been challenging and this has limited our understanding of their structure, distribution and effects in Parkinson's disease. The work presented in this thesis addresses two aspects of the role of alpha-synuclein oligomers in Parkinson's disease. Firstly, I describe the development of a novel technique, the alpha-synuclein proximity ligation assay (AS-PLA), which specifically detected alpha-synuclein oligomers in vitro and in post-mortem brain tissue. In a blinded study with post-mortem brain tissue from eight Parkinson's disease patients and eight controls, AS-PLA revealed widespread, previously unrecognised pathology in the form of extensive diffuse deposition of alpha-synuclein oligomers. Furthermore, AS-PLA preferentially detected early-stage, loosely compacted Parkinson's disease lesions such as pale bodies, whereas Lewy bodies, considered heavily compacted late lesions were only very exceptionally stained. The oligomeric species detected by AS-PLA displayed a unique, intermediate proteinase K resistance profile, suggesting the detection of a conformer that is different from both physiological pre-synaptic alpha-synuclein (proteinase K sensitive) and highly aggregated alpha-synuclein within Lewy bodies (proteinase K resistant). In addition, AS-PLA revealed the age-dependent accumulation of alpha-synuclein oligomers in the substantia nigra of a BAC transgenic mouse model of Parkinson's disease that overexpresses human wild-type alpha-synuclein, SNCA-OVX. Secondly, the detection of early pathology in Parkinson's disease brain tissue using AS-PLA suggests that oligomeric species of alpha-synuclein could represent a potential target for therapeutic intervention. Therefore, I undertook a screen to identify compounds that can prevent the formation of alpha-synuclein oligomers in vitro. Using bimolecular fluorescence complementation constructs, I identified nine compounds capable of reducing the fluorescence indicative of the formation of alpha-synuclein oligomers. Two of these compounds showed dose-dependent activity. Future work will confirm the hits in vitro before studying whether Parkinson's-like phenotypes in the SNCA-OVX mice can be ameliorated or reversed by treatment with the compounds.

Quantitation of the amount of finish applied during fiber manufacturing is an important industrial quality control process. Finish levels that are too low result in excessive fiber and mechanical wear. On the other hand, overly high finish levels may cause residue buildup on the processing equipment. Removal of the finish has traditionally been done with solvents such as chloroform or Freon followed by gravimetric or spectroscopic analysis of the removed material. Quantitation of low molecular weight oligomeric material is another important quality control practice for the fiber industry in that the presence of these species and their concentration affect the physical properties of the polymer. Also, excessively high concentrations of oligomers may result in residue deposits on processing equipment. Typical conventional methods for determining the concentration of oligomers present in fibers involve large quantities of organic solvent for removal of the oligomers followed by chromatographic analysis. Increased government regulation of chlorinated and other solvents has led to investigations of alternate methods of extraction. Several studies have shown that supercritical fluid extraction (SFE) using carbon dioxide as the extraction fluid is an important alternative to conventional organic solvent extraction for the removal of both textile finishes and oligomeric material. This research seeks to extend the previous studies regarding the application of SFE for the quantitation of finish and oligomers from nylon 6,6 fibers. The effects of pressure, extraction temperature, modifier percentage, static extraction time, and dynamic extraction time on the supercritical fluid extraction efficiency of nylon 6,6 oligomers were examined. Results from the SFE methods for both finish and oligomer extractions were compared to results from conventional solvent extraction. The extracted oligomers were identified by HPLC with coupled on-line atmospheric pressure chemical ionization mass spectrometry (APCI-MS) and HPLC fractionation coupled with off-line Liquid Secondary Ion Mass Spectrometry (LSIMS). / Master of Science