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Probing The Early Stages Of Polyglutamine Aggregation With Computational Methods, Andreas Vitalis
Probing The Early Stages Of Polyglutamine Aggregation With Computational Methods, Andreas Vitalis
All Theses and Dissertations (ETDs)
Exonic CAG repeat diseases are a class of neurodegenerative age-of-onset diseases caused by an unstable trinucleotide expansion in a coding region of a gene. The most prominent example is Huntington's disease: HD) whose symptoms are characterized by loss of motor control and cognitive deficits. For all nine of the known CAG repeat diseases, pathology is ascribed to the mutant proteins which carry expanded stretches of glutamine residues: polyglutamine). The length of the polyglutamine segment is inversely correlated with the disease age-of-onset. Protein aggregates are routinely found in postmortem tissue samples of brains of HD patients. These findings suggest a prominent …
Photochemical Delivery Of Bleomycin In Malignant Glioma Cells, Joseph William Blickenstaff Iii
Photochemical Delivery Of Bleomycin In Malignant Glioma Cells, Joseph William Blickenstaff Iii
UNLV Theses, Dissertations, Professional Papers, and Capstones
Despite continued efforts, glioblastoma multiforme (GBM) remains an incurable form of primary brain cancer. Surgical resection followed by radiation treatment and chemotherapy have been the most effective modalities in prolonging median survival time to 14 months. This research aims to study the response of two different cell culture models to a novel drug delivery method termed photochemical internalization (PCI). PCI is a technique to improve the utilization of macromolecules (e.g. the chemotherapeutic drug bleomycin) in site-specific cancer therapy. This concept is based on the use of specially designed photosensitizers (e.g. aluminum phthalocyanine disulfonate; AlPcS 2a ) which preferentially localize in …
"Chasing A Ghost": Addressing The Opalescence/Aggregation Relationship Of An Igg 1 Antibody, John C. Champagne
"Chasing A Ghost": Addressing The Opalescence/Aggregation Relationship Of An Igg 1 Antibody, John C. Champagne
Doctoral Dissertations
This study was conducted to address the aggregation/opalescence relationship of an IgG 1 therapeutic antibody under a variety of conditions. The opalescence characteristics of three antibodies, Mab 1, 2 and 3, were examined as a function of salt dependence, protein concentration and temperature, using a variety of biophysical techniques. The high molecular weight species were initially identified using batch static and dynamic light scattering and separated by asymmetric flow field flow fractionation. When the salt dependence was examined, any structural changes were characterized using differential scanning calorimetry, circular dichroism and fluorescence, while the association state and temperature dependence was measured …
The Fate Of Salmonella Tennessee And Salmonella Typhimurium In Peanut Butter Subjected To Electron Beam Irradiation, Andrea Lynn Hvizdzak
The Fate Of Salmonella Tennessee And Salmonella Typhimurium In Peanut Butter Subjected To Electron Beam Irradiation, Andrea Lynn Hvizdzak
Graduate Theses, Dissertations, and Problem Reports
Peanut butter and peanut paste products were implicated as the vehicle of contamination in an outbreak of Salmonella Typhimurium that began in September 2008 and in the November 2006 outbreak of Salmonella Tennessee; therefore based on the apparent need for intervention measure, the purpose of this research was to evaluate the effectiveness of non-thermal electron beam irradiation for reduction of Salmonella serovars Tennessee (ATCC 10722) and Typhimurium (ATCC 14028) in creamy peanut butter. Each strain was studied independently. Peanut butter samples were inoculated with approximately 7.0 log CFU/g of Salmonella and exposed to e-beam doses ranging from 0--3.1 kGy. Doses …
Exploring Electron Transfer In Myoglobin-Based Transistors, Debin Li
Exploring Electron Transfer In Myoglobin-Based Transistors, Debin Li
Graduate Theses, Dissertations, and Problem Reports
Electron transfer in proteins is an issue of fundamental importance in biochemistry. This is especially true for proteins whose functionality relies on redox reactions, which by definition means that electron exchange must take place between the protein and another protein, a cofactor, or the external environment. An important example consists of proteins containing heme groups, where the iron ion in the protoporphyrin ring changes valence state depending on the whether an electron is accepted or given up by the protein. Much experimental work has been carried out since the late 1950s in order to develop an understanding of protein electron …
Advances In Computational Solvation Thermodynamics, Matthew Wyczalkowski
Advances In Computational Solvation Thermodynamics, Matthew Wyczalkowski
All Theses and Dissertations (ETDs)
The aim of this thesis is to develop improved methods for calculating the free energy, entropy and enthalpy of solvation from molecular simulations. Solvation thermodynamics of model compounds provides quantitative measurements used to analyze the stability of protein conformations in aqueous milieus. Solvation free energies govern the favorability of the solvation process, while entropy and enthalpy decompositions give insight into the molecular mechanisms by which the process occurs. Computationally, a coupling parameter λ modulates solute-solvent interactions to simulate an insertion process, and multiple lengthy simulations at a fixed λ value are typically required for free energy calculations to converge; entropy …
Computational And Experimental Investigation Of Allosteric Communication In The Transcriptional Regulator Nikr, Michael Bradley
Computational And Experimental Investigation Of Allosteric Communication In The Transcriptional Regulator Nikr, Michael Bradley
All Theses and Dissertations (ETDs)
The Ni2+ and DNA binding protein NikR is involved in nickel regulation in Escherichia coli through transcriptional repression of the NikABCDE nickel permease. NikR is a homotetramer and each chain contains both a DNA binding ribbon-helix-helix: RHH) domain and a Ni2+ binding regulatory ACT: aspartokinase, chorismate mutase, TyrA) fold. Work herein combines computational modeling of NikR structure with experimental studies aimed at understanding allosteric communication between the ACT and RHH domains. Hydrogen/deuterium exchange mass spectrometry shows a Ni2+ specific NikR conformational change relative to bound Cu2+, Co2+, and Zn2+. Concurrent coordination geometry and in vivo repressor function studies show that …