ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- Creators: Pan, Rong
- Creators: Ghirlanda, Giovanna
Interactions driving the collapse of islet amyloid polypeptide: implications for amyloid aggregation
Implicit in the design criteria of current ALT designs is the assumption that the form of the acceleration model is correct. This is unrealistic assumption in many real-world problems. Chapter 3 provides an approach for ALT optimum design for model discrimination. We utilize the Hellinger distance measure between predictive distributions. The optimal ALT plan at three stress levels was determined and its performance was compared to good compromise plan, best traditional plan and well-known 4:2:1 compromise test plans. In the case of linear versus quadratic ALT models, the proposed method increased the test plan's ability to distinguish among competing models and provided better guidance as to which model is appropriate for the experiment.
Chapter 4 extends the approach of Chapter 3 to ALT sequential model discrimination. An initial experiment is conducted to provide maximum possible information with respect to model discrimination. The follow-on experiment is planned by leveraging the most current information to allow for Bayesian model comparison through posterior model probability ratios. Results showed that performance of plan is adversely impacted by the amount of censoring in the data, in the case of linear vs. quadratic model form at three levels of constant stress, sequential testing can improve model recovery rate by approximately 8% when data is complete, but no apparent advantage in adopting sequential testing was found in the case of right-censored data when censoring is in excess of a certain amount.
Post Translational Modifications (PTMs) are a series of chemical modifications with the capacity to expand the structural and functional repertoire of proteins. PTMs can regulate protein-protein interaction, localization, protein turn-over, the active state of the protein, and much more. This can dramatically affect cell processes as relevant as gene expression, cell-cell recognition, and cell signaling. Along these lines, this Ph.D. thesis examines the role of two of the most important PTMs: glycosylation and phosphorylation.
In chapters 2, 3 and 4, a 10,000 peptide microarray is used to analyze the glycan variations in a series lipopolysaccharides (LPS) from Gram negative bacteria. This research was the first to demonstrate that using a small subset of random sequence peptides, it was possible to identify a small subset with the capacity to bind to the LPS of bacteria. These peptides bound to LPS not only in the solid surface of the array but also in solution as demonstrated with surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and flow cytometry. Interestingly, some of the LPS binding peptides also exhibit antimicrobial activity, a property that is also analyzed in this work.
In chapters 5 and 6, the role of protein phosphorylation, another PTM, is analyzed in the context of human cancer. High risk neuroblastoma, a very aggressive pediatric cancer, was studied with emphasis on the phosphorylations of two selected oncoproteins: the transcription factor NMYC and the adaptor protein ShcC. Both proteins were isolated from high risk neuroblastoma cells, and a targeted-directed tandem mass spectrometry (LC-MS/MS) methodology was used to identify the phosphorylation sites in each protein. Using this method dramatically improved the phosphorylation site detection and increased the number of sites detected up to 250% in comparison with previous studies. Several of the novel identified sites were located in functional domain of the proteins and that some of them are homologous to known active sites in other proteins of the same family. The chapter concludes with a computational prediction of the kinases that potentially phosphorylate those sites and a series of assays to show this phosphorylation occurred in vitro.