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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Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
Description
While exercising mammalian muscle increasingly relies on carbohydrates for fuel as aerobic exercise intensity rises above the moderate range, flying birds are extraordinary endurance athletes and fuel flight, a moderate-high intensity exercise, almost exclusively with lipid. In addition, Aves have long lifespans compared to weight-matched mammals. As skeletal muscle mitochondria account for the majority of oxygen consumption during aerobic exercise, the primary goal was to investigate differences in isolated muscle mitochondria between these species and to examine to what extent factors intrinsic to mitochondria may account for the behavior observed in the intact tissue and whole organism. First, maximal enzyme activities were assessed in sparrow and rat mitochondria. Citrate synthase and aspartate aminotransferase activity were higher in sparrow compared to rat mitochondria, while glutamate dehydrogenase activity was lower. Sparrow mitochondrial NAD-linked isocitrate dehydrogenase activity was dependent on phosphate, unlike the mammalian enzyme. Next, the rate of oxygen consumption (JO), electron transport chain (ETC) activity, and reactive oxygen species (ROS) production were assessed in intact mitochondria. Maximal rates of fat oxidation were lower than for carbohydrate in rat but not sparrow mitochondria. ETC activity was higher in sparrows, but no differences were found in ROS production between species. Finally, fuel selection and control of respiration at three rates between rest and maximum were assessed. Mitochondrial fuel oxidation and selection mirrored that of the whole body; in rat mitochondria the reliance on carbohydrate increased as the rate of oxygen consumption increased, whereas fat dominated under all conditions in the sparrow. These data indicate fuel selection, at least in part, can be modulated at the level of the mitochondrial matrix when multiple substrates are present at saturating levels. As an increase in matrix oxidation-reduction potential has been linked to a suppression of fat oxidation and high ROS production, the high ETC activity relative to dehydrogenase activity in avian compared to mammalian mitochondria may result in lower matrix oxidation-reduction potential, allowing fatty acid oxidation to proceed while also resulting in low ROS production in vivo.
ContributorsKuzmiak, Sarah (Author) / Willis, Wayne T (Thesis advisor) / Mandarino, Lawrence (Committee member) / Sweazea, Karen (Committee member) / Harrison, Jon (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
Description
Endocrine disruptors are chemicals that interact with the hormone system to negative effect. They ‘disrupt’ normal processes to cause diseases like vaginal cancer and obesity, reproductive issues like t-shaped uteri and infertility, and developmental abnormalities like spina bifida and cleft palate. These chemicals are ubiquitous in our daily lives, components in everything from toothpaste to microwave popcorn to plastic water bottles. My dissertation looks at the history, science, and regulation of these impactful substances in order to answer the question of how endocrine disruptors appeared, got interpreted by different groups, and what role science played in the process. My analysis reveals that endocrine disruptors followed a unique science policy trajectory in the US, rapidly going from their proposal in 1991 to their federal regulation in 1996, even amid intense and majority scientific disagreement over whether the substances existed at all. That trajectory resulted from the work of a small number of scientist-activists who constructed a concept and category as scientific, social, and regulatory. By playing actors from each sphere against each other and advancing a very specific scientific narrative that fit into a regulatory and social window of opportunity in the 1990s, those scientist-activists made endocrine disruptors a national issue that few could ignore. Those actions resulted in the Endocrine Disruptor Screening Program, a heavily-criticized and ineffective regulatory program. My dissertation tells a story of the past that informs the present. In 2018, the work of researchers, public media, and policymakers in the 1990s continues to play out, evident in the deep scientific division over endocrine disrupting effects and the inability of the European Union to settle on even a definition of endocrine disruptors for regulation purposes.
ContributorsAbboud, Alexis J (Author) / Maienschein, Jane A (Thesis advisor) / Crow, Michael M. (Committee member) / Hurlbut, J. Benjamin (Committee member) / Marchant, Gary E (Committee member) / Arizona State University (Publisher)
Created2018
Description
This dissertation investigates how ideas of the right relationships among science, the public, and collective decision-making about science and technology come to be envisioned in constructions of public engagement. In particular, it explores how public engagement has come to be constructed in discourse around gene editing to better understand how it holds together with visions for good, democratic governance of those technologies and with what effects. Using a conceptual idiom of the co-production of science and the social order, I investigate the mutual formation of scientific expertise, responsibility, and democracy through constructions of public engagement. I begin by tracing dominant historical narratives of contemporary public engagement as a continuation of public understanding of science’s projects of social ordering for democratic society. I then analyze collections of prominent expert meetings, publications, discussions, and interventions about development, governance, and societal implications human heritable germline gene editing and gene drives that developed in tandem with commitments to public engagement around those technologies. Synthesizing the evidence from across gene editing discourse, I offer a constructive critique of constructions of public engagement as expressions and evidence of scientific responsibility as ultimately reasserting and reinforcing of scientific experts' authority in gene editing decision-making, despite intentions for public engagement to extend decision-making participation and power to publics. Such constructions of public engagement go unrecognized in gene editing discourse and thereby subtly reinforce broader visions of scientific expertise as essential to good governance by underwriting the legitimacy and authority of scientific experts to act on behalf of public interests. I further argue that the reinforcement of scientific expert authority in gene editing discourse through public engagement also centers scientific experts in a sociotechnical imaginary that I call “not for science alone.” This sociotechnical imaginary envisions scientific experts as guardians and guarantors of good, democratic governance. I then propose a possible alternatives to public engagement alone to improve gene editing governance by orienting discourse around notions of public accountability for potential shared benefits and collective harms of gene editing.
ContributorsRoss, Christian (Author) / Hurlbut, James B. (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Collins, James P. (Committee member) / Crow, Michael M. (Committee member) / Sarewitz, Daniel R. (Committee member) / Arizona State University (Publisher)
Created2021