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
Induced pluripotent stem cells (iPSCs) are an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. We describe the establishment of primary dermal fibroblasts cells lines from 28 autopsy donors. These fibroblasts were used to examine the proliferative effects of establishment protocol, tissue amount, biopsy site, and donor age. As proof-of-principle, iPSCs were generated from fibroblasts from a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. To our knowledge, this is the first study describing autopsy donor-derived somatic cells being used for iPSC generation and subsequent neural differentiation. This unique approach also enables us to compare iPSC-derived cell cultures to endogenous tissues from the same donor. We utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, supported by (i) a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P < 0.05), consistent with the transcriptional complexity of the brain, (ii) an increase in CpG methylation after neural differentiation that resembled the epigenomic signature of the endogenous tissue, and (iii) a significant decreasing monotonic correlation between the days of our timecourse and the percent of in vitro to brain-tissue differences (P < 0.05) for tissue-specific protein-coding genes and all putative lincRNAs. These studies support the utility of autopsy donors' somatic cells for iPSC-based neurological disease models, and provide evidence that in vitro neural differentiation can result in physiologically progression.
ContributorsHjelm, Brooke E (Author) / Craig, David W. (Thesis advisor) / Wilson-Rawls, Norma J. (Thesis advisor) / Huentelman, Matthew J. (Committee member) / Mason, Hugh S. (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation develops a framework for the analysis of fiscal sustainability among U.S. local governments. Fiscal sustainability is defined as a type of fiscal condition that allows a government to continue service provision now and in the future without introducing disruptive revenue or expenditure patterns. An assessment of local fiscal sustainability is based on three types of indicators: pension liability funding, debt burden, and budgetary balance. Three main factors affect a government's long-term financial condition: government structure, financial structure and performance, and local economic base. This dissertation uses a combination of the U.S. Census Bureau Annual Survey of Government Finances and Employment, the U.S. Census Bureau Decennial Census, the Bureau of Labor Statistics data, and the Government Finance Officers Association financial indicators database to study the effects of the three factors on local fiscal sustainability. It is a pioneer effort to use government-wide accounting information from Comprehensive Annual Financial Reports to predict local fiscal sustainability status. The results of econometric models suggest that pension liability funding is most affected by the size of government, debt burden is most strongly associated with the size of local economic base; and budgetary balance is influenced by the degree of local own-source revenue diversification.
ContributorsGorina, Evgenia (Author) / Chapman, Jeffrey I. (Thesis advisor) / Herbst, Chris M. (Committee member) / Miller, Gerald J (Committee member) / Arizona State University (Publisher)
Created2013
Description
Speciation is the fundamental process that has generated the vast diversity of life on earth. The hallmark of speciation is the evolution of barriers to gene flow. These barriers may reduce gene flow either by keeping incipient species from hybridizing at all (pre-zygotic), or by reducing the fitness of hybrids (post-zygotic). To understand the genetic architecture of these barriers and how they evolve, I studied a genus of wasps that exhibits barriers to gene flow that act both pre- and post-zygotically. Nasonia is a genus of four species of parasitoid wasps that can be hybridized in the laboratory. When two of these species, N. vitripennis and N. giraulti are mated, their offspring suffer, depending on the generation and cross examined, up to 80% mortality during larval development due to incompatible genic interactions between their nuclear and mitochondrial genomes. These species also exhibit pre-zygotic isolation, meaning they are more likely to mate with their own species when given the choice. I examined these two species and their hybrids to determine the genetic and physiological bases of both speciation mechanisms and to understand the evolutionary forces leading to them. I present results that indicate that the oxidative phosphorylation (OXPHOS) pathway, an essential pathway that is responsible for mitochondrial energy generation, is impaired in hybrids of these two species. These results indicate that this impairment is due to the unique evolutionary dynamics of the combined nuclear and mitochondrial origin of this pathway. I also present results showing that, as larvae, these hybrids experience retarded growth linked to the previously observed mortality and I explore possible physiological mechanisms for this. Finally, I show that the pre-mating isolation is due to a change in a single pheromone component in N. vitripennis males, that this change is under simple genetic control, and that it evolved neutrally before being co-opted as a species recognition signal. These results are an important addition to our overall understanding of the mechanisms of speciation and showcase Nasonia as an emerging model for the study of the genetics of speciation.
ContributorsGibson, Joshua D (Author) / Gadau, Jürgen (Thesis advisor) / Harrison, Jon (Committee member) / Pratt, Stephen (Committee member) / Verrelli, Brian (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
Description
The principle of Darwinian evolution has been applied in the laboratory to nucleic acid molecules since 1990, and led to the emergence of in vitro evolution technique. The methodology of in vitro evolution surveys a large number of different molecules simultaneously for a pre-defined chemical property, and enrich for molecules with the particular property. DNA and RNA sequences with versatile functions have been identified by in vitro selection experiments, but many basic questions remain to be answered about how these molecules achieve their functions. This dissertation first focuses on addressing a fundamental question regarding the molecular recognition properties of in vitro selected DNA sequences, namely whether negatively charged DNA sequences can be evolved to bind alkaline proteins with high specificity. We showed that DNA binders could be made, through carefully designed stringent in vitro selection, to discriminate different alkaline proteins. The focus of this dissertation is then shifted to in vitro evolution of an artificial genetic polymer called threose nucleic acid (TNA). TNA has been considered a potential RNA progenitor during early evolution of life on Earth. However, further experimental evidence to support TNA as a primordial genetic material is lacking. In this dissertation we demonstrated the capacity of TNA to form stable tertiary structure with specific ligand binding property, which suggests a possible role of TNA as a pre-RNA genetic polymer. Additionally, we discussed the challenges in in vitro evolution for TNA enzymes and developed the necessary methodology for future TNA enzyme evolution.
ContributorsYu, Hanyang (Author) / Chaput, John C (Thesis advisor) / Chen, Julian (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation is an exploratory study that examined the differences in perceptions about supply chain management strategy, topics, tools, and techniques between procurement professionals in public and private sector organizations. This was accomplished through a survey of procurement professionals in a Fortune 500 company and a municipality in Arizona. The data were analyzed to understand how perceptions of supply chain management differed within this sample and whether the differences in perceptions were associated with formal education levels. Key findings indicate that for this or similar samples, public procurement respondents viewed their organizations' approach to supply chain management as a narrow function within purchasing while private sector respondents viewed their organization's approach to supply chain management as a strategic purchasing perspective that requires the coordination of cross functional areas. Second, public procurement respondents reported consistent and statistically significant lower levels of formal education than private sector respondents. Third, the supply chain management topics, tools, and techniques seem to be more important to private sector respondents than the public sector respondents. Finally, Respondents in both sectors recognize the importance of ethics and ethical behavior as an essential part of supply chain management.
ContributorsHeller, Jacob (Author) / Cayer, Joseph (Thesis advisor) / Lan, Gerald (Committee member) / Eden, Catherine (Committee member) / Arizona State University (Publisher)
Created2013
Description
Synechocystis sp PCC 6803 is a photosynthetic cyanobacterium that can be easily transformed to produce molecules of interest; this has increased Synechocystis’ popularity as a clean energy platform. Synechocystis has been shown to produce and excrete molecules such as fatty acids, isoprene, etc. after appropriate genetic modification. Challenges faced for large–scale growth of modified Synechocystis include abiotic stress, microbial contamination and high processing costs of product and cell material. Research reported in this dissertation contributes to solutions to these challenges. First, abiotic stress was addressed by overexpression of the heat shock protein ClpB1. In contrast to the wild type, the ClpB1 overexpression mutant (Slr1641+) tolerated rapid temperature changes, but no difference was found between the strains when temperature shifts were slower. Combination of ClpB1 overexpression with DnaK2 overexpression (Slr1641+/Sll0170+) further increased thermotolerance. Next, we used a Synechocystis strain that carries an introduced isoprene synthase gene (IspS+) and that therefore produces isoprene. We attempted to increase isoprene yields by overexpression of key enzymes in the methyl erythritol phosphate (MEP) pathway that leads to synthesis of the isoprene precursor. Isoprene production was not increased greatly by MEP pathway induction, likely because of limitations in the affinity of the isoprene synthase for the substrate. Finally, two extraction principles, two–phase liquid extraction (e.g., with an organic and aqueous phase) and solid–liquid extraction (e.g., with a resin) were tested. Two–phase liquid extraction is suitable for separating isoprene but not fatty acids from the culture medium. Fatty acid removal required acidification or surfactant addition, which affected biocompatibility. Therefore, improvements of both the organism and product–harvesting methods can contribute to enhancing the potential of cyanobacteria as solar–powered biocatalysts for the production of petroleum substitutes.
ContributorsGonzalez Esquer, Cesar Raul (Author) / Vermaas, Willem (Thesis advisor) / Chandler, Douglas (Committee member) / Bingham, Scott (Committee member) / Nielsen, David (Committee member) / Arizona State University (Publisher)
Created2013
Description
A void exists in public administration, criminology, and criminal justice research as it relates to the study of power in American policing agencies. This has significant ramifications for academia and practitioners in terms of how they view, address, study, and interpret behaviors/actions in American policing agencies and organizations in general. In brief, mainstream research on power in organizations does not take into account relationships of power that do not act directly, and immediately, on others. By placing its emphasis on an agency centric perspective of power, the mainstream approach to the study of power fails to recognize indirect power relationships that influence discourse, pedagogy, mechanisms of communication, knowledge, and individual behavior/actions. In support of a more holistic inquiry, this study incorporates a Foucauldian perspective of power along with an ethnographical methodology and methods to build a greater understanding of power in policing organizations. This ethnography of an American policing organization illuminates the relationship between the exercise of power and the objectification of the subject through the interplay of relationships of communication, goal oriented activities, and relationships of power. Specifically, the findings demonstrate that sworn officers and civilian employees are objectified distinctly and dissimilarly. In summary, this study argues that the exercise of power in this American policing organization objectifies the civilian employee as a second class citizen.
ContributorsBentley, Paul C (Author) / Catlaw, Thomas (Thesis advisor) / Musheno, Michael (Committee member) / Lucio, Joanna (Committee member) / Arizona State University (Publisher)
Created2013
Description
The purpose of the current study was to use structural equation modeling-based quantitative genetic models to characterize latent genetic and environmental influences on proneness to three discrete negative emotions in middle childhood, according to mother-report, father-report and in-home observation. One primary aim was to test the extent to which covariance among the three emotions could be accounted for by a single, common genetically- and environmentally-influenced negative emotionality factor. A second aim was to examine the extent to which different reporters appeared to be tapping into the same genetically- and environmentally-influenced aspects of each emotion. According to mother- and father-report, moderate to high genetic influences were evident for all emotions, with mother- and father-report of fear and father-report of anger showing the highest heritability. Significant common environmental influences were also found for mother-report of anger and sadness in both univariate and multivariate models. For observed emotion, anger was moderately heritable with no evidence for common environmental variance, but sadness, object fear and social fear all showed modest to moderate common environmental influences and no significant genetic variance. In addition, cholesky decompositions examining genetic and environmental influences across reporter suggested that despite considerable overlap between mother-report and father-report, there was also reporter-specific variance on anger, sadness, and fear. Specifically, there were significant common environmental influences on mother-report of anger- and sadness that were not shared with father-report, and genetic influences on father-report of sadness and fear that were not shared with mother-report. In-home observations were not highly correlated enough with parent-report to support multivariate analysis for any emotion. Finally, according to both mother- and father-report, a single set of genetic and environmental influences was sufficient to account for covariance among all three negative emotions. However, fear was primarily explained by genetic influences not shared with other emotions, and anger also showed considerable emotion-specific genetic variance. In both cases, findings support the value of a more emotion-specific approach to temperament, and highlight the need to consider distinctions as well as commonalities across emotions, reporters and situations.
ContributorsClifford, Sierra (Author) / Lemery, Kathryn (Thesis advisor) / Shiota, Michelle (Committee member) / Eisenberg, Nancy (Committee member) / Arizona State University (Publisher)
Created2013
Description
In many respects, the current public child welfare system closely resembles that of over 100 years ago. Then, as well as now, nonprofit child welfare agencies are the critical providers of service delivery to vulnerable children and their families. Contemporary nonprofits, however, are confronted with social and fiscal pressures to conform to normative practices and behaviors of governmental and for-profit organizations. Simultaneously, these agencies may also feel compelled to behave in accordance with a nonprofit normative ethic. Yet, scholars and practitioners are often unaware of how these different forces may be shaping the practices of child welfare agencies and, the nonprofit sector in general. This multi-paper dissertation examines how managerial and organizational practices of child welfare nonprofits are influenced business, government, and other nonprofit organizations and the extent to which processes process of institutional isomorphism in child welfare nonprofits are happening. Data was collected from a national ample of 184 child welfare administrators to explore marketization practices, collaboration behaviors, and managerial priorities of these agencies. Multinomial logistic, ordered logistic, and ordinary least squares regression, and historical analysis help shed light on the contemporary practices of these agencies. The results reveal that these agency's behaviors are shaped by government control, influences from the business community, identification with a nonprofit mindset (i.e., nonprofitness), funding streams, and various other factors. One key finding is that identification with a nonprofit mindset encourages certain behaviors like collaboration with other nonprofits and placing greater importance on key managerial priorities, but it does not reduce the likelihood of adopting business management strategies. Another important finding is that government control and funding does not have as strong as an influence on child welfare nonprofits as expected; however, influence from the business community does strongly affect many of their practices. The implications of these findings are discussed for child welfare agencies and the nonprofit sector in general. The consequences of nonprofits operating similarly to business and government are considered.
ContributorsRobichau, Robbie Waters (Author) / Catlaw, Thomas (Thesis advisor) / Nahavandi, Afsaneh (Committee member) / Gustavsson, Nora (Committee member) / Wang, Lili (Committee member) / Arizona State University (Publisher)
Created2013
Description
In the United States, under the provisions set forth by a policy known as community benefit, nonprofit hospitals receive special tax exemptions from government in exchange for providing a wide range of health care services to the communities in which they are located. In recent years, nonprofit hospitals have claimed billions of dollars as community benefit justifying their tax-exempt status. However, growing criticism by numerous stakeholders has questioned the extent to which the level of community benefit claimed by nonprofit hospitals reflects the exemptions they receive. In addition, a dearth of research exists to understand the relationship between community benefit claims and the impact they have on improving the health of communities. In an effort to better understand the relationship between community benefit claims, tax status, and community health outcomes this study examines the community benefit policies of a nonprofit healthcare system representing hospitals in California, Nevada, and Arizona. It does so by reviewing materials produced by the system, her hospitals, vested stakeholders, and government that have shaped the development, implementation, and assessment of community benefit policy processes. Findings of the study suggest that the majority of nonprofit hospital community benefit claims are consumed by shortfalls reported between costs associated with providing care to Medicare and Medicaid patients and the compensation nonprofit hospitals receive from government. Results of the study also demonstrate that community benefit policies do positively impact the health of communities. However, future community benefit policies need to be refined to include measures that capture the magnitude of community health improvement if the relationship between policy and health outcomes is to be fully realized.
ContributorsMartz, Mark Patrick (Author) / Cayer, Joseph (Thesis advisor) / Glaser, Mark (Committee member) / Corley, Elizabeth (Committee member) / Arizona State University (Publisher)
Created2013