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
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
Research examining the long-term impacts of federal interventions under the Civil Rights of Institutionalized Persons Act on correctional institutions has been scant. The result has been a failure to understand the sustainability of reforms aimed at protecting the civil rights of confined persons. This dissertation examined the long-term reforms at the Arizona Department of Juvenile Corrections following a consent decree with the U.S. Department of Justice from 2004 to 2007. Interviews were conducted with current and former ADJC employees, juvenile justice advocates across Arizona, and county court representatives to determine how each of these groups perceived the status of the reforms at the ADJC. The findings of the current dissertation suggest that long-term reforms following consent decrees imposed on correctional institutions are possible. At the ADJC, the methods for securing the reform required that the agency reform its culture, implement a Quality Assurance process, revamp the Investigations and Inspections unit at the agency, and consider the perspectives of external agencies. One of the primary reasons why the department has been committed to making these reforms is because of the perceived loss of legitimacy and resources that would occur if they failed to reform. Such a failure for the agency could have potentially resulted in a closure of the agency. However, the increase in punitive and preventive policies used to enforce the reforms may have negative repercussions on the organizational culture in the long term. Policy implications for future CRIPA consent decrees are outlined, limitations are addressed, and suggestions for future research are made.
ContributorsTaylor, Melanie Ann (Author) / Decker, Scott H. (Thesis advisor) / Katz, Charles M. (Committee member) / Fox, Kathleen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Knowing that disorder is related to crime, it has become essential for criminologists to understand how and why certain individuals perceive disorder. Using data from the Perceptions of Neighborhood Disorder and Interpersonal Conflict Project, this study uses a fixed photograph of a neighborhood, to assess whether individuals "see" disorder cues. A final sample size of n=815 respondents were asked to indicate if they saw particular disorder cues in the photograph. The results show that certain personal characteristics do predict whether an individual sees disorder. Because of the experimental design, results are a product of the individual's personal characteristics, not of the respondent's neighborhood. These findings suggest that the perception of disorder is not as clear cut as once thought. Future research should explore what about these personal characteristics foster the perception of disorder when it is not present, as well as, how to fight disorder in neighborhoods when perception plays such a substantial role.
ContributorsScott, Christopher (Author) / Wallace, Danielle (Thesis advisor) / Katz, Charles (Committee member) / Ready, Justin (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
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
ABSTRACT Research on self-control theory (Gottfredson & Hirschi, 1990) consistently supports its' central proposition that low self-control significantly affects crime. The theory includes other predictions, which have received far less empirical scrutiny. Among these is the argument that self-control is developed early in childhood and that individual differences then persist over time. Gottfredson and Hirschi contend that once established by age ten, self-control remains relatively stable over one's life-course (stability postulate). To determine the empirical status of Gottfredson and Hirschi's "stability postulate," a meta-analysis on existing empirical studies was conducted. Results for this study support the contentions made by Gottfredson and Hirschi, however the inclusion of various moderating variables significantly influenced this relationship. Keywords: self-control, self-control stability, absolute stability, relative stability
ContributorsMeyers, Travis J (Author) / Pratt, Travis (Thesis advisor) / Burt, Callie (Committee member) / Wright, Kevin (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
There has been a tremendous amount of innovation in policing over the last 40 years, from community and problem-oriented policing to hot spots and intelligence-led policing. Many of these innovations have been subjected to empirical testing, with mixed results on effectiveness. The latest innovation in policing is the Bureau of Justice Assistance's Smart Policing Initiative (2009). Created in 2009, the SPI provides funding to law enforcement agencies to develop and test evidence-based practices to address crime and disorder. Researchers have not yet tested the impact of the SPI on the funded agencies, particularly with regard to core principles of the Initiative. The most notable of these is the collaboration between law enforcement agencies and their research partners. The current study surveyed SPI agencies and their research partners on key aspects of their Initiative. The current study uses mean score comparisons and qualitative responses to evaluate this partnership to determine the extent of its value and effect. It also seeks to determine the areas of police agency crime analysis and research units that are most in need of enhancement. Findings indicate that the research partners are actively involved in a range of aspects involved in problem solving under the Smart Policing Initiative, and that they have positively influenced police agencies' research and crime analysis functions, and to a lesser extent, have positively impacted police agencies' tactical operations. Additionally, personnel, technology, and training were found to be the main areas of the crime analysis and research units that still need to be enhanced. The thesis concludes with a discussion of the implications of these findings for police policy and practice.
ContributorsMartin-Roethele, Chelsie (Author) / White, Michael D. (Thesis advisor) / Ready, Justin (Committee member) / D'Anna, Matthew (Committee member) / Arizona State University (Publisher)
Created2013