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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- All Subjects: Genetics
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
I study the performance of hedge fund managers, using quarterly stock holdings from 1995 to 2010. I use the holdings-based measure built on Ferson and Mo (2012) to decompose a manager's overall performance into stock selection and three components of timing ability: market return, volatility, and liquidity. At the aggregate level, I find that hedge fund managers have stock picking skills but no timing skills, and overall I do not find strong evidence to support their superiority. I show that the lack of abilities is driven by the large fluctuations of timing performance with market conditions. I find that conditioning information, equity capital constraints, and priority in stocks to liquidate can partly explain the weak evidence. At the individual fund level, bootstrap analysis results suggest that even top managers' abilities cannot be separated from luck. Also, I find that hedge fund managers exhibit short-horizon persistence in selectivity skill.
ContributorsKang, MinJeong (Author) / Aragon, George O. (Thesis advisor) / Hertzel, Michael G (Committee member) / Boguth, Oliver (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
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
"YouTube Shakespeares" is a study of Shakespeare online videos and the people who create, upload, and view them on YouTube. Employing an interdisciplinary approach, this work is a remix of theories and methodologies from literary, performance, (social) media, fan, and Internet studies that expands the field of Shakespeare studies. This dissertation explores the role of YouTube users and their activities, the expansion of literary research methods onto digital media venues, YouTube as site of Shakespeare performance, and YouTube Shakespeares' fan communities. It analyzes a broad array of Shakespeare visual performances including professional and user-generated mashups, remixes, film clips, auditions, and high school performances. A rich avenue for the study of people's viewing and reception of Shakespeare, YouTube tests the (un)limitations of Shakespeare adaptation. This work explores the ethical implications of researching performances that include human subjects, arguing that their presence frequently complicates common concepts of public and private identities. Although YouTube is a "published" forum for social interactivity and video repository, this work urges digital humanities scholars to recognize and honor the human users entailed in the videos not as text, but as human subjects. Shifting the study focus to human subjects demands a revision of research methods and publications protocols as the researcher repositions herself into the role of virtual ethnographer. "YouTube Shakespeares" develops its own ethics-based, online research method, which includes seeking Institutional Board Review approval and online interviews. The second half of the dissertation shifts from methodology to theorizing YouTube Shakespeares' performance spaces as analogs to the interactive and imaginary areas of Shakespeare's early modern theatre. Additionally, this work argues that YouTube Shakespeares' creators and commentators are fans. "YouTube Shakespeares" is one of the first Shakespeare-centric studies to employ fan studies as a critical lens to explore the cultural significance and etiquette of people's online Shakespeare performance activities. The work ends with a conversation about the issues of ephemerality, obsolescence, and concerns about the instability of digital and online materials, noting the risk of evidentiary loss of research materials is far outweighed by a scholarly critical registration of YouTube in the genealogy of Shakespeare performance.
ContributorsFazel, Valerie Margaret (Author) / Thompson, Ayanna (Thesis advisor) / Ryner, Bradley (Committee member) / Fox, Cora (Committee member) / Arizona State University (Publisher)
Created2013
Description
The integration of yoga into the music curriculum has the potential of offering many immediate and life-long benefits to musicians. Yoga can help address issues such as performance anxiety and musculoskeletal problems, and enhance focus and awareness during musical practice and performance. Although the philosophy of yoga has many similarities to the process of learning a musical instrument, the benefits of yoga for musicians is a topic that has gained attention only recently. This document explores several ways in which the practice and philosophy of yoga can be fused with saxophone pedagogy as one way to prepare students for a healthy and successful musical career. A six-week study at Arizona State University was conducted to observe the effects of regular yoga practice on collegiate saxophone students. Nine participants attended a sixty-minute "yoga for musicians" class twice a week. Measures included pre- and post- study questionnaires as well as personal journals kept throughout the duration of the study. These self-reported results showed that yoga had positive effects on saxophone playing. It significantly increased physical comfort and positive thinking, and improved awareness of habitual patterns and breath control. Student participants responded positively to the idea of integrating such a course into the music curriculum. The integration of yoga and saxophone by qualified professionals could also be a natural part of studio class and individual instruction. Carrie Koffman, professor of saxophone at The Hartt School, University of Hartford, has established one strong model for the combination of these disciplines. Her methods and philosophy, together with the basics of Western-style hatha yoga, clinical reports on performance injuries, and qualitative data from the ASU study are explored. These inquiries form the foundation of a new model for integrating yoga practice regularly into the saxophone studio.
ContributorsAdams, Allison Dromgold (Author) / Norton, Kay (Thesis advisor) / Hill, Gary (Committee member) / McAllister, Timothy (Committee member) / Micklich, Albie (Committee member) / Standley, Eileen (Committee member) / Arizona State University (Publisher)
Created2012
Description
Well-established model systems exist in four out of the seven major classes of vertebrates. These include the mouse, chicken, frog and zebrafish. Noticeably missing from this list is a reptilian model organism for comparative studies between the vertebrates and for studies of biological processes unique to reptiles. To help fill in this gap the green anole lizard, Anolis carolinensis, is being adapted as a model organism. Despite the recent release of the complete genomic sequence of the A. carolinensis, the lizard lacks some resources to aid researchers in their studies. Particularly, the lack of transcriptomic resources for lizard has made it difficult to identify genes complete with alternative splice forms and untranslated regions (UTRs). As part of this work the genome annotation for A. carolinensis was improved through next generation sequencing and assembly of the transcriptomes from 14 different adult and embryonic tissues. This revised annotation of the lizard will improve comparative studies between vertebrates, as well as studies within A. carolinensis itself, by providing more accurate gene models, which provide the bases for molecular studies. To demonstrate the utility of the improved annotations and reptilian model organism, the developmental process of somitogenesis in the lizard was analyzed and compared with other vertebrates. This study identified several key features both divergent and convergent between the vertebrates, which was not previously known before analysis of a reptilian model organism. The improved genome annotations have also allowed for molecular studies of tail regeneration in the lizard. With the annotation of 3' UTR sequences and next generation sequencing, it is now possible to do expressional studies of miRNA and predict their mRNA target transcripts at genomic scale. Through next generation small RNA sequencing and subsequent analysis, several differentially expressed miRNAs were identified in the regenerating tail, suggesting miRNA may play a key role in regulating this process in lizards. Through miRNA target prediction several key biological pathways were identified as potentially under the regulation of miRNAs during tail regeneration. In total, this work has both helped advance A. carolinensis as model system and displayed the utility of a reptilian model system.
ContributorsEckalbar, Walter L (Author) / Kusumi, Kenro (Thesis advisor) / Huentelman, Matthew (Committee member) / Rawls, Jeffery (Committee member) / Wilson-Rawls, Norma (Committee member) / Arizona State University (Publisher)
Created2012
Description
The Holocaust and the effects it has had upon witnesses has been a topic of study for nearly six decades; however, few angles of research have been conducted relating to the long-term effects of the Holocaust upon the children and grandchildren of Holocaust survivors--the After Generations. The After Generations are considered the proof--the living legacies--that their parents and grandparents survived. Growing up with intimate knowledge of the atrocities that occurred during the Holocaust, members of the After Generations not only carry with them their family's story, but also their own vicarious experience(s) of trauma. From this legacy comes a burden of responsibility to those who perished, their survivor parents/grandparents, the stories that were shared, as well as to future generations. Using grounded theory method, this study not only explores the long-term effects of the Holocaust upon members of the After Generations, but what it means to responsibly remember the stories from the Holocaust, as well as how individuals might ethically represent such stories/memories. Findings that developed out of an axial analysis of interview transcripts and journal writing, as well as the later development of a performance script, are embodied in a manner that allows the actual language and experiences of the participants to be collectively witnessed both symbolically and visually. Through their desire to remember, members of the After Generations demonstrate how they plan to carry on traditions, live lives that honor those that came before them, and maintain hope for the future. In so doing, the stories shared reveal the centrality of the Holocaust in the lives of members of the After Generations through their everyday choices to responsibly and actively remember through their art, writings, life-work, as well as from within their work in their local communities. Such acts of remembrance are important to the education of others as well as to the construction and maintenance of the After Generations' identities. The representation of these voices acts as a reminder of how hatred and its all-consuming characteristics can affect not only the person targeted, but multiple generations, as well.
ContributorsRath, Sandra (Author) / de la Garza, Sarah Amira (Thesis advisor) / Underiner, Tamara (Committee member) / Corey, Frederick C. (Committee member) / Eisenberg, Judith (Committee member) / Arizona State University (Publisher)
Created2012