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
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 philosophical inquiry explores the work of philosophers Gilles Deleuze and Félix Guattari and posits applications to music education. Through the concepts of multiplicities, becoming, bodies without organs, smooth spaces, maps, and nomads, Deleuze and Guattari challenge prior and current understandings of existence. In their writings on art, education, and how might one live, they assert a world consisting of variability and motion. Drawing on Deleuze and Guattari's emphasis on time and difference, I posit the following questions: Who and when are we? Where are we? When is music? When is education? Throughout this document, their philosophical figuration of a rhizome serves as a recurring theme, highlighting the possibilities of complexity, diverse connections, and continual processes. I explore the question "When and where are we?" by combining the work of Deleuze and Guattari with that of other authors. Drawing on these ideas, I posit an ontology of humans as inseparably cognitive, embodied, emotional, social, and striving multiplicities. Investigating the question "Where are we?" using Deleuze and Guattari's writings as well as that of contemporary place philosophers and other writers reveals that humans exist at the continually changing confluence of local and global places. In order to engage with the questions "When is music?" and "When is education?" I inquire into how humans as cognitive, embodied, emotional, social, and striving multiplicities emplaced in a glocalized world experience music and education. In the final chapters, a philosophy of music education consisting of the ongoing, interconnected processes of complicating, considering, and connecting is proposed. Complicating involves continually questioning how humans' multiple inseparable qualities and places integrate during musical and educative experiences. Considering includes imagining the multiple directions in which connections might occur as well as contemplating the quality of potential connections. Connecting involves assisting students in forming variegated connections between themselves, their multiple qualities, and their glocal environments. Considering a rhizomatic philosophy of music education includes continually engaging in the integrated processes of complicating, considering, and connecting. Through such ongoing practices, music educators can promote flourishing in the lives of students and the experiences of their multiple communities.
ContributorsRicherme, Lauren Kapalka (Author) / Stauffer, Sandra (Thesis advisor) / Gould, Elizabeth (Committee member) / Schmidt, Margaret (Committee member) / Sullivan, Jill (Committee member) / Tobias, Evan (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 In this work, I provide two novel pieces of evidence in favor of the view that there is pragmatic encroachment on knowledge. First, I present an empirical case via the results of a series of recent experiments to show that folk-knowledge attributions may be sensitive to time constraints even when the latter are construed in a non-truth relevant manner. Along the way, I consider some comments made by Jonathan Schaffer (2006) as it pertains to interpreting time constraints-sensitivity in a manner that supports contextualism, before offering reasons to resist such a treatment. I proceed by applying interest relative invariantism to adjudicate a conflict in the epistemology of testimony namely, the positive reasons requirement a la, reductionism vs. non-reductionism. In particular, I highlight how whether an epistemic subject H needs positive non-testimonial reasons to be justified in accepting S's testimony that p, depends on what is at stake for H in believing that p and how much time H has in deliberating about p.
ContributorsShin, Joseph Ellis (Author) / Pinillos, N. Angel (Thesis advisor) / Reynolds, Steven L (Committee member) / White, Michael J. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Emergentism offers a promising compromise in the philosophy of mind between Cartesian substance dualism and reductivistic physicalism. The ontological emergentist holds that conscious mental phenomena supervene on physical phenomena, but that they have a nature over and above the physical. However, emergentist views have been subjected to a variety of powerful objections: they are alleged to be self-contradictory, incompatible with mental causation, justified by unreliable intuitions, and in conflict with our contemporary scientific understanding of the world. I defend the emergentist position against these objections. I clarify the concepts of supervenience and of ontological novelty in a way that ensures the emergentist position is coherent, while remaining distinct from physicalism and traditional dualism. Making note of the equivocal way in which the concept of sufficiency is used in Jaegwon Kim's arguments against emergent mental causation, I argue that downward causation does not entail widespread overdetermination. I argue that considerations of ideal a priori deducibility from some physical base, or "Cosmic Hermeneutics", will not themselves provide answers to where the cuts in the structure of nature lie. Instead, I propose reconsidering the question of Cosmic Hermeneutics in terms of which cognitive resources would be required for the ideal reasoner to perform the deduction. Lastly, I respond to the objection that emergence in the philosophy of mind is in conflict with our contemporary scientific understanding of the world. I suggest that a kind of weak ontological emergence is a viable form of explanation in many fields, and discuss current applications of emergence in biology, sociology, and the study of complex systems.
ContributorsWatson, Jeffrey (Author) / Kobes, Bernard W (Thesis advisor) / Pinillos, Nestor (Committee member) / Horgan, Terence (Committee member) / Reynolds, Steven (Committee member) / Arizona State University (Publisher)
Created2013
Description
This thesis explores the conceptual span and plausibility of emergence and its applicability to the problem of mental causation. The early parts of the project explicate a distinction between weak and strong emergence as described by Jaegwon Kim. They also consider Kim's objections regarding the conceptual incoherence of strong emergence and the otiose nature of weak emergence. The paper then explores Mark Bedau's in-between conception of emergence and ultimately finds that middle conception to be both coherent and useful. With these three emergence distinctions in hand, the thesis goes on to explore Evan Thompson's recent work - Mind in Life (2010). In that work, Thompson advances a strong emergence approach to mind, whereby he concludes the incipient stages of cognition are found at the most basic levels of life, namely - biologic cells. Along the way, Thompson embraces holism and a nonfundamental
onhierarchical physics in order to counter Jaegwon Kim's objections to the notion of downward causation needed for strong emergence. The thesis presents arguments against Thompson's holism and nonfundamental physics, while supporting his assertion regarding the incipient stages of cognition. It then combines an important distinction between mental causation and the experience of mental causation with Thompson's notion of incipient cognition to arrive at a dual realms approach to understanding mental causation.
onhierarchical physics in order to counter Jaegwon Kim's objections to the notion of downward causation needed for strong emergence. The thesis presents arguments against Thompson's holism and nonfundamental physics, while supporting his assertion regarding the incipient stages of cognition. It then combines an important distinction between mental causation and the experience of mental causation with Thompson's notion of incipient cognition to arrive at a dual realms approach to understanding mental causation.
ContributorsFournier, Thomas (Author) / Kobes, Bernard W (Thesis advisor) / Reynolds, Steven L (Committee member) / Armendt, Brad (Committee member) / Arizona State University (Publisher)
Created2013
Description
Saying, "if Mary had watered Sam's plant, it wouldn't have died," is an ordinary way to identify Mary not watering Sam's plant as the cause of its death. But there are problems with this statement. If we identify Mary's omitted action as the cause, we seemingly admit an inordinate number of omissions as causes. For any counterfactual statement containing the omitted action is true (e.g. if Hillary Clinton had watered Sam's plant, it wouldn't have died). The statement, moreover, is mysterious because it is not clear why one protasis is more salient than any alternatives such as "if Sam hadn't gone to Bismarck." In the burgeoning field of experimental metaphysics, some theorists have tried to account for these intuitions about omissive causes. By synthesizing this data and providing a few experiments, I will suggest that judgments - and maybe metaphysics - about omissive causes necessarily have a normative feature. This understanding of omissive causes may be able to adequately resolve the problems above.
ContributorsHenne, Paul (Author) / Kobes, Bernard W (Thesis advisor) / Pinillos, Nestor A (Thesis advisor) / Reynolds, Steven (Committee member) / Arizona State University (Publisher)
Created2013
Description
With the number of internationally-run clinical drug trials increasing, the double standards between those in developed nations and those in developing nations are being scrutinized under the ethical microscope. Many argue that several pharmaceutical companies and researchers are exploiting developing nation participants. Two issues of concern are the use of a placebo control when an effective alternative treatment exists and the lack of drug availability to the country that hosted the clinical trial should the experimental drug prove effective. Though intuitively this seems like an instance of exploitation, philosophically, exploitation theories cannot adequately account for the wrongdoing in these cases. My project has two parts. First, after explaining why the theories of Alan Wertheimer, John Lawrence Hill, and Ruth Sample fail to explain the exploitation in clinical drug research, I provide an alternative account of exploitation that can explain why the double standard in clinical research is harmful. Rather than craft a single theory encompassing all instances of exploitation, I offer an account of a type, or subset, of exploitation that I refer to as comparative exploitation. The double standards in clinical research fall under the category of comparative exploitation. Furthermore, while many critics maintain that cases of comparative exploitation, including clinical research, are mutually beneficial, they are actually harmful to its victims. I explain the harm of comparative exploitation using Ben Bradley's counterfactual account of harm and Larry May's theory of sharing responsibility. The second part of my project focuses on the "standard of care" argument, which most defenders use to justify the double standard in clinical research. I elaborate on Ruth Macklin's position that advocates of the "standard of care" position make three faulty assumptions: placebo-controlled trials are the gold standard, the only relevant question responsive to the host country's health needs is "Is the experimental product being studied better than the 'nothing' now available to the population?", and the only way of obtaining affordable products is to test cheap alternatives to replace the expensive ones. In the end, I advocate moving towards a universalizing of standards in order to avoid exploitation.
ContributorsFundora, Danielle (Author) / McGregor, Joan (Thesis advisor) / Brake, Elizabeth (Committee member) / Portmore, Douglas (Committee member) / Arizona State University (Publisher)
Created2013