Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
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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
Sustainable development in an American context implies an ongoing shift from quantitative growth in energy, resource, and land use to the qualitative development of social-ecological systems, human capital, and dense, vibrant built environments. Sustainable urban development theory emphasizes locally and bioregionally emplaced economic development where the relationships between people, localities, products, and capital are tangible to and controllable by local stakeholders. Critical theory provides a mature understanding of the political economy of land development in capitalist economies, representing a crucial bridge between urban sustainability's infill development goals and the contemporary realities of the development industry. Since its inception, Phoenix, Arizona has exemplified the quantitative growth paradigm, and recurring instances of land speculation, non-local capital investment, and growth-based public policy have stymied local, tangible control over development from Phoenix's territorial history to modern attempts at downtown revitalization. Utilizing property ownership and sales data as well as interviews with development industry stakeholders, the political economy of infill land development in downtown Phoenix during the mid-2000s boom-and-bust cycle is analyzed. Data indicate that non-local property ownership has risen significantly over the past 20 years and rent-seeking land speculation has been a significant barrier to infill development. Many speculative strategies monopolize the publicly created value inherent in zoning entitlements, tax incentives and property assessment, indicating that political and policy reforms targeted at a variety of governance levels are crucial for achieving the sustainable development of urban land. Policy solutions include reforming the interconnected system of property sales, value assessment, and taxation to emphasize property use values; replacing existing tax incentives with tax increment financing and community development benefit agreements; regulating vacant land ownership and deed transfers; and encouraging innovative private development and tenure models like generative construction and community land trusts.
ContributorsStanley, Benjamin W (Author) / Boone, Christopher G. (Thesis advisor) / Redman, Charles (Committee member) / Bolin, Robert (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
During the months from June to November 2012, the city of Bangalore was faced with a serious solid waste management (SWM) crisis. In the wake of the upheaval, the state court declared source segregation to be mandatory. Yet, while the legislation was clear, the pathway towards a course of action for the transition was not clear and hence, Bangalore was stuck in a state of limbo. The objectives for this thesis spiraled organically from this crisis. The first objective was to examine the gaps in Bangalore's transition to a more sustainable SWM system. Six particular gaps were identified, which in essence, were opportunities to re-shape the system. The gaps identified included: conflicting political agendas, the exclusion of some key actors, and lack of adequate attention to cultural aspects, provision of appropriate incentives, protection of livelihoods and promotion of innovation. Opportunities were found in better incentivization of sustainable SWM goals, protecting livelihoods that depend on waste, enhancing innovation and endorsing local, context based SWM solutions. Building on this understanding of gaps, the second objective was to explore an innovative, local, bottom-up waste-management model called the Vellore Zero Waste Model, and assess its applicability to Bangalore. The adaptability of the model depended on several factors such as, willingness of actors to redefine their roles and change functions, ability of the municipality to assure quality and oversight, willingness of citizen to source segregate, and most importantly, the political will and collective action needed to ensure and sustain the transition. The role of communication as a vital component to facilitate productive stakeholder engagement and to promote role change was evident. Therefore, the third objective of the study was to explore how interpersonal competencies and communication strategies could be used as a tool to facilitate stakeholder engagement and encourage collective action. In addressing these objectives, India was compared with Austria because Austria is often cited as having some of the best SWM practices in the world and has high recycling rates to show for its reputation.
ContributorsRengarajan, Nivedita (Author) / Aggarwal, Rimjhim (Thesis advisor) / Chhetri, Nalini (Committee member) / Manuel-Navarrete, David (Committee member) / Arizona State University (Publisher)
Created2013
Description
Mixed-income housing policy has been an approach to address the problem of concentrated poverty since the 1990s. The idea of income mix in housing is founded on the proposition that economic opportunities of the poor can be expanded through the increasing of their social capital. The current in-depth case study of Vineyard Estates, a mixed-income housing development in Phoenix, AZ tests a hypothesis that low-income people improve their chances of upward social mobility by building ties with more affluent residents within the development. This study combines qualitative and quantitative methods to collect and analyze information including analysis of demographic data, resident survey and in-depth semi-structured interviews with residents, as well as direct observations. It focuses on examining the role of social networks established within the housing development in generating positive economic outcomes of the poor. It also analyzes the role of factors influencing interactions across income groups and barriers to upward social mobility. Study findings do not support that living in mixed-income housing facilitates residents' upward social mobility. The study concludes that chances of upward social mobility are restrained by structural factors and indicates a need to rethink the effectiveness of mixed-income housing as an approach for alleviating poverty.
ContributorsDurova, Aleksandra (Author) / Kamel, Nabil (Committee member) / Pfeiffer, Deirdre (Committee member) / Lucio, Joanna (Committee member) / Arizona State University (Publisher)
Created2013
Description
Sustainable urbanism offers a set of best practice planning and design prescriptions intended to reverse the negative environmental consequences of urban sprawl, which dominates new urban development in the United States. Master planned developments implementing sustainable urbanism are proliferating globally, garnering accolades within the planning community and skepticism among social scientists. Despite attention from supporters and critics alike, little is known about the actual environmental performance of sustainable urbanism. This dissertation addresses the reasons for this paucity of evidence and the capacity of sustainable urbanism to deliver the espoused environmental outcomes through alternative urban design and the conventional master planning framework for development through three manuscripts. The first manuscript considers the reasons why geography, which would appear to be a natural empirical home for research on sustainable urbanism, has yet to accumulate evidence that links design alternatives to environmental outcomes or to explain the social processes that mediate those outcomes. It argues that geography has failed to develop a coherent subfield based on nature-city interactions and suggests interdisciplinary bridging concepts to invigorate greater interaction between the urban and nature-society geographic subfields. The subsequent chapters deploy these bridging concepts to empirically examine case-studies in sustainable urbanism. The second manuscript utilizes fine scale spatial data to quantify differences in ecosystem services delivery across three urban designs in two phases of Civano, a sustainable urbanism planned development in Tucson, Arizona, and an adjacent, typical suburban development comparison community. The third manuscript considers the extent to which conventional master planning processes are fundamentally at odds with urban environmental sustainability through interviews with stakeholders involved in three planned developments: Civano (Tucson, Arizona), Mueller (Austin, Texas), and Prairie Crossing (Grayslake, Illinois). Findings from the three manuscripts reveal deep challenges in conceptualizing an empirical area of inquiry on sustainable urbanism, measuring the outcomes of urban design alternatives, and innovating planning practice within the constraints of existing institutions that facilitate conventional development. Despite these challenges, synthesizing the insights of geography and cognate fields holds promise in building an empirical body of knowledge that complements pioneering efforts of planners to innovate urban planning practice through the sustainable urbanism alternative.
ContributorsTurner, Victoria (Author) / Gober, Patricia (Thesis advisor) / Eakin, Hallie (Committee member) / Kinzig, Ann (Committee member) / Talen, Emily (Committee member) / Arizona State University (Publisher)
Created2013
Description
Canal oriented development (COD) is a placemaking concept that aims to create mixed use developments along canal banks using the image and utility of the waterfront as a natural attraction for social and economic activity. COD has the potential to for landlocked cities, which are lacking a traditional harbor, to pursue waterfront development which has become an important economic development source in the post-industrial city. This dissertation examines how COD as a placemaking technique can and has been used in creating urban development. This topic is analyzed via three separate yet interconnecting papers. The first paper explores the historical notion of canals as an urban economic development tool with particular attention paid to the Erie Canal. The second paper explores the feasibility of what it would take for canal development to occur in the Phoenix region. The third and final paper explores the importance of place in urban design and the success or nonsuccess of COD as a place maker through the examination of three different CODs.
ContributorsBuckman, Stephen Thomas (Author) / Talen, Emily (Thesis advisor) / Ellin, Nan (Committee member) / Crewe, Katherine (Committee member) / Arizona State University (Publisher)
Created2013
Description
Land transformation under conditions of rapid urbanization has significantly altered the structure and functioning of Earth's systems. Land fragmentation, a characteristic of land transformation, is recognized as a primary driving force in the loss of biological diversity worldwide. However, little is known about its implications in complex urban settings where interaction with social dynamics is intense. This research asks: How do patterns of land cover and land fragmentation vary over time and space, and what are the socio-ecological drivers and consequences of land transformation in a rapidly growing city? Using Metropolitan Phoenix as a case study, the research links pattern and process relationships between land cover, land fragmentation, and socio-ecological systems in the region. It examines population growth, water provision and institutions as major drivers of land transformation, and the changes in bird biodiversity that result from land transformation. How to manage socio-ecological systems is one of the biggest challenges of moving towards sustainability. This research project provides a deeper understanding of how land transformation affects socio-ecological dynamics in an urban setting. It uses a series of indices to evaluate land cover and fragmentation patterns over the past twenty years, including land patch numbers, contagion, shapes, and diversities. It then generates empirical evidence on the linkages between land cover patterns and ecosystem properties by exploring the drivers and impacts of land cover change. An interdisciplinary approach that integrates social, ecological, and spatial analysis is applied in this research. Findings of the research provide a documented dataset that can help researchers study the relationship between human activities and biotic processes in an urban setting, and contribute to sustainable urban development.
ContributorsZhang, Sainan (Author) / Boone, Christopher G. (Thesis advisor) / York, Abigail M. (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2013