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
Intermittent social defeat stress induces cross-sensitization to psychostimulants and escalation of drug self-administration. These behaviors could result from the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. Brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) is persistently elevated after social defeat stress, and may contribute to the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. BDNF modulates synaptic plasticity, and facilitates stress- and drug-induced neuroadaptations in the mesocorticolimbic system. The present research examined the role of mesolimbic BDNF signaling in social defeat stress-induced cross-sensitization to psychostimulants and the escalation of cocaine self-administration in rats. We measured drug taking behavior with the acquisition, progressive ratio, and binge paradigms during self-administration. With BDNF overexpression in the ventral tegmental area (VTA), single social defeat stress-induced cross-sensitization to amphetamine (AMPH) was significantly potentiated. VTA-BDNF overexpression also facilitates acquisition of cocaine self-administration, and a positive correlation between the level of VTA BDNF and drug intake during 12 hour binge was observed. We also found significant increase of DeltaFosB expression in the nucleus accumbens (NAc), the projection area of the VTA, in rats received intra-VTA BDNF overexpression. We therefore examined whether BDNF signaling in the NAc is important for social defeat stress-induced cross-sensitization by knockdown of the receptor of BDNF (neurotrophin tyrosine kinase receptor type 2, TrkB) there. NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization to psychostimulant. Also social defeat stress-induced increase of DeltaFosB in the NAc was prevented by TrkB knockdown. Several other factors up-regulated by stress, such as the GluA1 subunit of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and BDNF in the VTA were also prevented. We conclude that BDNF signaling in the VTA increases social defeat stress-induced vulnerability to psychostimulants, manifested as potentiated cross-sensitization/sensitization to AMPH and escalation of cocaine self-administration. Also BDNF signaling in the NAc is necessary for the stress-induced neuroadaptation and behavioral sensitization to psychostimulants. Therefore, TrkB in the NAc could be a therapeutic target to prevent stress-induced vulnerability to drugs of abuse in the future. DeltaFosB in the NAc shell could be a neural substrate underlying persistent cross-sensitization and augmented cocaine self-administration induced by social defeat stress.
ContributorsWang, Junshi (Author) / Hammer, Ronald (Thesis advisor) / Feuerstein, Burt (Committee member) / Nikulina, Ella (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
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
Alzheimer's Disease (AD) is a progressive neurodegenerative disease accounting for 50-80% of dementia cases in the country. This disease is characterized by the deposition of extracellular plaques occurring in regions of the brain important for cognitive function. A primary component of these plaques is the amyloid-beta protein. While a natively unfolded protein, amyloid-beta can misfold and aggregate generating a variety of different species including numerous different soluble oligomeric species some of which are precursors to the neurofibrillary plaques. Various of the soluble amyloid-beta oligomeric species have been shown to be toxic to cells and their presence may correlate with progression of AD. Current treatment options target the dementia symptoms, but there is no effective cure or alternative to delay the progression of the disease once it occurs. Amyloid-beta aggregates show up many years before symptoms develop, so detection of various amyloid-beta aggregate species has great promise as an early biomarker for AD. Therefore reagents that can selectively identify key early oligomeric amyloid-beta species have value both as potential diagnostics for early detection of AD and as well as therapeutics that selectively target only the toxic amyloid-beta aggregate species. Earlier work in the lab includes development of several different single chain antibody fragments (scFvs) against different oligomeric amyloid-beta species. This includes isolation of C6 scFv against human AD brain derived oligomeric amyloid-beta (Kasturirangan et al., 2013). This thesis furthers research in this direction by improving the yields and investigating the specificity of modified C6 scFv as a diagnostic for AD. It is motivated by experiments reporting low yields of the C6 scFv. We also used the C6T scFv to characterize the variation in concentration of this particular oligomeric amyloid-beta species with age in a triple transgenic AD mouse model. We also show that C6T can be used to differentiate between post-mortem human AD, Parkinson's disease (PD) and healthy human brain samples. These results indicate that C6T has potential value as a diagnostic tool for early detection of AD.
ContributorsVenkataraman, Lalitha (Author) / Sierks, Michael (Thesis advisor) / Rege, Kaushal (Committee member) / Pauken, Christine (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
This dissertation explores the use of bench-scale batch microcosms in remedial design of contaminated aquifers, presents an alternative methodology for conducting such treatability studies, and - from technical, economical, and social perspectives - examines real-world application of this new technology. In situ bioremediation (ISB) is an effective remedial approach for many contaminated groundwater sites. However, site-specific variability necessitates the performance of small-scale treatability studies prior to full-scale implementation. The most common methodology is the batch microcosm, whose potential limitations and suitable technical alternatives are explored in this thesis. In a critical literature review, I discuss how continuous-flow conditions stimulate microbial attachment and biofilm formation, and identify unique microbiological phenomena largely absent in batch bottles, yet potentially relevant to contaminant fate. Following up on this theoretical evaluation, I experimentally produce pyrosequencing data and perform beta diversity analysis to demonstrate that batch and continuous-flow (column) microcosms foster distinctly different microbial communities. Next, I introduce the In Situ Microcosm Array (ISMA), which took approximately two years to design, develop, build and iteratively improve. The ISMA can be deployed down-hole in groundwater monitoring wells of contaminated aquifers for the purpose of autonomously conducting multiple parallel continuous-flow treatability experiments. The ISMA stores all sample generated in the course of each experiment, thereby preventing the release of chemicals into the environment. Detailed results are presented from an ISMA demonstration evaluating ISB for the treatment of hexavalent chromium and trichloroethene. In a technical and economical comparison to batch microcosms, I demonstrate the ISMA is both effective in informing remedial design decisions and cost-competitive. Finally, I report on a participatory technology assessment (pTA) workshop attended by diverse stakeholders of the Phoenix 52nd Street Superfund Site evaluating the ISMA's ability for addressing a real-world problem. In addition to receiving valuable feedback on perceived ISMA limitations, I conclude from the workshop that pTA can facilitate mutual learning even among entrenched stakeholders. In summary, my doctoral research (i) pinpointed limitations of current remedial design approaches, (ii) produced a novel alternative approach, and (iii) demonstrated the technical, economical and social value of this novel remedial design tool, i.e., the In Situ Microcosm Array technology.
ContributorsKalinowski, Tomasz (Author) / Halden, Rolf U. (Thesis advisor) / Johnson, Paul C (Committee member) / Krajmalnik-Brown, Rosa (Committee member) / Bennett, Ira (Committee member) / Arizona State University (Publisher)
Created2013
Description
Current policies subsidizing or accelerating deployment of photovoltaics (PV) are typically motivated by claims of environmental benefit, such as the reduction of CO2 emissions generated by the fossil-fuel fired power plants that PV is intended to displace. Existing practice is to assess these environmental benefits on a net life-cycle basis, where CO2 benefits occurring during use of the PV panels is found to exceed emissions generated during the PV manufacturing phase including materials extraction and manufacture of the PV panels prior to installation. However, this approach neglects to recognize that the environmental costs of CO2 release during manufacture are incurred early, while environmental benefits accrue later. Thus, where specific policy targets suggest meeting CO2 reduction targets established by a certain date, rapid PV deployment may have counter-intuitive, albeit temporary, undesired consequences. Thus, on a cumulative radiative forcing (CRF) basis, the environmental improvements attributable to PV might be realized much later than is currently understood. This phenomenon is particularly acute when PV manufacture occurs in areas using CO2 intensive energy sources (e.g., coal), but deployment occurs in areas with less CO2 intensive electricity sources (e.g., hydro). This thesis builds a dynamic Cumulative Radiative Forcing (CRF) model to examine the inter-temporal warming impacts of PV deployments in three locations: California, Wyoming and Arizona. The model includes the following factors that impact CRF: PV deployment rate, choice of PV technology, pace of PV technology improvements, and CO2 intensity in the electricity mix at manufacturing and deployment locations. Wyoming and California show the highest and lowest CRF benefits as they have the most and least CO2 intensive grids, respectively. CRF payback times are longer than CO2 payback times in all cases. Thin film, CdTe PV technologies have the lowest manufacturing CO2 emissions and therefore the shortest CRF payback times. This model can inform policies intended to fulfill time-sensitive CO2 mitigation goals while minimizing short term radiative forcing.
ContributorsTriplican Ravikumar, Dwarakanath (Author) / Seager, Thomas P (Thesis advisor) / Fraser, Matthew P (Thesis advisor) / Chester, Mikhail V (Committee member) / Sinha, Parikhit (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
Many manmade chemicals used in consumer products are ultimately washed down the drain and are collected in municipal sewers. Efficient chemical monitoring at wastewater treatment (WWT) plants thus may provide up-to-date information on chemical usage rates for epidemiological assessments. The objective of the present study was to extrapolate this concept, termed 'sewage epidemiology', to include municipal sewage sludge (MSS) in identifying and prioritizing contaminants of emerging concern (CECs). To test this the following specific aims were defined: i) to screen and identify CECs in nationally representative samples of MSS and to provide nationwide inventories of CECs in U.S. MSS; ii) to investigate the fate and persistence in MSS-amended soils, of sludge-borne hydrophobic CECs; and iii) to develop an analytical tool relying on contaminant levels in MSS as an indicator for identifying and prioritizing hydrophobic CECs. Chemicals that are primarily discharged to the sewage systems (alkylphenol surfactants) and widespread persistent organohalogen pollutants (perfluorochemicals and brominated flame retardants) were analyzed in nationally representative MSS samples. A meta-analysis showed that CECs contribute about 0.04-0.15% to the total dry mass of MSS, a mass equivalent of 2,700-7,900 metric tonnes of chemicals annually. An analysis of archived mesocoms from a sludge weathering study showed that 64 CECs persisted in MSS/soil mixtures over the course of the experiment, with half-lives ranging between 224 and >990 days; these results suggest an inherent persistence of CECs that accumulate in MSS. A comparison of the spectrum of chemicals (n=52) analyzed in nationally representative biological specimens from humans and MSS revealed 70% overlap. This observed co-occurrence of contaminants in both matrices suggests that MSS may serve as an indicator for ongoing human exposures and body burdens of pollutants in humans. In conclusion, I posit that this novel approach in sewage epidemiology may serve to pre-screen and prioritize the several thousands of known or suspected CECs to identify those that are most prone to pose a risk to human health and the environment.
ContributorsVenkatesan, Arjunkrishna (Author) / Halden, Rolf U. (Thesis advisor) / Westerhoff, Paul (Committee member) / Fox, Peter (Committee member) / Arizona State University (Publisher)
Created2013
Description
Nitrate is the most prevalent water pollutant limiting the use of groundwater as a potable water source. The overarching goal of this dissertation was to leverage advances in nanotechnology to improve nitrate photocatalysis and transition treatment to the full-scale. The research objectives were to (1) examine commercial and synthesized photocatalysts, (2) determine the effect of water quality parameters (e.g., pH), (3) conduct responsible engineering by ensuring detection methods were in place for novel materials, and (4) develop a conceptual framework for designing nitrate-specific photocatalysts. The key issues for implementing photocatalysis for nitrate drinking water treatment were efficient nitrate removal at neutral pH and by-product selectivity toward nitrogen gases, rather than by-products that pose a human health concern (e.g., nitrite). Photocatalytic nitrate reduction was found to follow a series of proton-coupled electron transfers. The nitrate reduction rate was limited by the electron-hole recombination rate, and the addition of an electron donor (e.g., formate) was necessary to reduce the recombination rate and achieve efficient nitrate removal. Nano-sized photocatalysts with high surface areas mitigated the negative effects of competing aqueous anions. The key water quality parameter impacting by-product selectivity was pH. For pH < 4, the by-product selectivity was mostly N-gas with some NH4+, but this shifted to NO2- above pH = 4, which suggests the need for proton localization to move beyond NO2-. Co-catalysts that form a Schottky barrier, allowing for localization of electrons, were best for nitrate reduction. Silver was optimal in heterogeneous systems because of its ability to improve nitrate reduction activity and N-gas by-product selectivity, and graphene was optimal in two-electrode systems because of its ability to shuttle electrons to the working electrode. "Environmentally responsible use of nanomaterials" is to ensure that detection methods are in place for the nanomaterials tested. While methods exist for the metals and metal oxides examined, there are currently none for carbon nanotubes (CNTs) and graphene. Acknowledging that risk assessment encompasses dose-response and exposure, new analytical methods were developed for extracting and detecting CNTs and graphene in complex organic environmental (e.g., urban air) and biological matrices (e.g. rat lungs).
ContributorsDoudrick, Kyle (Author) / Westerhoff, Paul (Thesis advisor) / Halden, Rolf (Committee member) / Hristovski, Kiril (Committee member) / Arizona State University (Publisher)
Created2013
Description
There is growing concern over the future availability of water for electricity generation. Because of a rapidly growing population coupled with an arid climate, the Western United States faces a particularly acute water/energy challenge, as installation of new electricity capacity is expected to be required in the areas with the most limited water availability. Electricity trading is anticipated to be an important strategy for avoiding further local water stress, especially during drought and in the areas with the most rapidly growing populations. Transfers of electricity imply transfers of "virtual water" - water required for the production of a product. Yet, as a result of sizable demand growth, there may not be excess capacity in the system to support trade as an adaptive response to long lasting drought. As the grid inevitably expands capacity due to higher demand, or adapts to anticipated climate change, capacity additions should be selected and sited to increase system resilience to drought. This paper explores the tradeoff between virtual water and local water/energy infrastructure development for the purpose of enhancing the Western US power grid's resilience to drought. A simple linear model is developed that estimates the economically optimal configuration of the Western US power grid given water constraints. The model indicates that natural gas combined cycle power plants combined with increased interstate trade in power and virtual water provide the greatest opportunity for cost effective and water efficient grid expansion. Such expansion, as well as drought conditions, may shift and increase virtual water trade patterns, as states with ample water resources and a competitive advantage in developing power sources become net exporters, and states with limited water or higher costs become importers.
ContributorsHerron, Seth (Author) / Ruddell, Benjamin L (Thesis advisor) / Ariaratnam, Samuel (Thesis advisor) / Allenby, Braden (Committee member) / Williams, Eric (Committee member) / Arizona State University (Publisher)
Created2013