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
Coccidioidomycosis, also known as Valley Fever, is a disease caused by the dimorphic soil-dwelling fungus, Coccidioides sp. Coccidioidomycosis is difficult to diagnose because symptoms are similar to community-acquired pneumonia. Current diagnostic tests rely on antibody responses, but immune responses can be delayed and aberrant, resulting in false negative diagnoses. Unlike serology, detection of coccidioidal proteins or other fungal components in blood could distinguish valley fever from other pulmonary infections and provide a definitive diagnosis. Using mass spectrometry (LC-MS/MS) we examined the plasma peptidome from patients with serologically confirmed coccidioidomycosis. Mass spectra were searched using the protein database from the Coccidioides species, generated and annotated by the Broad Institute. 15 of 20 patients with serologically confirmed coccidioidomycosis demonstrated the presence of a peptide in plasma, "PGLDSKSLACTFSQV" (PGLD). The peptide is derived from an open reading frame from a "conserved hypothetical protein" annotated with 2 exons, and to date, found only in the C. posadasii strain Silviera RMSCC 3488 genomic sequence. In this thesis work, cDNA sequence analysis from polyadenylated RNA confirms the peptide sequence and genomic location of the peptide, but does not indicate that the intron in the gene prediction of C. posadasii strain Silviera RMSCC 3488 is present. A monoclonal antibody generated against the peptide bound to a 16kDa protein in T27K coccidioidal lysate. Detecting components of the fungus plasma could be a useful diagnostic tool, especially when serology does not provide a definitive diagnosis.
ContributorsDuffy, Stacy Leigh (Author) / Lake, Douglas (Thesis advisor) / Magee, Dewey Mitch (Committee member) / Antwi, Kwasi (Committee member) / Arizona State University (Publisher)
Created2013
Description
It is commonly known that the left hemisphere of the brain is more efficient in the processing of verbal information, compared to the right hemisphere. One proposal suggests that hemispheric asymmetries in verbal processing are due in part to the efficient use of top-down mechanisms by the left hemisphere. Most evidence for this comes from hemispheric semantic priming, though fewer studies have investigated verbal memory in the cerebral hemispheres. The goal of the current investigations is to examine how top-down mechanisms influence hemispheric asymmetries in verbal memory, and determine the specific nature of hypothesized top-down mechanisms. Five experiments were conducted to explore the influence of top-down mechanisms on hemispheric asymmetries in verbal memory. Experiments 1 and 2 used item-method directed forgetting to examine maintenance and inhibition mechanisms. In Experiment 1, participants were cued to remember or forget certain words, and cues were presented simultaneously or after the presentation of target words. In Experiment 2, participants were cued again to remember or forget words, but each word was repeated once or four times. Experiments 3 and 4 examined the influence of cognitive load on hemispheric asymmetries in true and false memory. In Experiment 3, cognitive load was imposed during memory encoding, while in Experiment 4, cognitive load was imposed during memory retrieval. Finally, Experiment 5 investigated the association between controlled processing in hemispheric semantic priming, and top-down mechanisms used for hemispheric verbal memory. Across all experiments, divided visual field presentation was used to probe verbal memory in the cerebral hemispheres. Results from all experiments revealed several important findings. First, top-down mechanisms used by the LH primarily used to facilitate verbal processing, but also operate in a domain general manner in the face of increasing processing demands. Second, evidence indicates that the RH uses top-down mechanisms minimally, and processes verbal information in a more bottom-up manner. These data help clarify the nature of top-down mechanisms used in hemispheric memory and language processing, and build upon current theories that attempt to explain hemispheric asymmetries in language processing.
ContributorsTat, Michael J (Author) / Azuma, Tamiko (Thesis advisor) / Goldinger, Stephen D (Committee member) / Liss, Julie M (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
Perceptual learning by means of coherent motion training paradigms has been shown to produce plasticity in lower and higher-level visual systems within the human occipital lobe both supra- and subliminally. However, efficiency of training methods that produce consolidation in the visual system via coherent motion has yet to be experimentally determined. Furthermore, the effects of coherent motion training on reading comprehension, in clinical and normal populations, are still nascent. In the present study, 20 participants were randomly assigned to one of four experimental conditions. Two conditions had a participation requirement of four days while two conditions required eight days of participation. These conditions were further divided into 500 or 1000 trials per day (4 x 500, 4 x 1000, 8 x 500, 8 x 1000). Additional pre-test and post-test days were used to attain timed pre- and post-tests on the Wide Range Achievement Test IV (WRAT IV) reading comprehension battery. Furthermore, a critical flicker fusion threshold (CFFT) score was taken on a macular pigment densitometer on the pre-test and post-test day. Participants showed significant improvement in CFFT levels, WRAT IV reading comprehension, and speed of completion between pre-test and post-test; however, degree of improvement did not vary as a function of training condition. An interaction between training condition and degree of improvement was evident in coherent dot motion contrast scores, with significant training plasticity occurring in the 4 x 1000 and 8 x 500 conditions.
ContributorsGroth, Anthony (Author) / Náñez, José E. (Thesis advisor) / Hall, Deborah (Committee member) / Risko, Evan F. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Modified and artificial water sources can be used as a management tool for game and non-game wildlife species. State, federal, and private agencies allocate significant resources to install and maintain artificial water sources (AWS) annually. Capture mark recapture methods were used to sample small mammal communities in the vicinity of five AWS and five paired control sites (treatments) in the surrounding Sonoran desert from October 2011 to May 2012. I measured plant species richness, density, and percent cover in the spring of 2012. A Multi-response Permutation Procedure was used to identify differences in small mammal community abundance, biomass, and species richness by season and treatment. I used Principle Component Analysis to reduce 11 habitat characteristics to five habitat factors. I related rodent occurrence to habitat characteristics using multiple and logistic regression. A total of 370 individual mammals representing three genera and eight species of rodents were captured across 4800 trap nights. Desert pocket mouse (Chaetodipus penicillatus) was the most common species in both seasons and treatments. Whereas rodent community abundance, biomass, and richness were similar between seasons, community variables of AWS were greater than CS. Rodent diversity was similar between treatments. Desert pocket mouse abundance and biomass were twice as high at AWS when compared to controls. Biomass of white-throated woodrat (Neotoma albigula) was five times greater at AWS. Habitat characteristics were similar between treatments. Neither presence of water nor distance to water explained substantial habitat variation. Occurrence of rodent species was associated with habitat characteristics. Desert rodent communities are adapted for arid environments (i.e. Heteromyids) and are not dependent on "free water". Higher abundances of desert pocket mouse at AWS were most likely related to increased disturbance and debris and not the presence of water. The results of this study and previous studies suggest that more investigation is needed and that short term studies may not be able to detect interactions (if any) between AWS and desert small mammal communities.
ContributorsSwitalski, Aaron (Author) / Bateman, Heather L (Thesis advisor) / Miller, William (Committee member) / Alford, Eddie (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