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- Genre: Doctoral Dissertation
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
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
Wind measurements are fundamental inputs for the evaluation of potential energy yield and performance of wind farms. Three-dimensional scanning coherent Doppler lidar (CDL) may provide a new basis for wind farm site selection, design, and control. In this research, CDL measurements obtained from multiple wind energy developments are analyzed and a novel wind farm control approach has been modeled. The possibility of using lidar measurements to more fully characterize the wind field is discussed, specifically, terrain effects, spatial variation of winds, power density, and the effect of shear at different layers within the rotor swept area. Various vector retrieval methods have been applied to the lidar data, and results are presented on an elevated terrain-following surface at hub height. The vector retrieval estimates are compared with tower measurements, after interpolation to the appropriate level. CDL data is used to estimate the spatial power density at hub height. Since CDL can measure winds at different vertical levels, an approach for estimating wind power density over the wind turbine rotor-swept area is explored. Sample optimized layouts of wind farm using lidar data and global optimization algorithms, accounting for wake interaction effects, have been explored. An approach to evaluate spatial wind speed and direction estimates from a standard nested Coupled Ocean and Atmosphere Mesoscale Prediction System (COAMPS) model and CDL is presented. The magnitude of spatial difference between observations and simulation for wind energy assessment is researched. Diurnal effects and ramp events as estimated by CDL and COAMPS were inter-compared. Novel wind farm control based on incoming winds and direction input from CDL's is developed. Both yaw and pitch control using scanning CDL for efficient wind farm control is analyzed. The wind farm control optimizes power production and reduces loads on wind turbines for various lidar wind speed and direction inputs, accounting for wind farm wake losses and wind speed evolution. Several wind farm control configurations were developed, for enhanced integrability into the electrical grid. Finally, the value proposition of CDL for a wind farm development, based on uncertainty reduction and return of investment is analyzed.
ContributorsKrishnamurthy, Raghavendra (Author) / Calhoun, Ronald J (Thesis advisor) / Chen, Kangping (Committee member) / Huang, Huei-Ping (Committee member) / Fraser, Matthew (Committee member) / Phelan, Patrick (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation investigates the long-term consequences of human land-use practices in general, and in early agricultural villages in specific. This pioneering case study investigates the "collapse" of the Early (Pre-Pottery) Neolithic lifeway, which was a major transformational event marked by significant changes in settlement patterns, material culture, and social markers. To move beyond traditional narratives of cultural collapse, I employ a Complex Adaptive Systems approach to this research, and combine agent-based computer simulations of Neolithic land-use with dynamic and spatially-explicit GIS-based environmental models to conduct experiments into long-term trajectories of different potential Neolithic socio-environmental systems. My analysis outlines how the Early Neolithic "collapse" was likely instigated by a non-linear sequence of events, and that it would have been impossible for Neolithic peoples to recognize the long-term outcome of their actions. The experiment-based simulation approach shows that, starting from the same initial conditions, complex combinations of feedback amplification, stochasticity, responses to internal and external stimuli, and the accumulation of incremental changes to the socio-natural landscape, can lead to widely divergent outcomes over time. Thus, rather than being an inevitable consequence of specific Neolithic land-use choices, the "catastrophic" transformation at the end of the Early Neolithic was an emergent property of the Early Neolithic socio-natural system itself, and thus likely not an easily predictable event. In this way, my work uses the technique of simulation modeling to connect CAS theory with the archaeological and geoarchaeological record to help better understand the causes and consequences of socio-ecological transformation at a regional scale. The research is broadly applicable to other archaeological cases of resilience and collapse, and is truly interdisciplinary in that it draws on fields such as geomorphology, computer science, and agronomy in addition to archaeology.
ContributorsUllah, Isaac (Author) / Barton, C. Michael (Thesis advisor) / Banning, Edward B. (Committee member) / Clark, Geoffrey (Committee member) / Arrowsmith, J. Ramon (Committee member) / Arizona State University (Publisher)
Created2013
Description
The dynamics of urban water use are characterized by spatial and temporal variability that is influenced by associated factors at different scales. Thus it is important to capture the relationship between urban water use and its determinants in a spatio-temporal framework in order to enhance understanding and management of urban water demand. This dissertation aims to contribute to understanding the spatio-temporal relationships between single-family residential (SFR) water use and its determinants in a desert city. The dissertation has three distinct papers to support this goal. In the first paper, I demonstrate that aggregated scale data can be reliably used to study the relationship between SFR water use and its determinants without leading to significant ecological fallacy. The usability of aggregated scale data facilitates scientific inquiry about SFR water use with more available aggregated scale data. The second paper advances understanding of the relationship between SFR water use and its associated factors by accounting for the spatial and temporal dependence in a panel data setting. The third paper of this dissertation studies the historical contingency, spatial heterogeneity, and spatial connectivity in the relationship of SFR water use and its determinants by comparing three different regression models. This dissertation demonstrates the importance and necessity of incorporating spatio-temporal components, such as scale, dependence, and heterogeneity, into SFR water use research. Spatial statistical models should be used to understand the effects of associated factors on water use and test the effectiveness of certain management policies since spatial effects probably will significantly influence the estimates if only non-spatial statistical models are used. Urban water demand management should pay attention to the spatial heterogeneity in predicting the future water demand to achieve more accurate estimates, and spatial statistical models provide a promising method to do this job.
ContributorsOuyang, Yun (Author) / Wentz, Elizabeth (Thesis advisor) / Ruddell, Benjamin (Thesis advisor) / Harlan, Sharon (Committee member) / Janssen, Marcus (Committee member) / Arizona State University (Publisher)
Created2013
Description
Farmers' markets are a growing trend both in Arizona and the broader U.S., as many recognize them as desirable alternatives to the conventional food system. As icons of sustainability, farmers' markets are touted as providing many environmental, social, and economic benefits, but evidence is mounting that local food systems primarily serve the urban elite, with relatively few low-income or minority customers. However, the economic needs of the market and its vendors often conflict with those of consumers. While consumers require affordable food, farmers need to make a profit. How farmers' markets are designed and governed can significantly influence the extent to which they can meet these needs. However, very little research explores farmers' market design and governance, much less its capacity to influence financial success and participation for underprivileged consumers. The present study examined this research gap by addressing the following research question: How can farmers' markets be institutionally designed to increase the participation of underprivileged consumers while maintaining a financially viable market for local farmers? Through a comparative case study of six markets, this research explored the extent to which farmers' markets in Central Arizona currently serve the needs of farmer-vendors and underprivileged consumers. The findings suggest that while the markets serve as a substantial source of income for some vendors, participation by low-income and minority consumers remains low, and that much of this appears to be due to cultural barriers to access. Management structures, site characteristics, market layout, community programs, and staffing policies are key institutional design features, and the study explores how these can be leveraged to better meet the needs of the diverse participants while improving the markets' financial success.
ContributorsTaylor, Carissa (Author) / Aggarwal, Rimjhim (Thesis advisor) / York, Abigail (Committee member) / Wharton, Christopher (Christopher Mack), 1977- (Committee member) / Arizona State University (Publisher)
Created2013
Description
Specific dendritic morphologies are a hallmark of neuronal identity, circuit assembly, and behaviorally relevant function. Despite the importance of dendrites in brain health and disease, the functional consequences of dendritic shape remain largely unknown. This dissertation addresses two fundamental and interrelated aspects of dendrite neurobiology. First, by utilizing the genetic power of Drosophila melanogaster, these studies assess the developmental mechanisms underlying single neuron morphology, and subsequently investigate the functional and behavioral consequences resulting from developmental irregularity. Significant insights into the molecular mechanisms that contribute to dendrite development come from studies of Down syndrome cell adhesion molecule (Dscam). While these findings have been garnered primarily from sensory neurons whose arbors innervate a two-dimensional plane, it is likely that the principles apply in three-dimensional central neurons that provide the structural substrate for synaptic input and neural circuit formation. As such, this dissertation supports the hypothesis that neuron type impacts the realization of Dscam function. In fact, in Drosophila motoneurons, Dscam serves a previously unknown cell-autonomous function in dendrite growth. Dscam manipulations produced a range of dendritic phenotypes with alteration in branch number and length. Subsequent experiments exploited the dendritic alterations produced by Dscam manipulations in order to correlate dendritic structure with the suggested function of these neurons. These data indicate that basic motoneuron function and behavior are maintained even in the absence of all adult dendrites within the same neuron. By contrast, dendrites are required for adjusting motoneuron responses to specific challenging behavioral requirements. Here, I establish a direct link between dendritic structure and neuronal function at the level of the single cell, thus defining the structural substrates necessary for conferring various aspects of functional motor output. Taken together, information gathered from these studies can inform the quest in deciphering how complex cell morphologies and networks form and are precisely linked to their function.
ContributorsHutchinson, Katie Marie (Author) / Duch, Carsten (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newfeld, Stuart (Committee member) / Smith, Brian (Committee member) / Orchinik, Miles (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
Firstly, this study uses community asset mapping guided by the Community Capitals Framework (CCF) to explore the linkages between Protected Areas (PAs), tourism and community livelihoods. Secondly, it assesses changes in community needs facilitated by community participation in wildlife-based tourism in a protected area setting. Thirdly and finally, the study assesses whether the introduction of community wildlife-based tourism in a protected area as a sustainable management tool has led to the spiraling up or down of community capitals. The study adopted qualitative research method approach and made use of data collected through community asset mapping supplemented by data from focus group discussions, households, key informants, and secondary data materials that were analyzed and interpreted in light of community capital framework. The Chobe National Park (CNP) and Chobe Enclave Conservation Trust (CECT); a community living adjacent to CNP in Botswana provides the context on which this study's discussion focuses. Results indicate that the accession of Botswana from colonialism through post colonialism era intertwined considerable institutional arrangement changes in the field of protected area governance that reflects evolutionary management styles. Protected areas, tourism and community livelihoods linkages are based on many inter-dependents of community capitals relationships which are dependent on community socio-economic activities. In assessing changes in community needs, the results indicate that participation in wildlife-based tourism has brought both positive and negative changes that have implications on both the status quo for community livelihoods and protected areas, namely; the influence of changes in community capitals dynamics, mechanization and commercialization of agriculture, government funded infrastructural development, income generation, and the commodification of some of the community capitals. Finally, the increased livelihoods options and diversification dynamics, fragile wildlife-livestock co-existence, heightened human-wildlife conflicts, environmental education and awareness are the emerging themes that explain how the introduction of tourism in a protected area setting affect the spiraling up and down of the community capitals dynamics.
ContributorsStone, Moren T. (Author) / Nyaupane, Gyan P (Thesis advisor) / Buduk, Megha (Committee member) / Thapa, Brijesh (Committee member) / Timothy, Dallen J. (Committee member) / Arizona State University (Publisher)
Created2013