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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- All Subjects: Biology
- Creators: LaBaer, Joshua
- Creators: Miller, William
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
Biological diversity is threatened by increasing anthropogenic modification of natural environments and increasing demands on natural resources. Sonoran desert tortoises (Gopherus morafkai) currently have Candidate status under the Endangered Species Act (ESA) based on health and habitat threats. To ensure this animal persists in the midst of multiple threats requires an understanding of the life history and ecology of each population. I looked at one physiological and one behavioral aspect of a population of tortoises at the Sugarloaf Mountain (SL) study site in central Arizona, USA. I used 21 years of capture-recapture records to estimate growth parameters of the entire population. I investigated habitat selection of juvenile tortoises by selecting 117 locations of 11 tortoises that had been tracked by radio-telemetry one to three times weekly for two years, selecting locations from both summer active season and during winter hibernation. I compared 22 microhabitat variables of tortoise locations to random SL locations to determine habitat use and availability. Male tortoises at SL reach a greater asymptotic length than females, and males and females appear to grow at the same rate. Juvenile tortoises at the SL site use steep rocky hillsides with high proportions of sand and annual vegetation, few succulents, and enclosed shelters in summer. They use enclosed shelters on steep slopes for winter hibernation. An understanding of these features can allow managers to quantify Sonoran desert tortoise habitat needs and life history characteristics and to understand the impact of land use policies.
ContributorsBridges, Andrew (Author) / Bateman, Heather L (Thesis advisor) / Miller, William (Committee member) / Ulrich, Jon (Committee member) / Arizona State University (Publisher)
Created2012
Description
Grassland habitat restoration activities are occurring within the semi-arid grasslands of the Agua Fria National Monument located 65 km north of Phoenix, AZ. The goal of these restoration activities is to reduce woody species encroachment, remove lignified plant materials and recycle nutrients within the ecosystem thus improving range conditions for both wildlife species and livestock. Broadcast burning, juniper thinning and slash pile burns are the principle tools used to accomplish resource objectives. Line cover, belt transect, densities, heights and biomass of vegetation data were collected to determine the response of the vegetative community to habitat restoration activities. Principal Component Analysis (PCA) was used to reduce data analysis to the more influential factors. Regression analysis was conducted for statistically significant response variables. Quadratic regression analysis found low predictive values. In broadcast burn treatment units, all important factors as identified by PCA had low predictive factors but significantly differed (R2 <0.01, p<0.05) between unburned and the years post treatment. Regression analysis found significant, albeit weak, relationships between time since treatment and independent variables. In pile burn treatment units, data reduction by PCA was not possible in a biologically meaningful way due to the high variability within treatment units. This suggests the effect of juniper encroachment on grassland vegetation persists long after junipers have been cut and burned. This study concluded that broadcast burning of the central Arizona grasslands does significantly alter many components of the vegetative community. Fuels treatments generally initially reduced both perennial woody species and grasses in number and height for two year post fire. However, palatable shrubs, in particular shrubby buckwheat, were not significantly different in broadcast burn treatment areas. The vegetative community characteristics of juniper encroached woodlands of central Arizona are unaffected by the removal and burning of junipers aside from the removal of hiding cover for predators for multiple years. It is recommended that habitat restoration activities continue provided the needs of wildlife are considered, especially pronghorn, with the incorporation of state and transition models specific to each of the respective ecological site descriptions and with the consideration of the effects of fire to pronghorn fawning habitat.
ContributorsSitzmann, Paul Roman (Author) / Miller, William (Thesis advisor) / Alford, Eddie (Committee member) / Green, Douglas (Committee member) / Arizona State University (Publisher)
Created2014
Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
Description
Once considered an abundant species in the eastern United States, local populations of red-shouldered hawks, Buteo lineatus, have declined due to habitat destruction. This destruction has created suitable habitat for red-tailed hawks, Buteo jamaicensis, and therefore increased competition between these two raptor species. Since suitable habitat is the main limiting factor for raptors, a computer model was created to simulate the effect of habitat loss in central Maryland and the impact of increased competition between the more aggressive red-tailed hawk. These simulations showed urban growth contributed to over a 30% increase in red-tailed hawk habitat as red-shouldered hawk habitat decreased 62.5-70.1% without competition and 71.8-76.3% with competition. However there was no significant difference seen between the rate of available habitat decline for current and predicted development growth.
ContributorsMurillo, Crystal (Author) / Whysong, Gary (Thesis advisor) / Alford, Eddie (Committee member) / Miller, William (Committee member) / Arizona State University (Publisher)
Created2011
Description
Human recreation on rangelands may negatively impact wildlife populations. Among those activities, off-road vehicle (ORV) recreation carries the potential for broad ecological consequences. A study was undertaken to assess the impacts of ORV on rodents in Arizona Uplands Sonoran Desert. Between the months of February and September 2010, rodents were trapped at 6 ORV and 6 non-ORV sites in Tonto National Forest, AZ. I hypothesized that rodent abundance and species richness are negatively affected by ORV use. Rodent abundances were estimated using capture-mark-recapture methodology. Species richness was not correlated with ORV use. Although abundance of Peromyscus eremicus and Neotoma albigula declined as ORV use increased, abundance of Dipodomys merriami increased. Abundance of Chaetodipus baileyi was not correlated with ORV use. Other factors measured were percent ground cover, percent shrub cover, and species-specific shrub cover percentages. Total shrub cover, Opuntia spp., and Parkinsonia microphylla each decreased as ORV use increased. Results suggest that ORV use negatively affects rodent habitats in Arizona Uplands Sonoran Desert, leading to declining abundance in some species. Management strategies should mitigate ORV related habitat destruction to protect vulnerable populations.
ContributorsReid, John Simon (Author) / Brady, Ward (Thesis advisor) / Miller, William (Committee member) / Bateman, Heather (Committee member) / Arizona State University (Publisher)
Created2012
Description
ABSTRACT The elephant tree, Bursera microphylla, is at the northern limit of its range in central Arizona. This species is sensitive to frost damage thus limiting its occurrence in more northern areas of the southwest. Marginal populations of B. microphylla are found in mountain ranges of Central Arizona and are known to occur in the rugged mountain range system of the South Mountain Municipal Park (SMMP). Little is known of the distribution of this species within the park and details relevant to the health of both individual plants and the population such as diameter and number of trunks, height, and presence of damage have not been examined. This study was designed, in part, to test the hypothesis that favorable microhabitats at SMMP are created by particular combinations of abiotic features including aspect, slope, elevation and solar radiation. Data on abiotic factors, as well as specific individual plant locations and characteristics were obtained for 100 individuals. Temperature data was collected in vertical transects at different altitudinal levels. Some of these data were used in spatial analyses to generate a habitat suitability model using GIS software. Furthermore, collected data was analyzed using Matlab© software to identify potential trends in the variation of morphological traits. In addition, for comparative purposes similar information at one hundred computer-generated randomly chosen points throughout SMMP was obtained. The GIS spatial analyses indicated that aspect, slope, elevation, and relative solar radiance are strongly associated as major climatic components of the microhabitat of B. microphylla. Temperature data demonstrated that there are significant differences in ambient temperature among different altitudinal gradients with middle elevations being more favorable. Furthermore, analyses performed using Matlab© to explore trends of elevation as a factor indicated that multiple trunk plants are more commonly found at higher elevations than single trunk plants, there is a positive correlation of trunk diameter with elevation, and that canopy volume has a negative correlation with respect to elevation. It was concluded that microhabitats where B. microphylla occurs at the northern limit of its range require a particular combination of abiotic features that can be easily altered by climatic changes.
ContributorsCordova, Cesar, M.S (Author) / Steele, Kelly P. (Thesis advisor) / Tridane, Abdessaman (Committee member) / Miller, William (Committee member) / Brady, Ward (Committee member) / Arizona State University (Publisher)
Created2011
Description
Emerging pathogens present several challenges to medical diagnostics. Primarily, the exponential spread of a novel pathogen through naïve populations require a rapid and overwhelming diagnostic response at the site of outbreak. While point-of-care (PoC) platforms have been developed for detection of antigens, serologic responses, and pathogenic genomes, only nucleic acid diagnostics currently have the potential to be developed and manufactured within weeks of an outbreak owing to the speed of next-generation sequencing and custom DNA synthesis. Among nucleic acid diagnostics, isothermal amplification strategies are uniquely suited for PoC implementation due to their simple instrumentation and lack of thermocycling requirement. Unfortunately, isothermal strategies are currently prone to spurious nonspecific amplification, hindering their specificity and necessitating extensive empirical design pipelines that are both time and resource intensive. In this work, isothermal amplification strategies are extensively compared for their feasibility of implementation in outbreak response scenarios. One such technology, Loop-mediated Amplification (LAMP), is identified as having high-potential for rapid development and PoC deployment. Various approaches to abrogating nonspecific amplification are described including a novel in silico design tool based on coarse-grained simulation of interactions between thermophilic DNA polymerase and DNA strands in isothermal reaction conditions. Nonspecific amplification is shown to be due to stabilization of primer secondary structures by high concentrations of Bst DNA polymerase and a mechanism of micro-complement-mediated cross-priming is demonstrated as causal via nanopore sequencing of nonspecific reaction products. The resulting computational model predicts primer set background in 64% of 67 test assays and its usefulness is illustrated further by determining problematic primers in a West Nile Virus-specific LAMP primer set and optimizing primer 3’ nucleotides to eliminate micro-complements within the reaction, resulting in inhibition of background accumulation. Finally, the emergence of Orthopox monkeypox (MPXV) as a recurring threat is discussed and SimCycle is utilized to develop a novel technique for clade-specific discrimination of MPXV based on bridging viral genomic rearrangements (Bridging LAMP). Bridging LAMP is implemented in a 4-plex microfluidic format and demonstrates 100% sensitivity in detection of 100 copies of viral lysates and 45 crude MPXV-positive patient samples collected during the 2022 Clade IIb outbreak.
ContributorsKnappenberger, Mark Daniel (Author) / Anderson, Karen S (Thesis advisor) / LaBaer, Joshua (Committee member) / Roberson, Robert (Committee member) / Lindsay, Stuart (Committee member) / Arizona State University (Publisher)
Created2023
Description
According to the World Health Organization, cancer is one of the leading causes of death around the world. Although early diagnostics using biomarkers and improved treatments with targeted therapy have reduced the rate of cancer related mortalities, there remain many unknowns regarding the contributions of the tumor microenvironment to cancer progression and therapeutic resistance. The tumor microenvironment plays a significant role by manipulating the progression of cancer cells through biochemical and biophysical signals from the surrounding stromal cells along with the extracellular matrix. As such, there is a critical need to understand how the tumor microenvironment influences the molecular mechanisms underlying cancer metastasis to facilitate the discovery of better therapies. This thesis described the development of microfluidic technologies to study the interplay of cancer cells with their surrounding microenvironment. The microfluidic model was used to assess how exposure to chemoattractant, epidermal growth factor (EGF), impacted 3D breast cancer cell invasion and enhanced cell motility speed was noted in the presence of EGF validating physiological cell behavior. Additionally, breast cancer and patient-derived cancer-associated fibroblast (CAF) cells were co-cultured to study cell-cell crosstalk and how it affected cancer invasion. GPNMB was identified as a novel gene of interest and it was shown that CAFs enhanced breast cancer invasion by up-regulating the expression of GPNMB on breast cancer cells resulting in increased migration speed. Lastly, this thesis described the design, biological validation, and use of this microfluidic platform as a new in vitro 3D organotypic model to study mechanisms of glioma stem cell (GSC) invasion in the context of a vascular niche. It was confirmed that CXCL12-CXCR4 signaling is involved in promoting GSC invasion in a 3D vascular microenvironment, while also demonstrating the effectiveness of the microfluidic as a drug screening assay. Taken together, the broader impacts of the microfluidic model developed in this dissertation include, a possible alternative platform to animal testing that is focused on mimicking human physiology, a potential ex vivo platform using patient-derived cells for studying the interplay of cancer cells with its surrounding microenvironment, and development of future therapeutic strategies tailored toward disrupting key molecular pathways involved in regulatory mechanisms of cancer invasion.
ContributorsTruong, Danh, Ph.D (Author) / Nikkhah, Mehdi (Thesis advisor) / LaBaer, Joshua (Committee member) / Smith, Barbara (Committee member) / Mouneimne, Ghassan (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2018
Cancer autoantibody biomarker discovery and validation using nucleic acid programmable protein array
Description
Currently in the US, many patients with cancer do not benefit from the population-based screening, due to challenges associated with the existing cancer screening scheme. Blood-based diagnostic assays have the potential to detect diseases in a non-invasive way. Proteins released from small early tumors may only be present intermittently and get diluted to tiny concentrations in the blood, making them difficult to use as biomarkers. However, they can induce autoantibody (AAb) responses, which can amplify the signal and persist in the blood even if the antigen is gone. Circulating autoantibodies is a promising class of molecules that have potential to serve as early detection biomarkers for cancers. This Ph.D thesis aims to screen for autoantibody biomarkers for the early detection of two deadly cancer, basal-like breast cancer and lung adenocarcinoma. First, a method was developed to display proteins in both native and denatured conformation on protein array. This method adopted a novel protein tag technology, called HaloTag, to covalently immobilize proteins on glass slide surface. The covalent attachment allowed these proteins to endure harsh treatment without getting dissociated from slide surface, which enabled the profiling of antibody responses against both conformational and linear epitopes. Next, a plasma screening protocol was optimized to significantly increase signal to noise ratio of protein array based AAb detection. Following this, the AAb responses in basal-like breast cancer were explored using nucleic acid programmable protein arrays (NAPPA) containing 10,000 full-length human proteins in 45 cases and 45 controls. After verification in a large sample set (145 basal-like breast cancer cases / 145 controls / 70 non-basal breast cancer) by ELISA, a 13-AAb classifier was developed to differentiate patients from controls with a sensitivity of 33% at 98% specificity. Similar approach was also applied to the lung cancer study to identify AAbs that distinguished lung cancer patients from computed-tomography positive benign pulmonary nodules (137 lung cancer cases, 127 smoker controls, 170 benign controls). In this study, two panels of AAbs were discovered that showed promising sensitivity and specificity. Six out of eight AAb targets were also found to have elevated mRNA level in lung adenocarcinoma patients using TCGA data. These projects as a whole provide novel insights on the association between AAbs and cancer, as well as general B cell antigenicity against self-proteins.
ContributorsWang, Jie (Author) / LaBaer, Joshua (Thesis advisor) / Anderson, Karen S (Committee member) / Lake, Douglas F (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015