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: Anderson, Karen S
- Creators: Bateman, Heather
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
Human-inhabited or -disturbed areas pose many unique challenges for wildlife, including increased human exposure, novel challenges, such as finding food or nesting sites in novel structures, anthropogenic noises, and novel predators. Animals inhabiting these environments must adapt to such changes by learning to exploit new resources and avoid danger. To my knowledge no study has comprehensively assessed behavioral reactions of urban and rural populations to numerous novel environmental stimuli. I tested behavioral responses of urban, suburban, and rural house finches (Haemorhous mexicanus) to novel stimuli (e.g. objects, noises, food), to presentation of a native predator model (Accipiter striatus) and a human, and to two problem-solving challenges (escaping confinement and food-finding). Although I found few population-level differences in behavioral responses to novel objects, environment, and food, I found compelling differences in how finches from different sites responded to novel noise. When played a novel sound (whale call or ship horn), urban and suburban house finches approached their food source more quickly and spent more time on it than rural birds, and urban and suburban birds were more active during the whale-noise presentation. In addition, while there were no differences in response to the native predator, rural birds showed higher levels of stress behaviors when presented with a human. When I replicated this study in juveniles, I found that exposure to humans during development more accurately predicted behavioral differences than capture site. Finally, I found that urban birds were better at solving an escape problem, whereas rural birds were better at solving a food-finding challenge. These results indicate that not all anthropogenic changes affect animal populations equally and that determining the aversive natural-history conditions and challenges of taxa may help urban ecologists better understand the direction and degree to which animals respond to human-induced rapid environmental alterations.
ContributorsWeaver, Melinda (Author) / McGraw, Kevin J. (Thesis advisor) / Rutowski, Ronald (Committee member) / Pratt, Stephen (Committee member) / Bateman, Heather (Committee member) / Deviche, Pierre (Committee member) / Arizona State University (Publisher)
Created2018
Description
The immune system plays a dual role during neoplastic progression. It can suppress tumor growth by eliminating cancer cells, and also promote neoplastic expansion by either selecting for tumor cells that are fitter to survive in an immunocompetent host or by establishing the right conditions within the tumor microenvironment. First, I present a model to study the dynamics of subclonal evolution of cancer. I model selection through time as an epistatic process. That is, the fitness change in a given cell is not simply additive, but depends on previous mutations. Simulation studies indicate that tumors are composed of myriads of small subclones at the time of diagnosis. Because some of these rare subclones harbor pre-existing treatment-resistant mutations, they present a major challenge to precision medicine. Second, I study the question of self and non-self discrimination by the immune system, which is fundamental in the field in cancer immunology. By performing a quantitative analysis of the biochemical properties of thousands of MHC class I peptides, I find that hydrophobicity of T cell receptors contact residues is a hallmark of immunogenic epitopes. Based on these findings, I further develop a computational model to predict immunogenic epitopes which facilitate the development of T cell vaccines against pathogen and tumor antigens. Lastly, I study the effect of early detection in the context of Ebola. I develope a simple mathematical model calibrated to the transmission dynamics of Ebola virus in West Africa. My findings suggest that a strategy that focuses on early diagnosis of high-risk individuals, caregivers, and health-care workers at the pre-symptomatic stage, when combined with public health measures to improve the speed and efficacy of isolation of infectious individuals, can lead to rapid reductions in Ebola transmission.
ContributorsChowell-Puente, Diego (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Anderson, Karen S (Thesis advisor) / Maley, Carlo C (Committee member) / Wilson Sayres, Melissa A (Committee member) / Blattman, Joseph N (Committee member) / Arizona State University (Publisher)
Created2016
Description
Resistance to existing anti-cancer drugs poses a key challenge in the field of medical oncology, in that it results in the tumor not responding to treatment using the same medications to which it responded previously, leading to treatment failure. Adaptive therapy utilizes evolutionary principles of competitive suppression, leveraging competition between drug resistant and drug sensitive cells, to keep the population of drug resistant cells under control, thereby extending time to progression (TTP), relative to standard treatment using maximum tolerated dose (MTD). Development of adaptive therapy protocols is challenging, as it involves many parameters, and the number of parameters increase exponentially for each additional drug. Furthermore, the drugs could have a cytotoxic (killing cells directly), or a cytostatic (inhibiting cell division) mechanism of action, which could affect treatment outcome in important ways. I have implemented hybrid agent-based computational models to investigate adaptive therapy, using either a single drug (cytotoxic or cytostatic), or two drugs (cytotoxic or cytostatic), simulating three different adaptive therapy protocols for treatment using a single drug (dose modulation, intermittent, dose-skipping), and seven different treatment protocols for treatment using two drugs: three dose modulation (DM) protocols (DM Cocktail Tandem, DM Ping-Pong Alternate Every Cycle, DM Ping-Pong on Progression), and four fixed-dose (FD) protocols (FD Cocktail Intermittent, FD Ping-Pong Intermittent, FD Cocktail Dose-Skipping, FD Ping-Pong Dose-Skipping). The results indicate a Goldilocks level of drug exposure to be optimum, with both too little and too much drug having adverse effects. Adaptive therapy works best under conditions of strong cellular competition, such as high fitness costs, high replacement rates, or high turnover. Clonal competition is an important determinant of treatment outcome, and as such treatment using two drugs leads to more favorable outcome than treatment using a single drug. Switching drugs every treatment cycle (ping-pong) protocols work particularly well, as well as cocktail dose modulation, particularly when it is feasible to have a highly sensitive measurement of tumor burden. In general, overtreating seems to have adverse survival outcome, and triggering a treatment vacation, or stopping treatment sooner when the tumor is shrinking seems to work well.
ContributorsSaha, Kaushik (Author) / Maley, Carlo C (Thesis advisor) / Forrest, Stephanie (Committee member) / Anderson, Karen S (Committee member) / Cisneros, Luis H (Committee member) / Arizona State University (Publisher)
Created2023
Description
When most people think of Phoenix, Arizona, they think of sprawling cityscapesand hot desert mountains full of saguaros and other cacti. They rarely think of water and
fish, and yet, the Arizona landscape is home to many lakes, ponds, rivers and streams,
full of both native fish and sportfish, including in the urban areas. According to the report
by DeSemple in 2006, between the years 2001 and 2006, the Rio Salado Environmental
Restoration Project worked to revitalize the dry river bed that runs through Phoenix, that
included the construction of two urban ponds, the Demonstration Pond and the Reservoir
Pond. At the start of this study, it was unknown what vertebrate species inhabited these
ponds, but it was known that these urban ponds have been used to dump unwanted
aquatic pets. The bluegill Lepomis macrochirus was found to reside in both ponds, and as
it is such an important sportfish species, it was chosen as the focal species for these
studies, which took place over periods in March, May, July, and September of 2021.
Single-season occupancy models were used to attempt to determine how L. macrochirus,
use the microhabitats within the system, and a multi-season model was used to estimate
their recruitment, and seasonal changes in occupancy. In addition, this study also
attempts to understand the size structures of the L. macrochirus population in the
Reservoir Pond and the population in the Demonstration Pond, and if that size structure
varies from March to September. As the populations of these ponds are physically
isolated from one another, statistical tests were also done to determine if the size
structures of the two populations of L. macrochirus differ from one another and found
that the two populations do indeed differ from one another, but only during two of the
sampling periods.
ContributorsKeister, Emily Jan (Author) / Saul, Steven (Thesis advisor) / Bateman, Heather (Committee member) / Suzart de Albuquerque, Fabio (Committee member) / Arizona State University (Publisher)
Created2022
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
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