Matching Items (1,409)
Filtering by
- Creators: Department of Psychology
- Creators: School of Sustainability
- Member of: Theses and Dissertations
- Member of: ASU Electronic Theses and Dissertations
Description
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
The majority of non-small cell lung cancer (NSCLC) patients (70%) are diagnosed with adenocarcinoma versus other histological subtypes. These patients often present with advanced, metastatic disease and frequently relapse after treatment. The tumor suppressor, Liver Kinase B1, is frequently inactivated in adenocarcinomas and loss of function is associated with a highly aggressive, metastatic tumor (1). Identification of the mechanisms deregulated with LKB1 inactivation could yield targeted therapeutic options for adenocarcinoma patients. Re-purposing the immune system to support tumor growth and aid in metastasis has been shown to be a feature in cancer progression (2). Tumor associated macrophages (TAMs) differentiate from monocytes, which are recruited to the tumor microenvironment via secretion of chemotaxic factors by cancer cells. We find that NSCLC cells deficient in LKB1 display increased secretion of C-C motif ligand 2 (CCL2), a chemokine involved in monocyte recruitment. To elucidate the molecular pathway regulating CCL2 up-regulation, we investigated inhibitors of substrates downstream of LKB1 signaling in A549, H23, H2030 and H838 cell lines. Noticeably, BAY-11-7082 (NF-κB inhibitor) reduced CCL2 secretion by an average 92%. We further demonstrate that a CCR2 antagonist and neutralizing CCL2 antibody substantially reduce monocyte migration to NSCLC (H23) cell line conditioned media. Using an in vivo model of NSCLC, we find that LKB1 deleted tumors demonstrate a discernible increase in CCL2 levels compared to normal lung. Moreover, tumors display an increase in the M2:M1 macrophage ratio and increase in tumor associated neutrophil (TAN) infiltrate compared to normal lung. This M2 shift was significantly reduced in mice treated with anti-CCL2 or a CCR2 antagonist and the TAN infiltrate was significantly reduced with the CCR2 antagonist. These data suggest that deregulation of the CCL2/CCR2 signaling axis could play a role in cancer progression in LKB1 deficient tumors.
ContributorsFriel, Jacqueline (Author) / Inge, Landon (Thesis advisor) / Lake, Douglas (Thesis advisor) / Blattman, Joseph (Committee member) / Arizona State University (Publisher)
Created2015
Description
Geology and its tangential studies, collectively known and referred to in this thesis as geosciences, have been paramount to the transformation and advancement of society, fundamentally changing the way we view, interact and live with the surrounding natural and built environment. It is important to recognize the value and importance of this interdisciplinary scientific field while reconciling its ties to imperial and colonizing extractive systems which have led to harmful and invasive endeavors. This intersection among geosciences, (environmental) justice studies, and decolonization is intended to promote inclusive pedagogical models through just and equitable methodologies and frameworks as to prevent further injustices and promote recognition and healing of old wounds. By utilizing decolonial frameworks and highlighting the voices of peoples from colonized and exploited landscapes, this annotated syllabus tackles the issues previously described while proposing solutions involving place-based education and the recentering of land within geoscience pedagogical models. (abstract)
ContributorsReed, Cameron E (Author) / Richter, Jennifer (Thesis director) / Semken, Steven (Committee member) / School of Earth and Space Exploration (Contributor, Contributor) / School of Sustainability (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Recent research has shown that reward-related stimuli capture attention in an automatic and involuntary manner, or reward-salience (Le Pelley, Pearson, Griffiths, & Beesley, 2015). Although patterns of oculomotor behavior have been previously examined in recent experiments, questions surrounding a potential neural signal of reward remain. Consequently, this study used pupillometry to investigate how reward-related stimuli affect pupil size and attention. Across three experiments, response time, accuracy, and pupil were measured as participants searched for targets among distractors. Participants were informed that singleton distractors indicated the magnitude of a potential gain/loss available in a trial. Two visual search conditions were included to manipulate ongoing cognitive demands and isolate reward-related pupillary responses. Although the optimal strategy was to perform quickly and accurately, participants were slower and less accurate in high magnitude trials. The data suggest that attention is automatically captured by potential loss, even when it is counterintuitive to current task goals. Regarding a pupillary response, patterns of pupil size were inconsistent with our predictions across the visual search conditions. We hypothesized that if pupil dilation reflected a reward-related reaction, pupil size would vary as a function of both the presence of a reward and its magnitude. More so, we predicted that this pattern would be more apparent in the easier search condition (i.e., cooperation visual search), because the signal of available reward was still present, but the ongoing attentional demands were significantly reduced in comparison to the more difficult search condition (i.e., conflict visual search). In contrast to our predictions, pupil size was more closely related to ongoing cognitive demands, as opposed to affective factors, in cooperation visual search. Surprisingly, pupil size in response to signals of available reward was better explained by affective, motivational and emotional influences than ongoing cognitive demands in conflict visual search. The current research suggests that similar to recent findings involving LC-NE activity (Aston-Jones & Cohen, 2005; Bouret & Richmond, 2009), the measure of pupillometry may be used to assess more specific areas of cognition, such as motivation and perception of reward. However, additional research is needed to better understand this unexpected pattern of pupil size.
ContributorsPhifer, Casey (Author) / Goldinger, Stephen D (Thesis advisor) / Homa, Donald J (Committee member) / McClure, Samuel M. (Committee member) / Papesh, Megan H (Committee member) / Arizona State University (Publisher)
Created2017
Description
Environmental changes are occurring at an unprecedented rate, and these changes will undoubtedly lead to alterations in resource availability for many organisms. To effectively predict the implications of such changes, it is critical to better understand how organisms have adapted to coping with seasonally limited resources. The vast majority of previous work has focused on energy balance as the driver of changes in organismal physiology. While energy is clearly a vital currency, other resources can also be limited and impact physiological functions. Water is essential for life as it is the main constituent of cells, tissues, and organs. Yet, water has received little consideration for its role as a currency that impacts physiological functions. Given the importance of water to most major physiological systems, I investigated how water limitations interact with immune function, metabolism, and reproductive investment, an almost entirely unexplored area. Using multiple species and life stages, I demonstrated that dehydrated animals typically have enhanced innate immunity, regardless of whether the dehydration is a result of seasonal water constraints, water deprivation in the lab, or high physiological demand for water. My work contributed greatly to the understanding of immune function dynamics and lays a foundation for the study of hydration immunology as a component of the burgeoning field of ecoimmunology. While a large portion of my dissertation focused on the interaction between water balance and immune function, there are many other physiological processes that may be impacted by water restrictions. Accordingly, I recently expanded the understanding of how reproductive females can alter metabolic substrates to reallocate internal water during times of water scarcity, an important development in our knowledge of reproductive investments. Overall, by thoroughly evaluating implications and responses to water limitations, my dissertation, when combined previous acquired knowledge on food limitation, will enable scientists to better predict the impacts of future climate change, where, in many regions, rainfall events are forecasted to be less reliable, resulting in more frequent drought.
ContributorsBrusch, George, IV (Author) / DeNardo, Dale F (Thesis advisor) / Blattman, Joseph (Committee member) / French, Susannah (Committee member) / Sabo, John (Committee member) / Taylor, Emily (Committee member) / Arizona State University (Publisher)
Created2019
Description
The purpose of this paper is to understand how companies are finding high potential employees and if they are leaving top talent behind in their approach. Eugene Burke stated in 2014 that 55% of employees that are labeled as a High Potential Employee will turn over and move companies. Burke (2014) also states that the average high potential employee tenure is five years. The Corporate Leadership Council says that on average, 27% of a company's development budget is spent on its high potential program (CEB 2017). For a midsize company, the high potential development budget is almost a million dollars for only a handful of employees, only to see half of the investment walking out the door to another company . Furthermore, the Corporate Leadership Council said that a study done in 2005 revealed that 50% of high potential employees had significant problems within their job (Kotlyar and Karkowsky 2014). Are time and resources are being given to the wrong employees and the right employees are being overlooked? This paper exams how companies traditionally select high potential employees and where companies are potentially omitting employees who would be better suited for the program. This paper proposes that how a company discovers their top talent will correlate to the number of turnovers or struggles that a high potential employee has on their job. Future research direction and practical considerations are also presented in this paper.
ContributorsHarrison, Carrie (Author) / Mizzi, Philip (Thesis director) / Ruediger, Stefan (Committee member) / Department of Management and Entrepreneurship (Contributor) / School of Sustainability (Contributor) / Department of Supply Chain Management (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This paper considers what factors influence student interest, motivation, and continued engagement. Studies show anticipated extrinsic rewards for activity participation have been shown to reduce intrinsic value for that activity. This might suggest that grade point average (GPA) has a similar effect on academic interests. Further, when incentives such as scholarships, internships, and careers are GPA-oriented, students must adopt performance goals in courses to guarantee success. However, performance goals have not been shown to correlated with continued interest in a topic. Current literature proposes that student involvement in extracurricular activities, focused study groups, and mentored research are crucial to student success. Further, students may express either a fixed or growth mindset, which influences their approach to challenges and opportunities for growth. The purpose of this study was to collect individual cases of students' experiences in college. The interview method was chosen to collect complex information that could not be gathered from standard surveys. To accomplish this, questions were developed based on content areas related to education and motivation theory. The content areas included activities and meaning, motivation, vision, and personal development. The developed interview method relied on broad questions that would be followed by specific "probing" questions. We hypothesize that this would result in participant-led discussions and unique narratives from the participant. Initial findings suggest that some of the questions were effective in eliciting detailed responses, though results were dependent on the interviewer. From the interviews we find that students value their group involvements, leadership opportunities, and relationships with mentors, which parallels results found in other studies.
ContributorsAbrams, Sara (Author) / Hartwell, Lee (Thesis director) / Correa, Kevin (Committee member) / Department of Psychology (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This study estimates the capitalization effect of golf courses in Maricopa County using the hedonic pricing method. It draws upon a dataset of 574,989 residential transactions from 2000 to 2006 to examine how the aesthetic, non-golf benefits of golf courses capitalize across a gradient of proximity measures. The measures for amenity value extend beyond home adjacency and include considerations for homes within a range of discrete walkability buffers of golf courses. The models also distinguish between public and private golf courses as a proxy for the level of golf course access perceived by non-golfers. Unobserved spatial characteristics of the neighborhoods around golf courses are controlled for by increasing the extent of spatial fixed effects from city, to census tract, and finally to 2000 meter golf course ‘neighborhoods.’ The estimation results support two primary conclusions. First, golf course proximity is found to be highly valued for adjacent homes and homes up to 50 meters way from a course, still evident but minimal between 50 and 150 meters, and insignificant at all other distance ranges. Second, private golf courses do not command a higher proximity premia compared to public courses with the exception of homes within 25 to 50 meters of a course, indicating that the non-golf benefits of courses capitalize similarly, regardless of course type. The results of this study motivate further investigation into golf course features that signal access or add value to homes in the range of capitalization, particularly for near-adjacent homes between 50 and 150 meters thought previously not to capitalize.
ContributorsJoiner, Emily (Author) / Abbott, Joshua (Thesis director) / Smith, Kerry (Committee member) / Economics Program in CLAS (Contributor) / School of Sustainability (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Many factors are at play within the genome of an organism, contributing to much of the diversity and variation across the tree of life. While the genome is generally encoded by four nucleotides, A, C, T, and G, this code can be expanded. One particular mechanism that we examine in this thesis is modification of bases—more specifically, methylation of Adenine (m6A) within the GATC motif of Escherichia coli. These methylated adenines are especially important in a process called methyl-directed mismatch repair (MMR), a pathway responsible for repairing errors in the DNA sequence produced by replication. In this pathway, methylated adenines identify the parent strand and direct the repair proteins to correct the erroneous base in the daughter strand. While the primary role of methylated adenines at GATC sites is to direct the MMR pathway, this methylation has also been found to affect other processes, such as gene expression, the activity of transposable elements, and the timing of DNA replication. However, in the absence of MMR, the ability of these other processes to maintain adenine methylation and its targets is unknown.
To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
ContributorsBoyer, Gwyneth (Author) / Lynch, Michael (Thesis director) / Behringer, Megan (Committee member) / Geiler-Samerotte, Kerry (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
This paper emphasizes how vital prosthetic devices are as tools for both congenital and acquired amputees in order to maximize this population's level of societal productivity, but several issues exist with the current technological focus of development by the prosthetic industry that creates unnecessary hurdles that amputees must surpass in order to truly benefit from these tools. The first major issue is that these devices are not readily available to all amputees. The astronomical cost of most prosthetic devices is a variable that restricts low income amputee populations from obtaining these vital tools regardless of their level of need, thus highlighting the fact that amputees who are not financially stable are not supported in a fashion that is conducive to their success. Also, cost greatly affects children who suffer from a missing appendage due to the fact that they are in constant need of prosthetic replacement because of physical growth and development. Another issue with the current focus of the prosthetic industry is that it focuses on acquired amputees because this population is much larger in comparison to congenital amputees and thus more lucrative. Congenital amputees' particular needs are often entirely ignored in terms of prosthetic innovation. Finally, low daily utilization is a major issue amongst the amputee population. Several variables exist with the use of prosthetic devices that cause many amputees to decide against the utilization of these tools, like difficulty of use and lack of comfort. This paper will provide solutions to cost, discrimination, issues in development, and daily utilization by emphasizing on how lowering the cost through alternative designs and materials, transitioning the focus of technological development onto the entire amputee population rather than targeting the most lucrative group, and advancing the design in a fashion to which promotes daily utilization will provide the largest level of societal support, so that the amputee population as a whole can maximize their level of productivity in a manner that will allow this group to conquer the hardships that are introduced into their lives due to a missing appendage.
ContributorsO'Connor, Casey Charles (Author) / Popova, Laura (Thesis director) / Graff, Sarah (Committee member) / Department of Psychology (Contributor) / School of Social Work (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05