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- Creators: Department of Psychology
- Member of: Theses and Dissertations
- Status: Published
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
The sensor industry is a growing industry that has been predicted by Allied Market Research to be a multi-billion industry by 2022. One of the many key drives behind this rapid growth in the sensor industry is the increase incorporation of sensors into portable electrical devices. The value for sensor technologies are increased when the sensors are developed into innovative measuring system for application uses in the Aerospace, Defense, and Healthcare industries. While sensors are not new, their increased performance, size reduction, and decrease in cost has opened the door for innovative sensor combination for portable devices that could be worn or easily moved around. With this opportunity for further development of sensor use through concept engineering development, three concept projects for possible innovative portable devices was undertaken in this research. One project was the development of a pulse oximeter devise with fingerprint recognition. The second project was prototyping a portable Bluetooth strain gage monitoring system. The third project involved sensors being incorporated onto flexible printed circuit board (PCB) for improved comfort of wearable devices. All these systems were successfully tested in lab.
ContributorsNichols, Kevin William (Author) / Redkar, Sangram (Thesis advisor) / Rogers, Brad (Committee member) / Sugar, Thomas (Committee member) / Arizona State University (Publisher)
Created2018
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
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 asks the question: does gender-based discrimination exists within Arizona State University's Army Reserve Officer Training Corps (ROTC), and if so, what are the effects of such discrimination? Within this study, discrimination is defined as: the treatment or consideration of, or making a distinction in favor of or against, a person or thing based on the group, class, or category to which that person or thing belongs, rather than on individual merit. The researcher predicted that this study would show that gender-based discrimination operates within the masculine military culture of Army ROTC at ASU, resulting from women's hyper-visibility and evidenced by their lack of positive recognition and disbelief in having a voice in the program. These expectations were based on background research claiming that the token status of women in military roles causes them to be more heavily scrutinized, and they consequentially try to attain success by adapting to the masculine military culture by which they are constantly measured. For the purposes of this study, success is defined as: the attainment of wealth, favor, or eminence . This study relies on exploratory interviews and an online survey conducted with male and female Army ROTC cadets of all grade levels at Arizona State University. The interviews and survey collected demographic information and perspectives on individual experiences to establish an understanding of privilege and marginalization within the program. These results do support the prediction that women in Army ROTC at ASU face discrimination based on their unique visibility and lack of positive recognition and voice in the program. Likewise, the survey results indicate that race also has a significant impact on one's experience in Army ROTC, which is discussed later in this study in regard to needs for future research. ASU Army ROTC includes approximately 100 cadets, and approximately 30-40 of those cadets participated in this study. Additionally, the University of Arizona and the Northern Arizona University Army ROTC programs were invited to participate in this study and declined to do so, which would have offered a greater sample population. Nonetheless, the results of this research will be useful for analysis and further discussion of gender-equality in Army ROTC at Arizona State University.
ContributorsAllemang, Lindsey Ann (Author) / Wood, Reed (Thesis director) / Switzer, Heather (Committee member) / School of Politics and Global Studies (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The number of undergraduate students participating in short-term experiences in global health (STEGHs) abroad has increased dramatically in recent years (Eyler 2002, Drain et al. 2007). These experiences, in tandem with classroom learning, are designed to help students master skills related to global health competencies, including cultural humility and sensitivity, collaborating with community partners, and sociocultural and political awareness. Although STEGHs offer potential benefits to both students and to sending institutions, these experiences can sometimes be problematic and raise ethical challenges. As the number of students engaged in STEGHs continues to increase, it is important to better understand the impact of these programs on student learning. Current ethical and best practice guidelines for STEGHs state that programs should establish evaluation methods to solicit feedback from students both during and on completion of the program (Crump et al. 2010). However, there is currently no established method for gathering this feedback because of the many different global health competency frameworks, types and duration of programs, and different models of student engagement in such programs. Assessing the quality of a STEGH is a profoundly important and difficult question that cannot be answered as succinctly and quantitatively as classroom performance, which has more standard and established assessment metrics. The goal of this project is to identify the most appropriate and useful assessment metric(s) for determining educational quality and impact for STEGHs at ASU by comparing a typical quantitative evaluation tool (pre-post survey with brief open-ended questions) to a more in-depth qualitative method (key informant interviews). In performing my analysis I seek to examine if the latter can produce a richer narrative of student experiences to inform ongoing program evaluations. My research questions are: 1. What are the current qualitative and quantitative evaluation methods available to assess student learning during short-term experiences in global health? 2. How can current methodology for assessing student experiences with short-term experiences in global health be adapted to collect the most information from students? 3. How do student knowledge and attitudes change before and after their short-term experience in global health? Why is understanding those changes important for adapting programs? My end goal would be to use these new, optimal assessment methods for gathering student perspectives and experiences to adapt pre-departure trainings and post-experience debriefings for study abroad programs, both of which I believe will lead to more sustainable partnerships and a healthier understanding of global health work for students.
ContributorsHale, Brittany Ann (Author) / Jehn, Megan (Thesis director) / Wutich, Amber (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Genocide studies have traditionally focused on the perpetrator’s intent to eradicate a particular identity-based group, using the Holocaust as their model and point of comparison. Although some aspects of the Holocaust were undoubtedly unique, recent scholars have sought to challenge the notion that it was a singular phenomenon. Instead, they draw attention to a recurring pattern of genocidal events throughout history by shifting the focus from intent to structure. One particular branch of scholars seeks to connect the ideology and tactics of imperialism with certain genocidal events. These anti-imperialist genocide scholars concede that their model cannot account for all genocides, but still claim that it creates meaningful connections between genocides committed by Western colonialist powers and those that have occurred in a neoimperialist world order shaped according to Western interests. The latter includes genocides in postcolonial states, which these scholars believe were shaped by the scars of their colonial past, as well as genocides in which imperial hegemons assisted local perpetrators. Imperialist and former colonial powers have contributed meaningfully to all of these kinds of genocides, yet their contributions have largely been ignored due to their own influence on the creation of the current international order. Incorporating the anti-imperialist perspective into the core doctrine of genocide studies may lead to breakthroughs in areas of related policy and practice, such as prevention and accountability.
ContributorsParker, Ashleigh Mae (Author) / Thies, Cameron (Thesis director) / Sivak, Henry (Committee member) / School of Politics and Global Studies (Contributor) / School of Social Transformation (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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