Barrett, The Honors College Thesis/Creative Project Collection
Barrett, The Honors College at Arizona State University proudly showcases the work of undergraduate honors students by sharing this collection exclusively with the ASU community.
Barrett accepts high performing, academically engaged undergraduate students and works with them in collaboration with all of the other academic units at Arizona State University. All Barrett students complete a thesis or creative project which is an opportunity to explore an intellectual interest and produce an original piece of scholarly research. The thesis or creative project is supervised and defended in front of a faculty committee. Students are able to engage with professors who are nationally recognized in their fields and committed to working with honors students. Completing a Barrett thesis or creative project is an opportunity for undergraduate honors students to contribute to the ASU academic community in a meaningful way.
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Description
Transient Receptor Potential (TRP) ion channels are a diverse family of nonselective, polymodal sensors in uni- and multicellular eukaryotes that are implicated in an assortment of biological contexts and human disease. The cold-activated TRP Melastatin-8 (TRPM8) channel, also recognized as the human body's primary cold sensor, is among the few TRP channels responsible for thermosensing. Despite sustained interest in the channel, the mechanisms underlying TRPM8 activation, modulation, and gating have proved challenging to study and remain poorly understood. In this thesis, I offer data collected on various expression, extraction, and purification conditions tested in E. Coli expression systems with the aim to optimize the generation of a structurally stable and functional human TRPM8 pore domain (S5 and S6) construct for application in structural biology studies. These studies, including the biophysical technique nuclear magnetic spectroscopy (NMR), among others, will be essential for elucidating the role of the TRPM8 pore domain in in regulating ligand binding, channel gating, ion selectively, and thermal sensitivity. Moreover, in the second half of this thesis, I discuss the ligation-independent megaprimer PCR of whole-plasmids (MEGAWHOP PCR) cloning technique, and how it was used to generate chimeras between TRPM8 and its nearest analog TRPM2. I review steps taken to optimize the efficiency of MEGAWHOP PCR and the implications and unique applications of this novel methodology for advancing recombinant DNA technology. I lastly present preliminary electrophysiological data on the chimeras, employed to isolate and study the functional contributions of each individual transmembrane helix (S1-S6) to TRPM8 menthol activation. These studies show the utility of the TRPM8\u2014TRPM2 chimeras for dissecting function of TRP channels. The average current traces analyzed thus far indicate that the S2 and S3 helices appear to play an important role in TRPM8 menthol modulation because the TRPM8[M2S2] and TRPM8[M2S3] chimeras significantly reduce channel conductance in the presence of menthol. The TRPM8[M2S4] chimera, oppositely, increases channel conductance, implying that the S4 helix in native TRPM8 may suppress menthol modulation. Overall, these findings show that there is promise in the techniques chosen to identify specific regions of TRPM8 crucial to menthol activation, though the methods chosen to study the TRPM8 pore independent from the whole channel may need to be reevaluated. Further experiments will be necessary to refine TRPM8 pore solubilization and purification before structural studies can proceed, and the electrophysiology traces observed for the chimeras will need to be further verified and evaluated for consistency and physiological significance.
ContributorsWaris, Maryam Siddika (Author) / Van Horn, Wade (Thesis director) / Redding, Kevin (Committee member) / School of Molecular Sciences (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
ContributorsDolan, Kattie (Author) / Leong, Karen (Thesis director) / Wilson, Bradley (Committee member) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The two chapters of this thesis focus on different aspects of DNA and the properties of nucleic acids as the whole. Chapter 1 focuses on the structure of DNA and its relationship to enzymatic efficiency. Chapter 2 centers itself on threose nucleic acid and optimization of a step in the path to its synthesis. While Chapter 1 discusses DNA and Uracil-DNA Glycosylase with regards to the base excision repair pathway, Chapter 2 focuses on chemical synthesis of an intermediate in the pathway to the synthesis of TNA, an analogous structure with a different saccharide in the sugar-phosphate backbone.
Chapter 1 covers the research under Dr. Levitus. Four oligonucleotides were reacted for zero, five, and thirty minutes with uracil-DNA glycosylase and subsequent addition of piperidine. These oligonucleotides were chosen based on their torsional rigidities as predicted by past research and predictions. The objective was to better understand the relationship between the sequence of DNA surrounding the incorrect base and the enzyme’s ability to remove said base in order to prepare the DNA for the next step of the base excision repair pathway. The first pair of oligonucleotides showed no statistically significant difference in enzymatic efficiency with p values of 0.24 and 0.42, while the second pair had a p value of 0.01 at the five-minute reaction. The second pair is currently being researched at different reaction times to determine at what point the enzyme seems to equilibrate and react semi-equally with all sequences of DNA.
Chapter 2 covers the research conducted under Dr. Chaput. Along the TNA synthesis pathway, the nitrogenous base must be added to the threofuranose sugar. The objective was to optimize the original protocol of Vorbrüggen glycosylation and determine if there were better conditions for the synthesis of the preferred regioisomer. This research showed that toluene and ortho-xylene were more preferable as solvents than the original anhydrous acetonitrile, as the amount of preferred isomer product far outweighed the amount of side product formed, as well as improving total yield overall. The anhydrous acetonitrile reaction had a final yield of 60.61% while the ortho-xylene system had a final yield of 94.66%, an increase of approximately 32%. The crude ratio of preferred isomer to side product was also improved, as it went from 18% undesired in anhydrous acetonitrile to 4% undesired in ortho-xylene, both values normalized to the preferred regioisomer.
Chapter 1 covers the research under Dr. Levitus. Four oligonucleotides were reacted for zero, five, and thirty minutes with uracil-DNA glycosylase and subsequent addition of piperidine. These oligonucleotides were chosen based on their torsional rigidities as predicted by past research and predictions. The objective was to better understand the relationship between the sequence of DNA surrounding the incorrect base and the enzyme’s ability to remove said base in order to prepare the DNA for the next step of the base excision repair pathway. The first pair of oligonucleotides showed no statistically significant difference in enzymatic efficiency with p values of 0.24 and 0.42, while the second pair had a p value of 0.01 at the five-minute reaction. The second pair is currently being researched at different reaction times to determine at what point the enzyme seems to equilibrate and react semi-equally with all sequences of DNA.
Chapter 2 covers the research conducted under Dr. Chaput. Along the TNA synthesis pathway, the nitrogenous base must be added to the threofuranose sugar. The objective was to optimize the original protocol of Vorbrüggen glycosylation and determine if there were better conditions for the synthesis of the preferred regioisomer. This research showed that toluene and ortho-xylene were more preferable as solvents than the original anhydrous acetonitrile, as the amount of preferred isomer product far outweighed the amount of side product formed, as well as improving total yield overall. The anhydrous acetonitrile reaction had a final yield of 60.61% while the ortho-xylene system had a final yield of 94.66%, an increase of approximately 32%. The crude ratio of preferred isomer to side product was also improved, as it went from 18% undesired in anhydrous acetonitrile to 4% undesired in ortho-xylene, both values normalized to the preferred regioisomer.
ContributorsTamirisa, Ritika Sai (Author) / Levitus, Marcia (Thesis director) / Stephanopoulos, Nicholas (Committee member) / Windman, Todd (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The Community Action Research Experiences (CARE) program collaborated with Singleton Moms, a local non-profit organization that provides financial, psychological, and social support services to single parents with cancer. The purpose of this action research project was to assess the volunteer program at Singleton Moms. Both past and present Singleton Moms' volunteers (N = 123; 87.0% female) completed an online survey assessing their motivation for volunteering and their satisfaction with the organization. A mixed ANOVA was conducted to identify the most important motivation and satisfaction domains and to see if the findings depended on whether the volunteers were current or past volunteers. For the motivation assessment, results indicated that the volunteers rate the cancer specific and moral/human kindness domains as the strongest reasons for motivating them to volunteer at Singleton Moms. In addition, results revealed that the social connection motivation domain was the only domain with differences between the ratings of the past and present volunteers. For the satisfaction assessment, results indicated that the volunteers rate the organizational climate domain as the most fulfilled area of satisfaction within the Singleton Moms' volunteer program. It was also revealed that there were no significant differences between the ratings of the past and present volunteers among all satisfaction domains. Both the quantitative and qualitative findings suggest that Singleton Moms' implications for action may include: 1) a volunteer database audit, 2) streamlining communications, 3) variability in volunteer times, and 4) bolstering volunteer motivation. Implementing some of these actions may help Singleton Moms increase volunteer motivation and satisfaction and thus create a more effective volunteer program. Ultimately, this may encourage volunteers to continue their services at Singleton Moms and thus help Singleton Moms expand their support programs and assist additional families.
ContributorsDubois, Courtney Michelle (Author) / Miller, Cindy (Thesis director) / Dumka, Larry (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2016-05
Description
Traumatic brain injury (TBI) is a leading cause of injury related death in the United States. The complexity of the injury environment that follows TBI creates an incomplete understanding of all the mechanisms in place to regulate chemotactic responses to TBI. The goal of this project was to develop a predictive in silco model using diffusion and autocrine/paracrine signaling specific to stromal cell derived factor-1α (SDF-1α) gradient formation after TBI and compare this model with in vivo experimental data. A COMSOL model using Fickian diffusion and autocrine/paracrine reaction terms was generated to predict the gradient formation observed in vivo at three physiologically relevant time points (1, 3, and 7 days). In vivo data was gathered and analyzed via immunohistochemistry and MATLAB. The spatial distribution of SDF-1α concentration in vivo more consistently demonstrated patterns similar to the in silico model dependent on both diffusion and autocrine/paracrine reaction terms rather than diffusion alone. The temporal distribution of these same results demonstrated degradation of SDF-1α at too rapid a rate, compared to the in vivo results. To account for differences in behavior observed in vivo, reaction terms and constants of 1st-order reaction rates must be modulated to better reflect the results observed in vivo. These results from both the in silico model and in vivo data support the hypothesis that SDF-1α gradient formation after TBI depends on more than diffusion alone. Future work will focus on improving the model with constants that are specific to SDF-1α as well as testing methods to better control the degradation of SDF-1α.
ContributorsFreeman, Sabrina Louise (Author) / Stabenfeldt, Sarah (Thesis director) / Caplan, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading to a median survival period of two to five years. B cells in the bone marrow are responsible for generating antigen-specific antibodies, but in MM the B cells express mutated, non-specific monoclonal antibodies. Therefore, it is hypothesized that antibody-based assay and therapy may be feasible for detecting and treating the disease. In this project, 330k peptide microarrays were used to ascertain the binding affinity of sera antibodies for MM patients with random sequence peptides; these results were then contrasted with normal donor assays to determine the "immunosignatures" for MM. From this data, high-binding peptides with target-specificity (high fluorescent intensity for one patient, low in all other patients and normal donors) were selected for two MM patients. These peptides were narrowed down to two lists of five (10 total peptides) to analyze in a synthetic antibody study. The rationale behind this originates from the idea that antibodies present specific binding sites on either of their branches, thus relating high binding peptides from the arrays to potential binding targets of the monoclonal antibodies. Furthermore, these peptides may be synthesized on a synthetic antibody scaffold with the potential to induce targeted delivery of radioactive or chemotherapeutic molecular tags to only myelomic B cells. If successful, this would provide a novel alternative to current treatments that is less invasive, has fewer side effects, more specifically targets the cause of MM, and reliably diagnoses the cancer in the presymptomatic stage.
ContributorsBerry, Jameson (Co-author) / Buelt, Allison (Co-author) / Johnston, Stephen (Thesis director) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Community Music Therapy for Cultural Cohesion is the name of the research initiative to create a community music therapy program that addresses community attitudes toward cultural diversity. The program created is titled "Many Peoples, One Voice." Theories and findings in the field of social psychology regarding the formation of intergroup bias and how to prevent it from taking hold inform the goals of the program. Current practices in and theories on community music therapy inform the content, qualities, and perspective of the program. Information from the field of ethnomusicology inform the specific world music traditions incorporated into the program. The culmination of this research and the program it birthed is described in detail to promote a better understanding of the goals, activities, cultural handouts, additional content considerations, and structure of the program as well as the populations it may serve and the adaptions it may include. Finally, the program is related to the current trends in the field of music therapy and its potential to expand into nontraditional need and population areas is considered.
ContributorsOstrowski, Jennifer Lauren (Author) / Rio, Robin (Thesis director) / Little, Bliss (Committee member) / School of Music (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
This study was conducted to observe the effects of vitamin C supplementation upon the expression of sICAM-1 in asthmatic subject. Two groups were created, each with a sample size of 4 subjects. One group was the vitamin C group (VC) and the other was the placebo group (PL). The study was analyzed through observing concentrations of biomolecules present within samples of blood plasma and nasal lavages. These included vitamin C, sICAM-1 expression, and histamine. The following P-values calculated from the data collected from this study. The plasma vitamin C screening was p=0.3, and after 18 days of supplementation, p=0.03. For Nasal ICAM p=0.5 at Day 0, p=0.4 at Day 4, and p=0.9 at Day 18. For the Histamine samples p=0.9 at Day 0 and p=0.9 at Day 18. The following P-values calculated from the data collected from both studies. The plasma vitamin C screening was p=0.8, and after 18 days of supplementation, p=0.03. The change of vitamin C at the end of this study and the combined data both had a P-value that was calculated to be lower than 0.05, which meant that this change was significant because it was due to the intervention and not chance. For Nasal ICAM samples p=0.7 at Day 0, p=0.7 at Day 4, and p=1 at Day 18. For the Histamine p=0.7 at Day 0 and p=0.9 at Day 18. This study carries various implications although the study data was unable to show much significance. This was the second study to test this, and as more research is done, and the sample size grows, one will be able to observe whether this really is the mechanism through which vitamin C plays a role in immunological functions.
ContributorsKapadia, Chirag Vinay (Author) / Johnston, Carol (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Biosimilar pharmaceuticals are new lower-cost drugs awaiting large-scale approval within the United States (U.S). Biosimilar pharmaceuticals or simply biosimilars, are complex, large-molecule, and biologically-derived drugs that are deemed molecularly similar to currently approved reference biologics. Biologics and biosimilars both treat a wide range of conditions with no clinically meaningful difference between them. However, numerous states, with help from large pharmaceutical companies lobbying, are passing legislation complicating the prescribing and dispensing process for biosimilars by mandating a "notification" or "communication" requirement. The notification requirement requires pharmacists to contact prescribers when dispensing an interchangeable biosimilar in place of its reference biologic. This type of mandate is not only unprecedented in current U.S. pharmaceutical law, but it also incentivizes pharmacists to dispense more expensive biologics in place of biosimilars. The notification or communication requirement also falsely gives consumers the appearance that biosimilars are more dangerous in comparison to other types of biological medicines. These two factors, pharmacist hesitation and consumer distrust, serve as barriers to successful biosimilar market entry. High research and development costs and forecasted poor sales inhibit biosimilar companies from making the investment in innovating new drugs. The lack of investment in research and development prevents new biosimilars from entering the market to compete with currently approved biologics. In turn, current biosimilar legislation is reducing pharmaceutical competition and increasing drug prices. Information Measurement Theory supports the notion that in climates without competition (caused by a lack of transparency) sparks low quality and high costs. Transparency and improved biosimilar market conditions can be achieved through repealing the large pharmaceutical company backed notification requirement.
ContributorsFelthouse, Karis Renee (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / School of Politics and Global Studies (Contributor) / School of Film, Dance and Theatre (Contributor) / School of Sustainability (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
There is a widespread inequality in health care access and insured rates suffered by the Latino, Spanish-speaking population in Arizona, resulting in poor health measures and economic burden. The passage of the Affordable Care Act in 2010 provided mechanisms to alleviate this disparity, however, many Latino communities lack accessible information and means to gain access to health insurance enrollment. Chicanos Por La Causa (CPLC) is a community based organizing that provides many services to low-income communities across Arizona, one of which is the CPLC Insurance Program. In collaboration with the Community Action Research Experiences (CARE) at Arizona State University, the program was studied to help address the need of a LOGIC model and evaluation plan to determine its effectiveness. Interviews with three executives within CPLC were conducted in conjunction with a literature review to determine the inputs, strategies, outputs, and outcomes of the LOGIC model that drive CPLC Insurance's mission. Evaluation measures were then created to provide the necessary quantitative data that can best show to what degree the program is achieving its goals. Specifically, the results indicated the key outcomes that drive the LOGIC model, and an evaluation plan designed to provide indicators of these outcomes was produced. The implications of this study are that the suggested data collection can verify how effectively the program's actions are creating positive change, as well as show where further improvements may be necessary to maximize effectiveness.
ContributorsCunningham, Matthew Lee (Author) / Fey, Richard (Thesis director) / Dumka, Larry (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2016-05