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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- Creators: Ankeny, Casey
Description
Breast and other solid tumors exhibit high and varying degrees of intra-tumor heterogeneity resulting in targeted therapy resistance and other challenges that make the management and treatment of these diseases rather difficult. Due to the presence of admixtures of non-neoplastic cells with polyclonal cell populations, it is difficult to define cancer genomes in patient samples. By isolating tumor cells from normal cells, and enriching distinct clonal populations, clinically relevant genomic aberrations that drive disease can be identified in patients in vivo. An in-depth analysis of clonal architecture and tumor heterogeneity was performed in a stage II chemoradiation-naïve breast cancer from a sixty-five year old patient. DAPI-based DNA content measurements and DNA content-based flow sorting was used to to isolate nuclei from distinct clonal populations of diploid and aneuploid tumor cells in surgical tumor samples. We combined DNA content-based flow cytometry and ploidy analysis with high-definition array comparative genomic hybridization (aCGH) and next-generation sequencing technologies to interrogate the genomes of multiple biopsies from the breast cancer. The detailed profiles of ploidy, copy number aberrations and mutations were used to recreate and map the lineages present within the tumor. The clonal analysis revealed driver events for tumor progression (a heterozygous germline BRCA2 mutation converted to homozygosity within the tumor by a copy number event and the constitutive activation of Notch and Akt signaling pathways. The highlighted approach has broad implications in the study of tumor heterogeneity by providing a unique ultra-high resolution of polyclonal tumors that can advance effective therapies and clinical management of patients with this disease.
ContributorsLaughlin, Brady Scott (Author) / Ankeny, Casey (Thesis director) / Barrett, Michael (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School for the Science of Health Care Delivery (Contributor)
Created2015-05
Description
Inflammation is part of the body’s response to invading pathogens, injury, and a wide range of diseases. Although inflammation is paramount to maintain a healthy immune system, unregulated inflammation can aggravate chronic conditions or cause severe, acute pathologies. Pyroptosis, a caspase-1-dependent, pro-inflammatory cell death that results in the release of IL-1β and IL-18, has been implicated in propagating an inflammatory response in the body. Pyroptosis has been shown to result from the activation of the NLRP3 inflammasome. Furthermore, multiple reports have demonstrated that intracellular potassium efflux and spleen tyrosine kinase (Syk) activity are both essential for facilitating the assembly of the NLRP3 inflammasome and proper processing and release of IL-1β and IL-18. The focus of this thesis was to determine the relationship between intracellular potassium efflux and Syk during key regulatory events in the activation of the NLRP3 inflammasome by identifying their effect on pro-inflammatory cytokine release, inflammasome assembly, mitochondrial reactive oxygen species (mROS) generation, and cell death. Both inhibiting potassium efflux from occurring and deactivating Syk significantly reduced the amount of pro-inflammatory cytokine released (70-100% reduction), the number of inflammasomes assembled (60-80% reduction), the amount of mROS generation, and the quantity of cell death (50-90% reduction). Moreover, it was discovered that potassium efflux was required for Syk activation, but Syk activation had no effect on potassium efflux. Their relationship proved to be unidirectional. This study provides the first demonstration of ion flux-dependent regulation of kinase activation in the NLRP3 inflammasome pathway and provides support for targeting ion regulation mechanisms and Syk kinase activity to manipulate macrophage-mediate inflammatory processes.
ContributorsRao, Mounica Yarlagadda (Author) / Meldrum, Deirdre R. (Thesis director) / Ankeny, Casey (Committee member) / Glenn, Honor (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2015-05
Description
Antibiotics, bacteria, and the continuing trend of antibiotic resistance increasing in various bacteria strains is a complex and multifaceted set of relationships explored in this thesis. Examining a variety of published literature in various sectors of influence, including the social, medical, and economic divisions, this thesis examined the core factors and combined them into a set of recommendations for future progress. In this way, the subject of antibiotic resistance in bacteria begins with an evaluation of the history then continued into an analysis of the economic factors, a social understanding of the subject, a medical evaluation of current procedure, and a concluding framework and general set of recommendations for future use. Ultimately, these factors require a multifaceted approach in order to combat the numerous factors and contributions to emerging antibiotic resistance in bacteria both in the United States of America and around the world.
ContributorsMurphy, Emily Ann (Author) / Chhetri, Netra (Thesis director) / Ankeny, Casey (Committee member) / Hamburg, Robert (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.
ContributorsFauer, Chase Alexander (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
To identify genes that can lead to obesity of Pima Native American heritage, an array of experiments can be conducted to determine possible candidate genes that can increase the likelihood of being obese in a set population. The studies available to identify these genes were (1) inspect follow-up genes identified by a previous genome wide associations studies, GWAS, previously conducted for the 1120 American Indian subjects data available, (2) to directly sequence candidate genes in literature, (3) to analyze whole sequence data from Native American subjects, and lastly (4) to perform functional studies on most promising variants associated with BMI. Analyzing the results presented from my work required the use of biological techniques such as: DNA sequencing, DNA large scale genotyping, PCR amplification, DNA transfections, DNA ligations, in vitro Luciferase assay and Cell culture. Inspecting the follow-up genes identified by the conducted GWAS showed the potential for the MAP2K3 gene to be a candidate to increase obesity in the set population, involve two single nucleotide polymorphisms (SNPs, rs12882548, rs11652094), to affect body weight through complex mechanisms involving food intake and hypothalamic inflammation. The follow-up genes identified in the GWAS that had an effect on obesity showed to affect it through the mechanism of reducing energy expenditure. Through the analysis of SNPs two variants (rs10507100 and rs17087518) were identified to test their roles in the reduction of energy expenditure. Rs17087518 showed to have a role in a relatively reduced EE resulting in weight gain. Directly sequencing a candidate gene known as MRAP2 showed that the SNP rs1928281 did not have a significant difference on obesity in the Native American subjects (p =.09). Analyzing whole genome sequencing SNPs gave rise to novel variants by association analyses with energy expenditure and BMI in 235 whole genomes, the most significant SNP, rs4984683, was examined to determine the variability in energy expenditures. With set quality control assessment a list of variants were received and were then later assessed with other data available to make a connection to EE. Performing functional studies showed the possibility for rs2001651 and rs1466314 to have an effect on MAP2K3 expression level. The initial functional studies gave way to a more in-depth study of this gene to predict BMI in Caucasians and Native Americans, which in turn showed an association with BMI. The use of these techniques have been an indicator for current research in the determination of candidate genes across many diseases. The works presented is an example of the current works in genetics and an exploration of new mechanism to detect, and possibly treat, disease through personalized sequencing.
ContributorsGale, Alex Mauricio Pompa (Author) / Ankeny, Casey (Thesis director) / Baier, Leslie (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
This project aims to address the current protocol regarding the diagnosis and treatment of traumatic brain injury (TBI) in medical industries around the world. Although there are various methods used to qualitatively determine if TBI has occurred to a patient, this study attempts to aid in the creation of a system for quantitative measurement of TBI and its relative magnitude. Through a method of artificial evolution/selection called phage display, an antibody that binds highly specifically to a post-TBI upregulated brain chondroitin sulfate proteoglycan called neurocan has been identified. As TG1 Escheria Coli bacteria were infected with KM13 helper phage and M13 filamentous phage in conjunction, monovalent display of antibody fragments (ScFv) was performed. The ScFv bind directly to the neurocan and from screening, phage that produced ScFv's with higher affinity and specificity to neurocan were separated and purified. Future research aims to improve the ScFv characteristics through increased screening toward neurocan. The identification of a highly specific antibody could lead to improved targeting of neurocan post-TBI in-vivo, aiding researchers in quantitatively defining TBI by visualizing its magnitude.
ContributorsSeelig, Timothy Scott (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
This paper explores multidisciplinary curricula, services, and experiential learning in higher education on sustainability. Researchers attempt to understand sustainability as a formalized degree program, what frameworks and techniques are used to improve new disciplines, and how Arizona State University's School of Sustainability (SOS) improves sustainability education in higher learning. Secondary research includes a discussion on the history of sustainability as a discipline, the university as a social system, the role of university administration, the roles of professors and students, benchmarking and process improvement for curriculum development, and methods to bridge epistemologies in SOS. The paper presents findings from a study of the SOS undergraduate student experience that used focus groups to gather qualitative data and statistical analysis to analyze that data quantitatively. Study findings indicate that that measuring student perception of SOS's academic services, and understanding the social system of the university, helps administration, faculty, and students collaborate more effectively to enhance learning experiences.
ContributorsTom, Sharyn Paige (Author) / Haglund, LaDawn (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Department of Marketing (Contributor) / School of Sustainability (Contributor)
Created2015-05