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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- All Subjects: Alzheimer's Disease
Description
Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
ContributorsBounds, Lexi Rose (Author) / Brafman, David (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Background: Noninvasive MRI methods that can accurately detect subtle brain changes are highly desirable when studying disease-modifying interventions. Texture analysis is a novel imaging technique which utilizes the extraction of a large number of image features with high specificity and predictive power. In this investigation, we use texture analysis to assess and classify age-related changes in the right and left hippocampal regions, the areas known to show some of the earliest change in Alzheimer's disease (AD). Apolipoprotein E (APOE)'s e4 allele confers an increased risk for AD, so studying differences in APOE e4 carriers may help to ascertain subtle brain changes before there has been an obvious change in behavior. We examined texture analysis measures that predict age-related changes, which reflect atrophy in a group of cognitively normal individuals. We hypothesized that the APOE e4 carriers would exhibit significant age-related differences in texture features compared to non-carriers, so that the predictive texture features hold promise for early assessment of AD. Methods: 120 normal adults between the ages of 32 and 90 were recruited for this neuroimaging study from a larger parent study at Mayo Clinic Arizona studying longitudinal cognitive functioning (Caselli et al., 2009). As part of the parent study, the participants were genotyped for APOE genetic polymorphisms and received comprehensive cognitive testing every two years, on average. Neuroimaging was done at Barrow Neurological Institute and a 3D T1-weighted magnetic resonance image was obtained during scanning that allowed for subsequent texture analysis processing. Voxel-based features of the appearance, structure, and arrangement of these regions of interest were extracted utilizing the Mayo Clinic Python Texture Analysis Pipeline (pyTAP). Algorithms applied in feature extraction included Grey-Level Co-Occurrence Matrix (GLCM), Gabor Filter Banks (GFB), Local Binary Patterns (LBP), Discrete Orthogonal Stockwell Transform (DOST), and Laplacian-of-Gaussian Histograms (LoGH). Principal component (PC) analysis was used to reduce the dimensionality of the algorithmically selected features to 13 PCs. A stepwise forward regression model was used to determine the effect of APOE status (APOE e4 carriers vs. noncarriers), and the texture feature principal components on age (as a continuous variable). After identification of 5 significant predictors of age in the model, the individual feature coefficients of those principal components were examined to determine which features contributed most significantly to the prediction of an aging brain. Results: 70 texture features were extracted for the two regions of interest in each participant's scan. The texture features were coded as 70 initial components andwere rotated to generate 13 principal components (PC) that contributed 75% of the variance in the dataset by scree plot analysis. The forward stepwise regression model used in this exploratory study significantly predicted age, accounting for approximately 40% of the variance in the data. The regression model revealed 5 significant regressors (2 right PC's, APOE status, and 2 left PC by APOE interactions). Finally, the specific texture features that contributed to each significant PCs were identified. Conclusion: Analysis of image texture features resulted in a statistical model that was able to detect subtle changes in brain integrity associated with age in a group of participants who are cognitively normal, but have an increased risk of developing AD based on the presence of the APOE e4 phenotype. This is an important finding, given that detecting subtle changes in regions vulnerable to the effects of AD in patients could allow certain texture features to serve as noninvasive, sensitive biomarkers predictive of AD. Even with only a small number of patients, the ability for us to determine sensitive imaging biomarkers could facilitate great improvement in speed of detection and effectiveness of AD interventions..
ContributorsSilva, Annelise Michelle (Author) / Baxter, Leslie (Thesis director) / McBeath, Michael (Committee member) / Presson, Clark (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The research objective is to maintain the A4 nanobody stability during dialysis. Various dialysis buffers were tested and compared, including PBS with varying amounts of the detergent, Tween: low, high, none. Furthermore, PBS, Tris, and HEPES, were tested and compared. PBS without Tween was the worst for preserving A4 stability. PBS was determined to be a better dialysis buffer than Tris or HEPES. To find the optimum buffer, other buffers will be tested and compared with PBS; methods such as gravity filtration and lyophilization will be considered as alternatives to dialysis.
ContributorsTao, Kevin Huang (Author) / Sierks, Michael (Thesis director) / Williams, Stephanie (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
Does assisted cycle therapy influence activities of daily living in older adults with Down syndrome?
Description
The aim of this study is to examine the relationship between Assisted Cycle Therapy, leisure time activity levels, fine motor control, and grip force in older adults with Down syndrome (DS), all of which affect activities of daily living (ADL) and therefore quality of life. This is relevant because this particular group is at risk for developing early onset Alzheimer's disease (AD), which presents itself uniquely in this population. The parent or guardian of six participants with DS completed Godin's Leisure Time Exercise Questionnaire and the participants themselves completed Purdue Pegboard and grip force assessments before and after an 8-week exercise intervention. The results were inconsistent with past research, with no change being seen in fine motor control or grip force and a decrease being seen in leisure activity. These findings are indicative of the importance of the effect of fatigue on leisure activity as well as maintaining elevated heart rate throughout exercise interventions.
ContributorsGomez, Elizabeth Danielle (Author) / Ringenbach, Shannon (Thesis director) / Coon, David (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
This piece aims to discuss the roles of emerging geographies within the context of global supply chains, approaching the conversation with a "systems" view, emphasizing three key facets essential to a holistic and interdisciplinary environmental analysis: -The Implications of Governmental & Economic Activities -Supply Chain Enablement Activities, Risk Mitigation in Emerging Nations -Implications Regarding Sustainability, Corporate Social Responsibility In the appreciation of the interdisciplinary implications that stem from participation in global supply networks, supply chain professionals can position their firms for continued success in the proactive construction of robust and resilient supply chains. Across industries, how will supply networks in emerging geographies continue to evolve? Appreciating the inherent nuances related to the political and economic climate of a region, the extent to which enablement activities must occur, and sustainability/CSR tie-ins will be key to acquire this understanding. This deliverable aims to leverage the work of philosophers, researchers and business personnel as these questions are explored. The author will also introduce a novel method of teaching (IMRS) in the undergraduate business classroom that challenges the students to integrate their prior experiences both in the classroom and in the business world as they learn to craft locally relevant solutions to solve complex global problems.
ContributorsVaney, Rachel Lee (Author) / Maltz, Arnold (Thesis director) / Kellso, James (Committee member) / Barrett, The Honors College (Contributor) / Department of Supply Chain Management (Contributor) / Department of Information Systems (Contributor)
Created2015-05
Description
There is no doubt that globalization has been a force in history , and especially in the past one hundred years. This is extremely evident in the implications of global epidemics. The global response to Severe Acute Respiratory Syndrome (SARS) revealed tensions between nation states and international health organization such as the World Health Organization) collectively called "Global Health Governance"). The issue was sovereignty. SARS showed us that there was more state-centric resistance to the Post-Westphalian world than previously thought. Where infectious diseases are concerned, however, the eventual compliance of states with the WHO shows reluctant but tacit compliance with international intervention.
ContributorsLaw, Stephanie (Author) / Rush, James (Thesis director) / Green, Monica (Committee member) / Lundry, Christopher (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
Description
Former two-time Costa Rican president Dr. Oscar Arias advocates for arms control between nations and, in some cases, complete disarmament as the first step in solving grave issues of international sustainability. The three spheres of sustainability—society, economy, and environment—are explained and the ultimate goal of the compromise between all three aspects is defined as the means to achieving sustainability. A brief history of the politics and culture of Costa Rica provides a glimpse into the values and society of this Central American country, including a consistent commitment to the appreciation and protection of its natural environment. Dr. Arias is credited as one of the founding fathers of the sustainable development movement, as evidenced by his political career and policies both with Costa Rica and with other international communities. A selection of Dr. Arias’ speeches and conversations of the past four decades illuminates the need for disarmament and peaceful political interactions as the catalyst for human progress and sustainable development.
ContributorsZywicki, Alexandra (Author) / Alarcon, Justo (Thesis director) / Printezis, Antonios (Committee member) / Sullivan, Claire (Committee member) / Barrett, The Honors College (Contributor)
Created2015-05
Description
In the current age, with media influence spreading through the entire world, formerly isolated regions and gated cultures became interconnected. With this globalization of culture came the communion between Japanese and Western media, especially animation and comics. Morality is often exemplified by heroes within a particular culture as figures for audiences to admire and draw values from, which can be a useful representation of that society's particular standards. The cultures' portrayal of heroism and morality through characterization and plot structure are emblematic not only of their original culture, but the new age of globalization as concepts previously considered unique to one region soon blended together through the world. From the Western "Hero's Journey" style mythos to the Japanese anime and manga heroes of the modern decades, we can see the growth and impact of globalization which caused new blends of portrayals and themes in revolutionary ways. The roots of the differences were found through research of popular culture and history of Japanese animation and Western comic books. Iconic Western comic book heroes such as Superman, Batman, and Wolverine are analyzed, followed by analysis and comparison to the Japanese parallel of the Japanese hero, specifically within Hirohiko Araki's acclaimed Jojo's Bizarre Adventure anime and manga franchise. Finally, the popular animated Western cartoon Avatar: The Last Airbender, known for its vast Eastern influence, meet the two worlds in the middle and epitomize the globalization of this concept of a hero's narrative. The purpose of this analysis is to understand the dynamics of cultural influence and cultural specificity, elucidating some stereotypes in contemporary culture brought by misconceptions and traditions in order to promote cross-cultural understanding.
ContributorsNguyen, Hau Trung (Author) / Wise, John MacGregor (Thesis director) / Wilson, Bradley (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The aims of this project are: (i) to identify structural and molecular changes in the brains of 3xTg-AD mice and (ii) to determine whether decreasing S6K1 protects the brain from these changes. To achieve our goals, we decided to remove one copy of the S6K1 gene in 3xTg-AD mice by breeding them with S6K1 knockout mice (S6K1+/-). In previous studies, we have seen that reducing S6K1 levels in 3xTg-AD mice improved spatial memory and synaptic plasticity which was associated with reduced A and tau pathology. Here, we used a multiparametric MRI to assess volumetric and blood flow changes in the brain of 20-month-old 3xTg-AD mice. We found that 3xTg-AD/S6K1+/- mice had higher blood flow and cortical volume compared to 3xTg-AD mice. However, we saw no significant differences between 3xTg-AD mice and NonTg mice. We further found A levels and plaque numbers were significantly lower in 3xTg-AD/S6K1+/- mice compared to 3xTg-AD mice. This reduction in plaques could account for the improvement in blood flow in 3xTg-AD/S6K1+/- mice. To try to understand the reason behind the increase in cortical volume in the 3xTg-AD/S6K1+/- when compared to the 3xTg-AD, we measured markers of synaptic density, PSD95, and synaptophysin. We found that PSD95 levels were not different between the four groups. However, synaptophysin levels were significantly lower in 3xTg-AD mice compared to NonTg levels and returned to baseline levels in 3xTg-AD mice lacking one copy of the S6K1 gene. This difference in synaptophysin could explain, at least in part, the difference in volume between the four groups analyzed. Overall, this represents the first evidence showing that reducing mTOR signaling improves blood flow and cortical volume in a mouse model of AD.
ContributorsShukla, Prakriti (Author) / Oddo, Salvatore (Thesis director) / Caccamo, Antonella (Committee member) / Jankowsky, Joanna (Committee member) / School of Molecular Sciences (Contributor) / School of Public Affairs (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Neuroinflammation is mediated by activated microglia, the chief immune response of the central nervous system. Mitochondrial 18kDa translocator protein (TSPO) is upregulated in activated microglia and has been used in PET scans to analyze peripheral and central inflammation with TSPO radioligand [18F]DPA-714. To test the hypothesis that TSPO is involved in microglial mediation of inflammatory responses to Aβ and other Alzheimer’s pathological elements, TSPO expression was evaluated in relation to microglia specific markers (IBA1 and LN3 antibodies) and markers for AD pathology, Aβ (6E10 antibody) and hyperphosphorylated tau (AT8 antibody). To test that TSPO is involved in inflammatory pathways, HEK cells transfected with TSPO plasmids were assessed for oxidative stress in response to Alzheimer’s disease pathogenic agents, β Amyloid (Aβ), and Parkinson’s disease α-synuclein (α-syn).
Fluorescence microscopy of TSPO transfected HEK cell cultures labeled with Carboxy-H2DCFDA and treated with Beta Amyloid (Aβ) and α-synuclein (α-syn) resulted in DAPI fluorescing Human Embryonic Kidney (HEK) nuclei in blue and Green Fluorescent Protein (GFP) fluorescing reactive oxygen species (ROS) or oxidative stress in cell cytoplasm in green. Preliminary study suggests TSPO transfected cells may be used to test oxidative stress with disease pathological elements (Aβ and α-synuclein). In IHC, TSPO immunoreactivity was observed in IBA1 and LN3 marked microglia with varying degrees of expression. Beaded structures were also observed with TSPO immunoreactivities, possibly representing microglia processes. TSPO immunoreactivity was observed in and surrounding amyloid plaques and p-tau immunoreactive neurites. This demonstrates that TSPO is predominantly expressed in microglia and are closely associated with Alzheimer’s disease pathological elements, suggesting involvement of TSPO-expressing microglia in neurodegenerative processes.
Fluorescence microscopy of TSPO transfected HEK cell cultures labeled with Carboxy-H2DCFDA and treated with Beta Amyloid (Aβ) and α-synuclein (α-syn) resulted in DAPI fluorescing Human Embryonic Kidney (HEK) nuclei in blue and Green Fluorescent Protein (GFP) fluorescing reactive oxygen species (ROS) or oxidative stress in cell cytoplasm in green. Preliminary study suggests TSPO transfected cells may be used to test oxidative stress with disease pathological elements (Aβ and α-synuclein). In IHC, TSPO immunoreactivity was observed in IBA1 and LN3 marked microglia with varying degrees of expression. Beaded structures were also observed with TSPO immunoreactivities, possibly representing microglia processes. TSPO immunoreactivity was observed in and surrounding amyloid plaques and p-tau immunoreactive neurites. This demonstrates that TSPO is predominantly expressed in microglia and are closely associated with Alzheimer’s disease pathological elements, suggesting involvement of TSPO-expressing microglia in neurodegenerative processes.
ContributorsWu, Michael (Author) / Lue, Lih-Fen (Thesis director) / Washo-Krupps, Delon (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05