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
- All Subjects: Electrical Engineering
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
Buck converters are a class of switched-mode power converters often used to step down DC input voltages to a lower DC output voltage. These converters naturally produce a current and voltage ripple at their output due to their switching action. Traditional methods of reducing this ripple have involved adding large discrete inductors and capacitors to filter the ripple, but large discrete components cannot be integrated onto chips. As an alternative to using passive filtering components, this project investigates the use of active ripple cancellation to reduce the peak output ripple. Hysteretic controlled buck converters were chosen for their simplicity of design and fast transient response. The proposed cancellation circuits sense the output ripple of the buck converter and inject an equal ripple exactly out of phase with the sensed ripple. Both current-mode and voltage-mode feedback loops are simulated, and the effectiveness of each cancellation circuit is examined. Results show that integrated active ripple cancellation circuits offer a promising substitute for large discrete filters.
ContributorsWang, Ziyan (Author) / Bakkaloglu, Bertan (Thesis director) / Kitchen, Jennifer (Committee member) / Electrical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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
This project was centered around designing a processor model (using the C programming language) based on the Coldfire computer architecture that will run on third party software known as Open Virtual Platforms. The end goal is to have a fully functional processor that can run Coldfire instructions and utilize peripheral devices in the same way as the hardware used in the embedded systems lab at ASU. This project would cut down the substantial amount of time students spend commuting to the lab. Having the processor directly at their disposal would also encourage them to spend more time outside of class learning the hardware and familiarizing themselves with development on an embedded micro-controller. The model will be accurate, fast and reliable. These aspects will be achieved through rigorous unit testing and use of the OVP platform which provides instruction accurate simulations at hundreds of MIPS (million instructions per second) for the specified model. The end product was able to accurately simulate a subset of the Coldfire instructions at very high rates.
ContributorsDunning, David Connor (Author) / Burger, Kevin (Thesis director) / Meuth, Ryan (Committee member) / Barrett, The Honors College (Contributor) / Computer Science and Engineering Program (Contributor)
Created2014-12
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
The world of a hearing impaired person is much different than that of somebody capable of discerning different frequencies and magnitudes of sound waves via their ears. This is especially true when hearing impaired people play video games. In most video games, surround sound is fed through some sort of digital output to headphones or speakers. Based on this information, the gamer can discern where a particular stimulus is coming from and whether or not that is a threat to their wellbeing within the virtual world. People with reliable hearing have a distinct advantage over hearing impaired people in the fact that they can gather information not just from what is in front of them, but from every angle relative to the way they're facing. The purpose of this project was to find a way to even the playing field, so that a person hard of hearing could also receive the sensory feedback that any other person would get while playing video games To do this, visual surround sound was created. This is a system that takes a surround sound input, and illuminates LEDs around the periphery of glasses based on the direction, frequency and amplitude of the audio wave. This provides the user with crucial information on the whereabouts of different elements within the game. In this paper, the research and development of Visual Surround Sound is discussed along with its viability in regards to a deaf person's ability to learn the technology, and decipher the visual cues.
ContributorsKadi, Danyal (Co-author) / Burrell, Nathaneal (Co-author) / Butler, Kristi (Co-author) / Wright, Gavin (Co-author) / Kosut, Oliver (Thesis director) / Bliss, Daniel (Committee member) / Barrett, The Honors College (Contributor) / Electrical Engineering Program (Contributor)
Created2015-05
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
Description
Parents in STEM careers are more apt to guide their kids towards STEM careers (Sherburne-Michigan, 2017). There are STEM programs and classes for students who are interested in related fields, but the conundrum is that students need to be interested in order to choose to participate. The goal of this creative project was to introduce engineering concepts in a high school class to reveal and investigate the ways in which engineering concepts can be successfully introduced to a larger student populace to increase interest in engineering programs, courses, and degrees. A lesson plan and corresponding materials - including circuit kits and a simulated ball launching station with graphical display - were made to accomplish this goal. Throughout the lesson students were asked to (1) use given materials to accomplish a goal, (2) predict outcomes based on conceptual understanding and mathematical calculations, (3) test predictions, (4) record data, and (5) analyze data to generate results. The students first created a simple circuit to understand the circuit components and learn general electrical engineering concepts. A simple light dimmer circuit let students demonstrate understanding of electrical concepts (e.g., voltage, current resistance) before using the circuit to a simulated motor in order to launch a ball. The students were then asked to predict the time and height of a ball launched with various settings of their control circuit. The students were able to test their theories with the simulated launcher test set up shown in Figure 25 and collect data to create a parabolic height versus time graph. Based on the measured graph, the students were able to record their results and compare calculated values to real-world measured values. The results of the study suggest ways to introduce students to engineering while developing hands-on concept modeling of projectile motion and circuit design in math classrooms. Additionally, this lesson identifies a rich topic for teachers and STEM education researchers to explore lesson plans with interdisciplinary connections to engineering. This report will include the inspiration for the product, related work, iterative design process, and the final design. This information will be followed by user feedback, a project reflection, and lessons learned. The report will conclude with a summary and a discussion of future work.
ContributorsBurgess, Kylee Rae (Author) / Jordan, Shawn (Thesis director) / Sohoni, Sohum (Committee member) / Kinach, Barbara (Committee member) / Engineering Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05