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: Stabenfeldt, Sarah
Description
Traumatic brain injury (TBI) can result in many pathologies, one of which being coagulopathy. TBI can progress to hemorrhagic lesions and increased intercranial pressure leading to coagulopathy. The coagulopathy has been linked to poor clinical outcomes and occurs in 60% of severe TBI cases. To improve hemostasis, synthetic platelets (SPs) have been repurposed. SPs are composed of a poly(N-isopropylacrylamide-co-acrylic-acid) microgel, conjugated with a fibrin-specific antibody and are biomimetic in their ability to deform and collapse within a fibrin matrix. The objective of this study is to diminish coagulopathy with a single, intravenous injection of SPs, and subsequently decrease neuropathologies. TBI was modeled in animal cohorts using the well-established controlled cortical impact and SPs were injected 2-3 hours post-injury. Control cohorts received no injection. Brain tissue was harvested at acute (24h) and delayed (7 days) time points post-TBI, and fluorescently imaged to quantify reactive astrocytes (GFAP+), microglial morphology and presence (Iba1+), and tissue lesion spared. SP-treatment resulted in significant reduction of GFAP expression at 7 days post-TBI. Furthermore, SP-treatment significantly reduced the percent difference from 24h to 7 days in microglia/macrophage per field compared to the control. For microglial morphology, SP-treated cohorts observed a significant percent difference in endpoints per soma from 24h to 7 days compared to untreated cohorts. However, microglial branch length significantly decreased in percent difference from 24h to 7 days when compared to the control. Finally, tissue sparing did not significantly decrease between 24h and 7 day for SP-treated cohorts as was observed in untreated cohorts, implying inhibition of delayed necrosis. Overall, these results suggest decreased neuroinflammation by 7 days, supporting SPs as potentially therapeutic post-TBI.
ContributorsTodd, Jordan Cecile (Author) / Stabenfeldt, Sarah (Thesis director) / Bharadwaj, Vimala (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative brain disease that results from repetitive brain trauma causing brain structure, personality, behavioral, and cognitive changes. CTE is currently undiagnosable and untreatable in living patients. This thesis investigates research surrounding CTE and presents a comparative discussion of the advantages and disadvantages of current diagnostic methods used for other neurodegenerative diseases that may be useful for the diagnosis of CTE.
ContributorsBlair, Sierra (Co-author) / Blair, Taylor (Co-author) / Brafman, David (Thesis director) / Stabenfeldt, Sarah (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
In June of 2016, the United Kingdom held a referendum for its citizens to decide whether to remain a part of the European Union or take their leave. The vote was close but ultimately the U.K. decided to leave, triggering the two-year process of negotiations that would shape the U.K.’s departure (Brexit). The question of what will become of the border between Northern Ireland and the Republic of Ireland is heavy with implications for the national identity of people living on either side of the border, and this makes it one of the more pressing concerns in Brexit discourse. This research analyzes how national identity is used as a rhetorical tactic in media to influence and persuade readers to vote in accordance with the author’s political goals. It does so by evaluating how borders shape national identity and analyzing newspaper articles from the two highest circulating Northern Irish daily newspapers (The Irish News and the Belfast Telegraph) during the week leading up to the June 23rd, 2016 referendum. In analyzing news articles relating to the Irish border issue of Brexit from The Irish News and the Belfast Telegraph during the time frame of June 16th-23rd, 2016, four analytical categories of how identity-related rhetoric was used were discovered: fear, self-interest, Irish Nationalism, and a negative association of the past. Further, it was hypothesized and confirmed the political leanings of the papers influenced which type of rhetorical tactic was used. In the broad realm of Brexit and media related discussion, this research could help strengthen understanding of how traditional media uses national identity to persuade readers to and influence voting behavior in the midst of such a divisive referendum.
Key Words: Brexit, Irish border, national identity, rhetoric, newspapers
Key Words: Brexit, Irish border, national identity, rhetoric, newspapers
ContributorsCaldwell, Tara (Author) / O'Flaherty, Katherine (Thesis director) / Ripley, Charles (Committee member) / School of Social Transformation (Contributor) / School of Politics and Global Studies (Contributor, Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Tissue engineering is an emerging field focused on the repair, replacement, and regeneration of damaged tissue. Engineered tissue consists of three factors: cells, biomolecular signals, and a scaffold. Cell-free scaffolds present a unique opportunity to develop highly specific microenvironments with tunable properties. Norbornene-functionalized hyaluronic acid (NorHA) hydrogels provide spatial control over biomolecule binding through a photopolymerization process. With this, biomimetic gradients can be produced to model a variety of tissue interfaces. To produce these patterns, a gradient mechanism was developed to function in tandem with a syringe pump. A conversion equation was derived to calculate a panel speed from the volumetric flow rate setting on the pump. Seven speeds were used to produce fluorophore gradients on the surface of NorHA hydrogels to assess changes in the length and slope of the gradient. The results indicated a strong positive linear correlation between the speed of the panel and the length of the gradient as well as a strong negative correlation between the speed of the panel and the slope of the gradient. Additionally, the mechanism was able to successfully produce several other types of gradients including multiregional, dual, and triregional.
ContributorsSogge, Amber (Author) / Holloway, Julianne (Thesis director) / Stabenfeldt, Sarah (Committee member) / Fumasi, Fallon (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Recent studies in traumatic brain injury (TBI) have found a temporal window where therapeutics on the nanometer scale can cross the blood-brain barrier and enter the parenchyma. Developing protein-based therapeutics is attractive for a number of reasons, yet, the production pipeline for high yield and consistent bioactive recombinant proteins remains a major obstacle. Previous studies for recombinant protein production has utilized gram-negative hosts such as Escherichia coli (E. coli) due to its well-established genetics and fast growth for recombinant protein production. However, using gram-negative hosts require lysis that calls for additional optimization and also introduces endotoxins and proteases that contribute to protein degradation. This project directly addressed this issue and evaluated the potential to use a gram-positive host such as Brevibacillus choshinensis (Brevi) which does not require lysis as the proteins are expressed directly into the supernatant. This host was utilized to produce variants of Stock 11 (S11) protein as a proof-of-concept towards this methodology. Variants of S11 were synthesized using different restriction enzymes which will alter the location of protein tags that may affect production or purification. Factors such as incubation time, incubation temperature, and media were optimized for each variant of S11 using a robust design of experiments. All variants of S11 were grown using optimized parameters prior to purification via affinity chromatography. Results showed the efficiency of using Brevi as a potential host for domain antibody production in the Stabenfeldt lab. Future aims will focus on troubleshooting the purification process to optimize the protein production pipeline.
ContributorsEmbrador, Glenna Bea Rebano (Author) / Stabenfeldt, Sarah (Thesis director) / Plaisier, Christopher (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Traumatic brain injury (TBI) is a major cause of disability, with approximately 1.7 million incidents reported annually. Following a TBI, patients are likely to sustain sensorimotor and cognitive impairments and are at an increased risk of developing neurodegenerative diseases later in life. Despite this, robust therapies that treat TBI neuropathology are not available in the clinic. One emerging therapeutic approach is to target epigenetic mediators that modulate a variety of molecular regulatory events acutely following injury. Specifically, previous studies demonstrated that histone deacetylase inhibitor (HDACi) administration following TBI reduced inflammation, enhanced functional outcomes, and was neuroprotective. Here, we evaluated a novel quisinostat-loaded PLA-PEG nanoparticle (QNP) therapy in treating TBI as modeled by a controlled cortical impact. We evaluated initial pharmacodynamics within the injured cortex via histone acetylation levels following QNP treatment. We observed that QNP administration acutely following injury increased histone acetylation specifically within the injury penumbra, as detected by Western blot analysis. Given this effect, we evaluated QNP therapeutic efficacy. We observed that QNP treatment dampened motor deficits as measured by increased rotarod latency to fall relative to blank nanoparticle- and saline-treated controls. Additionally, open field results show that QNP treatment altered locomotion following injury. These results suggest that HDACi therapies are a beneficial therapeutic strategy following neural injury and demonstrate the utility for nanoparticle formulations as a mode for HDACi delivery following TBI.
ContributorsMousa, Gergey (Author) / Stabenfeldt, Sarah (Thesis director) / Newbern, Jason (Committee member) / Sirianni, Rachael (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Time-Lapse Visualization of Microglia Cell Processes using Fluorescent Miniature (Miniscope) Imaging
Description
In the United States, an estimated 2 million cases of traumatic brain injury (TBI) resulting in more than 50,000 deaths occur every year. TBI induces an immediate primary injury resulting in local or diffuse cell death in the brain. Then a secondary injury occurs through neuroinflammation from immune cells in response to primary injury. Microglia, the resident immune cell of the central nervous system, play a critical role in neuroinflammation following TBI. Microglia make up 10% of all cells in the nervous system and are the fastest moving cells in the brain, scanning the entire parenchyma every several hours. Microglia have roles in both the healthy and injured brain. In the healthy brain, microglia can produce neuroprotective factors, clear cellular debris, and organize neurorestorative processes to recover from TBI. However, microglia mediated neuroinflammation during secondary injury produces pro-inflammatory and cytotoxic mediators contributing to neuronal dysfunction, inhibition of CNS repair, and cell death. Furthermore, neuroinflammation is a prominent feature in many neurodegenerative diseases such as Alzheimer’s, and Parkinson’s disease, of which include overactive microglia function. Microglia cell morphology, activation, and response to TBI is poorly understood. Currently, imaging microglia can only be performed while the animal is stationary and under anesthesia. The Miniscope technology allows for real-time visualization of microglia in awake behaving animals. The Miniscope is a miniature fluorescent microscope that can be implanted over a craniectomy to image microglia. Currently, the goals of Miniscope imaging are to improve image quality and develop time-lapse imaging capabilities. There were five main sub-projects that focused on these goals including surgical nose cone design, surgical holder design, improved GRIN lens setup, improved magnification through achromatic lenses, and time-lapse imaging hardware development. Completing these goals would allow for the visualization of microglia function in the healthy and injured brain, elucidating important immune functions that could provide new strategies for treating brain diseases.
ContributorsNelson, Andrew Frederick (Author) / Stabenfeldt, Sarah (Thesis director) / Lifshitz, Jonathan (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05