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Computational Modeling and Analysis of Protein Interactions at Multiple Coarse-grained Levels in Biological Systems
No full textProteins, composed of unique amino acid sequences, fold into compact, functional structures. These proteins often form large complexes that interact with other proteins and genes to regulate cellular processes. Studying these interactions is challenging due to their transient nature. This thesis em- ploys coarse-graining techniques to simplify protein structures while preserving their behavior to analyze protein interactions in different systems and address specific research questions. We focus on the Superoxide Dismutase 1 (SOD1) protein, which can cause aggregation and Amyotrophic Lateral Sclerosis (ALS) when mutated. Despite numerous studies on SOD1 folding, understanding the interplay between crowding, folding and aggregation in vivo remains lacking. Using an atomic- level coarse-graining approach, approximating amino acid residues as beads-on-chain, we find that electrostatics play a crucial role in SOD1’s folding pathway, with mutations potentially impacting protein aggregation. Additionally, we model protein assemblies in crowded cellular environments using molecule-level coarse-graining, approximating protein subunits as Lennard Jones spheres. While some protein complexes form structures visible with imaging, many remain unsolved due to dynamic associations. We model clusters of protein assemblies from multiple subunits, capturing the distribution of high-order clusters in the protein complex Succinate Dehydrogenase (SDH). Our findings show crowding stabilizes clusters not present in dilute conditions and the spatial arrange- ments of the subunits vary with cell types. We also explore protein interactions in gene regulatory networks. Extensive studies on these networks often require expensive simulations. Using system- level coarse-graining, we represent proteins and genes as nodes and their interactions as edges. We develop centrality measures and metrics to rank node importance and predict network properties from topologies, negating the need for network dynamics simulations. We further group nodes according to cell phenotypes governed by gene regulatory networks. Different systems require dif- ferent coarse-graining techniques based on the scientific questions being probed. Emerging research involves simulations with multiple levels of coarse-graining within the same system, tailored to the complexity needed for specific properties. This thesis builds toward that approach, applying in- creasing levels of coarse-graining across diverse systems. Doing so enhances our understanding of the complex processes underlying life, showing how various levels of simplification can reveal intricate interactions governing cellular functions
Neotectonic Investigation of the Red Rock Fault: Sheep Creeks Segment
No full textThe Intermountain Seismic Belt (ISB) is an area of high seismic risk located in the Rocky Mountains. Its northern section extends through Yellowstone National Park (YNP) into southwestern Montana and southern Idaho where two notable large earthquakes struck: the 1983 magnitude 6.9 Borah Peak earthquake and 1959 magnitude 7.3 Hebgen Lake earthquake. In 2023, YNP was the 4th most visited national park in the United States, exposing a large population to earthquake-related hazards. Seismic risk maps show this entire region to be at high risk; however, the risk remains under-constrained along the earthquake producing Red Rock fault (RRF). To evaluate potential size of a future earthquake, geologic mapping and field surveys using a real-time kinematics (RTK) GPS system to obtain high resolution topographic profiles were conducted to estimate age of last rupture for different areas along the RRF. Fault scarp profiling results give rupture ages ranging from 58 to 2 kyr, suggesting there has been multiple slip events. Rupture scenario calculations indicate there is risk of a 6.5 magnitude earthquake, which would produce widespread ground shaking and soil liquefaction in areas with unconsolidated sediments. Moreover, a large earthquake event on the RRF could trigger another earthquake on an adjacent fault by transferring stress. Infrastructure like dams, hospitals, and highways such as I-15 (facilitates tourism and commerce) are vulnerable to intense shaking; damage could negatively impact local economies. This study concludes the RRF to be a young, active normal fault with high seismic risk, highlighting the need for geologically informed planning.Earth and Atmospheric Sciences, Department ofHonors Colleg
Visual Voices: Hispanic and African American Youth Perspectives on Neighborhood and School Health
No full text<b>Background/Objectives</b>: Youth perceptions of their environments provide critical insight into the social and physical determinants of health. This study investigated how Hispanic and African American children conceptualize health within their neighborhood and school settings. <b>Methods</b>: A total of 44 participants (29 Hispanic, 15 African American; <i>Mean age</i> = 9.27 years, <i>SD</i> = 1.28 years) participated in a photovoice project, capturing photographs and quotes in response to two guiding prompts: (1) &ldquo;<i>What does your dream of a healthy community look like?</i>&rdquo; and (2) &ldquo;<i>What should we do to make your community healthier?</i>&rdquo; <b>Results</b>: Thematic analysis of participants&rsquo; quotes and photographs yielded four overarching themes across both neighborhood and school environments: (1) access to nutritious food options, (2) opportunities for physical activity and recreation, (3) clean and safe spaces, and (4) access to extracurricular and community-based programs. A fifth theme, emergency preparedness and response, emerged uniquely within school context. Participants also proposed context-specific solutions to address identified health concerns. <b>Conclusions</b>: These findings emphasize the importance of environmental context in shaping child and preadolescent health perceptions and priorities. The results support the development of children and adolescent-informed, community-level interventions aimed at improving environmental health conditions, particularly in underserved communities disproportionately affected by poverty and structural inequities
DARTPHROG: A Superscalar Homomorphic Accelerator
No full textFully Homomorphic Encryption (FHE) allows a client to share their data with an external server without ever exposing their data. FHE serves as a potential solution for data breaches and the marketing of users&rsquo; private data. Unfortunately, FHE is much slower than conventional asymmetric cryptography, where data are encrypted only between endpoints. Within this work, we propose the Dynamic AcceleRaTor for Parallel Homomorphic pROGrams, DARTPHROG, as a potential tool for accelerating FHE. DARTPHROG is a superscalar architecture, allowing multiple homomorphic operations to be executed in parallel. Furthermore, DARTPHROG is the first to utilize the new Hardware Optimized Modular-Reduction (HOM-R) system, showcasing the uniquely efficient method compared to Barrett and Montgomery reduction. Coming in at 40.5 W, DARTPHROG is one of the smaller architectures for FHE acceleration. Our architecture offers speedups of up to 1860 times for primitive FHE operations such as ciphertext/plaintext and ciphertext/ciphertext addition, subtraction, and multiplication when operations are performed in parallel using the superscalar feature in DARTPHROG. The DARTPHROG system implements an assembler, a unique instruction set based on THUMB, and a homomorphic processor implemented on a Field Programmable Gate Array (FPGA). DARTPHROG is also the first superscalar evaluation of homomorphic operations when the Number Theoretic Transform (NTT) is excluded from the design. Our processor can therefore be used as a base case for evaluation when weighing the resource and execution impact of NTT implementations
Optimizing Tobacco-Free Workplace Programs: Applying Rapid Qualitative Analysis to Adapt Interventions for Texas Healthcare Centers Serving Rural and Medically Underserved Patients
No full textBackground: Tobacco use is disproportionately high in rural areas, contributing to elevated cancer mortality, yet it often goes untreated due to limited access to care, high poverty and uninsured rates, and co-occurring substance use disorders (SUDs). This study explored the utility of using rapid qualitative analysis (RQA) to guide the adaptation of a tobacco-free workplace program (TFWP) in Texas healthcare centers serving adults with SUDs in medically underserved areas. Methods: From September&ndash;December 2023 and May&ndash;July 2024, we conducted 11 pre-implementation, virtual semi-structured group interviews focused on adapting the TFWP to local contexts (N = 69); 7 with providers (<i>n</i> = 34) and managers (<i>n</i> = 12) and 4 with patients (<i>n</i> = 23) in 6 healthcare centers. Two qualified analysts independently summarized transcripts, using RQA templates of key domains drawn from interview guides to summarize and organize data in matrices, enabling systematic comparison. Results: The main themes identified were minimal organizational tobacco cessation support and practices, and attitudinal barriers, as follows: (1) the need for program materials tailored to local populations; (2) limited tobacco cessation practices and partial policies&mdash;staff requested guidance on enhancing tobacco screenings and cessation delivery, and integrating new interventions; (3) contradictory views on treating tobacco use that can inhibit implementation (e.g., wanting to quit yet anxious that quitting would cause SUD relapse); and (4) inadequate environmental supports&mdash;staff requested treating tobacco-use training, patients group cessation counseling; both requested nicotine replacement therapy. Conclusions: RQA identified key areas requiring capacity development through participants&rsquo; willingness to adopt the following adaptations: program content (e.g., trainings and tailored educational materials), delivery methods/systems (e.g., adopting additional tobacco care interventions) and implementation strategies (e.g., integrating tobacco cessation practices into routine care) critical to optimizing TFWP fit and implementation. The study findings can inform timely formative evaluation processes to design and tailor similar intervention efforts by addressing site-specific needs and implementation barriers to enhance program uptake
Secondary Literacy Educators’ Perceptions and Use of ChatGPT
No full textBackground: In November 2022, OpenAI, a U.S. artificial intelligence company, launched ChatGPT, a generative pre-trained transformer chatbot, for public, voluntary research beta testing. This announcement immediately became a hot topic in the news and educational technology. Being among the first publicly available AI-based tools used to transform education in, ways of working, and policy in education, ChatGPT emerged on the heels of the COVID-19 pandemic and during a time of widespread teacher shortages and technology fatigue among educators. The introduction of ChatGPT and generative AI triggers another significant shift in education technology, prompting a dynamic continuum of responses to the opportunities and risks of generative AI tools in literacy classrooms. Purpose: This dissertation research elevated six veteran secondary literacy educators’ voices on the perceived value of generative AI as a tool for educators. It explores the following research questions. Research Questions: What are secondary literacy educators’ perceptions and use of ChatGPT? Do these perceptions and use of the application change after participating in an asynchronous, online professional learning cohort? This action research study's theoretical foundation incorporates the Technology Acceptance Model (TAM) framework and adult learning theory. Data Analysis: The quantitative survey questions are represented in averages, percentages, and narrative statements. Qualitative data analysis of the narrative dialog from the discussion board was coded as themes. These codes were grouped in weekly learnings to convey findings. Method: Data collection included a baseline survey, a four-week online asynchronous book study in Facebook groups, and an end-of-study survey. The two surveys consisted of open- and closed-survey questions, and the discussion board followed a semi-structured questioning model with follow-up prompts from both the researcher and participants. After the preliminary data analysis, participants completed a member check to review the findings and verify the accuracy of participant representation. Results: The pre- and post-survey data conveyed educator perception shifts in value, ease of learning, effort of learning, and perceived value of ChatGPT to save educators time to prepare lessons and perform daily tasks. While the weekly narratives conveyed some effort was needed to learn prompt engineering, the result of saving time on tasks opened up opportunities for educators to be more creative and strengthened their pedagogy. The study’s findings indicated that secondary literacy educators’ perceptions shifted after participating in a four-week ChatGPT-focused professional learning cohort. Conclusion: As AI is everywhere, further educational research, policy, and technology-focused professional learning opportunities are needed across our education system to ensure the safe and ethical use of ChatGPT by educators. Secondary literacy educators who participated in this study expressed excitement and hope about using AI tools to support their effectiveness as educators
Examining the Effects of Biological Sex and Pain Interference on PTSD Symptom Severity
No full textBackground: Approximately 70% of U.S. adults have experienced at least one traumatic event, making trauma exposure a significant public health concern. Trauma is linked to mental health issues, including emotional dysregulation, substance abuse, and PTSD, which can severely disrupt daily functioning. Pain interference is common among individuals with PTSD and can worsen symptoms and recovery. Given known sex differences in pain perception and response, further research is needed to examine how pain interference and biological sex influence PTSD symptom severity. Methods: The current study sought to examine the effects of biological sex and pain interference on PTSD symptom severity through a hierarchical regression analysis approach. Participants included 370 adults (Mage = 39.7, SD = 10.9, 53.5% female) who have been previously exposed to a traumatic event. Participants were recruited via Qualtrics Panels to complete a short survey online. Results: Our findings suggest that pain interference is a powerful predictor of PTSD symptom severity, stressing the need of pain management measures in PTSD treatment. Furthermore, sensitivity to traumatic stress was the strongest predictor overall, emphasizing the need for trauma-focused therapies. Interestingly, our findings also indicated that pain interference impacts PTSD symptoms similarly across sexes, implying that additional factors may be at work in shaping individual experiences of PTSD and pain. Conclusion: The current study contributes to our overall understanding of PTSD and pain comorbidity by providing light on its potential predictors. Our findings emphasize the necessity of integrated therapy approaches that target both chronic pain and PTSD symptoms, ultimately contributing to better care for trauma-exposed patients.Psychology, Department ofHonors Colleg
Monitoring RNA AGG-Quadruplexes in BMI-1 mRNA
No full textG-quadruplexes are secondary structures formed by Hoogsteen hydrogen bonding prevalent in regions of mRNA rich in guanine bases serving as a binding site for molecules which effects the rates of translation. Based on the primary mRNA sequence, it is theorized that the oncogene BMI-1 contains one of these G-quadruplex structures. This complex could serve as a target for novel cancer treatment in certain cancers not responding to current treatments, or in relapsing cancers. The BMI-1 protein is a key regulator of the Polycomb Regulatory Complex-1 (PRC1), which in turn regulates the transcription of the tumor suppressor genes p16Ink4a and p14Arf. Overexpression of BMI-1 has been thought to an increase in the stem state of tumors and increase tumors resistance to treatments, while a decrease to protein levels can cause apoptosis and increased responses to treatments. G-quadruplex domains can prevent translation from initiating by blocking ribosomes from scanning the mRNA for a binding site. Proteins and monovalent cations can bind to a quadruplex to increase its stability as a 3-dimensional structure. By inducing mutations in the region of the mRNA encoding for the G-quadruplex of BMI-1, we can observe the level of control the domain has on translation. We can also introduce substances that increase the stability of G-quadruplexes and observe the effects this has on translation. With these two methods, we can compare each method to see which would be the most ideal mode to inhibit the translation of BMI-1 in cancer cells.Biology and Biochemistry, Department ofHonors Colleg
An 81-Year-Old Geriatric Patient with Metastatic Pancreatic Cancer Demonstrating Excellent Response and Well Tolerance to NALIRIFOX: A Case Report and Literature Review
No full text<b>Background and Clinical Significance:</b> Pancreatic cancer was the third leading cause of cancer-related mortality in the United States in 2020 after lung and colorectal cancers. The prevalence of pancreatic cancer has been increasing and is projected to continue rising through 2040, with an estimated 355,317 additional cases expected. We present the case of an 81-year-old patient with metastatic pancreatic ductal adenocarcinoma (PDAC) who tolerated NALIRIFOX for a year with grade 1 adverse events. <b>Case presentation:</b> An 81-year-old Asian male presented with abdominal pain associated with weight loss and fatigue. An abdominal computed tomography (CT) scan showed a mass in the body of the pancreas measuring 3.5 cm with an infiltrative appearance invading the retroperitoneum and encasing the splenic artery. A biopsy confirmed poorly differentiated PDAC. The patient received 13 cycles of NALIRIFOX in a palliative setting over the course of one year, demonstrating excellent tolerance aside from minor toxicities, including worsening of pre-existing macrocytic anemia, treatment-related grade 1 neuropathy, diarrhea, and thrombocytopenia. A subsequent CT scan revealed disease progression, and the patient was switched to second-line therapy. However, per his preference, the patient was referred to hospice care and passed away a few days later. <b>Conclusions:</b> This case highlights the excellent tolerability of NALIRIFOX in an elderly patient, with minimal adverse events observed, which is uncommon among similar patient populations
"Co-creating" Operation Fusion: A Collaborative Approach to Bridging Health and Culture for Immigrant & Refugee Youth
No full textA sense of belonging and self-agency helps immigrant and refugee youth navigate migration-related challenges like forming social bonds and maintaining cultural identity. Culturally diverse classrooms that embrace intercultural and heritage learning empower these students to overcome such obstacles. Through Operation Fusion, undergraduate volunteers and Project Heads from the University of Houston lead activity-based lessons blending culture and personal health with immigrant and refugee elementary students at Las Americas Newcomer School. To improve engagement, we adopted a "co-creation" model, where UH volunteers, Project Heads, and students collaboratively shape the program. Rather than traditional pre- and post-surveys, we shifted to conversational strategies like post-session debriefs, focus groups, and activity-planning workshops to foster inclusivity and shared ownership of learning. This approach has bolstered student engagement, with students reporting greater interest and a stronger sense of agency over their learning experience. Volunteers also showed deeper cultural awareness, stronger leadership development, and increased motivation to participate. The collaborative model fostered stronger community partnerships, further reinforcing program sustainability and growth. "Co-creation" shifts Operation Fusion from a top-down approach to a collaborative framework where students and volunteers become active contributors, not passive participants. This model empowers students to take ownership of their learning while enhancing volunteers' roles and experiences. Ultimately, co-creation offers a sustainable and adaptable framework for public health programs aiming to foster self-advocacy and personal health across culturally diverse populations, ensuring both engagement and impact in immigrant and refugee communities.Honors Colleg