• Characterizing Ore Particle Size for Sag Mill Feed Control

  Risso, Nathalie; Saavedra, Matias; Momayez, Moe; Tenorio, Victor (The University of Arizona., 2025)

  This thesis presents a comprehensive, data-driven study for predicting the particle size distribution (PSD) at the feed of a semi-autogenous grinding (SAG) mill. A consistent PSD is essential for efficient energy use, stable throughput, and effective downstream processing. However, feed variability, caused by ore heterogeneity, stockpile segregation, and reactive blending, makes prediction challenging. The first part of this work reviews the current state of research and industrial practice, synthesizing insights from over 45 peer-reviewed studies on ore blending, stockpile management, and the application of machine learning in mineral processing. The review identifies a gap between the growing availability of high-frequency sensor data and its limited use in real-time predictive tools, highlighting the need for systems that forecast PSD and support data-informed operational understanding. Building on these insights, the second part develops and validates a machine learning framework using two years of high-resolution operational data from a copper mining operation. The methodology integrates unsupervised clustering with Random Forest regression to forecast key PSD metrics (F10–F90 and TOPSIZE) based on variables such as feeder speeds, stockpile levels, and ore throughput. Cluster-specific models capture nonlinear, regime-dependent behaviors with high accuracy ($R^2 > 0.90$). In addition to prediction, the thesis presents a data-driven sensitivity analysis to evaluate how changes in input variables, such as individual feeder rates, influence PSD outcomes. This analysis shows that coarser PSD metrics, such as F70 and TOPSIZE, are more responsive to input changes than finer ones. A variability analysis further demonstrates the model’s ability to quantify and explain fluctuations in PSD, with predicted distributions exhibiting up to a 15% reduction in standard deviation compared to historical data. All components are integrated into a web-based application that allows users to explore model behavior, visualize PSD forecasts, and assess the impact of operating scenarios in real time. This work advances the field by demonstrating how machine learning and clustering can be effectively applied to model and interpret SAG mill feed variability. The resulting framework offers a practical approach for enhancing predictive insight in mineral processing operations.
• Validation of Cardiomems Pulmonary Artery Pressure Monitor Using the Donovan Mock Tank

  Largent-Milnes, Tally M.; DeLucia, Claire; Tran, Phat L.; Wong, Raymond K. (The University of Arizona., 2025)

  Maintenance of HF symptoms requires patients to monitor changes in limb edema, sudden weight gain and edema as markers for progressing or worsening HF. However, these symptoms can occur suddenly and can lead to decompensation and hospitalization if not addressed in a timely manner. The CardioMEMS HF System was developed to monitor patient pulmonary artery pressures and catch worsening heart failure before symptoms of fluid overload manifest. Indeed, the CardioMEMS has been shown to reduce HF hospitalizations by up to 30% with great reliability and reproducibility. Recently, a case report at Banner University Medical Center Tucson highlighted potential pitfalls in treating patients with CardioMEMS based on faulty readings from the Smart Pillow home system, highlighting a need for further understanding of potential biases in CardioMEMS readings against a known pressure. This study aimed to characterize CardioMEMS Hospital System and Smart Pillow (home system) readings against the Donovan Mock Circulation Tank (Mock Tank) – a chamber used to test and validate mechanical circulatory support devices. A series of groups was devised to represent a spectrum of pulmonary artery pressures and readings were taken from the PAP chamber of the Mock tank and compared to readings from the CardioMEMS device using the Hospital System. Linear regressions confirmed great agreement between the two measurement methods (R squared >0.95, p<0.0001) and Bland-Altman plots revealed a negative proportional bias (-1.272mmHg, p<0.0001) that suggested the CardioMEMS underestimation was greater at higher PAP chamber pressures. Biases in CardioMEMS measurements should be considered and additional confirmations of fluid overload should be considered when changing the treatment plan of patients with HF.
• Quantification of Antithrombin III via Flow Velocity Profiling in Microfluidic Paper-Based Devices

  Yoon, Jeong-Yeol; Mathews, Ashley Karimalathu; Wong, Raymond K.; Tran, Phat (The University of Arizona., 2025)

  Antithrombin III (ATIII) is a protein which plays a critical role within the regulation of the coagulation cascade. When the concentration of ATIII is found to be insufficient, thrombotic conditions that are caused by hypercoagulability increase in its likelihood to occur. This can result in life-threatening events, such as myocardial infarction or stroke. Methods that are currently available in order to detect ATIII levels lack the ability to be portable and prompt. These inefficiencies result in the inability to effectively serve as a point-of-care (POC) test in urgent and critical settings. This thesis presents a novel method for detecting levels of ATIII through the use of a particle-based assay which is driven through a model involving capillary flow. The platform uses a microfluidic paper-based device (µPAD) in order to measure flow velocity profiling through the quantification of capillary flow alterations which are caused by the immunoagglutination of the antigen, ATIII and anti-ATIII antibody conjugated microparticles. A smartphone was used to take video recordings of the tested samples which traveled through the channels of the µPAD and in addition, cloud-based Google Colab was used to analyze the videos in order to automatically provide raw data tracking the fluid front of the sample as it moves down the channel. ATIII spiked concentrations of 0 ng/mL, 0.5 ng/mL, 1 ng/mL, 3 ng/mL, 6 ng/mL and 12 ng/mL were tested in PBS, 0.5% plasma and 0.1% plasma. In addition, 0 ng/mL, 0.5ng/mL and 1 ng/mL spiked concentrations were tested in 0.001% plasma. All the samples and their flow profiles were determined. Our definition of flow profile represented the flow velocity slope. The average flow velocity slope was found which allowed for a correlation to be seen between the degree of immunoagglutination of ATIII and anti-ATIII antibody conjugated microparticle as it caused alterations in interfacial tension and viscosity for each of the concentration tested. Samples that had a higher concentration of ATIII led to a higher profile of flow velocity slope. The gold standard immunoassay for ATIII quantification is the enzyme linked immunosorbent assay (ELISA) which provided us with proper quantification of endogenous levels of ATIII in 0.001% plasma and this allowed for steps in the optimization of the assay. This assay does not require intensive training but rather, is affordable, portable, and also capable of rapidly detecting ATIII levels which make it appealing to use within the clinical setting. The work done in this thesis has proven logarithmic linear trends of increasing flow velocity in relation to increasing concentrations of ATIII, providing insight towards developing a foundation in future POC tests targeting ATIII and potentially other biomarkers.
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  Eutectic and Peritectic Equilibria in Coherent Binary Alloys

  Latypov, Marat I.; Hassan, Samiah; Deymier, Pierre; Muralidharan, Krishna (The University of Arizona., 2025)

  Phase equilibria in a coherent binary alloy for the eutectic and peritectic systems are ana lyzed in this study to construct a theoretical model that will provide conditions for three-phase equilibrium in the presence of coherency stress between the solid phases. Our analysis employs simple quadratic functions for the Gibbs energy for individual phases, considering the solid phases to be temperature-independent. To facilitate an analytical solution, we used simplified assumptions about the system, explicitly considering an infinite volume occupied by three phases and the solid phases being isotropic and linearly elastic. We use a mathematical optimization method, Lagrange multiplier, to minimize the functions of Gibbs free energy subject to the constraints of volume fractions and phase compositions that satisfy the equilibrium conditions. This theoretical study demonstrates the effect of coherency stress on invariant points of phase diagrams, including a liquid leveraging the original Larche-Cahn formulation to evaluate the impact of coherency stress on eutectic and peritectic points in binary alloys. The common tangent construction is not applicable in the presence of strain energy between the solids, and the Gibbs phase rule no longer holds. Our findings demonstrated that coherency stress has distinct consequences on the eutectic and peritectic equilibria due to the difference in compositions between one solid and liquid phase and the difference in the melting points of the solid phases; therefore, instead of forming the three-phase region, usual to eutectic equilibria, a two-phase region with one solid and liquid becomes more dominant in the peritectic equilibria.
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  Dealing with Insults, Sex, and Cleanliness: Telemachus's Speech to the Enslaved Women in Odyssey 22

  Park, Arum; Stokes, Ethan; Groves, Robert; McCallum, Sarah (The University of Arizona., 2025)

  This thesis explores the terms καθαρός (“clean”), ὄνειδος (“abuse”), and καταχέω (“pour down”) in Homer’s Iliad and Odyssey as a way to analyze and understand the nature of Telemachus’s accusations towards the disloyal slave women in his speech to them immediately before killing them. With a clearer understanding of each of the words, some ambiguities surrounding Telemachus’s claims become clearer and allow insight into both his own worldview and broader Homeric concepts of cleanliness, insults, and pouring.In Chapter 1, the somewhat generic verb καταχέω (“pour down”) is analyzed with respect to its various types of direct objects, making the meaning of the unique instance of ὄνειδος as the direct object in Telemachus’s speech clearer. Chapter 2, examining the term ὄνειδος (“abuse”), looks at some of the ways that the term can be used to threaten the status of important men—a concern for maturing Telemachus—and the potential for nuances in gendered opposition with the word. Chapter 3 examines the relatively few occurrences of καθαρός (“clean”) in Homer and the reasons why Telemachus’s use of the word stands out particularly oddly in comparison to the rest. The word is not linked to death in any other use, so there seems to be some kind of shift in meaning, but there are important gendered connotations behind the word that are brought out from the other examples.
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  Impact of Teaching in Conflict Zones on Educators’ Well-Being and Pedagogical Strategies in Rio de Janeiro

  Bacelar da Silva, Antonio José; Witko, Kristine; Graeter, Stefanie; Brewer-Osorio, Susan (The University of Arizona., 2025)

  In Rio de Janeiro, Brazil, violence between criminal groups and state actors often erupts without warning, leaving teachers and students caught in the crossfire. In this qualitative study, I sought to understand the experiences of educators working in conflict zones located in North and South Zone favelas. This research analyzes the experiences of educators, the impact of armed conflict on their well-being and that of their students, and their pedagogical strategies in response to violence. Semi-structured interviews and participant observation at educational nonprofits in Rio de Janeiro highlighted several themes, including the unpredictability of violence, the favela as a war zone, self-sacrifice, trauma, the normalization of violence, and resilience. The educators described several coping strategies to manage the psychological toll of armed conflict and employed a range of strategies in their attempt to help students navigate their traumas. While Rio de Janeiro’s perpetual state of exception forces some educators to teach in unbearable conditions where violence is an ever-present threat, they still use the potentiality of the classroom as a way to navigate and reconstitute the possibility of hope for their students. In this sense, the classroom becomes a site of resistance. This thesis addresses a gap in the literature regarding the perspectives of educators in conflict zones and contributes to a broader understanding of how they exercise their agency in the classroom despite structural barriers and urban violence in Latin America.
• Cardiologists’ Perspectives on Pharmacogenomics: Utilization, Barriers, And the Role of Genetic Counselors

  Schaibley, Valerie; Alexander, Erin Rebecca; Heise, Will; Sabrowsky, Sonia; Stallman, Chris (The University of Arizona., 2025)

  Pharmacogenomics (PGx) has the potential to personalize cardiovascular treatment byoptimizing drug efficacy and minimizing adverse drug reactions. Despite well-established guidelines for PGx-informed prescribing, its integration into cardiology remains limited. In this study, we conducted a nationwide survey to assess cardiologists’ knowledge, utilization, and perceptions of PGx testing, as well as their views on the role of genetic counselors in this space. The survey was distributed via email, flyers, and social media, utilizing a snowball sampling method. A total of 63 responses were included in the analysis. The majority of respondents were white, male, and practicing adult general cardiology. Most (58%) reported having no or only limited knowledge of PGx, and 55% had never ordered PGx testing in their practice. We found statistically significant positive correlations between provider degree of PGx knowledge and the frequency of test ordering (p = 1.226e-09), provider confidence in result interpretation, (p < 2.349e-16) and confidence with communicating test results (p = 6.968e-13). Additionally, many cardiologists expressed some interest in the integration of genetic counselors into PGx workflows, highlighting an opportunity for increased interdisciplinary collaboration. Notably, there was a statistically significant positive correlation between cardiologists’ perceived impact of genetic counselors involved in PGx and their likelihood to refer patients to them for PGx testing (p = 3.004x10⁻⁶). PGx is an emerging field with the potential to improve patient outcomes and reduce healthcare costs, yet gaps in provider knowledge and confidence hinder its clinical use. Expanding provider education and incorporating genetic counselors into cardiology and PGx workflows may facilitate broader adoption of PGx testing and enhance personalized treatment strategies in cardiovascular care.
• Risk and Rainfall: Specification Sensitivity in Estimating Smallholder Risk Preferences

  Josephson, Anna; Michler, Jeffrey D.; Branham, Reece Erika; Aglasan, Serkan (The University of Arizona., 2025)

  Rainfall variability in Sub-Saharan Africa creates significant production risks for subsistencefarmers who rely on rainfed agriculture. Weather shocks can alter farmers’ risk preferences, potentially influencing their decision to adopt adaptation strategies. We employ a moments- based approach (Antle, 1983, 1987) to estimate risk aversion among smallholder farmers in Ethiopia, Malawi, and Nigeria in response to weather shocks. Using this framework, we esti- mate Arrow-Pratt and downside risk coefficients across more than 200 model specifications, incorporating various rainfall and rainfall shock metrics derived from six remote sensing weather products. Our findings reveal that estimates of farmers’ risk preferences are highly sensitive to the choice of weather product, while risk preferences are relatively insensitive to different weather shocks. This underscores how data source and model specification choices critically shape risk preference estimates, highlighting key limitations in current empirical methods.
• Accelerating the Design of Sustainable Concrete with CDW Through Adaptive Experiments and Machine Learning for Conventional and Additive Manufacturing Applications

  Kim, Hee-Jeong; Latypov, Marat; Tawiah Baah, Thomas; Muralidharan, Krishna (The University of Arizona., 2025)

  This study presents an integrated computational framework combining machine learning (ML), Bayesian optimization (BO), and experimental validation to design sustainable concrete incorporating construction and demolition waste (CDW) for both conventional and 3D concrete printing (3DCP) applications. In traditional mortar, ML models accurately predict 28-day compressive strength using early-age results, enabling nearly 10× acceleration of mixture design cycles. Optimized mixtures achieved up to 50 % reduction in ordinary Portland cement (OPC) while maintaining strengths above 40 MPa. For 3DCP, a multi-objective BO framework simultaneously maximized buildability and CDW content. Experimental results validated enhanced buildability (up to 10 printed layers) and compressive strengths up to 60 MPa in cast samples and 52 MPa in 3D printed samples, even with up to 97 % CDW. The study highlights the potential of data-driven methods to transform sustainable material design in the construction industry.
• Mitigating Device-Level Vulnerabilities in Post-CMOS Machine Learning Accelerators

  Salehi, Soheil; Chowdhury, Md Muhtasim Alam; Satam, Pratik; Roveda, Janet Meiling (The University of Arizona., 2025)

  Hardware-based acceleration approaches for Machine Learning (ML) workloads have been embracing the significant potential of post-CMOS switching devices to attain reduced footprint and/or energy-efficient execution relative to transistor-based GPU and/or TPU-based accelerator architectures. Meanwhile, the promulgation of fabless IC chip manufacturing paradigms has heightened the hardware security concerns inherent in such approaches. Namely, unauthorized access to various stages of the supply chain may expose significant vulnerabilities that cause malfunctions, including subtle adversarial outcomes via the malicious generation of differentially corrupted output. Whereas the Spin-Orbit Torque Magnetic Tunnel Junction (SOT-MTJ) is a leading spintronic device for use in ML accelerators, as well as holding security tokens, their manufacturing-only security exposures are identified and evaluated herein. The experimental results indicate a novel vulnerability profile whereby an adversary without access to the circuit netlist could differentially influence the behavior of the machine learning application. Specifically, ML recognition outputs can be significantly swayed via a global modification of oxide thickness (Tox) resulting in bit-flips of the weights in the crossbar array, thus corrupting the recognition of selected digits in MNIST dataset differentially creating an opportunity for an adversary. With just 0.05% of bits in crossbar having a flipped resistance state, digits ‘4’ and ‘5’ show highest overall error rates and digit ‘9’ exhibit the lowest impact, with recognition accuracy of digits ‘2’, ‘3’, and ‘8’ unaffected by changing the oxide thickness of SOT-MTJs uniformly from 0.75 nm to 1.2 nm without modifying the netlist nor even having access to the circuit design itself. Exposures and mitigation approaches to such novel and potentially damaging manufacturing-side intrusions are identified, postulated and quantitatively assessed. In conclusion, this thesis showcases the potential of SOT-MRAM process variation to trigger stealthy, application-impacting bitflips in ML accelerators. Early-stage protection against physical-level threats ensures post-silicon ML accelerators remain robust and trustworthy in future AI-enabled systems.
• Exploring Metabolic Memory Following Glucose Changes During Media Replacement in HEK293T Cells

  Cusanovich, Darren; Johnson, Lydia Anne; Ledford, Julie; Romanoski, Casey (The University of Arizona., 2025)

  Metabolic memory refers to the persistence of cellular changes resulting from previous metabolic states, which may contribute to prolonged adverse effects in conditions like diabetes even after glucose normalisation. This study explores the potential mechanisms underlying metabolic memory, focusing on how changes in glucose concentration affect chromatin accessibility in HEK293T cells. Using ATAC-sequencing, we investigated whether chromatin accessibility changes previously observed in macrophages are conserved in other cell types. Cells initially cultured in high glucose (HG, 22.5mM) that were switched to low glucose (LG, 5mM) showed approximately 3000 genomic regions with increased accessibility compared to controls, while cells maintained in high glucose exhibited fewer changes. Transcription factor motif analysis identified several transcription factors potentially regulating these responses, including CTCF, AP-1, P53, and NRF2. Notably, CTCF transcription factor motifs showed increased accessibility in stable high-glucose conditions but decreased accessibility following glucose reduction, suggesting its potential role as a master regulator of metabolic memory. Pathway analysis revealed enrichment of apoptotic signalling in the HGLG condition, while sustained high glucose was associated with decreased accessibility in developmental and patterning pathways. The experiment conducted in the reverse direction (LGHG) yielded insufficient data quality for conclusive analysis. These findings expand our understanding of how previous metabolic environments shape the epigenome, providing insights into the molecular underpinnings of metabolic memory that could inform therapeutic approaches for metabolic diseases such as diabetes.
• Development of txci-CAB as a New Single-cell Approach to Study Chromatin Modifications and Accessibility Across the Genome

  Cusanovich, Darren; Rathi, Radhika; Romanoski, Casey; Ledford, Julie (The University of Arizona., 2025)

  Understanding the epigenomic landscape of single cells is critical for uncovering the regulatorymechanisms that govern cell identity, differentiation, and function. Traditional chromatin profiling methods often measure a single modality per assay, limiting the ability to directly capture the interplay between chromatin accessibility and histone modifications. To overcome this limitation, we developed txci-CAB (10x-compatible combinatorial indexing of CUT&Tag and ATAC both) by combining combinatorial indexing with a droplet-based microfluidic system. In this thesis, we work on systematic optimization of ATAC-seq and CUT&Tag protocols in order to integrate them within the same workflow to simultaneously profile accessible chromatin states as well as specific modifications in individual cells. The txci-CAB protocol incorporates Tn5-based combinatorial barcoding for chromatin accessibility followed by pA-Tn5-guided CUT&Tag for histone modifications. Although several multimodal single-cell sequencing techniques exist, txci-CAB is designed to enhance scalability, sensitivity and overall convenience of use, both in terms of input reagents and protocol workflow. Our approach also emphasizes increased library complexity while maintaining robustness and reproducibility. Notably, we observed higher estimated complexity in our bulk datasets, demonstrating the method's effectiveness in simultaneously capturing two chromatin modalities at single-cell resolution.
• WNT Pathway Transcriptional Responses in Colorectal Cancer Organoids and Cell Lines

  Ellis, Nathan; Zeitman, Andrea; Thorne, Curtis; Pond, Kelvin (The University of Arizona., 2025)

  Colorectal cancer (CRC) affects approximately 10% of people worldwide. Cases in older persons are decreasing due to the impact of increased CRC screenings. However, early-onset CRC cases have been increasing since 1995; the factors driving this trend are unknown. Mutation in the adenomatous polyposis coli (APC) gene, which regulates WNT/β-catenin signaling, is the most common somatic mutational mechanism driving initiation of CRC development, yet in early-onset CRC cases, APC mutations are not as frequent. WNT/β-catenin signaling is nearly always upregulated in CRC, consequently identification of other mechanisms of WNT/β-catenin dysregulation is necessary to understand tumorigenesis in APC mutation-negative CRCs. To investigate this question, we studied 13 patient-derived CRC organoids, 6 APC mutation-negative and 7 APC mutation-positive organoids, and 1 normal colon organoid. Of the CRC organoids two, one APC mutation positive and one mutation-negative, were selected that exhibited microsatellite instability. Two mechanisms of CRC development, independent from APC, may be found in LGR5 and MYC. LGR5 and MYC are WNT/β-catenin target genes that have been known to play a role in CRC development. LGR5 is a stem cell marker found in cells at the base of colonic crypts. LGR5-negative stem cells in mice have shown decreased self-renewal and WNT-responsive gene expression, but the actual mechanism behind LGR5-driven carcinogenesis is not well understood. Previous organoid studies investigated LGR5 mRNA in response to L-WRN conditioned media and WNT alone, showing an up-regulation LGR5 with L-WRN conditioned media, but notably did not show the same result with WNT alone. These results led us to question which component of L-WRN was causing LGR5 up-regulation. We tested the individual components of L-WRN, the results of which showed LGR5 mRNA is overexpressed in 11 out of 13 patient-derived organoids when exposed to Noggin, a bone-morphogenetic protein (BMP) antagonist. MYC is a proto-oncogene whose over-expression is implicated in a multitude of cancers. Compound 895 was developed as a novel WNT-inhibitor, and is hypothesized to simultaneously inhibit cyclin-dependent kinases and CDC2-like kinases that regulate WNT signaling. Multiple WNT/β-catenin target genes were analyzed for the purpose of viewing post-transcriptional effects of 895. These results demonstrated an up-regulation of MYC mRNA, specifically, in all 13 organoids as well as 3 human cell lines. These results indicate a potential compensatory mechanism allowing for MYC up-regulation that needs to be further investigated.
• ERG Interactome as a Regulator for Endothelial Dysfunction in Human Aortic Endothelial Cells

  Romanoski, Casey; Careaga, Cecilia Madelina; Langlais, Paul R.; McGhee, Alexander J. (The University of Arizona., 2025)

  Atherosclerotic cardiovascular disease is one of the leading causes of death worldwide, forpeople of all demographics. The development of atherosclerosis is primarily dependent on certain risk factors such as levels of low density lipoproteins (LDLs), sedentary lifestyle, and genetic predispositions. Risk factors such as diet, and activity levels can be controlled by each individual in order to avoid developing the pathology, however, genetic predisposition explains about half of the risk. Some factors involved in genetic predispositions to the development of atherosclerosis are, however, currently poorly understood. Endothelial injury is thought to be the initiating event that leads to atherosclerosis. An important place to start in understanding the events that lead to endothelial dysfunction is understanding the regulation of endothelial specific genes. The regulation of these genes is controlled by proteins that act as transcription factors, chromatin remodeling machinery, epigenetic modifiers, splicing factors, etc. Gene regulation typically occurs as a result of a well coordinated activity between transcription factors, chromatin remodeling machinery, and post-transcriptional modifiers. Since we know that one important player in the regulation of endothelial specific genes is the transcription factor ERG, it is important to characterize the other proteins that interact with ERG during, before, and after transcription. In this project, we characterize a list of potential interactors of ERG and further validate some that have known roles in regulation of transcription.
• Social Connectedness for International Student-Athletes in Collegiate Athletics

  Bacelar da Silva, Antonio J.; Ramos Sacaria, Diana Carolina; Rabie, Deina; Stipek, Jesse M. (The University of Arizona., 2025)

  This study explores the experiences of international student-athletes (ISAs) of Latin American origin at a National Collegiate Athletic Association (NCAA) Division I (D1) 4-year public institution in the Western part of the United States. ISAs of Latin American origin comprise less than 1% of the entire NCAA D1 student-athlete population (NCAA 2023). ISAs of Latin American origin navigate their new day-to-day lives without a trusted support system. Social connectedness means feeling supported, valued, and cared for by others with a sense of belonging (CDC 2024). Drawing on discourse analysis, which is informed by the linguistic anthropology field, this research study employs interviews to examine the impact of social connectedness in the college-athletic experience of ISAs of Latin American origin. The findings reveal the challenges ISAs face and how social connectedness helps them overcome them. I conclude by reiterating the sociopolitical climate in the U.S., including Trump’s executive orders (2025) and how it can impact the college experience of ISAs of Latin American origin.
• Examining Relationships Between Food Security, Nutrition Security, and Diet Quality Among Low-Resource Patients with Type 2 Diabetes: Baseline Findings from a Community-Based Intervention

  Hingle, Melanie; Pena, Nicole A.; Roe, Denise; Taren, Douglas (The University of Arizona., 2025)

  Background: The co-existence of food insecurity and poor diet quality is associated with poorer outcomes for low-resource persons with type 2 diabetes (T2D). Diet quantity and quality are critical to diabetes management, yet few studies have simultaneously assessed food security, nutrition security and diet quality among low-resource populations with T2D. This baseline analysis aimed to explore relationships among these factors to inform a community-based, medically tailored grocery intervention – Food and Resource Expanded to Support Health and type 2 diabetes FRESH-T2D. Methods: Participants were adults with diagnosed T2D and screened positive for being at risk for food insecurity, recruited from a Federally Qualified Health Center to participate in a 12-month, randomized controlled trial. Food security was assessed using the U.S. Household Food Security Survey 6-item Short Form and nutrition security was assessed using the Center for Nutrition and Health Impact 4-item Household Nutrition Security tool. Diet quality was assessed using the HEI-2020, based on two non-consecutive, interviewer-administered 24-hour dietary recalls. Fisher’s exact test and a two-sample t-test examined associations between food, nutrition security, and diet quality. Multivariable linear regression was used to evaluate the independent effects of food security and nutrition security (independent variables) on diet quality (dependent variable), while adjusting for sociodemographic factors. Results: Of 71 enrolled participants, 53 completed baseline assessments. Most (87%) were classified as low/very low food secure and 66% were nutrition insecure (mean nutrition security score: 2 out of 4). Eighteen (34%) were both food and nutrition insecure. Food security and nutrition security were significantly associated (p = 0.004). The mean HEI score was 59.9 (out of 100 possible). No significant differences in diet quality were found between food secure and insecure groups (mean HEI = 58.7 ± 7.8 vs. 60.2 ± 2.2; p = 0.85), or between nutrition secure and insecure groups (mean HEI = 60.6 ± 2.6 vs. 58.9 ± 3.9; p = 0.72). The reference group –females with less than a high school education, income of <$25,000, household size of 1-2, and English as preferred language – was not significantly associated with diet quality. (F =1.8, p = .08, R² = .35). After adjusting for covariates, neither food security (β = -5.8, 95% CI: –22.45, 10.84, p = .48) nor nutrition security (β = 3.4, 95% CI: –9.5, 16.2, p = .59) were significant predictors of diet quality. Only household size of 3-4 was significantly associated with lower HEI scores ((β = –15.4, 95% CI: –26.3, –4.5; p = 0.007). Conclusion: Among food insecure adults with T2D, lower food security was associated with lower nutrition security, although neither was significantly related to diet quality. Overall, diet quality was suboptimal. These findings highlight the complexity of addressing dietary disparities in vulnerable populations. Ongoing research will evaluate how the FRESH-T2D medically tailored grocery intervention impacts these outcomes over time.
• Identification of Cancer Stem Cell Susceptibility to Targeted Therapies in a Unique Subset of Colorectal Cancer

  Pond, Kelvin W.; Thorne, Curtis A.; Daptardar, Shravani Shashikant; Cress, Anne E. (The University of Arizona., 2025)

  The colonic epithelium has a fascinating renewal capacity and turns over every 3-4 days. Colorectal cancer develops when the same epithelial cells collect mutations over time which leads to carcinoma. CRC is one of the leading causes of morbidity in the United States and other parts of the world. Classical adenoma formation in the epithelium follow the Vogelstein model of progression, where the driver mutations are sequential. Consensus Molecular Subtypes suggests CRC can be divided into 4 subtypes based on their genetic signature. This has been widely accepted in the field and researchers are finding new categories to understand, diagnose and treat CRC. Driving mutations in CRC usually involve the Wnt Pathway and MAPK Pathway and a lot of the treatments target these pathways to improve patient outcome. CRC is inherently heterogenous in nature and treatment often fails to improve overall survivalin patients with chances of remission and chemoresistance. One unique subset of tumours which have been understudied are BRCA/BRAF tumours. These tumours have driver mutations B-RAF which induce survival and hyperproliferation along with BRCA mutations that protect the tumours from apoptosis. These tumours are said to have high immune infiltration and thus benefit from checkpoint inhibitor therapies. They are treated with B-RAF inhibitors along with EGFR and VEGFR inhibitors. But several studies have shown increased resistance to these therapies and high probability of relapse in patient outcomes. Chemoresistance is a big bottleneck which has been studied over the years to overcome. Studies suggest that resistant populations may either lay dormant or not respond to the treatment and thus increase the probability of relapse. This study aims to understand this unique understudied set of tumours and their response to conventionally used chemotherapeutics. We utilized patient-derived organoid models to characterize chemotherapeutic responses in BRCA/BRAF mutant CRC. We evaluated the efficacy of FDA-approved RAF and PARP inhibitors, as well as DYR895, a novel CLK/DYRK kinase inhibitor targeting the Wnt and AKT pathways. High content single-cell imaging and phenotypic profiling revealed that while RAF inhibitors were largely ineffective, PARP inhibitors and DYR895 significantly reduced viable tumor cell populations and induced DNA damage. Subpopulation analysis highlighted dynamic shifts, particularly the depletion of cancer stem-like (CD44v9+) cells, suggesting potential avenues to overcome chemoresistance. Our findings underscore the importance of targeting both DNA repair deficiencies and survival signaling pathways in BRCA/BRAF-mutant CRC and demonstrate the utility of organoid models for preclinical drug evaluation and personalized therapy development.
• Androgen-Induced WNT Signaling in Prostate Stromal Cells: Implications for Stromal-Epithelial Crosstalk and Prostate Homeostasis

  Miranti, Cynthia; Sundaram, Samyukta; Cress, Anne E.; Warfel, Noel (The University of Arizona., 2025)

  Background: WNT signaling is crucial for prostate tissue homeostasis, regulating cell proliferation, differentiation, and function. Its dysregulation is linked to prostate cancer and benign prostatic hyperplasia, yet the specific role of stromal WNT signaling in prostate development and disease remains unclear. Understanding how stromal WNT influences epithelial cells and interacts with other pathways is key for identifying potential therapeutic targets. Approach: Differentiated and undifferentiated human prostate stromal cells were cultured and assessed for WNT signaling activity upon R1881 induction using qPCR and TaqMan™ WNT pathway arrays. Expression of WNT ligands, receptors, and inhibitors was validated by western blotting. Functional assays using recombinant WNT proteins (WNT3A, WNT7B) were conducted on basal epithelial cells to assess downstream canonical and non-canonical signaling. FZD receptor function was evaluated using shRNA-mediated knockdown in epithelial cells. Results: We found that WNT5A, WNT2, and WNT4 were the most abundant WNT ligands in benign prostate fibroblasts, smooth muscle cells, and basal epithelial cells, respectively. Androgen stimulation upregulated WNT3A transcription in stromal cells but led to reduced protein levels, suggesting post-transcriptional regulation. FZD10 was highly expressed in prostate cancer cells, implicating it as a potential mediator of tumor associated WNT signaling. Recombinant WNT treatment revealed context-dependent epithelial responses, favoring non-canonical signaling and β-catenin degradation. Conclusions: This study reveals cell type–specific expression and regulation of WNT ligands and receptors in the prostate that supports epithelial quiescence and tissue homeostasis. Disruptions to this balance may contribute to prostate cancer progression and represent potential targets for future therapeutic strategies.
• Reframing the “Slave Landscape”: Interpreting Slavery at Virginia’s Presidential Plantation Museums

  Romano, Irene B.; Moorman, Alyssa B.; Romano, Irene B; Widdifield, Stacie G.; Moore, Sarah J. (The University of Arizona., 2025)

  This thesis examines how George Washington’s Mount Vernon, Thomas Jefferson’s Monticello, and James Madison’s Montpelier interpret the history of slavery, analyzing the extent to which these sites have moved beyond traditional narratives that romanticize the Antebellum South. Historically, plantation museums have struggled to reconcile their roles as sites of national memory with the need to present a fuller, more accurate account of the enslaved individuals who lived and labored there. In response to ongoing calls for decolonization and multivocal interpretive methods, these sites have worked to revise their approaches to slavery. Applying theories and methods from art history, museum studies, material culture, and public history, alongside analysis of plantation websites and site visits, this thesis evaluates how each site engages with its history of slavery. Findings indicate that while Mount Vernon, Monticello, and Montpelier have implemented initiatives that foreground the lives of the enslaved, challenges remain regarding consistency across interpretive programming and the depth of engagement with slavery’s legacies. Ultimately, this thesis argues for a more dynamic and proactive approach to interpreting slavery at plantation museums. By implementing strategies such as deeper descendant involvement and arts-based interpretive methods, these plantation museums can more effectively humanize the enslaved, challenge white-centric narratives entrenched in the nation’s history, and foster deeper public engagement with the realities of slavery.
• Defining Endogenous Clearance Mechanisms of Full-Length TDP-43 and Its Disease-Prone Isoforms

  Buchan, Ross; Marcinowski, Sophia Lucille; Hester, Susan; Weinert, Ted (The University of Arizona., 2025)

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron atrophy, resulting in paralysis and respiratory failure. A pathological hallmark in >95% of ALS patients is the cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43. Pathological N- or C-terminal truncated TDP-43 isoforms are associated with ALS, and reducing their levels, along with full-length cytoplasmic TDP-43, improves viability in various ALS cell models. However, the mechanisms by which cells normally degrade full-length and truncated TDP-43 isoforms remain incompletely understood. Here, I demonstrate that in addition to previously identified degradation pathways, the endolysosomal pathway plays a significant role in TDP-43 clearance. In yeast, I identified adaptors of the E3 Ub ligase Rsp5 that aid in TDP-43 degradation. In HEK293 cells, I confirmed that NEDD4 (Rsp5 homolog) ubiquitinates TDP-43 with K63-linked ubiquitin chains, consistent with endolysosomal degradation. To further investigate endogenous full-length TDP-43 and isoform-specific clearance mechanisms, I have constructed various full-length TDP-43 and isoform-expressing yeast strains under β-estradiol inducible promoters for use in genome-wide dot blot screens. These screens will identify which genes or drugs have the most significant effect on full-length TDP-43/isoform levels within the cell, which can then be further explored in human cells. This approach may allow for the identification of isoform-specific degradation pathways that do not target full-length TDP-43, uncovering new therapeutic strategies for ALS that mitigate toxicity without compromising the essential functions of full-length TDP-43.

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