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The Development and Evaluation of a Single Session Intervention for Parent Distress Tolerance
No full textInterventions for child internalizing and externalizing disorders increasingly utilize parent-directed approaches that rely on caregivers to facilitate treatment skills. However, parents experiencing emotional difficulties and their children demonstrate less benefit from child treatments compared to parents with greater emotion regulation capacity. Improving parent emotion coping may be key to increasing child treatment efficacy. Parents may also be unlikely to prioritize their emotion coping over their child’s due to limited resources and/or other significant time and cost burdens related to seeking their own services. The current study sought to develop and test a single-session intervention (SSI) for parent distress tolerance (DT) using a mixed-methods design. The current study used rapid qualitative analysis to inform the development of a SSI focused on parent DT. The SSI, named Parents THRIVE, was then compared to a control SSI using a randomized-controlled trial (RCT) with N = 55 parents of children 6-17 years old. Measures were collected before and two-weeks after receiving the SSI. Following the RCT, participants who received Parents THRIVE completed qualitative interviews. Results showed significant group differences from baseline to post-treatment in the DT appraisal subscale such that, controlling for baseline parent experiential avoidance, Parents THRIVE participants reported improvements in appraisals of distress while participants in the control condition reported decreases in their appraisal DT. Results also showed trending group differences over time in depression, favoring the Parents THRIVE condition. SSIs that focus on single mechanisms of change can offer a fast, free, digital, and potentially effective approach to helping parents improve their capacity to tolerate distress and may enhance their ability to benefit from child treatments. Future directions should utilize feedback obtained from participants to improve and further test the SSI as a stand-alone and adjunctive intervention for parents experiencing emotional distress.</p
Privacy-Preserving Algorithms for Inventory Control
No full textIn the era of data-driven decision-making, feature-based inventory analysis has emerged as a powerful approach for enhancing operational efficiency by leveraging contextual data. However, the growing concerns over data privacy—especially with sensitive customer information—pose significant challenges to the practical deployment of such methods. This dissertation addresses this critical gap by developing a comprehensive framework for privacy-preserving inventory control under differential privacy (DP) constraints.The dissertation comprises two main projects and one minor project. The first project focuses on the offline setting, where a differentially private algorithm is developed to solve the classical newsvendor problem. The proposed method utilizes smoothed empirical risk minimization and clipped noisy gradient descent within the Gaussian differential privacy (GDP) framework. The algorithm not only guarantees rigorous privacy protection but also achieves favorable statistical performance with provably low excess risk. The second project investigates the online setting, where data arrive sequentially and decisions must be made in real time. A novel differentially private stochastic sub-gradient method is proposed to address two fundamental challenges: censored demand and non-perishable inventory. The algorithm is designed to satisfy a strengthened form of local differential privacy (LDP). Despite the complexity introduced by data dependence and partial observability, the algorithm attains a sublinear regret bound. Overall, this work contributes to the fields of operations management and privacy-preserving machine learning by bridging theoretical rigor and practical relevance. It demonstrates that effective and privacy-compliant inventory control is achievable in both static and dynamic environments, paving the way for secure data utilization in modern supply chains. My dissertation also includes a minor project related to policy evaluation in reinforcement learning (RL).</p
Downstream Effector Pathways of G-Protein Signaling in the Caenorhabditis elegans Egg-Laying Circuit
No full textNeuromodulators signal through G-protein-coupled receptors to regulate neural circuit activity through a variety of complex signaling pathways. Studies in various systems have found that G-protein signaling pathways can facilitate vesicle release, regulate calcium flow within the cell, activate protein kinases, modulate ion channels, and regulate transcription pathways. Many questions remain, however, about the exact mechanisms by which these pathways regulate neural circuit activity and how distinct G-protein signaling pathways work together to fine-tune the rate and intensity of neural circuit activity in response to signals from other circuits, such as sensory cues. The nematode worm Caenorhabditis elegans has proven to be an invaluable model organism to study the genetic determinants of synaptic transmission. Its simple nervous system and behaviors make it amenable to forward genetic screens using simple phenotype analysis, which have been used to map a diverse array of conserved synaptic and signaling proteins to simple neural circuits. Its transparent body allows for the in vivo use of optogenetic techniques and of transgenically expressed fluorescent proteins, which have been used to identify useful cell-specific promoters, acutely and specifically manipulate cell activity in model circuits, and measure changes in real-time cell activity patterns in response to genetic and acute perturbations. In this dissertation, I present a series of studies in which I have explored how G-protein signaling pathways regulate the egg-laying circuit and tested candidate ion channels as effectors of these pathways. </p
The Effects of Adaptive Coping on the Relationship between Discrimination, Alcohol Use, and Substance Use in Black Women Living with HIV
No full textBlack women living with HIV (BWLWH) experience higher rates of posttraumatic stress disorder (PTSD), anxiety, and depression. They experience HIV stigma and discrimination, gender discrimination, and racial discrimination. These experiences of discrimination have been tied to negative physiological, biological, and psychological mental health outcomes. Alcohol and substance use are commonly associated with coping in BWLWH. Protective factors like religious coping, resilience, and social support have been reported to dampen discrimination, alcohol use, and substance use in BWLWH. To better understand factors that contribute to alcohol and substance use in BWLWH, using structural equation modeling the present study examined the relationships among discrimination, alcohol use, and substance use. The indirect effects of trauma and depression were evaluated in models that also included resilience, social support, and religious coping. Participants were 255 BWLWH enrolled in a longitudinal cohort study in South Florida. Results of direct effect analysis showed that discrimination was directly and positively associated with substance use disorder (SUD) and negatively associated with alcohol use disorder (AUD). Indirectly, PTSD symptoms were positively associated with heavy alcohol use, AUD symptoms, and AUD. This study also assessed resilience, religious coping, and social support as moderators and potential protective factors of the relationship between discrimination and alcohol or substance use. Religious coping, as an interaction, decreased the relationship between discrimination and heavy alcohol use as well as discrimination and AUD. The interaction effect of resilience also decreased the relationship between discrimination and heavy alcohol use. Understanding adversities contributing to alcohol and substance use among BWLWH as well as factors that reduce alcohol and substance use may help guide prevention and intervention strategies to minimize its effects, enhance mental health, and increase the quality of life for BWLWH.</p
A Lockean Theory of Intuition
No full textThis dissertation attempts to extract a Lockean theory of general intuitions from Locke’s various commitments. It starts by identifying the intentional object of Lockean intuitions based on his ontological commitments. This is followed by a characterization of the mental content of Lockean intuitions and their relations to their representata and subjects. Finally, it identifies the nature of Lockean general intuitions based on previous considerations and Locke’s position on knowledge and judgment. It argues that the intentional objects of general intuitions are abstract ideas, which are also the mental content of general intuitions. These conclusions, in addition to Locke’s position on knowledge and judgment, support the view that the Lockean theory of general intuitions is nominalist naïve realism.</p
Mechanisms by Which Low-Dose IL-2/CD25 Fusion Protein Limits Diabetes in NOD Mice
No full textSuppression of autoreactive T cells by regulatory T cells (Tregs) is essential for immune tolerance and homeostasis. Interleukin-2 (IL-2) is critical for Treg development, function, and maintenance. Tregs constitutively express the high-affinity IL-2 receptor (IL-2R), enabling them to respond to much lower IL-2 levels compared to T effector (Teff) cells. Many autoimmune and inflammatory diseases exhibit quantitative and qualitative defects in Tregs and IL-2/IL-2R signaling. Clinical trials in autoimmune patients receiving low-dose (LD) recombinant (r) IL-2 have shown increases in Tregs and improvement in clinical outcomes. However, achieving robust control of autoimmunity is unlikely due to poor pharmacodynamics of rIL-2 which cannot sustain a constant elevation of highly functional Tregs. Here we utilize the NOD mouse model of type 1 diabetes and a novel, long-lasting IL-2-based biologic, where mouse IL-2 is covalently linked to mouse IL-2R CD25 subunit, to investigate the cellular mechanisms underlying the tolerance-enhancing effects of LD IL-2. By varying the administration of IL-2/CD25 fusion protein, we show that a sustained, but not a periodic increase in Tregs is highly effective in inhibiting autoimmunity. Analyses of pancreatic islets using flow cytometry and single-cell RNA sequencing revealed that IL-2/CD25 rapidly changes the islet immune microenvironment. IL-2/CD25 induces a marked increase in activated effector (e) Tregs, particularly ST2+ eTregs, type 2 innate lymphoid cells (ILC2s), and cytokine-producing regulatory natural killer (NK) cells, while islet antigen-reactive CD4+ and CD8+ T cells decrease. T cell receptor repertoire analysis revealed a reduction in multiple dominant clonotypes associated with effector CD4+ and CD8+ T cells. These effects were amplified upon extended treatment with IL-2/CD25. Thus, sustained suppression of self-reactive CD4+ and CD8+ Teff cells and robust control of autoimmunity requires a constant elevation of Tregs and suggests a potential beneficial role for ILC2s and cytokine-producing NK cells. </p
Sociodemographic Characteristics of Cancer Survivors Referred to Exercise Oncology Services: Who Follows Up?
No full textIntroduction: Healthcare providers are important for promoting positive health behavior changes in cancer survivors (CS) and well-positioned to refer to exercise physiologists. Analysis of referral habits using electronic medical record systems can help cancer centers understand and improve their referral pathways. The goal of this thesis was to understand sociodemographic characteristics of CS referred to exercise oncology (EO) support services. Methods: This study was a retrospective analysis between October 2019 - December 2023. Data was extracted from the University of Miami Health System’s systems through My Wellness Check Platform (MWCP) and EPIC (Electronic medical record system through the University of Miami) for a total sample of 1,847 CS. Descriptive statistics were used to describe frequencies (%) of referrals made to EO by the referral channels. Sociodemographic differences in CS who followed up vs did not follow up with EO services were examined using logistic regression. Statistical analyses were performed using SAS version 9.4 statistical software. Results: Of the 1,847 CS referred between October 2019-December 2023, 94% (n=1740) were referred through EPIC and 6% (n=107) from MWCP. The CS were primarily female (79%), non-Hispanic (50%), White (81%), English-speaking (75%), married (55%), insured (67%), and breast CS (52%). Forty-nine percent (n=906) followed up with EO services. Of the 107 CS referred from MWCP, 67% (n=72) followed up with EO services. Of the 1,740 CS referred from EPIC, 48% (n=834) followed up with EO services. CS who were ≥ 60 years old (vs < 60 years old; OR=1.33, 95% CI=1.08-1.63, p<0.05), Non-Hispanic (vs. Hispanic; OR=0.75, 95% CI= 0.61-0.92, p<0.05), and referred through the MWCP (vs. EPIC: OR=0.47, 95% CI=0.31-0.72, p<0.05) were more likely to follow up with EO services. Conclusions: Findings from this study provide a better understanding of referral follow up with EO services at a large, cancer center. Results suggest that EHR-integrated referral pathways may serve as important tools to increase reach to EO services
Tandem Repeat Variation in Human Genomes and Its Role in Health and Disease: Insights from Long-Read Sequencing
No full textUnderstanding the genetic basis of both rare and common diseases remains a major challenge. Despite advances in genomics, over half of individuals with rare diseases still lack a genetic diagnosis. This diagnostic gap suggests that conventional approaches may miss complex or unconventional forms of variation, such as tandem repeats (TRs)—sequences of repeated DNA motifs that vary in structure and length.TRs are highly mutable and historically dismissed as "junk DNA," yet they are now implicated in over 60 rare diseases, including Fragile X syndrome and Huntington’s disease. Increasing evidence also suggests that TRs regulate gene expression and have biological function. However, due to the limitations of short-read sequencing, the variability and clinical relevance of most TRs remain poorly characterized. With the advent of long-read sequencing, it is now possible to study these regions at high resolution and scale. In this dissertation, I analyze TR variation across more than 1,000 long-read human genomes from the All of Us Research Program, aiming to map TR polymorphism and investigate its roles in disease.To do this, I built a population-scale control database of TRs and developed novel computational tools for analyzing their genetic and functional complexity. Using TRGT, I generated high-resolution TR genotypes from PacBio HiFi data and benchmarked them against short-read ExpansionHunter calls. I profiled known pathogenic loci and compared them to non-pathogenic loci, developing new methods to decompose, visualize, and quantify TR sequence structure. These tools enabled discoveries in non-coding pentanucleotide TRs, an emerging class of pathogenic variation.Together, these findings provide foundational resources and insights for the study of tandem repeats in rare disease, common traits, and human evolution. </p
Photochemistry and Photophysics of Organic Molecules Modulated by Supramolecular Effects
No full textThis dissertation investigates how supramolecular encapsulation within octa acid (OA), a water-soluble deep-cavity cavitand, can be used to control the photophysical and photochemical behavior of organic molecules in aqueous environments. Conventional photochemical studies in water are often limited by solubility issues, aggregation, and quenching by molecular oxygen. OA offers a confined hydrophobic cavity that isolates guest molecules from bulk solvent, enabling modulation of their excited-state behavior. Room-temperature phosphorescence (RTP) of thiocoumarin (TC) derivatives is significantly enhanced upon encapsulation, as shown in Chapter 2, with microsecond triplet lifetimes observed. Chapter 3 explores photorelease of acidic products from OA-encapsulated TCs, where confinement enables solubilization and promotes triplet-mediated bond cleavage. Chapter 4 introduces sequential and orthogonal photorelease by encapsulating structurally distinct PRPGs with different absorption profiles, allowing wavelength-selective and sequential guest release in water. Chapter 5 focuses on [2+2] photocycloaddition of 1,n-dienes, where OA confinement facilitates selective triplet-sensitized cycloaddition without external sensitizers. Across these studies, OA acts not only as a host but also as a reaction modulator and, in some cases, an intrinsic triplet donor. Collectively, this work demonstrates the utility of OA as a supramolecular platform for harnessing and controlling light-driven reactivity in aqueous media, with implications for phototriggered drug delivery, biological imaging, and green photochemistry.</p
Molecular Encapsulation Enforces Selectivity on the Reactivity of Excited Organic Molecules
No full textSupramolecular photochemistry uses molecular encapsulation to control excited-state reactions with exceptional precision. Confinement within host cavities tunes reaction pathways, stabilizes reactive intermediates, and suppresses competing processes—enabling outcomes often inaccessible in bulk solution. This work explores the water-soluble host Octa Acid (OA) capsule as a nanoscale reactor that imposes structural and dynamical constraints on guests, directing their photochemistry. In water, β-ionyl derivatives above ~0.5–1 mM form nano-aggregates, competing with host binding. OA encapsulation overcomes this self-assembly and enables unique reactivity. The high-energy 7-cis-β-ionone is stabilized in OA, reaching ~40% yield after UV irradiation compared to ~10% in bulk, as confinement suppresses cyclization. Visible-light E→Z isomerization of β-ionyl derivatives becomes regioselective in OA, selectively targeting one alkene and stabilizing higher-energy Z-isomers. Unexpected triplet energy transfer between OA and anionic sensitizers reveals “like-charge attraction” effects in water. The OA capsule accelerates the “catalysis-resistant” dimerization of cyclopentadiene by >2000-fold via guest pre-organization and sequential turnover, demonstrating confinement-driven catalysis. For arylazoisoxazole molecular switches, OA encapsulation restricts mobility but maintains reversible E/Z isomerization. CH–π interactions and substituents shift photostationary equilibria and thermal reversion rates, tuning switching performance over many cycles without host dissociation. Overall, OA enables stabilization of fleeting species, precise control of selectivity, unexpected energy-transfer pathways, dramatic rate enhancements, and modulation of photoswitch behavior. These findings establish supramolecular encapsulation in water as a powerful strategy for designing precision photochemical systems and expand the conceptual toolkit for controlling light-driven processes in aqueous environments.</p