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    Hydrogen Absorption on Single Palladium Nanoparticles

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    Thesis (Master's)--University of Washington, 2025This study presents a comprehensive investigation into the electrocatalytic behavior of single palladium nanopar-ticles (Pd NPs) during the hydrogen evolution reaction (HER), with a particular focus on their unique ability to absorb hydrogen into the bulk lattice. Using stochastic single-particle collision experiments at carbon fiber ultramicroelec- trodes, we captured and analyzed transient current signals arising from individual NP–electrode interactions under acidic conditions. These current traces revealed distinct kinetic phases associated with hydrogen adsorption (Volmer step), hydrogen evolution (Heyrovsky and Tafel steps), and subsurface hydrogen absorption. Quantitative analysis shows that Pd NPs absorb a significant fraction of the adsorbed hydrogen, leading to reduced HER efficiency compared to bulk Pd electrodes. The observed steady-state and transient currents suggest a strong competition between HER and hydrogen absorption, which alters the effective reaction pathway and suppresses molecular hydrogen formation. Systematic evaluation of proton concentration and applied overpotential further revealed that the HER kinetics on Pd NPs deviate from classical mechanisms, exhibiting unusually low transfer coefficients and small apparent rate constants. These findings indicate that hydrogen absorption—not hydrogen desorption—is the rate-limiting step under many experimental conditions. By isolating single-particle responses, this work provides critical mechanistic insight into nanoscale hydrogen electrosorption and establishes single-NP collision electrochemistry as a powerful tool for resolving complex catalytic processes involving coupled interfacial and bulk transformations

    Taiwanese primary care physicians’ experience and confidence in genetic service delivery: A pilot survey study

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    Thesis (Master's)--University of Washington, 2025BackgroundWith the rapid advancement of genetic testing technologies and their increasing application in preventive care, the role of primary care physicians (PCPs) in genetic service delivery is gaining importance. In Taiwan, where direct-to-consumer genetic testing is prohibited and the certified genetics workforce is limited and unevenly distributed, PCPs may serve as crucial entry points for patient access to genetic services. However, little is known about Taiwanese PCPs’ current experience, confidence, and attitudes toward delivering these services. Objectives This study aims to explore the experiences, perceived barriers, and training needs of Taiwanese PCPs in the context of ordering genetic tests and referring patients for genetic counseling. Findings are intended to inform policy and workforce development strategies to improve the integration of genetic services into primary care in Taiwan. Methods An anonymous online survey was conducted between November 2024 and March 2025 among Taiwanese PCPs. The 58-item survey included questions on physician characteristics, experience with genetic services, attitudes toward genetic testing, confidence in genetic knowledge, and views on genetic education and certification. Descriptive statistics and Fisher’s exact tests were used to analyze the data. Results A total of 96 PCPs completed the survey. More than half (57.3%) had ordered genetic tests, and 79% had referred patients to genetic specialists. Common barriers to ordering tests included patients’ financial concerns (69.8%) and uncertainty about test selection (64.6%), while referral barriers included unclear pathways (57.3%), uncertainty about referral options (57.3%), and patients’ financial concerns (52.0%). Only a small proportion of respondents reported confidence in interpreting genetic reports (23.9.0%) or understanding legal (14.6%) and insurance-related (11.5%) issues. Although most respondents agreed that current genetic knowledge among PCPs is insufficient and that enhanced genetic education during medical school can be beneficial, opinions were divided on the effectiveness of continuing education and the necessity of board certification. Conclusion Taiwanese PCPs encounter multiple barriers in delivering genetic services, particularly related to knowledge gaps, referral infrastructure, and policy ambiguity. Addressing these challenges through tailored education, clear service models, and health system support is essential for enabling PCPs to meet the growing demand for genetic services in Taiwan’s primary care settings

    Manipulating Nanoparticle Assembly with Precision and Predictability using High Information Content Building Blocks

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    Thesis (Ph.D.)--University of Washington, 2025Controlling the stimuli-responsive assembly and disassembly of inorganic nanoparticles under mild conditions and with precision and predictability remains a key challenge in the design of next-generation nanomaterials. This dissertation describes experimental, theoretical, and machine learning approaches for programmable nanoparticle assembly using solid-binding proteins, a class of genetically encoded, high information content building blocks. In a first series of studies, bifunctional silica-binding proteins were used to mediate the reversible clustering of silica nanoparticles (SiNPs) between a fully dispersed state at pH 8.5 and large aggregates at pH 7.5. A multiscale simulation framework incorporating input from classical colloidal theory and atomistic molecular dynamics (MD) calculations into a rigid body simulation energetically benchmarked by scattering experiments successfully predicted assembly behavior and cluster size under various conditions of pH and electrolyte concentrations. Changes in the sequence and location of the silica-binding segments, and the introduction of steric forces using PEGylated monofunctional silica-binding proteins were further used to modulate SiNP assembly and achieve fine control over cluster size, polydispersity, and Förster Resonance Energy Transfer (FRET) between fluorescent protein blocks and dye-loaded SiNPs. A second set of studies extended the approach to thermoresponsive systems. Here, elastin-like polypeptides (ELPs) modified with a C-terminus cysteine (Cys) residue were used to decorate gold nanoparticles (AuNPs) and to demonstrate that the size of the clusters obtained upon liquid-liquid phase separation could be controlled through both the amount of free ELPs added to the solution and the diameter of the constituent AuNPs. The reversible nature of the assemblies was exploited for precision loading and release of small molecular cargos such as Nile Red and tetracycline. Additionally, we used Click chemistry to couple a Cys-modified ELP to an oligonucleotide and control the assembly-disassembly behavior of AuNPs over specific windows of temperatures. Finally, a dual variational autoencoder machine learning strategy was deployed to predict cluster size as a function of temperature from UV-visible spectra acquired by hyperspectral microscopy. Together, these studies lay the foundation for versatile strategies for nanoparticle assembly, combining genetic programmability, responsive behavior, and predictive modeling to advance the development of functional hybrid nanomaterials

    Lymphatic chain gradients regulate the magnitude and heterogeneity of T cell responses to vaccination

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    Thesis (Ph.D.)--University of Washington, 2025Upon activation, T cells proliferate and differentiate into diverse populations, including highly differentiated effector and memory precursor subsets. Initial diversification is influenced by signals sensed during T cell priming within lymphoid tissues. However, the rules governing how cellular heterogeneity is spatially encoded in vivo remain unclear. Here, we show that immunization establishes concentration gradients of antigens and inflammation across interconnected chains of draining lymph nodes (IC-LNs). While T cells are activated at all sites, individual IC-LNs elicit divergent responses: proximal IC-LNs favor the generation of effector cells, whereas distal IC-LNs promote formation of central memory precursor cells. Although both proximal and distal sites contribute to anamnestic responses, T cells from proximal IC-LNs preferentially provide early effector responses at inflamed tissues. Conversely, T cells from distal IC-LNs demonstrate an enhanced capacity to generate long-lasting responses to chronic antigens in cancer settings, including after checkpoint blockade therapy. Therefore, formation of spatial gradients across lymphatic chains following vaccination regulates the magnitude, heterogeneity, and longevity of T cell responses

    StackBERT-Enhancer: A Dual-Layer BERT-Based Framework for Enhancer Identification and Strength Classification in Genomic Data

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    Thesis (Master's)--University of Washington, 2025Accurately identifying and classifying crucial regulatory DNA sequences known as enhancers is a significant challenge, as traditional computational methods often struggle with their complex, context-dependent nature and lack interpretability. This thesis introduces StackBERT-Enhancer, a novel deep learning framework to address these limitations, focusing on two primary tasks: distinguishing enhancer sequences from non-enhancer sequences and classifying identified enhancers by their activity levels. The proposed framework employs multiple transformer-based language models, each independently trained on DNA sequences tokenized with different k-mer sizes, allowing for the capture of sequence dependencies across various scales. These individual models are then integrated into a stacking ensemble architecture, which significantly boosts classification accuracy, robustness, and generalization, achieving state-of-the-art results of 83.5% in enhancer identification and 99.0% in enhancer strength classification. The framework utilizes distributed multi-GPU systems for efficient model training and incorporates interpretability techniques such as SHapley Additive exPlanations (SHAP) for feature importance and attention score analysis for sequence motif discovery, bridging predictive power with biological insight. This advanced approach offers a robust and interpretable tool for enhancer analysis, holding strong potential for applications in disease modeling and broader biomedical research

    Predator-Prey Interactions of Hermit Crabs and Sea Stars of the Salish Sea

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    Hermit crabs will react with greater evasive maneuvers to larger sea stars than they will to smaller sea stars in a twenty minute timeframe. This will be studied using six Pagurus sp. Hermit crabs collected on San Juan island and three species of sea stars collected from San Juan island: Evasterias troschelii, Mediaster aequalis, and Crossaster papposus

    Pharmacological profiling of conventional antiseizure medicines against seizures and kindling acquisition in female mice

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    Thesis (Master's)--University of Washington, 2025Rationale: Historical ASM discovery has primarily relied on demonstration of efficacy in clinically validated acute seizure models evoked in male, wild-type rodents (e.g., maximal electroshock, subcutaneous pentylenetetrazol, or kindling). However, little work has been done to establish ASM response profiles in female rodents with acute or chronic seizures. Therefore, this thesis aimed to build on our previously established female C57BL/6J studies (Lehmann & Barker-Haliski 2023) to fill this knowledge gap and to define the acute median effective dose (ED50) of 4 FDA-approved ASMs (levetiracetam (LEV), carbamazepine (CBZ), valproic acid (VPA), and phenobarbital (PB)) in female outbred CF-1 mice using the 6 Hz 32 mA model of focal seizures. Further, no compound has yet been found to prevent the development of epilepsy so we propose a moderate-throughput anti-epileptogenesis drug screening paradigm for early compound profiling via repeated administration of anticonvulsant doses of VPA to assess the potential to prevent the formation of chronic hyperexcitable neuronal network or modify the severity of behavioral comorbidities of epilepsy in male versus female mice using the corneal kindled mouse (CKM) model of chronic seizures. Methods: Female outbred CF-1 mice were used to quantify of an ED50 of candidate ASMs (n=8 mice/dose) in a 6 Hz 32 mA test. Motor impairment was assessed via performance on a fixed speed rotarod. To establish a moderate-throughput, early-stage disease modification screening paradigm, male (n=40) and female (n=45) CF-1 mice underwent 60 Hz corneal kindling, a model of chronic network hyperexcitability, for 3-4 weeks in the presence or absence of twice daily VPA (150 mg/kg, intraperitoneal – i.p.) or vehicle administration. Mice were monitored twice daily for the presence and severity of evoked behavioral seizures until all animals met the kindled seizure endpoint. Following the kindling acquisition period, all CKM were challenged in an open field test to quantify the extent to which ASM administration during the kindling process modified anxiety-like behavioral comorbidities of epilepsy. Results: The calculated ED50 [and 95% confidence intervals] in female CF-1 mice for VPA (100 mg/kg [60.5-139]), CBZ (14.0 mg/kg [8.77-23.1]), LEV (14.3 mg/kg [0.591-36.0]) and PB (18.3 mg/kg [6.8-30.4]) were consistent with our previously reported values in the 6 Hz test in inbred female C57BL/6J mice (Lehmann and Barker-Haliski 2023). Notably, CBZ was poorly tolerated in CF-1 female mice: 87.5% of female mice were impaired on a rotarod at the highest dose tested. No other motor impairment was noted. In both male and female corneal kindling acquisition studies, VPA prevented kindled seizure presentation. The number of CKM reaching the fully kindled state was lower in both female (2/10) and male (2/11) mice than in VEH-treated female (8/10) and male (14/15) mice (male: X2 value = 18.57, p < 0.001; female: X2 value = 12.77, p < 0.001). However, repeated VPA administration did not significantly impact CKM activity in the center of an open field versus the activity of VEH-treated mice, suggesting no disease modifying effect of VPA administration on the anxiety-like behavioral comorbidity of epilepsy. Conclusion: This study establishes the anticonvulsant properties of four prototypical ASMs in wild-type outbred female CF-1 mice to inform future preclinical epilepsy studies using novel investigational compounds. This work also establishes the feasibility of a disease-modification drug screening paradigm for epilepsy in male and female mice using the corneal kindled mouse model and open field test of anxiety-like behaviors, a known clinical comorbidity of epilepsy. Altogether, this work offers a strategy on which to rapidly assess the anticonvulsant and disease modifying potential of candidate investigational treatments for the symptomatic management, and possibly prevention, of epilepsy

    Correlates of Active Commuting Frequency: Investigating Associations between Student Characteristics and Walking and Biking to School in Seattle and Washington State

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    Thesis (Master's)--University of Washington, 2025This research examines the correlates of active commuting among students, comparing Seattle and statewide populations in Washington State. Utilizing descriptive statistics and correlation analyses, the study identifies critical factors associated with students' decisions to walk or bike to school. Key findings include obesity negatively predicting active commuting, notably reducing daily walking rates. Conversely, frequent physical activity significantly correlates with higher active commuting behaviors, suggesting mutually reinforcing health practices. Notably, commuting frequency peaks at Grade 8 and declines in later grades, emphasizing the need for age-specific interventions. Additionally, urban infrastructure significantly supports higher active commuting rates in Seattle compared to statewide averages.Recommendations emerging from these findings emphasize prioritizing infrastructure development in suburban and rural areas, enhancing Safe Routes to School programs, and implementing comprehensive health education curricula. Schools should introduce motivational initiatives like walking school buses or incentive programs, particularly targeting students in higher grades. These targeted interventions promise to enhance student health outcomes and foster sustainable commuting practices, addressing both local and broader community contexts

    Sea Star Wasting: Investigations in Disease Ecology and Environmental Dynamics

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    A literature review was conducted to present information on current and preceding works regarding sea star wasting disease (SSWD), more accurately termed as a syndrome. This project aimed to provide a background surrounding ecological impacts and disease ecology as it is related to sea star wasting disease. While much research has been done to satisfy these critical areas in knowledge surrounding SSWD, extensive work is still needed to further the understanding of microbial relationships to SSWD, multi-host system dynamics, species-species variability, immunology of asteroids in response to wasting, and larval susceptibility and transmission

    Expanding Shoreline Historical Museum, the Archives Project

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    Thesis (Master's)--University of Washington, 2025My project, "Expanding Shoreline Historical Museum, the Archives Project" examines one-way museums can become relatable and more accessible with their local communities. Additionally, the museum archives are undergoing development so this archival project can foster new trysts of accession programs for the museum to encourage while up lifting the project creators. For the duration of this project I worked alongside Shoreline Historical Museum, a history museum based in Shoreline WA, to create a public program in collaboration with a local community group sourced from the general area of Shoreline. The target audience who we worked with resulted were teenagers, a commonly underrepresented group not seen within museum programs. Teenagers were the chosen target audience to work with as an inclusive way to portray how Shoreline intends to expand their social outreach methods using models that address the public in a far more relatable and expressive manner. Over a period of two months this project was weekly facilitated by said students, their facilitator from Shorewood High School, and the director of Shoreline Museum. As a BIPOC facilitator myself, the work and effort placed in the wellbeing of these students allowed this project to become a public programming which uplifts and encourages its participants rather than restraining their creativity for stricter guidelines and practices. Additionally, the project went on to demonstrate how crucial the need is for museums to invest in their communities beyond their familiarity to earn authentic partnerships kindred with unrepresented and BIPOC communities who deserve more recognition within museums

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