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Coherent Structures and Optimal Control Theory
No full textThesis (Ph.D.)--University of Washington, 2025Coherent structures are persistent, large-scale spatiotemporal features in fluid flow fields. Optimal control theory is a branch of mathematics highly relevant to engineering for manipulating the behavior of dynamical systems. In this work, we explore the interplay and connections that arise between these two concepts in two different contexts. In the first context, we are motivated by the problem of path planning of ocean drifters moving within flow fields. Here, we are interested in how the background coherent structures characterized by the Lyapunov exponents of the flow impact and shape energy efficient trajectories of the robot moving within. In the second context, we investigate a strategy for controlling the dynamics of swirling vortex structures in flow fields. In this case, we consider “coherent structures” of the flow field characterized by Koopman eigenfunctions. In particular, we investigate how formulating control in terms of these eigenfunctions changes the vortex dynamics. Given that there has been much recent work in data-driven computation of these coherent structures, we anticipate this work to be of considerable interest to scientists and engineers
The Association of Family and Neighborhood Characteristics with Utilization of the Seattle Fresh Bucks Program, Fruit and Vegetable Consumption, and Food Security
No full textThesis (Ph.D.)--University of Washington, 2025This dissertation evaluates heterogeneities in associations between the Fresh Bucksprogram in Seattle, Washington and program outcomes by household and
neighborhood characteristics. Fresh Bucks provides $40 per month to lower-income
households in Seattle for purchases of fruits and vegetables to increase consumption
and improve rates of food security. This dissertation first examines heterogeneities in
Fresh Bucks benefit utilization and changes to fruit and vegetable consumption and
food security by family composition following program enrollment. Next, I measure
associations between Fresh Bucks benefit utilization and neighborhood characteristics.
Finally, I examine associations between changes to fruit and vegetable consumption
and food security and neighborhood characteristics following program enrollment.
Findings from this work may provide context to decision-makers seeking to increase
equitable access to nutrition benefit programs like Fresh Bucks
Behavioral responses to heat stress in a North Pacific bivalve (Macoma nasuta)
No full textTo assess the effects of heat stress on bent-nosed clams (Macoma nasuta) I measure
relative siphon length as a behavioral response for individual bivalves kept at their preferred
temperatures and for those placed in a heated tank, over a period of five hours. The results of this
study provide no evidence to support a link between water temperature and siphon extension;
however, bivalves placed in a heated tank do appear to show a reduced or entirely absent siphon
retraction response when threatened, though further study is needed to provide definitive support
for this trend and the mechanism behind it
Evaluating the Gaseous Chlorine-containing Byproducts from the Use of an HOCl-derived Disinfectant
No full textThesis (Master's)--University of Washington, 2025This study investigates the gas-phase chlorine-containing byproducts generated from HOCl solutions under controlled conditions using Time-of-Flight Chemical Ionization Mass Spectrometry (TOF-CIMS). We analyzed how delivery flow rate, ambient humidity, and nebulization time influence the speciation and concentration of volatile Cl₂, HOCl, and NCl₃ within a sealed Teflon environment using relatively clean, compressed house air as the medium. Our results show that increasing the delivery flow rate enhances the detection of volatile HOCl while suppressing Cl₂ levels, suggesting that in the absence of strong delivery flow, Cl₂ dominates the headspace composition. Humidification of the carrier air substantially increased Cl₂ formation while accelerating the decomposition of HOCl. The use of clean house air led to minimal NCl₃ levels under the majority of conditions. These findings demonstrate the capability of TOF-CIMS to identify and quantify gaseous chlorinated byproducts with high time resolution and highlight the potential hazards of using HOCl-based disinfectants in poorly ventilated environments. Future experiments will focus on localized HOCl application to authentic laboratory / office furniture near the IMR inlet and refined stepwise dosing protocols to support calibration curve development and health risk estimation
Advancing Additive Nanomanufacturing of Quantum Optoelectronics
No full textThesis (Ph.D.)--University of Washington, 2025The fabrication of quantum optoelectronic devices faces significant challenges due to the limitations of conventional nanomanufacturing techniques, which hinder the precise integration of quantum materials with nanophotonic structures. This dissertation investigates electrohydrodynamic inkjet (EHDIJ) printing as a transformative nanomanufacturing approach that enables additive, high-resolution patterning at the nanoscale. First, EHDIJ printing is used to heterointegrate colloidal emitters onto suspended nanophotonic cavities, enhancing device performance while preserving structural integrity. Next, the technique is refined to achieve deterministic placement of single quantum dots, enabling integration into complex photonic architectures. Finally, EHDIJ printing is applied as a femtoscale reactor for synthesizing single perovskite nanocrystals with spatial and structural precision. These contributions establish EHDIJ printing as a versatile platform that unifies synthesis and integration, offering a scalable path toward sustainable manufacturing of quantum optoelectronic devices. This work opens new possibilities for quantum photonic circuits, on-chip single-photon sources, and hybrid device architectures previously limited by fabrication constraints
Detecting the Effects of Variant STING Agonist Administration on Dendritic Cell Endosomal pH Using the Ratiometric Method
No full textThesis (Master's)--University of Washington, 2025Peptide cancer vaccines have had limited clinical success despite their safety, characterization, and production advantages. We hypothesize that the poor immunogenicity of peptides can be surmounted by delivery vehicles that overcome the systemic and cellular drug delivery barriers faced by peptides. We introduce polySTING and NPSTING, copolymerized, mannosylated variants of the STING-3 agonist known to activate the cGAS-STING signaling pathway, promoting the release of type-1 interferons and pro-inflammatory cytokines leading to effective tumor immunogenicity. The STING-3 agonist is a non-nucleotide molecule that successfully activates the STING pathway, but it has poor solubility, which limits its usage in vivo. The developed poly-STING platform improves the drug's solubility and provides enzyme-triggered drug release upon delivery, which has been shown to induce improved therapeutic efficacy compared to the free STING-3 agonist. The Pun lab seeks to investigate modalities for optimization of the cGAS-STING pathway activation through investigating effects caused by mannosylation of the polymer. Dendritic cells (DCs) are crucial for initiating cytotoxic T-cell responses through antigen presentation via the MHC class-I pathway. The cGAS-STING signaling pathway enhances DC maturation and antigen cross-presentation but may interfere with pH-dependent antigen release systems such as the VIPER nanocarrier. This thesis investigates whether STING agonist variants alter DC endosomal pH, potentially affecting VIPER-mediated antigen escape. A ratiometric assay using FITC and Alexa Fluor 647-conjugated dextrans was developed and optimized for flow cytometry-based endosomal pH measurement. Protocol refinements—such as transitioning to a 96-well plate format and implementing valinomycin/nigericin permeabilization—enabled robust, high-throughput analysis with improved cell viability. Results confirmed biologically relevant endosomal acidification profiles over time in DCs. Experimentation showed that co-treatment with STING variants does not drastically alter the acidification trend when compared to PBS, but rather there is a slight delayed acidification. This implies that STING activation effects on endosomal pH might require time to become apparent. A 30-minute pretreatment experiment showed minor delayed acidification in experimental groups compared to PBS, with PolySTING being the most drastic. This assay lays the groundwork for evaluating how variant STING agonists, particularly polySTING and NPSTING, modulate endosomal pH and thereby influence antigen release and immune activation, guiding the design of more effective cancer vaccine delivery platforms
Nesting Ground
No full textThesis (Master's)--University of Washington, 2025Nesting Ground reflects on the hostile patterns and structures established through interpersonal connections. Formal investigations are efforts to understand the environment and systems the body finds itself in, and to relinquish a need for the sense of control. Included works navigate the body’s response to toxic relations, and how defensive reactions may prove detrimental to individual and community wellness. The structures of entwined bodies made from clay reference the dance of emotional entanglements and their static detriment. Built coil by coil, these forms parallel the relations and patterns I have traversed, materializing the outcome for recognition by the viewer of a shared experience
The Landscape of Brain Artery Network: Database Foundation, Graph Analysis, and Biomarker Application
No full textThesis (Ph.D.)--University of Washington, 2025The cerebrovascular network plays a critical role in brain health, with its structural and functional characteristics linked to various neurological and cardiovascular conditions. Despite this importance, current approaches to cerebrovascular analysis face significant limitations: they often rely on isolated morphological features that inadequately capture complex network properties, utilize tools with limited 3D manipulation capabilities, lack large-scale harmonized datasets, and employ analytical methods not optimized for vascular networks’ graph-like nature. These limitations hinder our understanding of how cerebrovascular architecture relates to neurological health and disease. This thesis establishes a comprehensive, reproducible framework for analyzing Brain Artery Networks (BANs) through graph-based approaches, integrating multimodal data to advance neurovascular health understanding across diverse populations. The framework consists of four major contributions. First, we created a harmonized, multi-site BAN dataset accompanied by demographic and clinical metadata, addressing data scarcity and heterogeneity through the development of VesselVoyager—an advanced 3D vessel annotation tool—and ComBat statistical harmonization. Second, we developed and improved advanced imaging sequences (iSNAP and CineMerge) that enable multi-contrast visualization and dynamic assessment of arterial pulsatility within a single acquisition, providing richer vascular characterization beyond static morphology. Third, we implemented specialized graph neu-ral networks tailored for vascular analysis, including a novel hierarchical graph transformer with edge-aware structural encoding that captures the intrinsic hierarchical organization of arterial networks. Fourth, we identified and validated clinically relevant biomarkers through systematic ablation studies. The impact of this work includes establishing a foundation for collaborative research through the Brain Artery Visualization & Analysis platform, enabling sophisticated quantitative analyses with lower barriers to entry. The long-term implications extend to precision medicine, where graph-derived vascular biomarkers may facilitate earlier disease detection, more accurate risk stratification, and personalized therapeutic monitoring in cerebrovascular diseases. Methodologically, our framework bridges imaging science and network theory, advancing analytical approaches that naturally represent the complex, interconnected nature of cerebrovascular systems. While limitations exist in demographic representativeness, imaging resolution, and causal inference capabilities, this thesis represents a significant step toward decoding the rich information contained in brain arterial networks, with the ultimate goal of improving outcomes for individuals affected by cerebrovascular conditions worldwide
Development of Third-Generation Gold Nanoparticles (CRISPR-AuNP) for Enhanced CRISPR Delivery to Hematopoietic Stem and Progenitor Cells
No full textThesis (Ph.D.)--University of Washington, 2025Efficient CRISPR ribonucleoprotein (RNP) delivery into hematopoietic stem and progenitor cells (HSPC, CD34+) enables stable genome editing with potential for lifelong therapeutic benefits from a single intervention. However, current methods like electroporation require specialized equipment and procedures, whereas viral vectors are costly and require living cells to assemble, limiting access in research and clinical translation. Synthetic nanoparticles offer a promising alternative. We previously reported a gold-based CRISPR-AuNP nanoformulation that delivered gene editing in HSPCs, favoring Cas12a over Cas9. Here, we demonstrate that Cas9 loads poorly into this formulation. By elucidating Cas9's physicochemical interactions with AuNP surfaces, we optimized the nanoformulation by pre-forming RNP complexes in a 2nd generation CRISPR-AuNP. This formulation demonstrated increased active Cas9 and Cas12a loading in tube but failed to deliver gene editing in primary cells in vitro. Further analysis of the CRISPR-AuNP physiochemistry with HPSC endosomes guided further optimization. Preformed RNP polyplexes were formed with thiolated poly(ethyleneimine)-poly(ethylene glycol) (PEI-PEG-SH) polymers at a 2 N/P ratio and conjugated to AuNP. This 3rd generation Cas9 CRISPR-AuNP achieved 13.23 ± 0.12% indels at the β-2-microglobulin (B2M) gene in HSPCs at a 100 pmol dose, with no observed loss in cell viability and cell entry within 6 hours. The platform's modularity extended to two additional CRISPR systems: Cas12a (15.07 ± 1.9% indels) and MG29-1 (13.39 ± 1.5% indels), highlighting its versatility. Most importantly, this nanoformulation can be assembled in a few hours at benchtop for <$70 per 1 million HSPC treated. We also demonstrate early data that this formulation can be modified with surface antibodies to facilitate active cellular targeting, with a future goal of testing these formulations in vivo for possible clinical translation. Very preliminary in vivo studies using untargeted 3rd generation Cas9 CRISPR-AuNP targeting the murine B2m gene in wild-type C57Bl6 mice showed detectable gene editing in multiple tissues with no elevated inflammatory responses or increased liver enzymes. These advancements position gold-polymeric nanoparticle hybrids as a simple, low-cost non-viral delivery system for CRISPR into HSPCs. The ability to rapidly assemble these particles with different CRISPR systems and polymers will greatly increase research access for multiple cell types
Healthcare Resource Utilization and Costs of Commercially Insured US Patients with Atopic Dermatitis Switching from First-line to Second-line Systemic Targeted Therapies
No full textThesis (Master's)--University of Washington, 2025Background: The recent expansion of Food and Drug Administration (FDA)-approved treatment options for moderate-to-severe atopic dermatitis (AD) has notably improved clinical management options. With the availability of these novel therapies, data on frequency of therapy switching and differences in healthcare resource utilization (HCRU) and costs between switchers and non-switchers are limited.Objective: To evaluate the frequency of treatment switching from first- to second-line systemic targeted therapies and compare HCRU and costs between switchers and non-switchers among commercially insured US patients with moderate-to-severe AD.
Methods: We conducted a retrospective cohort study using MarketScan health insurance claims data. Adult patients with AD initiating a first systemic targeted therapy (index date) between January 1, 2022 and December 31, 2022 were identified and followed for at least one year from index date. Two cohorts were classified based on whether switching occurred over follow-up, which was defined as discontinuation of first systemic targeted therapy and initiation of second systemic targeted therapy. All-cause and AD-related HCRU outcomes, including hospitalizations, emergency department (ED) visits, and outpatient services, were compared between switchers and non-switchers during the follow-up period. Total healthcare costs were also evaluated, categorized by medical and drug costs. Statistical significance was defined as a two-sided p-value of < 0.05.
Results: After a year following the initiation of first-line systemic targeted therapy, 466 (5.8%) switched to second-line systemic targeted therapy among the 8,063 patients with moderate-to-severe AD included in this study. Nearly all switchers (96.4%) had at least one AD-related outpatient service compared to 82.8% for non-switchers (p < 0.0001), and the mean number of visits was higher among switchers compared to non-switchers (5.12 vs. 3.20, p < 0.0001). AD-related hospitalizations and ED visits were rare. Mean total AD-related healthcare costs also were significantly higher among switchers compared to non-switchers (53,004; p < 0.0001), with drug costs accounting for approximately 99% of AD-related healthcare expenditures in both groups.
Discussion: We found a small proportion (5.8%) of patients switched from first- to second-line systemic targeted therapy after a median follow-up of approximately one year. Patients who switched therapies incurred significantly higher AD-related outpatient service use and total healthcare costs compared to non-switchers, which may potentially reflect either worsening disease severity or inadequate response or intolerability to first-line therapy. These findings emphasize the increased importance of personalized considerations for the selection of first-line systemic targeted therapy for patients with moderate-to-severe AD to reduce downstream economic burden. As additional therapies become available, future research exploring reasons for treatment switching and patient factors influencing response will be critical to guide clinical and formulary decision-making in this evolving treatment landscape