Bioculture Journal
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Understanding cardiac metabolism through elucidation of mitochondrial protein-protein interactions
No full textThesis (Ph.D.)--University of Washington, 2021Cardiovascular disease is the leading cause of death worldwide, yet developments of new treatment has been stalled for nearly three decades and novel concepts and strategies are urgently needed. Mitochondria play a central role in cardiac physiology due to the extraordinary energy demands of the heart. It is well recognized that mitochondrial and metabolic remodeling can be maladaptive in the cardiac response to acute and chronic stress, therefore, treatments that specifically target mitochondrial metabolism would be highly desirable. Our limited understanding of mechanisms that connect mitochondrial dysfunction to cellular responses to stress has hindered progress of therapeutic innovation. In order to gain a more comprehensive understanding of the mitochondrial compartment, we used cross-linking mass spectrometry to determine the protein interaction landscape in respiring isolated mitochondria, intact cardiac tissue, and from animal models of heart failure. These efforts uncovered structural insight into how proteins behave in their native environments and in the presence of pathological stress. Comprehensive visualization of the diverse mitochondrial protein landscape is expected to pave for new therapies and novel drug candidates for heart failure. Furthermore, advancement of a technological strategy for system-wide study of proteins is applicable across a wide range of both physiological and pathological systems and models
Optimization Formulations and Algorithms for Cancer Therapy
No full textThesis (Ph.D.)--University of Washington, 2021Underlying all cancer therapy protocols are the competing objectives of maximizing tumor control and minimizing normal-tissue complications. As such, we can formulate many aspects of the cancer treatment planning workflow as optimization problems, enabling the development of mathematically rigorous treatment planning methods. In this dissertation, we present three novel optimization approaches to problems in cancer treatment planning: 1) a Markov decision process approach for optimizing multi-modality cancer therapy that balances the trade-off between tumor control and normal-tissue complication, 2) a nonconvex relaxation for the fluence map optimization problem for intensity-modulated radiation therapy that is well adapted to handle nonconvex dose-volume constraints, and 3) a hyperparameter optimization formulation for stereotactic body radiation therapy that has the potential to improve treatment plan quality and reduce the time needed to create a clinically acceptable treatment plan. We demonstrate the feasibility and potential benefit of each approach through numerical examples using synthetic and clinical cancer patient datasets. All project data and code are made openly available on GitHub
Development of an Expedient Two-Stage Gas Gun
No full textThesis (Master's)--University of Washington, 2021The ram accelerator is a hypervelocity launcher that accelerates projectiles through a tube filled with gaseous propellant. Combustion is initiated by the passage of the projectile and will overtake the projectile unless it enters the tube at a sufficiently high Mach number. With economical propellant mixtures such as methane/air, the projectile must be launched into the tube at approximately 1000 m/s. This limit on ram operation restricts projectile launch duties in smoothbore ram accelerators to powder guns and light gas guns.The baffled-tube ram accelerator (BTRA) retards the travel of the combustion-driven shock front with a series of baffles, preventing combustion from overtaking the projectile at low Mach numbers. Recent experiments with low velocity starting in the University of Washington’s BTRA have confirmed that successful ram operation can occur at a projectile entrance velocity of 650 m/s in a BTRA operating with methane/air propellant. These results open the door to using poorer-performing launchers than have previously been contemplated for ram projectile launch.
A subscale two-stage gas gun was constructed to determine the feasibility of ram starting with a gun that achieves these low entrance velocities through pressure and temperature multiplication of an extremely low-cost propellant, such as nitrogen or compressed air. Projectile launch conditions were predicted with the isentropic relations and gun performance was compared to a model of a single-stage infinite-breech gas gun. A high-speed camera was used to directly measure muzzle velocity and to infer pressure at the nozzle. The measured ballistic efficiency of the launcher indicates that substantial increases in propellant temperature and pressure were achieved, in line with predictions
Electric Vehicle Infrastructure Decision Support System
No full textThesis (Ph.D.)--University of Washington, 2021Electric vehicles (EVs) need DC fast-charging stations (DCFC) for long-distance trips. DCFCs are costly investments and so charging station companies want to install them in locations where they expect high utilization. Further, government agencies are usually interested in ensuring that DCFCs are available on all roads and adequately spaced so that residents do not feel anxious about EV ownership. DCFC deployment therefore must balance the private and public objectives. This thesis presents a framework, ChargEVal, for simulating charging station deployment scenarios using agent-based modeling (ABM). The ABM utilizes behavioral models for simulating vehicle choice for the trip and charging choice during a trip. ChargEVal supports multiple users to submit multiple simulations simultaneously. ChargEVal also has a dedicated results viewer for viewing the simulation summary statistics and agent state values facilitating detailed insight and simulation comparison. Results from a few sample runs, model verification, and sensitivity analysis are shown. We also answer the question of whether it is more cost-effective to create a new charging station vs upgrading an existing station with more plugs. While the current implementation of ChargEVal is specific to the state of WA, USA; the underlying framework is generic enough to be applied to any geography at any scale
Dreaming of the Great Migration
No full textThesis (Master's)--University of Washington, 2021Dreaming of the Great Migration is a hybrid of literary fiction, poetry, images and familial interviews that intersects and fills the space in between my families’ migration story and the imaginative and creative characters of North, a projected literary novel that I hope to complete in my continuous exploration of fiction writing
Community-Based Collections Training: Producing Indigenous Museum Professionals
No full textThesis (Master's)--University of Washington, 2021Tribal institutions need to meet specific western museum standards and provide culturally appropriate care for their cultural objects. Currently, there is a lack of training opportunities in the museological field addressing how tribal museums can meet the needs of their communities, maintain museum standards, and develop professional staff to fulfill museum mission and goals. This project aims to assist tribal museums build an in-house training program to fit their specific cultural and community needs. Research supporting this work found best practice examples of museums creating inclusive opportunities for community stakeholders through content development, workshop facilitation, and serving in an advisory capacity. Current museum decolonization efforts mirror these practices and expand upon them by providing in-person access to collections, hands-on learning opportunities, and repatriation of objects through relationship building. Logic models used in evaluative processes assist in planning the training program, resource listing, and desirable outcomes. This training toolkit emphasizes the pre-planning envisioning process and brainstorming sessions between the tribal museum and its collaborative partners. Training elements include western museum skill-building, the prioritization of culturally appropriate collections care, incorporating community voice and experiences, the activation of local resources, and the integration of cultural traditions. Using this toolkit, tribal museums identify culturally relevant experiences to meet their training goals. Upon completion, trainees have museum work experience, personal relationships in the community, and a deeper connection to the culture. This effort culminates in furthering efforts to diversify the museum field through the production of Indigenous museum professionals
Hematologic parameters and bone marrow flow cytometry features in patients with GATA2 and RUNX1 germline mutations ; Evaluation of frequency of 11q aberrations in patients with Burkitt-like lymphoma and other aggressive B cell lymphomas: correlation with histopathology and clinical characteristics
No full textThesis (Master's)--University of Washington, 2021For patients presenting with cytopenias, the clinical presentation and histopathological distinction between an inherited (germline) bone marrow failure syndrome and an acquired bone marrow failure/myelodysplastic syndrome (MDS) can be challenging. Prompt and precise diagnosis of is critical to inform appropriate management before a leukemic transformation. GATA2 and RUNX1 are known germline pre-disposition mutations affecting master transcription factors important in lineage development. Here we aimed to develop a screening assay to help assess patients found to have germline GATA2 mutation and assist in germline variant curation. We compared the hematologic parameters and early bone marrow flow cytometric features in 8 patients with germline GATA2 mutations to 15 patients with aplastic anemia at our institution. To further consider the specificity of the findings in GATA2 deficiency patients, we compared their findings to 9 patients with germline RUNX1 mutations. Consistent with prior studies, our patients with GATA2 mutations showed less pronounced anemia and thrombocytopenia than those with aplastic anemia. Findings in the marrow, including the absence of hematogones, and reduction in NK cells, also support prior studies. Furthermore, compared to patients with RUNX1 mutations, patients with GATA2 mutations showed significantly lower B cells (of lymphocytes) and NK cells (of lymphocytes), and higher T cells (of lymphocytes). Interestingly, we also identified patients with RUNX1 mutations to have significantly more PDCs than patients with GATA2 mutations. Differences in our findings from prior studies, including similar peripheral blood absolute white counts, absolute neutrophils, absolute monocytes, absolute lymphocyte counts, and B cells or monocytes in the marrows of our patients with germline GATA2 mutations, are due to the small size of patient cohorts given the rarity of these germline variants as well as to variable disease status at presentation for evaluation/inclusion in these studies (i.e., pre-MDS, MDS). The combined findings contributed to the understanding of how these mutations establish variable pre-leukemic states predisposing to myeloid malignancies and supported the development of effective screening strategies. Burkitt-like lymphoma with 11q aberration (BLL-l1q) is one of the newly described provisional entities with morphologic features, immunophenotype, and gene expression profile similar to Burkitt lymphoma (BL) but lacks MYC rearrangement. Whether this entity is a distinct category or a variant of BL, diffuse large B cell lymphoma (DLBCL), or high-grade B cell lymphoma is still controversial. Few cases have been reported, leading to poor understanding of clinical presentations, treatment regimens, or full understanding of the landscape of mutations/copy-number alterations in BLL-11q. Here we aimed to evaluate the frequency of 11q aberration in our patients and their histopathologic characteristics, clinical presentations, and responses to therapy received. Thus, we performed genomic array on 10 BL patients in all ages, 5 DLBCL or HGBCL patients with CD10 or BCL6 positive and BCL2 negative under 60 years old (“Burkitt-like” group), and 4 DLBCL or HGBCL patients with CD10 or BCL6 positive and BCL2 positive under 60 years old. No typical 11q gain/loss pattern were found in our patients according to WHO classification at this time point. One patient in the BL group was identified with 11q terminal deletion, which is within the regions identified by prior BLL-11q studies. In addition to 11q aberrations, other findings in the BL group and the DLBCL or HGBCL with BCL2+ group further reflect previous studies on patients with BL and DLBCL. We concluded that the groups of patients are currently too limited for meaningful statistical assessment of the frequency of 11q aberrations, but suggest that 11q aberrations are not highly frequent in our “Burkitt-like” cases. We also observed the limitations on performing genomic array on older FFPE samples. Our future directions include requesting and running more recent samples, using stored RNA for transcriptome, and considering other significant findings in Burkitt-like patients without 11q aberrations
Test of Effortful Control as a Moderator of the Relation between RSA & Temperament
No full textThesis (Master's)--University of Washington, 2021Prior research examining associations between negative affect (NA) in childhood and respiratory sinus arrythmia (RSA) has found mixed results. One possible explanation for inconsistent findings may be that there are moderating factors. One potential moderating factor is effortful control, such that the effect of RSA on negative affect depends on a child’s level of effortful control. Another possible explanation is that there may be an understudied quadratic effect of RSA. We hypothesize that 1) at low levels of effortful control there will be a quadratic relation between NA (fear and frustration) and baseline RSA, but at high levels there will be no relation; and 2) these patterns of relations will be the same for RSA reactivity (RSA task – RSA baseline). The present study utilized a sample of 306 children (Mage = 3.05, SDage = 0.07). Results did not support curvilinear or interactive effects in the prediction of frustration, however, there was a significant, quadratic interactive effect when using baseline RSA as a predictor of fear. The results suggest the association of RSA with children’s negative affect is complex and might depend on the specific emotion
Adaptive or absent: A critical review of building system resilience in the LEED rating system
No full textThesis (Master's)--University of Washington, 2021With time spent indoors dominating the lives of individuals across developed nations particularly within Europe, North America, and Australia, protecting indoor environmental quality becomes critical to protecting human health, and building systems play a critical role in doing so. As stressors like COVID-19 appear, conflicting system priorities can underline the need for resilience in all building systems. Sustainability rating frameworks are used in the engineering and architectural fields to motivate and reward the use of sustainable practices. As such, it is crucial to ensure these frameworks genuinely encourage resilience in building systems. This paper conducts a review of the LEED BD+C v4.1 framework for New Construction through a credit-level analysis. This is done to determine the extent to which resilience of building systems beyond the scope of structure is encouraged. In order to do so, relevant credits were identified, tabulated and deconstructed according to four key resilience properties: diversity, efficiency, adaptability, and cohesion. This analysis is expanded to the LEED Gold certified Husky Union Building on the University of Washington’s Seattle campus. Specifically, the ventilation systems and the related awarded credits are evaluated along the same resilience properties to better understand how the LEED framework rewards resilience in practice. An analysis of the ventilation performance in terms of indoor CO2 concentration over three academic quarters is also conducted to determine how the LEED certification relates to performance. The findings conclude that while efficiency is well supported in LEED, diversity, adaptability, and cohesion can be enhanced. The HUB is found to reflect diversity and efficiency within the ventilation design but performs inadequately, failing to maintain healthy CO2 levels 9.8% and 22.4% of the time during the Autumn and Winter quarters respectively. The author concludes that the existing rating system does not adequately encourage the wide adoption of resilience needed for long- term sustainability but provides a strong base upon which improvements can be made. In short, LEED proffers credits that would reward resilient designs but does not yet actively inspire them
Inverse problems for fractional operators involving a magnetic potential
No full textThesis (Ph.D.)--University of Washington, 2021In this thesis, we study forward and inverse problems for fractional operators involving a magnetic potential. We show that many properties of fractional operators are preserved under the perturbation by a magnetic potential. Besides, we carefully use Runge approximation properties to obtain strong results when we study inverse problems. More precisely, we determine both the magnetic potential and the electric potential from exterior partial measurements of the Dirichlet-to-Neumann map in the linear fractional inverse problem by using the Runge approximation property and an integral identity; we also determine both the magnetic potential and the non-linearity in the semi-linear fractional inverse problem by using the Runge approximation property and a first order linearization