Lysosomal Membrane Permeabilization Triggers GSDMD-mediated Pyroptosis through Cytosolic Release of Cathepsin B and L

Lysosomal membrane permeabilization (LMP) in macrophages by detergents, crystals and infectious agents triggers an inflammatory cell death, called pyroptosis, which is caused by cleavage and activation of a pore-forming protein, called gasdermin D (GSDMD), that disrupts mitochondrial and cell membranes and serves as a conduit that releases inflammatory cytokines. LMP-mediated cell death has been shown to play an important role in atherosclerosis caused by cholesterol crystals, gout caused by uric acid crystals, silicosis caused by silica crystals and asbestosis caused by asbestos fibers. Pyroptosis in macrophages is often caused by activation of cytosolic sensors of invasive infection or signs of intracellular damage, called inflammasomes, that recruit a family of inflammatory death-inducing proteases called caspases to cleave gasdermin D. However, the mechanism responsible for LMP-induced inflammatory cell death is not well studied. Here, we show that LMP in mouse and human macrophages triggers gasdermin D-dependent pyroptosis that is unexpectedly independent of the caspases and the inflammasome NLRP3 previously thought to cause pyroptosis in response to LMP. Instead, we show that LMP caused by crystals and lysosomal detergents releases the lysosomal proteases, cathepsins B and L, into the cytosol, where they activate gasdermin D to induce pyroptosis. Pharmacological inhibition of cathepsin B and L suppresses LMP-induced pyroptosis. Knockout of either cathepsin B or L on its own does not inhibit LMP-induced pyroptosis, but knockout of both cathepsins strongly blunts pyroptosis, indicating that either cathepsin can activate gasdermin D. Genetic deficiency of both cathepsins also reduces the release of the inflammatory cytokine interleukin-1beta (IL-1beta) ) from LMP-induced pyroptotic macrophages. However, unlike cell death, IL-1beta release also requires NLRP3 activation of caspase-1 to cleave pro-IL-1beta to its mature form, since it is blocked by the NLRP3 inhibitor MCC950, indicating that pro-IL-1beta is not a substrate of the cathepsins. Thus, lysosomal rupture triggered by macrophage phagocytosis of disease-causing crystals leads to release of cathepsins B and L into the cytosol, where they activate gasdermin D to form membrane pores, triggering caspase-independent pyroptosis.Graduate Educatio

Essays in Environmental Economics and Public Health

This dissertation comprises three essays focused intersection of environmental economics and public health, each examining a consequence of wildfire smoke exposure. The first chapter investigates the causal impact of short-term smoke exposure on hospital care utilization in Oregon. Using daily ZIP code-level panel fixed effects models (2008-2022), I show that wildfire smoke significantly increases both emergency department visits and inpatient admissions. I further estimate the cost savings under a counterfactual reduction of 2020-2022 smoke levels to those in 2008-2010, finding that avoided inpatient stays account for 80 percent of total healthcare savings. The second chapter examines behavioral responses to fine particulate pollution (PM2.5) and wildfire smoke across three domains: information seeking, recreation, and mobility. Leveraging weekly Google Trends at the DMA-level, monthly National Park visitation data, and daily traffic counts in Oregon, I find that increasing PM2.5 unexpectedly dampens search interest for most air-quality topics, heavier density smoke plumes reduce park visits especially in outdoor-focused parks, and smoke exposure reduces local travel volume. The third and final chapter focuses on the impacts of smoke plumes on health by examining monthly mortality in U.S. counties from 2006 to 2019. Using CDC mortality data, I find an additional smoke day raises all-cause mortality rates (per 100,000), with larger effects at higher plume densities and among older adults. I also highlight the robustness of smoke to different configurations (smoke days, binned, continuous measures).Public Polic

Artificial intelligence and fake reefs: what privative inferences and LLMs tell us about adjective-noun composition

The fact that people understand completely novel phrases is often taken as an argument that linguistic meaning is composed from the meaning of its parts. Thus, a central concern for the study of meaning is how that meaning is composed, especially for open-class content words like adjectives and nouns. This dissertation studies meaning composition and its interaction with context through the lens of adjective-noun modification and the privative inferences that sometimes result (e.g., a fake gun is (usually) not a gun, and a stone lion is not a (living) lion). This dissertation shows that privativity is not limited to a particular class of adjectives, which leads to a new, non-intersective semantics for adjective-noun composition which handles potential contradictions as part of composition. Further, we find that humans and modern large language models (LLMs) can generalize to the inferences of adjective-noun combinations that they have not seen before. Working with LLMs foregrounds the possibility that these inferences could be drawn by other means than meaning composition, such as memorization or analogy. In fact, success on this task is not explained by analogical generalization, as a computational analogy model and a human experiment involving analogy do not yield the expected inferences for all of the dataset. More broadly, the necessary adaptation in experiment design as well as reflection on our standards of evidence feeds into the broader, currently emerging discussion about how to study compositionality in humans and language models alike.Linguistic

Real–time Wireless Sensing at the Edge for In Situ Multi-Robot Deployment

Autonomous robots are increasingly being deployed in complex, unstructured, and often GPS-denied environments to support critical tasks such as search and rescue, wildlife monitoring, and exploration. In these domains, coordination among multiple robots is essential for improving task efficiency, spatial coverage, and resilience. Achieving effective multi-robot coordination, however, hinges on access to global state information such as relative positions, which is often difficult to obtain when robots operate under communication constraints and must rely on local onboard sensing alone. Visual sensors such as LiDAR and cameras offer a means of local observation, but their utility degrades significantly in the presence of occlusions or poor visibility. To overcome these limitations, wireless signals have emerged as a complementary sensing modality. By leveraging signal phase variations during a robot’s motion, it is possible to emulate a virtual antenna array and estimate bearing directions to signal sources. However, integrating this capability into mobile robotic systems, and extending it to multi-robot coordination tasks, presents several key challenges related to sensing accuracy, algorithmic scalability, platform constraints, and real-world deployment. The central objective of this thesis is to establish wireless signal-based directionality sensing as a robust and scalable onboard modality for coordination in in situ multi-robot tasks, particularly under constrained communication and sensing conditions. To realize this, the thesis makes contributions at the intersection of algorithm design, systems development, and real-world validation. In the first part, we develop a decentralized and distributed coordination algorithms for multi-robot exploration and mapping, relying on bearing estimates derived from signal-phase measurements using commercial off-the-shelf Wi-Fi cards. This approach eliminates the need for a shared map or a global coordinate frame, enabling coordination in GPS-denied and infrastructure-sparse environments. The system is validated under strict communication constraints where robots share only minimal information. In the second part, we extend this capability beyond traditional 2D planar or linear motion to unconstrained 3D free-space motion, allowing aerial robots to perform coordination. We introduce algorithmic and systems-level advances that generalize the bearing estimation process to three-dimensional trajectories and integrate them into a software toolbox deployable on mobile robots with onboard sensing and computation. Finally, we broaden the applicability of this sensing modality by demonstrating compatibility with low-power, off-the-shelf fish tracking tags operating in the very high frequency (VHF) band. These tags are widely used in marine wildlife research to enable remote sensing at long distances. We integrate this capability into a lightweight drone platform and demonstrate real world deployment in challenging marine environments while accounting for stringent size, weight, and power (SWaP) constraints. Overall, this thesis takes a significant step toward making wireless sensing a core primitive for mo- bile robotic systems. It presents novel algorithmic frameworks, open-source system implementations, and extensive empirical validation—both in simulation and in field deployments—that collectively establish wireless-based directionality as a powerful and general-purpose tool for multi-robot coordination in communication-constrained and unstructured environments.Engineering and Applied Sciences - Computer Scienc

Exploring Acoustic Couplings to the SiV center in diamond

The negatively charged Silicon Vacancy (SiV) center in diamond has shown extraordinary promise for quantum information applications, in particular quantum networking, due to its long-lived spin memory and high-cooperativity spin-photon interface. In addition to these excellent demonstrations towards quantum networking, the SiV center has also been demonstrated to exhibit a large susceptibility to acoustic phonons. While this susceptibility is typically considered a drawback for necessitating low-temperature operation, it also presents an opportunity to study the strong interactions of SiV centers with acoustic fields. In this thesis, we will discuss several results that focus on the integration of SiV centers with diamond nanostructures with interesting acoustic properties. Through this integration, we will show both how the SiV center can be used as an unprecedented probe of these engineered acoustic environments and conversely how controlling the acoustic environment can be used to unlock new potential for SiV center based quantum networks. Together, these results point towards the SiV center as an exciting candidate for realizing novel hybrid quantum systems composed of photon-mediated quantum networks in the optical domain and phonon-mediated quantum systems in the microwave domain.Engineering and Applied Sciences - Applied Physic

Fluency in Oral and Silent Reading: Creating a Balanced Foundation for Reading Comprehension

Fluency is a critical skill in many theories of reading development. This is because a hallmark of fluency—automatic word recognition—is theorized to facilitate the ability to read grade-level text with comprehension. Too many US children, however, are struggling to demonstrate adequate levels of fluency in oral and silent reading, and ultimately to comprehend grade level texts. Consequently, critical theoretical and practical questions for the field are: what text-matching approach is most effective for improving young children’s reading fluency, what levels of fluency are needed to succeed on grade-level reading comprehension tests, and where should educators focus to ensure children matriculate with the fluency skills needed to undergird grade-level reading comprehension? This dissertation responds to these questions in three thematically related papers that address the role of fluency in children’s reading comprehension. Paper 1 meta-analyzes the literature on fluency interventions to consider whether children should practice with texts that align to their grade level or to their individual ability. It compares the benefits of exposure to grade-level versus reader-matched texts. Paper 2 examines the role of fluency during silent reading and investigates the relationships between silent reading rate, stamina, and reading comprehension. It provides important insights pertaining to adequate fluency in the silent mode, which is essential for success on silent reading comprehension tests. Paper 3 integrates the findings in the first two papers and offers a practical guide to educators who provide targeted reading intervention support. It presents a revised model for identifying the primary need in reading intervention, explicitly attending to silent reading rate and stamina, and provides recommendations for supporting silent reading comprehension in Grade 3. Together, these studies increase our understanding of the factors that influence fluency acquisition in oral and silent contexts. In doing so, they contribute to our understanding of how to create a balanced foundation for reading comprehension and support children who fail grade-level silent reading comprehension tests due to inadequate fluency.Educatio

U.S. Rural-Urban Breast Cancer Screening Inequities: Leveraging Contextual Heterogeneity to Identify Solutions

Breast cancer screening is a critical tool for early detection and prevention, yet rural populations in the U.S. face persistent inequities in access and uptake. Existing research often treats rural communities as a monolith, overlooking contextual differences that may shape health outcomes. This dissertation unpacks rural settings' multidimensional characteristics to better understand and address inequities in breast cancer screening. Drawing on the Community Capitals Framework and guided by Public Health Critical Race Praxis, this mixed-methods dissertation examines how varying rural contexts influence health behaviors and aims to develop tools for identifying place- and equity-centered intervention pathways. The first paper addresses the limitations of standard rural definitions by developing a novel typology of rurality at the census tract level using latent class analysis (LCA). To do so, we compiled nationally representative data across seven domains of community capital — natural, cultural, human, social, political, financial, and built — for all rural census tracts in the U.S. (n=15,643). The LCA identified four distinct rural typologies: Outlying, Developed, Well-Resourced, and Adaptable Rural. These rural types varied in community capital profiles and social vulnerability, underscoring the need for more nuanced definitions in population health. Paper two builds from these findings using qualitative methods to explore how contextual heterogeneity shapes screening behaviors in two rural types, Outlying and Well-Resourced, in South-Central Washington State. Community focus groups identified how barriers such as gender norms, seasonal labor, geographic isolation, and uneven resource distribution emerge across community capitals. Though both rural types reported barriers, their underlying mechanisms differed. Four key themes emerged: seasonality and resource prioritization; distance as a resource-dependent barrier; gender roles and healthcare access; and race and place shaping resource distribution. These findings suggest that targeting barriers that cut across mechanisms, such as cultural and social barriers, may lead to larger impacts than uniform interventions. The third paper introduces a prototype agent-based model (ABM) simulating breast cancer screening behavior across the four rural types identified in Paper 1, using qualitative findings from Paper 2 to inform model rules and contextual parameters. Simulated agents represent screening-eligible women with four characteristics: remoteness, racial identity, poverty status, and insurance status. We found that screening behavior evolves based on these attributes and social network influence. Results show that insurance, poverty, and social connectivity most strongly shape outcomes. Social connectivity improved screening across all groups but had a more pronounced impact among insured and higher-income agents, suggesting connectivity may amplify access where structural barriers are lower. As a theory-building tool, the model clarifies which contextual factors may influence screening and provides a platform to test targeted multilevel interventions before implementation. Together, these studies challenge the notion of rurality as a singular category and propose an equity-centered framework for understanding how place-based differences shape health. By integrating quantitative, qualitative, and simulation methods, this dissertation advances efforts to design interventions aligned with the unique strengths and needs of diverse rural communities. These findings highlight the importance of context-specific, justice-oriented approaches to achieving health equity in cancer prevention and control.Population Health Science

scissor theories: biology, engineering, art

Most beautiful things we encounter in life (Taylor expansions, Jean Genet’s "Un Captif Amoureux", a California burrito, etc.) do not consist of a lattice of scissor mechanisms carefully interconnected to enable global mechanical deformations. This dissertation studies three objects which do. More formally, this dissertation examines the geometry, mechanics, and dynamics of systems which share the common geometric motif of a two-bar linkage – what we will call a scissor mechanism. First, we discuss the tail of the T4 bacteriophage – the contractile injection system – and demonstrate a coarse grained analytical model which allows us to treat the geometry and energetics of its contraction process. Next, we turn to the morphology of woven materials, and indicate the surprising geometric complexity of this quotidian regime. Finally, we introduce a class of metamaterials assembled from lattices of scissor mechanisms and trace a mathematical analogy to origami and kirigami which in turn inspires their name: “hasamigami”.Physic

China’s Command Revolution: Reforms, Adaptation, and Emerging Innovations in Chinese Military Command Capabilities

How and why has the Chinese People’s Liberation Army’s (PLA) approach to military command evolved across its modern history against the backdrop of technological advancements? The PLA’s continued development of command capabilities, consisting of functional components of theories, structures, and systems that enable command, along with political work and human factors, will be consequential in shaping its future battlefield decision-making and performance. The prevalent perspectives articulated within salient academic literatures and among U.S. military observers have anticipated that the PLA, as a force subject to political control of the Chinese Communist Party (CCP), could struggle to innovate and would likely maintain a highly centralized, relatively inflexible approach to command, which could be disadvantageous in conflict. However, this dissertation contends such expectations about China’s command capabilities and its limited potential to achieve innovative developments should be reevaluated, in historical perspective and considering significant transformations ongoing in the PLA today. The reality is far more nuanced and reflects a system that, within certain limits, can be centrally controlled but also capable of facilitating greater initiative and decentralized warfighting. Indeed, the PLA’s approach to command has evolved dynamically in reaction to technological transformations that are expected to reshape future warfare. For the full extent of changes observed to occur without learning from and imminent pressures of conflict and despite expected bureaucratic impediments, is puzzling relative to prevailing expectations. The adaptations and innovations that have emerged across multiple aspects of Chinese military command are tantamount to a revolution in command with significant implications for Chinese military power. The existing literature provides several alternative explanations, to include the influence of strategic culture, dynamics of civil-military relations, organizational explanations, and military learning through emulation. However, I contend the impacts of ideation about technology in future warfare, as constructed through expert networks reacting to leadership guidance, can provide a more compelling explanation for the full extent of changes in Chinese military command and constitutes a dynamic that can be generalizable to other major domains of Chinese innovation. In the process, Chinese leaders have tended to adjust styles of command across domains and levels of warfare in a manner that balances between political control and autonomy based on a calculus of risks and benefits. This dissertation introduces a theory of command innovation based on ideation that accounts for major changes in China’s approach to military command. Chapter 1 and 2 introduce that theory and its primary mechanism, examining the process through which ideation about technology in future warfare takes shape through a dynamic involving not only high-level direction on priorities from senior leadership but also construction and socialization of new concepts among key strategic, military, and scientific experts. In the process, I argue the PLA tends to be informed by not only its study of global trends in technology and assessments of foreign military approaches but also its uniquely scientific outlook on warfare, as reflected in its evolving approach within the discipline of military command science. Chapters 3-7 center on a series of case studies examining each major functional component of Chinese command capabilities, based on an approach of process tracing that considers changes in Chinese command concepts, structures, political work, systems, and approach to human factors (i.e., training and education of commanders) respectively. To that end, I leverage a range of primary source materials, including close reading of Chinese military textbooks, journals, and media products, as well as vignettes from Chinese military history and contemporary operations. Chapter 8 continues by examining current debates and the ideation process ongoing today within the Chinese military and scientific spheres focused on implications of artificial intelligence (AI) for future warfare. The final chapter concludes by considering how this theory of command innovation contributes to literatures on military and defense innovation, while evaluating theoretical generalizability and implications. This dissertation also seeks to contribute to understanding the implications of these trends for the future of command and evolving military balance. Across recent decades, the PLA has pursued informatization (信息化), an agenda centered on leveraging information technology as a core enabler of military power, which has reshaped dynamics of command. Presently, the PLA is pursuing an agenda of military intelligentization (智能化) to capitalize upon advances in artificial intelligence (AI) and related technologies. These trends have generated debates within the PLA on the complex interplay of human factors and technology, which PLA scientists and strategists believe necessitates renewed emphasis on human-machine integration, especially in command. Among impactful applications are support to military decision-making, including through automated processing and integration of intelligence information. Looking forward, Chinese leaders regard emerging capabilities as critical to contesting advantage in future conflict scenarios, yet the ultimate impacts on the military balance remain uncertain. Such uncertainty about impacts of disruptive technologies and their applications could increase the risks of misperception, especially as international competition intensifies, and could exacerbate security dilemmas. PLA efforts to operationalize new complex systems might increase frictions that could undercut intended advantages for decision-making, while potentially increasing the possibility of accidents, crisis instability, or misperceptions. In this regard, the PLA’s evolving approach to command decision-making also has significant implications for future strategic stability and deterrence.Governmen

Building Resilience Out of Air: Reimagining a Typology of Thin Shell Air-formed Shelters

In recent decades, a novel form of disaster architecture has emerged on grade-school campuses across the U.S. Midwest and Gulf Coast as thin-shell concrete monolithic domes. Constructed using pneumatic formwork, these FEMA-rated domes possess exceptional structural capacity to resist catastrophic loads, serving an everyday function for schools, most often as gymnasiums, while doubling as public shelters during high-wind events. This typology demonstrates a form of resilient architecture that is anticipatory rather than reactionary, permanent rather than temporary, and multipurpose rather than single purpose. However, structural optimization has overshadowed all other possibilities, producing spaces that privilege performance at the expense of experience. Historically, pneumatic and surface structures pushed the limits of architectural imagination, yet these structures have fallen into banal repetition. Heavy, bunker-like, and spatially austere, contemporary disaster shelters are more often utilitarian than visionary. While windowless hollow forms are an effective approach as a brief reactionary response, anticipatory architecture has an untapped potential to create shelters that provide dignity and comfort to a community in and beyond crisis. This thesis explores the possibility of building resilience out of air by reimagining FEMA-rated dome shelters through the experimental spirit of Frei Otto, Dante Bini, and Heinz Isler. Through a physical form-finding process that employs strategically restrained pneumatic forms to create solid casts, it investigates the unrealized formal and spatial potential of pneumatic formwork construction. Maintaining the community-scale and construction logic of existing FEMA domes, this research challenges the typology’s structural and programmatic conventions, proposing imaginative shelters that unite daily use and disaster preparedness with the aim of fostering resilient communities.Department of Architectur