UCLA

Degenerative disc disease of the cervical spine is a highly prevalent condition, commonly requiring surgical intervention. While anterior cervical discectomy and fusion (ACDF) has long been the surgical standard of care, its limitations, including degeneration of the adjacent segments and complete loss of motion, have prompted the development of alternative solutions. Notably, cervical disc replacements (CDRs) were introduced to preserve the range of motion and reduce the likelihood of adjacent segment degeneration. However, despite their increase in popularity, clinical outcomes have indicated that mechanical failure of these devices can lead to early revision surgery.Based on the available clinical data, one of the most frequently reported mechanical causes for CDR removal is loosening and/or migration. In large joint arthroplasty, it is typically reported that relative cyclic motions between the bone-implant interface need to be below 40–150um to achieve successful long-term fixation. Failure to meet this threshold can lead to migration of the implant over time, resulting in an increase likelihood of implant failure. Specifically, migration- related failures are the leading cause of cervical device revisions cases, with 84% of CDR revisions and 96% of all adverse events being removed due to migration as reported in the FDA adverse event reporting database. Moreover, specific devices vary substantially in the reported rates of migration-related reasons for failure. Interestingly, these devices can vary widely in design features that could affect bony fixation and stability. Unfortunately, current preclinical testing may not be adequate in addressing implant fixation with relatively few biomechanical studies evaluating CDR fixation in the literature. In contrast, studies of loosening and migration have formed the cornerstone for preclinical testing of arthroplasty implants in the hip and knee. These studies have successfully predicted the clinical performance of joint replacements. Typically, investigations of migration in large joint literature utilizes composite long bones, which have been made commercially available. However, no such model exists for the cervical spine. The absence of a validated biomechanical testing model may have led to this lack of migration studies over the last two decades for CDR, representing a major deficiency in the current field of spine arthroplasty. Therefore, the overall objective of this dissertation is to develop comprehensive testing methodology to evaluate cervical device fixation and initial implant stability, through the fabrication of an in vitro biomimetic model and analysis of current devices for the relative contributions of specific design features to the overall stability of the device. Accordingly, this dissertation is the first step in developing a protocol to systematically assess fixation of CDRs. Chapter 1: Retrieval Analysis A retrieval analysis conducted as the first component of this dissertation established a clinical record of migration-related failures in current cervical disc replacements. Specifically, analysis of explanted devices revealed a significantly higher incidence of anterior migration in a ball-and-socket design compared to a fixed-core counterpart. These findings highlighted the role of implant design features in influencing fixation and stability. This clinical insight motivated the development of a preclinical testing platform to systematically assess the biomechanical behavior of CDRs under physiologic loading conditions. Chapter 2: Creation of a 3D-Printed Model To address the lack of established preclinical models for evaluating cervical implant fixation, a novel 3D-printed cervical vertebral body model was developed and validated. This biomimetic model featured a nonhomogeneous cancellous core designed to replicate the ultrastructure and material properties of human cervical bone. A range of lattice architectures and material densities were explored to produce a tunable and cost-effective platform for biomechanical testing. Uniaxial compression and shear testing confirmed that the model could replicate the load response of cervical bone, though limitations in replicating viscoelastic and ductile properties remain. Chapter 3: Comparison of a 3D Model and Polyurethane Foam Model The 3D-printed model created in chapter 2 was then benchmarked against a rigid polyurethane foam model, commonly used to simulate cancellous bone in long bone models, to assess their respective abilities to predict clinical performance. Through micromotion testing of multiple CDR designs the rigid polyurethane foam model was more sensitive in detecting differences in clinical observed migration and micromotion differences observed in retrieval data in chapter 1, suggesting it may be better suited for distinguishing clinical performance outcomes across varying implant designs. However, the 3D-printed model exhibited superior consistency and repeatability across trials. These findings underscore a trade-off between sensitivity and reliability in model selection and suggest that each platform offers distinct advantages. The foam model may be more appropriate for comparative micromotion testing across devices, while the 3D-printed model provides a robust and reproducible framework for future development of more accurate testing models. Chapter 4: Micromotion Testing of Five Different Cervical Device Designs Five distinct cervical disc replacement designs were evaluated using the validated testing model under both singular and combined loading conditions. Device design characteristics such as keel height, articulation type, ball-and-socket contact arc, and ball coverage angle were measured for each device and motions were assessed as a function of each feature. The results demonstrated that larger keel heights, smaller ball contact arcs, and greater ball coverage angles significantly reduced micromotion at the bone-implant interface. These findings suggest that specific implant geometries play a critical role in achieving primary stability and minimizing the risk of migration, which could inform future device design and regulatory approval pathways. This dissertation addresses a critical clinical need in cervical spine arthroplasty literature by developing a methodology for preclinical testing to evaluate the contribution of implant design features to overall device stability. By integrating clinical retrieval data with in vitro testing, this work establishes a comprehensive protocol for assessing fixation-related design features in CDRs. The insights gained offer a roadmap for improving implant design, predicting long-term clinical performance, and refining preclinical testing standards, ultimately contributing to safer and more reliable cervical spine arthroplasty solutions.

As California begins implementing Ethnic Studies as a high school graduation requirement, environmental advocates and educators are pushing for integrating climate literacy into K-12 education so students can attend to our worsening climate crisis. Ethnic Studies is poised to incorporate climate literacy since the climate crisis and environmental injustice most often and disparately impact low-income Black, Indigenous, and people of color (BIPOC) communities. Indigenous Land education affirms the importance of moral relationships with Land (Whyte, 2018) and centers the political goals of decolonization (Brayboy & Maughan, 2009; Cajete, 2000), making its approach to climate change congruous with the goals of Ethnic Studies. This dissertation examines how an earnest engagement with Indigenous Land education can expand curricular possibilities within Ethnic Studies classrooms, the difficulties encountered, and the support such an undertaking requires. Drawing on Critical Indigenous Research Methodologies as a guiding paradigm and Participatory Design Research as a meta-methodology, I collaborated with an early career Ethnic Studies educator of color working in a public high school in Los Angeles, California, as we sought to implement Indigenous Land Education into their classroom over ten months. The following research questions guided this work: 1) When co-designing an Ethnic Studies a year-long scope and sequence that seeks to embed foundational concepts of Indigenous Land Education embodied in the units, what design questions arise? 2) How is the design of the year-long scope and sequence enacted? 3) What challenges and opportunities arise during co-design and enactment? I use case study methods and narrative inquiry to describe and examine our processes. Working with a collection of information sources, including interviews, planning meetings, curriculum materials, and my research memos, I present the story of our design process, foregrounding the challenges faced and the supports needed to transform lessons and engage with Indigenous Land Education. This dissertation provides insights into how engaging with Indigenous Land Education develops the pedagogical and political commitments of Ethnic Studies educators as we face growing societal and ecological challenges.

The purpose of this research is to design and demonstrate a novel mechanism that harnesses lost energy during the absorption phase of the running stance by storing and then productively releasing it to assist with forward propulsion prior to toe-off. The mechanism is designed to reside within the geometric space of a running shoe midsole. Conventional running shoe midsoles rely on foams and other materials to cushion the shoe as it lands, resulting in energy loss. The device in this study functions by using the vertical impact force experienced in the rearfoot to pull back flexures in the forefoot into a latched position. When the weight is later transferred to the forefoot, the latch release is triggered. The energy stored in the flexures is then gradually released as the foot approaches toe-off. A prototype device has been tested on a uniaxial testing machine as well as under-foot. Test results show that the prototype midsole can provide a net energy return of 2.06J during propulsion, or a 154% energy return in the forefoot. The prototype operates under dynamic loads of up to 3400N, which corresponds to the running loads of a 220lb athlete. Individual parts in the prototypes were fabricated from FDM printed plastics (polycarbonate and carbon-fiber embedded PET) and spring steel. Stainless steel pins were used to assemble joints. The design is parametric and can be tuned to account for the weight or shoe size of different athletes, resulting in different energy return and loading magnitudes. Future directions for this work include reducing the weight and improving the stability of the device as well as improving large-scale manufacturability.

Eutrophication, the excess nutrient input to marine systems, can intensify harmful algal blooms (HABs) and contribute to ecosystem stressors such as hypoxia and ocean acidification. Along the U.S. West Coast, blooms of Pseudo-nitzschia spp. (PN), producers of the neurotoxin domoic acid (DA), pose risks to ecosystems, human health, and coastal economies. Understanding how natural and anthropogenic nutrient sources influence bloom dynamics is essential to assess ecosystem vulnerability and inform coastal management. This dissertation investigates the physical and biogeochemical drivers of PN HABs along the California coast, focusing on terrestrial nutrient inputs and their impacts on bloom intensity, toxin production, and co-occurring stressors.Chapter 1 outlines the scientific context and research questions, synthesizing prior work on eutrophication and HABs in the region. Chapter 2 uses a 20-year observational dataset to analyze spatial and temporal patterns of PN HABs across three hotspots: Monterey Bay, Santa Barbara Channel, and San Pedro Channel. Coastwide, DA events are linked to upwelling intensity, elevated chlorophyll-a, and silicic acid limitation. However, regional differences emerge—Monterey Bay events often occur under nutrient-poor, low-upwelling conditions, while PN blooms in the Santa Barbara and San Pedro Channels are associated with colder, nitrogen-rich waters. Chapter 3 implements a mechanistic DA production model within a three-dimensional hydrodynamic-biogeochemical framework for the Southern California Bight. Simulations show that anthropogenic nutrient inputs shift nutrient limitation from nitrogen to silica, enhancing DA production and increasing surface pDA by ~25%. Chapter 4 expands this modeling approach to the San Francisco–Monterey Bay region, incorporating nutrient inputs from rivers, wastewater, and San Francisco Bay. Terrestrial inputs increase coastal nitrogen by 11.4%, primary production by 6.5%, and chlorophyll by 4.5%, raising the likelihood of HAB-favorable chlorophyll concentrations by 10–45%. Declines in oxygen and pH are more localized. Chapter 5 synthesizes findings, emphasizing the importance of including terrestrial nutrient sources in predictive HAB models and ecosystem management strategies. The results highlight the value of integrated modeling for understanding and mitigating coastal biogeochemical change under increasing human and climate pressures.

This dissertation undertakes a cultural materialist approach to analyze residual and emerging feelings toward metanarratives of Basques and Basque-language culture as somehow innately radical, in light of the idea that we live in a time in which there is no alternative to the current late capitalist modes of production. What does it mean for one’s identity to embody resistance when resistance is seemingly futile? In the post-crisis context in which hegemonic power increasingly relies upon a precariously maintained consensus, what feelings of pride, confusion, cynicism, and hope are emerging? The objective is not to verify the truth behind such metanarratives of Basque exceptionalism, but rather to acknowledge their presence in political discourse and ideology, and to trace ways in which structures of feeling are being reshaped in the ongoing post-crisis, post-ETA context of the Basque Country.

The first chapter begins by tracing the nature and origins of both Basque exceptionalism and Basque ostracization, focusing in particular on the development of a counter-hegemonic Basque political and cultural movement in the 1960s and its evolution up to the current period. I then introduce Jacques Rancière’s concept of post-democracy and his critiques of consensus politics as theoretical tools for understanding how dissent and political contestation are neutralized within the Basque context, providing a panoramic, materialist perspective on contemporary cultural production and establishing the context for the subsequent chapters. The second chapter analyzes Fermin Muguruza’s Black is Beltza transmedia project (2014–2022), exploring its affirmations of a singular and radical Basque solidarity with ties to the African Diaspora and Third World liberation struggles. The third chapter looks at the clash of cosmopolitanism, professional-managerial class identity, and post-ETA Basque politics in Katixa Agirre’s novel Los turistas desganados (2017) and Aixa de la Cruz’s novel La línea del frente (2017), examining how both texts shed light on generational shifts in Basque identity, public perception of radical activism, and the cultural logic of late capitalism. The fourth and final chapter compares the music of the Pamplona-based groups Chill Mafia and Tatxers, focusing on how their work reflects generational critiques of neoliberalism and post-ETA consensus politics, as the former group highlights the contradictions underlying metanarratives of capitalism and Basque exceptionalism through meta-ironic humor and hedonism, while the latter group has led a post-punk revitalization of the Basque underground scene, emphasizing aesthetic innovation and appeals to material politics over Basque ethnocentrism.

Coral reefs are vital marine ecosystems increasingly threatened by disease and other lesions of unknown causes. Key knowledge gaps include the distribution, prevalence, intensity of lesions on coral, the identity of the causal agents, and whether human-induced factors influence lesion dynamics. Stony corals in the genus Porites respond to damage by developing small multifocal swollen pink spots (SMSPS). To explore these gaps, I quantified two recent SMSPS outbreaks along the north shore of Mo’orea, French Polynesia using three approaches. Overall, my dissertation furthers our understanding of the factors contributing to SMSPS in the South Pacific with results suggesting SMSPS are linked to human-induced stressors from developed watersheds. I first analyzed spatial patterns of SMSPS on Porites during outbreaks in 2016 and 2021. The highest prevalence and intensity of both outbreaks occurred in human-impacted bays, while SMSPS were less prevalent and intense along the less impacted north shore, suggesting a positive relationship between SMSPS and human influences. The dispersion of SMSPS during the outbreaks was Poisson distributed, likely due to factors such as the life cycles of the causative agents, and selective predation. Second, I documented temporal dynamics of prevalence, intensity, and weekly percentage change in SMSPS during the 2021 outbreak. A four-week photographic time series of affected colonies in the impacted bays revealed SMSPS were consistently in high prevalence and intensity, in all but one site. Further, SMSPS outbreaks consistently increased in intensity in one bay but fluctuated in the other. This has led to several testable hypotheses about the role of ecological factors in outbreaks of SMSPS. Third, I used three methods to identify agents causing SMSPS on Porites. I collected coral samples with lesions over three sampling periods using photography, histology, and tissue squashing. I found that both endosymbiont barnacles and trematodes were in polyps with SMSPS but never in unaffected polyps and that both agents can exist simultaneously within a colony. I made a novel discovery that these agents can coexist within an individual polyp. I also found several unidentified structures in SMSPS that deserve further investigation.

Dental caries remain highly prevalent worldwide, underscoring the need for more accurate and efficient diagnostic methods in dental education. Traditional radiographic interpretation, though essential, often suffers from variability and limited sensitivity, prompting exploration of artificial intelligence (AI) as a supportive tool. This study evaluated whether an AI platform (Second Opinion®) could enhance radiographic caries detection in a dental school setting by comparing its diagnostic performance to that of second-year dental students and by assessing its impact on faculty accuracy and consensus. AI performance was compared with caries detection exam results from second-year dental students in the 2023 cohort (Cohort 1). The same exam was later repurposed as a self-assessment quiz for the 2024 cohort (Cohort 2), and their performance was compared with that of the AI. Subsequently, a new AI-assisted caries detection exam was developed for Cohort 2, incorporating ≥75% faculty agreement as the gold standard for lesion classification. Diagnostic metrics (sensitivity, specificity, accuracy, precision, and F1 score) were calculated for students, AI, and faculty members—both without and with AI annotations. The AI platform outperformed both student cohorts, achieving higher sensitivity (89.5%) and accuracy (93.6%). Cohort 2 demonstrated significant improvement after structured self-assessment, with accuracy increasing from 40.4% in the self-assessment to 61.7% in the caries detection exam. Notably, Cohort 2 surpassed Cohort 1’s first attempt pass rate (96.25% vs. 55.8%). Among faculty, three of four members showed increased sensitivity and accuracy with AI annotations, and unanimous (4/4) consensus improved from 73.33% to 86.67%. The AI platform consistently exhibited higher diagnostic performance than second-year dental students, reinforcing its potential as a reliable adjunct in caries detection training. Moreover, AI-assisted workflows streamlined exam development and improved faculty consensus. While AI provides diagnostic support, it should complement—rather than replace—clinician-led education and judgment. With careful curriculum integration, AI holds substantial potential for elevating diagnostic standards and refining dental training.

As political contentions in the last few decades have structured and restructured reproductive healthcare in the United States, Los Angeles’ Black, Indigenous and birthworkers of color communities (BIPOC) have grown, both in person and online. Through the analysis of the history of obstetrics in the U.S., this project aims to give context to the particular methods of care practiced by BIPOC birthworkers in Los Angeles. Using ethnographic research done between 2022 and 2023, this analysis centers three birthworker-hosted events, and interviews conducted with three different birthworkers local to the area. The dissection of the data is framed through theories of empathy and haunting to help elucidate the way contemporary BIPOC birthworkers approach birthwork, especially when caring for fellow Black, Indigenous, and people of color. Intimate knowledge of the violent and racist history of obstetrics in the U.S. may provide BIPOC birthworkers a unique perspective of reproductive health, and can influence the work they do to create formal and physical birthworker spaces in Los Angeles.

Chimeric antigen receptor (CAR)-T cell therapy has shown impressive efficacy against deleterious hematological malignancies; however, CAR-T cell activity against solid tumors is curtailed by an immunosuppressive tumor microenvironment (TME) and a lack of targetable antigens homogeneously expressed by the malignant cells. To overcome these hurdles to effective immunotherapy, we and others have investigated CAR-T cells engineered to overexpress cytokines and other immune modulators. In addition to their ability to directly target and kill tumor cells, these “armored” CAR-T cells gain further functionality encoded in the armor, such TME reprogramming towards a more anti-tumor state, or autocrine cytokine stimulation to potentiate enhanced T-cell efficacy. In particular, macrophages constitute an abundant and immunosuppressive population within the tumor, yet they remain highly susceptible to polarization by molecules expressed by armored–CAR-T cells and have the potential to orchestrate endogenous anti-tumor immunity not restricted to the CAR-targeted antigen. In this dissertation, we evaluate CAR-T cells armed with novel armor combinations—intended to polarize macrophages towards an anti-tumoral phenotype—against orthotopic syngeneic solid tumors. After discovering CAR-T cells armored with interleukin (IL)-12 plus decoy resistant IL-18 (DR-18, CAR-12.DR18 T cells) are remarkably efficacious, we attempt to optimize the armor transgenes and their expression cassette to minimize cytokine leakiness or excessive expression, and present a novel solution to in vivo toxicity—a critical step for clinical translation—of pooling CAR-12.DR18 T cells with CAR-T cells engineered to overexpress an anti-VEGF scFv. Finally, we probe the mechanistic underpinnings of armored CAR-T cell efficacy and their effects on the TME, and demonstrate that pooled CAR-T cells are efficacious against antigen-heterogeneous glioma.

Protein-ligand and protein-protein interactions are essential in many biological processes. Therefore, it is important to characterize protein complexes, identify the specific binding sites and key residues involved in the interactions to better understand protein functions and design effective inhibitors. In particular, membrane proteins, which often exist in large oligomeric structures, are significant targets, as they account for more than half of drug targets. However, high-resolution structures of membrane proteins by traditional approaches prove to be challenging due to their large size, hydrophobicity, and low abundance. Native top-down mass spectrometry (TD-MS) has emerged as a powerful tool for structural characterization. Noncovalent interactions can be preserved while the intact mass of a native protein complex is measured to determine subunit stoichiometry, ligand interaction, and topology. Subsequent activation of the precursor ion dissociates the complex and/or produces fragment ions to identify sequence and post-translational modifications, also known as proteoforms. My dissertation research expands the applications of native TD-MS to characterize protein-ligand complexes and designs effective approach to extract higher order structural information of membrane proteins. The work here establishes unique fingerprints in native TD-MS reveal binding sites between proteins and phosphate-containing ligands, such as ATP and NADP+/NADPH. Electrostatic interactions between positively charged residues and the negatively charged phosphate moieties are strengthened in the gas phase to almost covalent-like. The interactions survive upon ion activation to produce fragments retaining ligand or the phosphate groups, leaving fingerprints to localize critical binding residues. In this work, we also applied native MS and TD-MS to characterize a model integral membrane protein bacteriorhodopsin (bR). Lipid-bound trimeric assemblies of bR are detected directly from the purple membrane. Next, fragmentation with collisionally activated dissociation (CAD) and electron capture dissociation (ECD) yields enhanced sequence coverage to unambiguously localize post-translational modifications and mutation sites, which can be used as a template to study G-protein coupled receptors (GPCRs). We hope to provide an initial guideline in studying membrane protein by MS. Inspired by the results from bR, we design and optimize native TD-MS with activated ion ECD (aiECD) to extract higher order structural information of three large membrane protein complexes. Controlled supplemental collision activation disrupts large membrane protein structures to release electron-based fragments, predominantly coming from the more exposed regions. On the other hand, cleavages from the more buried region require higher supplemental activation to be released. We demonstrate that electron-based dissociation is superior to all other methods because it can correlate fragmentation patterns to the native membrane protein structures. We continue to apply aiECD to investigate structural stabilization of membrane proteins induced by lipid binding. Lipid binding imparts resistance to fragment release compared to apo-forms, with each additional lipid binding event further decreasing the number of ECD fragments released. The selective lipid that displays drastic resistance to fragment release correlates to one that are important to protein structure and function. Lastly, this work also describes a different MS-based direction to characterize a novel enzyme ApnU that is otherwise challenging to obtain high-resolution structures by traditional approaches. From the intact mass analysis, the active enzyme is discovered to have a unique form as a covalently linked homodimer. Disulfide peptide mapping coupled with isotopic labelling identifies correct disulfide pairing, which is subsequently used as a constraint in building a predictive model. This thesis aims to develop mass spectrometry into an integrated tool for studying higher order structures, particularly to challenging candidates such as membrane proteins. Future applications of these methods could include discovering specific inhibitors and probing structural changes in membrane proteins.