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Statins and PDGFRA Inhibition: A Synergistic Strategy Against Diffuse Midline Glioma
No full textDiffuse midline glioma (DMG) is a fatal pediatric brain tumor with limited treatment options. While PDGFRA inhibitors, like avapritinib, have shown some promise in the clinic, DMGs have been shown to develop resistance to treatment through metabolic adaptations, including increased fatty acid synthesis and oxidative phosphorylation (OXPHOS). This study explores the metabolic basis of DMG treatment resistance to avapritinib and seeks to identify novel drugs that could synergize with avapritinib to provide a durable treatment effect. We demonstrate that atorvastatin synergizes with avapritinib, enhancing cytotoxicity in DMG cells by disrupting lipid metabolism, subsequently leading to increased apoptosis. Furthermore, we reveal that DMG cells treated with long-term avapritinib, called avapritinib-persister cells, exhibit a heightened dependency on OXPHOS and are subsequently more susceptible to statin therapy. Our findings highlight that metabolic reprogramming is a key driver of DMG treatment escape and supports the further consideration of statins as potential metabolic inhibitors when treating DMG with PDGFRA-targeted therapy. Given their established safety and widespread usage, repurposing statins in combination therapy for DMG warrants further preclinical investigation to determine if this approach improves outcomes for DMG patients.Graduate Educatio
A Fieldhouse in the City: On the Image and Form of a Civic Amenity
No full textArchitectural imagery has come to possess a certain duality within contemporary discourse. As the mode of the image as a digital output – the computer-generated visualization of an architectural response – is increasingly overwhelmed by technical availability and outsourced labor, its productive role is seemingly diminishing. But concurrently, as a second, less tangible mode of imagery – the physical form and appearance of an architectural response – is increasingly pressured to address various external priorities, its civic responsibility is seemingly expanding. This conflict of necessity between the “architectural image” and the “image of architecture” raises the question: can imagery and form more critically interact to produce a civic effect?
This thesis proposes a reciprocal method in which both the image and form of a new civic building are designed and developed recursively. It foregrounds the computer-generated visualization as a constructive instrument that rationalizes an architectural response and projects its resultant metaphysical effects – conceptually generating a civic image and form simultaneously. The proposal subverts a conventional workflow by absolving the visualization from a predetermined artifice and leveraging its productive potential instead. It considers the park district fieldhouse, once a grand symbol of pride and equality among Chicago’s culturally diverse neighborhoods, a test case for the proposed method. Here, the project challenges the presumed form and democratizes the realized image of a new, prototypical civic typology. Ultimately, the thesis seeks to re-legitimize the architectural image as a vital medium to expand architecture’s communicative agency and capacity in the public domain.Department of Architectur
Nano-scale Noise Spectroscopy for Materials Applications
No full textThe rise of two-dimensional (2D) materials has opened new frontiers for exploring low-dimensional physics. These systems exhibit distinct electronic and spin behaviors compared to their 3D counterparts, and offer tunability through stacking, twisting, and thicknesses control. Yet, their micrometer-scale lateral size and atomic-scale thickness pose a major challenge for conventional condensed matter probes, calling for highly sensitive, local measurement techniques.
In parallel, quantum information science has also made exciting technological advancements in the past decades. Quantum sensing, built on the precise control of coherent quantum systems, has become a powerful tool in precision metrology, biosensing, and condensed matter physics. Among various platforms, nitrogen-vacancy (NV) centers in diamond, originally developed for quantum networks, have emerged as a highly sensitive, non-invasive nanoscale probe for studying spin and charge dynamics.
NV centers have already proven their value through pioneering studies of magnetic and electronic properties in quantum materials, often cross-validated by optical spectroscopy and electronic transport. These early efforts paved the foundation for using NV magnetometry as a standalone probe to uncover new physics. With a mature understanding of device fabrication, spin–sample coupling, and coherent control techniques, NV-based sensing now accesses previously unreachable regimes of spatial, spectral, and temporal resolution in condensed matter systems.
This thesis is driven by the question: What makes NV centers uniquely powerful as magnetometers for condensed matter research? Specifically, how do their quantum coherence and sensitivity in momentum and frequency space enable access to new physical phenomena?
The thesis presents work that spans both validation and discovery. First, we used NV AC magnetometry to measure the magnetic penetration depth in the 2D cuprate superconductor BSCCO, obtaining values and temperature scaling consistent with established results. This part is discussed in Chapter 5. More significantly, we uncovered a new regime of spin transport in atomically thin Heisenberg ferromagnets: magnon hydrodynamic transport. Through the coherent spin response of NV centers, we directly observed magnon second sound—an analog of collective density wave in fluid. This work also expands the experimental toolkit for studying fluctuation–dissipation phenomena in low-dimensional magnets with spin decoherence properties.
This thesis begins with an overview of quantum sensing with NV centers and recent advances in understanding 2D magnetic materials. I then introduce NV noise spectroscopy—the central technique enabling the discovery of magnon hydrodynamics. Chapters 3 and 4 present experimental observations and theoretical insights into magnon hydrodynamic transport. Finally, Chapter 5 summarizes our independent BSCCO measurements and ongoing efforts toward wide-field NV methodologies, providing a complete record of our contributions to this emerging field.Engineering and Applied Sciences - Applied Physic
Three Essays on Data-Driven Personalization and Targeting for Marketing Interventions
No full textCompanies today face significant challenges in personalizing marketing interventions while balancing long-term objectives, adhering to privacy regulations, and managing complex decision spaces. This dissertation addresses these core issues through three interconnected essays and provides practical methodologies for enhancing personalized marketing interventions in today’s data-driven environment.
The first essay (Chapter 1) demonstrates and tackles the challenges of optimizing long-term business performance through targeted interventions. It highlights how cumulative unexplained variations in repeated customer behavior can weaken the direct optimization of long-term out- comes. To address this, the essay introduces a surrogate index methodology using short-term signals, coupled with a novel separate imputation strategy to handle the churn and purchase processes driving customer value. Through simulations and a real-world marketing application, the essay demonstrates that the proposed approach significantly outperforms traditional methods in enhancing long-term targeting effectiveness.
The second essay (Chapter 2) examines how Local Differential Privacy (LDP) — a strong privacy technique that introduces noise into individual-level data — affects the accuracy of personalized marketing interventions based on Conditional Average Treatment Effect (CATE) predictions. We show that LDP induces heterogeneous and model-dependent errors that hinder accurate personalization. To address these limitations, we propose an honest post-processing method using an unbiased but noisy proxy combined with iterative boosting and a subgroup cross-learning strategy to ensure honesty and mitigate overfitting. Empirical tests demonstrate that our method significantly improves prediction accuracy and treatment prioritization, enabling organizations to achieve effective personalization despite privacy constraints.
The final essay (Chapter 3) introduces Incrementality Representation Learning (IRL), a novel multitask framework for predicting heterogeneous causal effects of marketing interventions. By leveraging past experiments, IRL efficiently designs and targets personalized interventions without extensive testing. It extracts generalizable low-dimensional representations of intervention features and customer covariates. Empirical validation using data from 274 promotional campaigns demon- strates that IRL significantly enhances targeting accuracy and effectively generalizes predictions to both known and untested interventions and customer segments, addressing challenges in high-dimensional decision spaces and cold-start scenarios. Additionally, the essay develops a decision framework and interpretation tool to assist firms in identifying critical design features and tailoring promotions for maximum profitability.Business Administratio
GAIA
No full textWhat is it like being bound to two places? Knowing that you must sustain both or
lose yourself? That is the feeling that Anthia, a young woman and Communer, must
contend with as she transitions into a Scavenger. Anthia hails from a universe where
planets are sentient and rely on their inhabitants to provide stability for them. These
planets bond to individuals known as Communers, entrusting them to speak on their
behalf and communicate their needs. These missives are passed to Scavengers, entrusted
by their home planet of Gaia to search the reaches of space and gather the resources
needed. But not everyone is appreciative of this connection. Others might even kill to get
it! When a pirate attack forces an emergency jump, Anthia and her team wind up stranded
on a foreign world. A foreign world that echoes hauntingly of home. To top it all off,
Anthia and her newfound companions find that everything is not quite shipshape on
board and threats exist within and withheld. Can they figure out why malignant forces
revived an ancient plague in time? And will Anthia choose to accept a bond to a place not
quite her own?
Gaia is a science fiction novel I wrote as a desire to answer that question for
myself. I am also from two places. I am fortunate in many ways because my parents
insisted on maintaining strong roots with our heritage and language. My hope is that by
presenting the experience of searching for connections through a sympathetic character,
other young adults might be able to find the answer for themselves.Extension Studie
Large Language Models and How We Train Them
No full textLarge language models (LLMs) are the technological revolution of the decade, yet the mechanisms behind how they were developed or how they work fundamentally are often misunderstood by the public—and even debated among AI researchers and industry leaders—despite their popularity. As a result, for many individuals, these models have become unexplainable black boxes, which can lead to misuse or over-reliance on LLMs as people fail to grasp how they work or what their current limitations are. Due to a dramatic increase in AI discussion over the last five years, there is also the problem of information overload. There are many resources on AI from academic papers, blogs, news articles, and more that cover many different topics in a vast literature, but few unify these ideas into a coherent framework that explains how modern LLMs are built and trained. Many resources are also inaccessible and assume deep background knowledge, or focus on narrow implementation-level and mathematical details. This thesis is a structured, theoretical introduction to large language models that aims to combine theory with intuitive explanations and bridge the gap between understanding AI and its usage.Computer Scienc
Trends and Disparities in Contamination by Per- and Polyfluoroalkyl Substances in United States Community Water Systems
No full textPer- and polyfluoroalkyl substances (PFAS) are a large class of anthropogenic compounds that have been widely used in consumer products and industrial processes for decades. Exposures to PFAS are ubiquitous and can occur through many routes. Hundreds of millions of United States (US) residents are estimated to be exposed to PFAS in drinking water and PFAS are detectable in the blood of nearly all US residents. Associations between PFAS exposures and several adverse health outcomes—including measures related to hepatotoxicity, immunotoxicity, and metabolic disruption—are well established. Despite the ubiquity of PFAS drinking water contamination and human exposure, past assessments have been limited by a lack of comprehensive PFAS drinking water monitoring and high reporting limits in drinking water datasets. Recently available statewide drinking water monitoring datasets provide an opportunity not only to re-examine the relationships between PFAS contaminated sites and drinking water concentrations in public water systems, but also to pursue environmental justice issues posed by PFAS contamination, which have been generally underexamined within the context of PFAS exposure routes and health risks. This dissertation first compiles a statewide monitoring dataset to examine sociodemographic disparities in PFAS contamination, further uses this dataset to investigate associations between PFAS-contaminated drinking water and COVID-19 mortality, and examines disparities in infrastructure to remedy PFAS contamination among water systems affected by PFAS contamination and at the national level.
In Chapter 1, I use monitoring data from 7,873 US community water systems (CWS) in 18 states and find that PFAS detections were positively associated with the number of PFAS sources and proportions of people of color served by these water systems. Numerous contamination sources, including industrial facilities, military fire training areas, airports, municipal solid waste landfills, and wastewater treatment plants, were associated with increases in drinking water concentrations of multiple PFAS (including perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS], perfluorohexanesulfonic acid [PFHxS], and perfluorobutanesulfonic acid [PFBS]). These associations were similar in directionality to prior work, despite differences in geographies, inclusion of a greater proportion of CWS serving smaller populations, and lower uniform detection limits. CWS sharing watersheds with PFAS sources served higher proportions of Hispanic/Latino and non-Hispanic Black residents compared to those without PFAS sources. CWS serving higher proportions of Hispanic/Latino and non-Hispanic Black residents had significantly increased odds of detecting several PFAS, which is likely a reflection of disparities in the siting of PFAS contamination sources. Results of this work suggest addressing environmental justice concerns should be a component of risk mitigation planning for areas affected by drinking water PFAS contamination.
In Chapter 2, I examine associations between PFAS contamination of US CWS and county-level COVID-19 mortality records prior to widespread availability of the COVID-19 vaccines. These analyses leverage two datasets: one at the subnational scale (5,371 CWS serving 621 counties; derived from the dataset compiled in Chapter 1) and one at the national scale (4,798 CWS serving 1,677 counties; derived from the US Environmental Protection Agency's (EPA) Third Unregulated Contaminant Monitoring Rule). These datasets are analyzed in parallel using multilevel quasi-Poisson regressions. In the subnational analysis, detection of at least one PFAS over 5 ng/L was associated with 12% higher [95% CI: 4%, 19%] COVID-19 mortality. In the national analysis, detection of at least one PFAS above the reporting limits (20-90 ng/L) was associated with 13% higher [95% CI: 8%, 19%] COVID-19 mortality. These findings support a positive association between county-level drinking water PFAS contamination and COVID-19 mortality. They also bolster the importance of systematic federal drinking water monitoring efforts for PFAS and remediation of contaminated areas for public health protection, potentially including infectious disease epidemics.
In Chapter 3, I evaluate whether water system characteristics and sociodemographic composition are associated with early adoption of advanced water treatment processes effective for PFAS removal (reverse osmosis, ion exchange, and activated carbon) among US CWS. I use time-to-event statistical methods to analyze US EPA treatment records available over the 2004-2022 period for 2,697 CWS with known PFAS detections and 36,611 CWS nationally. I find that, among systems not reporting use of the target treatment processes at baseline, 5.1% of systems (serving an estimated 20% of the population) reported adoption by the end of the follow-up period. Among systems with known PFAS detections and systems nationally, large and very large systems (serving larger populations) were significantly more likely to report adoption of the treatment processes. Racial/ethnic disparities were observed and were consistent across system sizes, particularly for the proportion of non-Hispanic Black residents. In contrast, disparities related to area-level socioeconomic status measures varied significantly by system size and I observed evidence of non-linear relationships for these measures. This study can inform ongoing national efforts to treat drinking water contamination by PFAS and its study design can be adopted to analyze the progress of drinking water regulations.
My dissertation presents evidence of sociodemographic disparities in PFAS contamination, the siting of PFAS-contaminated sites, and access to the treatment processes that can be used to remedy contamination. It also presents new evidence on the population health impacts of widespread PFAS drinking water contamination. Conclusions from this thesis further highlight not only the problem of PFAS contamination, but also the necessity of drinking water monitoring and national efforts to remediate contamination while ensuring environmental justice.Population Health Science
Borderland Architecture: Translating and Building Skills at the U.S.-Mexico Border
No full textThe Borderlands of the United States and Mexico are a unique area primed by two cultures on opposing sides of the Rio Grande River. This region of cultural exchange and ambiguity along the border is referred to as Mestizo and Chicano, varying wildly from static border fencing rooted in the defensive infrastructure of warfare that lines the western borderlands. Today, approximately twenty percent of the U.S. construction industry consists of unofficial migrant workers. Many laborers and their families face extensive barriers to gaining personal capital. In addition to labor exploitation, many of these laborers lack formal training.
Border towns in the Rio Grande Valley region rank low in U.S. educational attainment statistics, especially for those ages 18 to 64. Therefore, by speculating the potential for the border to be a place for educational access and exchange, the border expands its scope from primarily transferring people, culture, and capital to transferring knowledge. A learning hub in McAllen, TX, aims to foster cross-disciplinary collaboration and community empowerment. By offers a non-traditional approach to U.S. immigration, the hub uses education to mediate the complexities of labor, migration, and building techniques in the Borderland. Through construction and architectural collaboration through pedagogy, the learning center creates a space for binational collaboration to prepare migrants for societal integration. To prompt this, one may question what the regions migrant workforce training development look like if the Secure Fence Act of 2006 was not passed?
The model speculates diverse spatial programming and outside resources to address the needs of a rapidly evolving community, particularly in border cities like McAllen and Reynosa, with high net migration. By using materials and building techniques of the region, the training center cultivates a culture of stewardship for building management and cultural retention. By designing a space for skill development, safety training, industrial research, and societal integration, the center aims to improve the quality of life for immigrant and local populations at the border. This proposal can transform industrialization’s impact on border towns in Mexico and the U.S. The proposal advocates for a new building configuration that bridges the gap between academia and labor, enhancing interdisciplinarity.Department of Architectur
From Flow To Frequency: Finding Rhythm in Healing-Centered Inquiry. The Transformative Power of Healing-Centered Research, Youth Development, & Leadership.
No full textThis capstone explores the transformative possibility of healing-centered engagement through a strategic project that aimed to scale Flourish Agenda’s Akili Youth Development Model and advance Emancipatory Inquiry as a healing-centered research practice. Flourish Agenda is a national nonprofit organization dedicated to transforming schools, youth-serving organizations, and communities by fostering well-being for young people of color. Grounded in the principles of Healing-Centered Engagement, Flourish Agenda challenges deficit-based models by centering culture, agency, relationships, meaning, aspirations, joy, and community connection as essential elements of healing.
Rooted in the guiding question, What is required to scale healing?, this project integrates elements of design thinking, healing-centered frameworks, and DJ rhetoric to create conditions for sustainable, healing-centered change. Drawing inspiration from the art of DJing—remixing the art of social change—this capstone presents leadership as an adaptive practice that requires moving between flow and frenzy. Just as a DJ curates soundscapes by sampling, blending, and improvising, this project emphasizes emergent leadership as a creative process of remixing strategies, practices, and approaches to foster healing and transformation.
This strategic project unfolds across two primary outcomes: 1) Developing and scaling an Akili Youth Development Model and 2) Documenting culturally-based healing practices to develop and scale Healing-Centered Research.
This capstone explores the challenges of navigating a fast-growing organization, the tension between honoring legacy and innovation, and the complexity of measuring healing outcomes in meaningful ways. Drawing from DJ literacy, this project reframes leadership as a dynamic process of remixing—blending ancestral wisdom, community voice, and institutional knowledge to create transformative change.
Ultimately, this project invites healing-centered leadership as both a personal commitment and a collective practice. By embracing the principles of flow, rhythm, and emergent strategy, this work seeks to inspire educational leaders, youth-serving organizations, and community partners to remix learning environments as ecosystems of healing, joy, and liberation.Educatio
The Effect on Extubation of Early vs. Late Definitive Closure of the Patent Ductus Arteriosus in Premature Infants: A Target Trial Emu-lation Using Electronic Health Records and A Target Trial Emulation Comparing High-frequency Jet Ventilation Management Strategies for Respiratory Acidosis among Neonates with Respiratory Failure
No full textIt’s well established that the key advantages of a randomized trial include: marginal exchangeability between groups, clear specification of time zero, and synchronization of eligibility check and treatment assignment with time zero. These features become even more apparent when considering the challenges of drawing causal conclusions from observational data. A reliable approach to maintaining the key attributes of randomized trials in observational analyses is to design them in a way that explicitly emulate a hypothetical randomized trial aimed at answering the causal research question — the target trial.
Premature infants are often referred for the definitive procedural closure of the patent ductus arteriosus (PDA) with the failure of, or contraindication to, pharmacotherapy and the inability to wean respiratory support. However, once this need is identified, the importance of expedited closure is unclear. We first specified a hypothetical randomized trial (the “target trial”) that would estimate the effect on extubation of early (0–4 days from referral) vs. late (5–14 days from referral) definitive PDA closure. We then emulated this target trial via inverse probability (IP) weighting, using a single-institution registry of premature infants (born weeks or with a birth weight 1500 g) who underwent the definitive closure of PDA between January 2014 and October 2023. The objective of this study was to compare the effect of the timing of definitive closure (i.e., surgical ligation or de-vice occlusion) on early respiratory outcomes in premature infants without complex congenital cardiac disease.
High-frequency jet ventilation (HFJV) is often used in neonatal intensive care units (NICUs) to treat respiratory failure. In neonates initiating HFJV for hypercarbic respiratory failure, clinicians aim to adjust ventilator settings to achieve a gradual reduction in pCO₂. Rapid correction with a large shift in pCO₂ may lead to cerebrovascular spasm and increase the risk of neurovascular injury. However, specific management of HFJV peak inspiratory pressure (PIP) varies across institutions. Here, we use EHR data and aim to compare two dynamic PIP management strategies by emulating a progmatic target trial. We illustrate the use of inverse probability (IP) weighting to adjust for time-varying confounding.Graduate Educatio