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We Never Said You Weren’t Exposed: Risk in the Aftermath of the Train Derailment in East Palestine, Ohio
No full textThis thesis focuses on the cleanup of the February 2023 train derailment in East Palestine, Ohio, and ensuing concerns over its management. The primary focus is on the Environmental Protection Agency’s (EPA) role in the response: did EPA and relevant authorities manage and communicate risk effectively? A particular emphasis is placed on the cleanup of local waterways, a controversy representative of the wider cleanup. This thesis analyzes risk management and communication within the stream cleanup and broader controversy in three manners. First, by a journalistic account of how residents have responded to uncertainty, displaying the narrative of the crisis and psychologies present in town in the aftermath of a crisis: people who can and can not ‘move on.’ This split is often based on personal experience or harm. Second: by analyzing the theoretical grounds for controversy over the cleanup, grounding East Palestine’s events in existing literature on risk perception and assessment. Dispute in East Palestine arose due to incongruities between authorities and residents in risk characterization, leading to a lack of trust between the two. This points to a need for the analytic-deliberative model of risk assessment in crisis situations. Finally, a preliminary risk assessment is conducted for the stream cleanup based on conclusions from previous chapters, employing environmental fate models to analyze authorities’ decisions. All analysis is informed by interviews with EPA officials, residents, and relevant third parties. East Palestine is a cautionary tale: once trust in government is lost, it may not be regained.Environmental Science and Engineering A
Molecular mechanisms underlying regulation within the ubiquitin proteasome pathway
No full textTight regulation of protein homeostasis is critical for maintaining cellular processes. The ubiquitin proteasome pathway (UPP), one of the core regulatory pathways within the cell, acts globally to orchestrates protein stability. Ubiquitin is a finely conserved, 76 amino acid protein, featuring a β-grasp fold with a six amino acid tail at its C-terminus. The covalent transfer of ubiquitin, a 76-amino acid (aa) post-translational modification, to a protein target is a tightly regulated process, enacted through a three-part cascade. First, ubiquitin activation by the E1 enzyme (n = 2, humans) results in ubiquitin thioester bond to a ubiquitin-conjugating E2 enzyme (n > 50, humans) in an ATP-dependent fashion. Following, the formation of ubiquitin-protein conjugates is catalyzed by E3 ubiquitin ligases (n > 600, humans). Substrate specificity of ubiquitin transfer is regulated by the diversity of E3 ubiquitin ligases, whereas specificity of ubiquitin transfer is regulated jointly by the E2 and E3 enzymes. Collectively, the ubiquitin proteasome pathway forms a reversible, interconnected quality control network self-organized through biophysical properties and subcellular compartmentalization.
A fundamental question is how substrate is selectively targeted for proteolysis. In part one of this thesis, through structural and biochemical techniques, we explore how a prototypical ubiquitin ligase uses a cryptic ubiquitin binding site to constrain activity and confer chain selectivity within its distal catalytic domain. We leverage cryogenic electron microscopy to determine an atomic model of the apo-ligase and low energy intermediates associate with ubiquitin transfer. We demonstrate that the ligase architecture and domain motions of the noncatalytic modules is finely conserved between S. cerevisiae ortholog Tom1 and human ortholog HUWE1. Our model sheds light on how patient mutations distal to the catalytic module could influence activity of the human HUWE1.Biological and Biomedical Science
The Geometry of Secondary Terms in Arithmetic Statistics
No full textIn this thesis, we prove the existence of a secondary term for the count of cubic extensions of the function field of fixed absolute norm of discriminant. We show that the number of cubic extensions with absolute norm of discriminant equal to is , where and are explicit constants and only depends on .
This builds on the work of Bhargava-Shankar-Tsimerman and Taniguchi-Thorne, who proved the existence of a secondary term for the count of cubic extensions of with bounded discriminant. Our approach uses a parametrization of Miranda and Casnati-Ekedahl, which can be seen as a geometric version of the classical parametrization by binary cubic forms used by Davenport-Heilbronn. This allows us to count and sieve for smooth curves embedded in Hirzebruch surfaces, in the same spirit as Zhao and Gunther.Mathematic
Peering from the Parapet of Perturbative QFT
No full textModern experiments such as the Large Hadron Collider probe new physics through precise measurements that over-constrain Standard Model parameters to sub-percent accuracy, alongside broad searches for beyond-Standard-Model signals. Central to these efforts is perturbation theory, which approximates quantum field theory computations as series expansions in small parameters. Although the complete result lies in the full series, only the first few terms are computationally accessible, raising the question: when can perturbative predictions be trusted, and what alternatives exist when they fail? In this dissertation, we demonstrate that effective field theories (EFTs) can restore convergence by resumming perturbative series to all orders in the coupling. We illustrate this approach with examples from backward scattering in gauge theories, and the extraction of the strong coupling constant using heavy jet mass distribution from electron-positron colliders. Furthermore, by leveraging precision experimental data, we refine power counting in bottom-up flavor EFTs, imposing strong constraints on UV models of the SM flavor hierarchy. Finally, we address the breakdown of perturbation theory--manifested in non-convergent asymptotic series—-by interpreting diagrammatic renormalons as saddle points of the effective action, thereby developing a new probe into their existence via the path integral.Physic
Regulation of CD8+ T cell tissue residency following influenza infection
No full textDurable CD8+ T cell memory is a defining feature of adaptive immunity to pathogens. Among memory CD8+ T cell subsets, tissue-resident memory (TRM) cells are locationally positioned within nonlymphoid tissues to respond rapidly to secondary antigen encounter. The generation of CD8+ TRM is known to require antigen and specific cytokine cues. Although CD8+ TRM constitutively express the coinhibitory receptor PD-1 in the absence of antigen stimulation, the functional significance of PD-1 in regulating CD8+ TRM differentiation and function remains unclear. Here, we investigated the regulatory role of PD-1 in CD8+ T cell differentiation into TRM following infection with influenza virus, which targets the lungs and nasal cavity. Genetic deletion of PD-1 in virus-specific CD8+ T cells resulted in significant expansion of virus-specific effector CD8+ T cells, yet compromised the establishment of durable, functional CD8+ TRM in the lungs and nasal mucosa following infection. Transcriptional studies suggest that PD-1 loss altered CD8+ T cell differentiation in the lymph node by altering the duration of the G1 phase of the cell cycle and modifying the utilization of pioneer transcription factors (TFs) that regulate chromatin accessibility. Loss of PD-1 impaired the ability of effector CD8+ T cells to express the adhesion molecule CD103 in response to TGF-β signaling. In addition, PD-1 KO CD8+ T cells had a reduced ability to downregulate the tissue egress receptors S1PR1 and CCR7 following entry into infected tissue. During the memory phase, PD-1 KO CD8+ T cells in the lung expressed TFs that antagonize tissue residency, including Klf2 and TCF-1/Tcf7. The deleterious impact of PD-1 deletion on TRM formation was partially tissue-dependent, with a more profound reduction in TRM accumulation in the lungs than the nasal mucosa. These two tissues display distinct viral infection kinetics, differing requirements for TRM formation, and distinct capacities to support life-long CD8+ TRM. These factors, individually or in combination, may determine the impact of PD-1 deletion on CD8+ T cell fate in each tissue. Collectively, these findings support a model in which PD-1 deficiency enhances CD8+ T cell proliferation in draining lymph nodes but compromises their adaptability within infected tissues. However, the consequences of PD-1 loss are also shaped by the specific characteristics of the infected tissue microenvironment.Immunolog
Exploring the mechanisms and structures of N-acyl-D-Asn prodrug peptidases
No full textBacteria engage in chemical warfare to compete with other microorganisms in their environment. Throughout our history, we have benefited from this warfare by using the specialized metabolites produced as the basis for potent antimicrobial agents. Thus, understanding how bacteria produce these potential therapeutics and pesticides can help us increase the yields of already known metabolites, illuminate undiscovered metabolites, and even design novel metabolites based on natural ones.
In this thesis, I further our understanding of a class of specialized metabolites produced by bacteria called the N-acyl-D-Asn prodrug toxins. In Chapter 1, I delve into the various prodrug mechanisms developed by bacteria with a focus on those employing N-acyl-D-Asn prodrug motifs. In Chapter 2, I present the first structural and mechanistic studies of a type II prodrug peptidase, ZmaM, revealing a unique domain arrangement and an interdependence between these modules. In Chapter 3, I further our understanding of type I prodrug peptidases by probing how the type I prodrug peptidase ClbP recognizes its substrate and exploring the possible transporter partners of ClbP. In Chapter 4, I discuss how these results apply to the broader family of prodrug peptidases and can lead to future discoveries.Chemical Biolog
Several problems in extremal combinatorics
No full textThis thesis presents three distinct contributions to extremal combinatorics. First, it
resolves a conjecture by Bollobás, Brightwell, and Leader on the prevalence of unate k-SAT
functions, proving that for all fixed k≥2, almost all k-SAT functions on n variables are
unate (i.e., monotone after negating certain variables).
Second, it addresses a question posed by Sapozhenko on the enumeration of q-ary t-error
correcting codes. Improving upon previous bounds, it demonstrates that for a broad range
of parameters, the number of such codes is tightly bounded by the Hamming bound.
Finally, it investigates the commonness and uncommonness of systems of linear equations
over finite fields. Answering questions of Kamčev, Liebenau, and Morrison, it shows that all
2*k linear systems with k even and girth k-1 are uncommon over sufficiently large finite
fields, and provides a near-complete classification of common 2*5 linear systems.
This thesis provides new insights into the structure of various combinatorial objects and
contributes to the broader understanding of extremal combinatorics.Mathematic
Ultracold Atom-Polar Molecule Interactions: Discoveries, Surprises and Puzzles
No full textStudying ultracold chemical reactions with quantum state resolution reveals details of the reaction processes, especially with single quantum state preparation of the reactants and state-selective detection of reaction products. In this thesis, we investigate two main processes: KRb + KRb → K2 + Rb2 reactions, and Rb and KRb atom-molecule collisions.
In the KRb bimolecular reaction, we demonstrate the preservation of quantum coherence in bimolecular reactions for the first time, which is surprising in a reaction considered to be largely chaotic. Additionally, we proposed a coherent control scheme to manipulate product yields across different product channels. These results represent a critical step toward probing quantum coherence and entanglement in the chemical reaction.
In atom-molecule collisions between Rb and KRb, we discovered an exceptionally long-lived intermediate complex, KRb2, which can be photo-excited by trapping light. The observed complex lifetime was orders of magnitude longer than theoretical
predictions, underscoring the limitations of the current theory. We further explored the dependence of complex lifetimes on the initial quantum states and external electric and magnetic fields, providing additional experimental benchmarks to guide future theoretical work.
Separately, we found that inelastic collisions between hyperfine-excited Rb atoms and KRb molecules can lead to rotation excitation of KRb post-collision. By probing the product state distribution, the result suggests that mechanical angular
momentum is coupled to the spins. Such couplings are too weak in the current theory models to explain the result. Moreover, our result contradicts state-of-the-art coupled-channel calculations. These suggest that some subtle effects, such as molecular vibration and conical intersections, play a critical role in the reaction dynamics.
The final piece of the thesis describes the observation of resonant interaction between a Rydberg atom and an ensemble of polar molecules. Such hybrid quantum systems have been proposed for a wide range of applications. Our work provides an
experimental demonstration of resonant dipolar interactions between Rydberg atoms and ultracold polar molecules, paving the way for the realization of hybrid systems for quantum computation and simulation.Chemical Physic
Mythologies and Sound: A Composition Portfolio
No full textBefore starting my doctoral studies at Harvard, I was primarily focused on both
the improvisatory nature of music making and conceptualisations of sound as image.
Over the six years I spent at Harvard developing my musical thinking, the
improvisatory approach toward music making remained at my core, while the mystery
of sound-as-image was the focus of my conceptual development.
A leap was made in my music when I began combining my drawings with my
music in the form of experimental stop animation. This approach, first attempted in
Animal (2022), developed significantly, both technically and aesthetically, through the
works Fabric of Sorrow (2023), Mom (2023), root (2023) and most recently in bluer
womb (2025) where a complex polyphony between sound and image is explored. Yet,
while literal images found a place in my music in 2022, for me, sound itself has always
been an image –– sound can be experienced as a landscape, as a color, or simply as a
line. While in the past this was wholly conceptual or personally experiential, in recent
works, this musical thinking has emerged as a tangible quality of my music.
While there is the literal image on a screen in many of my recent works, my
conceptualisation of sound-as-image drove my compositional language in a new
direction during this degree –– wide polyphonies of musical material exist in my recent
works; compositional systems of material interrelation in which the form of the work is
‘opened’ as a space and this space can become a landscape which the materials
themselves sustain and move through. This can be seen in my works with animation,
but also in the instrumental works without visuals included in this portfolio: children's
games (2023), flocks of birds flying out of her belly (2024), 10am is when you come to
me (2025).
Working on these pieces, at some point it occurred to me that my works have
always been an expression of my nostalgic relationship with childhood. This nostalgia
exists as sensory fragmentations: stories, memories, spaces, people, landscapes, sounds.
As a child I would create stories, fantasies as a way to escape. Now, as an adult I create
images of nostalgia to reconnect with what I was trying to escape from. In this way, the
music I make is nostalgic. It is a translation of childhood nostalgias, a sonification of
these sensory fragments, these images, these flashes of feeling.
For me, my nostalgia runs deeper than a simple melancholy for ‘what was
before’. Nostalgia is in a sense mystical. While being deeply personal, my nostalgia is
also beyond me. It is a feeling that connects us to something larger than ourselves; it is a
connection to a shared, generational, foundational something. It’s in this way that I
believe nostalgia is mythological in a true sense –– nostalgia is a foundational,
somehow shared story that we appeal to for our sense of identity, and, in my work,
nostalgia presents itself as a work of art.
By engaging with the individual and their myth, the personal and shared, my
works become political –– as a myth and as a space, it’s my hope that my music is
something an audience could take refuge in and in which their nostalgia (their myths)
can be reactivated and, potentially, reshaped.Musi
Who We Are Is How We Win: Ethnic-Racial Identity as a Universal Developmental Asset for the Culture, the Credits, & College Student Success
No full textCompleting college is an educational milestone that has meaningful longer-term implications for students in the U.S. (e.g., economic mobility) and their children (Chetty et al., 2017; Reeves & Krause, 2018). Despite the prevalence of ethnoracially minoritized students in the K-12 and overall U.S. populations, Black and Latine students complete college at lower rates than their peers (Department of Education, 2020; U.S. Census, 2020), thus making economic opportunity harder to attain. College completion and healthy progression into adulthood require similar developmental tasks, e.g., defining one’s career, academic goals, and personal identities (Carnevale et al., 2010, 2013; Chickering & Reisser, 1997; Magolda, 2007). Thus, it is possible that a richer, more complex understanding of personal identity development as it relates to college success, career development, and race/ethnicity (i.e., ethnic-racial identity; Umaña-Taylor et al., 2014) would help close college success gaps. Ethnic-racial identity processes are linked with myriad positive developmental outcomes (e.g., Umaña-Taylor, 2023) and have been leveraged, along with concepts such as campus racial climate (e.g., Hurtado & Carter, 1997; Paris & Alim, 2014), to ground various K-12 reform efforts, collegiate cultural/affinity supports, and culturally relevant/sustaining educator programs. However, less work has explored systematically incorporating ethnic-racial identity, with its multi-dimensional, psychological construction, into models or the practice of college student success. I address this gap in my dissertation by first reviewing leading models for young adult development and college success and presenting a new model of postsecondary success that incorporates ethnic-racial identity. Then, I explored preliminary evidence of the model’s theoretical notions using a nationwide survey of 755 U.S. undergraduate college students—a convenience sample recruited online from multiple U.S. regions. Finally, I assessed the feasibility of bringing an ethnic-racial identity curriculum (i.e., The Identity Project) to college campuses using qualitative interview and survey data gathered during a campus-based pilot study with 48 undergraduate students enrolled at one private college. In doing so, I illuminate possible ways for colleges to leverage student ethnic-racial identity—the fuller, contextualized psychological understanding of race/ethnicity—as an asset on campus and, in turn, increase the probability of all college students attaining educational success and economic opportunity.Educatio