Quantifying Noise in Optical Redox Ratio Imaging

Characterizing cellular metabolism through noninvasive imaging of metabolic cofactors NAD(P)H and FAD has become a powerful diagnostic tool, with the Optical Redox Ratio (ORR) serving as a key quantitative metric. However, widespread adoption of ORR imaging is hindered by the lack of standardized image quality requirements. This study addresses that gap by analytically deriving expressions for the variance of ORR measurements as a function of photon shot noise and dark current contributions. Using statistical conditioning, we modeled the expected pixelwise ORR variance and verified the model through simulated image sets and experimental data. We observed that variance decreases with higher photon counts and frame averaging, aligning with theoretical predictions. The results showed strong correlation between analytical and empirical variance, even under varying noise conditions. This work provides a quantitative foundation for evaluating ORR image quality and can inform future acquisition protocols and data processing. Ongoing efforts include developing a MATLAB application for variance analysis and preparing a manuscript to disseminate these findings

Shell Quilt: Piecing Memory through Quilting, Collage, and Printmaking

Shell Quilt is a mixed media quilt and accompanying book which collect an amalgamation of found, hand dyed, and printed fabric pieces. This project serves as a visual tether and inquiry into my late grandmother Sylvia’s life and a way of piecing together memories of my time with her. As a conceptual frame for my thesis project, Shell Quilt, I have looked to the process of femmage, a term initially coined by Miriam Schapiro and Melissa Meyer, which I interpret as a portmanteau of feminism and collage. Through the lens of femmage, I explore the processes of collage, quilting, and print mediums and processes, in the work of the Folly Cove Designers, as well as artists like Margaret Kilgallen, Hương Ngô, Kiki Smith, and Faith Ringgold

Weep No More, My Lady (Oh! Weep No More Today): Love, Violence, Printmaking, and Kentuckian Futurity

Situated within a regressive political climate, this essay considers the writer’s thesis artwork Weep No More, My Lady as a simultaneous account of Southern gendered violence and a desire for healing. Through personal and historical connections to Kentucky’s material culture, the work navigates binaries of class, race, and gender that have dictated the dominant contemporary conception of the region. Placing the competing forces of care and brutality in dialogue, Weep No More, My Lady translates these theoretical challenges into formal attributes. The work suggests modes of making — stitching, unraveling, tearing — can act against the construction and naturalization of hierarchy in the United States. Similarly, its use of printmaking mirrors historical discourse, since printmaking is both archival and able to meaningfully break from its own repetitive precedent. Therefore, Weep No More, My Lady attempts to reconcile a harmful past with sentimental longing, seeing a way forward in the process

Retirement Plan Access among Low-Wage Workers in 2024: Implications for SECURE 2.0

Households in the United States struggle to save for retirement, and the problem is acute for low- to moderate-income (LMI) households. In 2022, the federal SECURE 2.0 Act created an expansive suite of policy approaches to facilitate saving in LMI households. This brief discusses key provisions of the act and presents findings from the Workforce Economic Inclusion and Mobility (WEIM) survey of a nationally representative sample of vulnerable workers in the United States. The findings suggest opportunities to improve upon the SECURE 2.0 Act’s provisions

SPINOR: Exploring the sub-30 MHz Radio Sky in Fine Resolution for the First Time

The SPINOR (Spinning Past-Ionospheric Network for Observation of Radio) program is developing tunable, narrow-band, resonant antenna networks for observing radio frequencies below 30 MHz. This frequency range has not been studied since exploratory missions in the 1960s due to ionospheric blockage requiring large space-based missions, but it offers unprecedented scientific observations. These include capturing direct observations of exoplanet magnetospheres and their interactions with solar magnetic fields, advancing heliophysics and space weather monitoring, exploring solar system magnetospheres and lightning, and mapping the redshifted 21 cm hydrogen line from the early universe. Most existing proposals to fill this observational gap employ large constellations of satellites for interferometry due to the long wavelengths. For example, GO-LoW is an MIT Haystack Observatory proposal for an interferometric mega constellation of 3U CubeSats with vector sensors. Its electrically short sensors enable simultaneous full-sky fine spatial and spectral resolution mapping, but their low sensitivity requires a very large constellation size to observe faint sources. SPINOR consists of spinning, deployable tethers with adjustable lengths to produce high-sensitivity maps across multiple resonant frequencies. This approach enables groundbreaking observations with a smaller constellation size compared to traditional interferometric designs. By leveraging modern super-resolution algorithms and a stable rotating beam pattern, SPINOR offers repeated all-sky coverage and unbiased surveys of the radio sky. Several technologies require demonstration, including low-noise readout electronics, tether deployment, precise attitude determination during slew, and deconvolution algorithms. High-altitude balloons, sounding rockets, and LEO, GTO, and cislunar CubeSats will be used to demonstrate this program’s feasibility

Digital and Physical Spaces: All at Once

In this thesis, I explore our experience of digital and physical spaces in the ever-increasing presence of technology. By investigating the intersections of these spaces, I focus on how our experiences in the physical world are processed through the digital space, to re-merge in lived spaces. Through digital collage paintings, I explore how assisted chance and machine destruction can be productive in the formation of space that is not possible on the screen. By using the drop shadow as primary content, my work takes on the arrangements of surface and space—rather than the requirements of the physical world. In addition, I use the physicality of paint to concretize the digital image into physical space and insert myself between both the digital and the physical world. Through my work, I hope to call attention to the way we process the digital space and physical space, all at once

Leveraging arginine catabolism to treat metabolic complications

Fasting and caloric restriction are effective to treat patients with pre-diabetes or metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), but intensive lifestyle changes are difficult for many to implement and sustain. Therefore, by identifying and studying fasting-mediated signals, we hope to elicit and convey the therapeutic effects of fasting against MASLD without actual physiological fasting. We discovered a key pathway in the liver through unbiased transcriptomic screening in fasted mice, a novel glucose fasting-activated effector: the amino acid hydrolase, arginase 2 (ARG2). Our previously published data demonstrates that forced hepatocyte-specific Arg2 overexpression is sufficient to reduce peripheral insulin resistance and hepatic steatosis in pre-diabetic and MASLD models in mice. In this thesis, I am to investigate how ARG2 conveys its therapeutic effects and examine its efficacy to bring forth new therapies that mimic the actions of ARG2 to ultimately treat MASLD and MASLD-related metabolic disease. In the first part of my thesis, I define the structure-function relationship between ARG2 mitochondrial localization, arginine hydrolase activity, and the metabolic effects of ARG2. I generated and tested two ARG2 mutant constructs, one lacking the putative N-terminal mitochondrial targeting sequence (MTS, Arg21-22) and the other lacking its ureahydrolytic activity (Arg2H160F). Hepatocyte-specific overexpression of the mutant constructs in obese, diabetic (db/db) mice showed ARG2 attenuates hepatic steatosis independent of mitochondrial localization or ureahydrolase activity, and that enzymatic activity is dispensable for ARG2 to augment total body energy expenditure. Furthermore, ARG2-mediated increase in glucose-, insulin tolerance, and glucose appearance suppression during hyperinsulinemic-euglycemic clamping requires both mitochondrial localization and ureahydrolase activity. Seahorse respirometry in hepatocytes in vitro, and quantification of heavy-isotope-labeled glucose oxidation in vivo further revealed that both Arg21-22 and Arg2H160F mutants failed to induce ARG2-mediated increase in hepatic and systemic oxidative metabolism, respectively. These results further complement our previous work in ARG2 by providing a structure-based mechanism of ARG2 with respect to its metabolic effects and demonstrating that hepatic Arg2 is a prominent metabolic gene. In the second part of my thesis, I investigate the contribution of and necessity for hepatocyte ARG2 in prevention against MASLD progression to confer the metabolic effects in the pathogenesis of MASLD and its related metabolic complications. The results demonstrate that hepatocyte-specific Arg2 deletion impairs ureagenesis, TCA cycle, and mitochondrial function which has real physiological metabolic consequences. Hepatocyte-specific Arg2-deficiency drives obesity, liver steatosis, and insulin resistance in aging-associated metabolic decline and diet-induced mouse models of MASLD. Mechanistically, impaired oxidative metabolism and MASH in Arg2LKO mice is reversible through supplementation of NAD+ via nicotinamide mononucleotide or nicotinamide riboside. Translationally, Arg2-deficiency generates metabolite alterations in nitrogen flux, TCA cycle flux, and oxidative metabolism which is consistent with biomarkers perturbation that independently predict severe incident MASLD/MASH nearly a decade in advance from 106,606 healthy participants in the UK Biobank. Therefore, hepatocyte-specific Arg2-deficiency represents as a new paradigm to demonstrate the urea cycle’s hierarchical control over TCA cycle flux to regulate mitochondrial oxidative metabolism. Together, providing mechanistic insight into the long-observed association between urea cycle impairment and MASLD. We then identified a readily available pharmacological reagent, ADI-PEG 20, and found arginine depletion via ADI-PEG 20 is viable and holds great therapeutic potential as a candidate for treatment against obesity and MASLD. Furthermore, ADI-PEG 20 treatment induced favorable metabolic effects that were independently abolished in mice with liver-specific Fgf21 and Becn1 deletion. This study reveals a novel role of arginine catabolism in the pathophysiology of MASLD which is dependent on liver-specific functions such as FGF21 and autophagy. Together, our findings suggest that hepatocyte arginine status is central and modifiable in treatments against MASLD and metabolic complications

The Conservative Case for Leaving Harvard Alone

The Supreme Court precedent allowing the IRS to revoke a university’s tax-exempt status is a textualist’s nightmare

Studies in Algebraic Cycles: Hodge Theory of Degenerations, Regulators, and Cluster Varieties

This dissertation brings together results in Hodge theory and the theory of cluster varieties. The second chapter, based on a paper written in collaboration with Devin Akman and Matt Kerr, uses admissible normal functions to establish the first finiteness result for zero-dimensional components of the Hodge locus. The third chapter, based on joint work with Matt Kerr, shows that weak polar- ized relations constrain possible adjacencies of mixed Hodge structures across boundary strata in geometric compactifications. The fourth chapter gives a geometric construction of a 6-dimensional cluster variety with a disconnected mutation graph, as discovered by Yan Zhou. These three chap- ters employ different techniques, but they are tied together by the common threads of algebraic cycles and the Hodge theory of degenerations

Real-time System Availability for Cyber-physical Systems

Cyber-physical systems (CPSs), such as autonomous vehicles, are increasingly being deployed. The sensing, control, and actuation loop in CPSs must complete within strict timing constraints. Missing a real-time deadline can lead to catastrophic consequences, as CPSs continuously interact with the physical world. This highlights the importance of real-time system availability (i.e., timely execution) in CPS tasks, going beyond traditional security goals that primarily focus on confidentiality and integrity. From a security perspective, two factors affect real-time system availability. First, attackers with access to hardware resources in CPSs may disrupt the execution timing of real-time tasks. Second, the deployment of security mechanisms inevitably introduces runtime overhead, which can also impact task execution timing. This dissertation presents security mechanisms designed to ensure real-time availability from the following two perspectives. Defending Against Denial-of-Service (DoS) Attacks from the Privileged Software Stack: Privileged software, such as the operating system, manages hardware resources. When compromised, it may prevent security-sensitive tasks in CPSs, such as control tasks, from accessing the CPU or I/O devices in a timely manner. This dissertation first presents a real-time trusted execution environment (RT-TEE) to guarantee secure and timely access to the CPU and I/O devices for security-critical CPU tasks, even under a compromised operating system. With the increasing deployment of GPUs in CPSs to accelerate AI workloads, ensuring the timely execution of GPU tasks has also become essential. To address this, the dissertation then presents a real-time trusted execution environment for GPUs, called AvaGPU, which guarantees secure and timely access to GPU resources for security-critical GPU tasks under a compromised operating system. Real-time Performance Guaranteed Security Mechanisms: Deploying security mechanisms in real-time systems can lead to deadline misses, posing challenges to system reliability. To address this, this dissertation proposes efficient security mechanisms that are designed with real-time performance in mind. In particular, it introduces ARI, a policy-based mechanism for attesting the integrity of real-time mission execution. ARI enables a practical trade-off between security and real-time performance, overcoming the high runtime overhead associated with existing state-of-the-art solutions