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Salient, resurgent, or a flash in the pan? A comparative legislative study of American industrial policy
Get PDFThis paper will conduct a comparative study of American industrial policy, focusing on the policies enacted during the late 1980s and under the Biden administration in response to high- tech challenges from Japan and China, respectively. It will build upon a model of transformation packages to understand how and why industrial policy gets implemented to argue that the recent pivot towards intervention and investment in federal decision-making stems from a good-faith desire to enhance innovation. That model will be deployed to theorize how the US will continue to compete with China into the future, and if new legislation like CHIPS and the IRA represent one-off measures or are part of a broader shift in American economic policymaking
Almost sure central limit theorems via chaos expansions and related results
No full textFirst author draf
Computational and experimental investigation into the self-limiting nature of electrodepositing ultrathin polymer films
Get PDF2025This master’s thesis presents a combined computational and experimental investigation of the electrodeposition process for ultrathin polymer films, with a particular focus on the self-limiting nature of the process. A numerical model, implemented using smoothed particle hydrodynamics within the LAMMPS framework, integrates Butler-Volmer kinetics and Stokes-Einstein equation-based approximation for polymer diffusion. The model, applied to both planar and pore electrode geometries, exhibits a distinct two-phase growth mechanism: an initial rapid deposition phase followed by a diffusion-limited regime which is continuously hindered by the forming polymer network and leads to self-limiting film growth. Complementary ex-situ and in-situ atomic force microscopy experiments corroborate the simulation results and are consistent with the two growth phases theory. These findings not only enhance the fundamental understanding of the electrodeposition process but have also laid the groundwork for future in-situ experiments and computational models
Quantifying pathological changes to myelin with high resolution birefringence microscopy and deep learning
Get PDF2025In the central nervous system (CNS), myelin, the insulating sheath around axons, enables rapid communication between brain regions, coordinating complex tasks such as cognition, memory, and motor function. However, insults to myelin due to neurodegeneration, aging, or injury lead to functional deficits, the underlying mechanisms of which remain incompletely understood. Accurate assessment of myelin integrity across large brain regions is essential for understanding disease progression and evaluating potential therapeutics. Electron microscopy and various optical imaging techniques have been demonstrated for high-resolution imaging of myelin pathology in post-mortem brain tissue, but lack the necessary imaging throughput and quantitative analysis required for true structural imaging of myelin. There remains a critical need for an imaging technique that combines high-resolution and high-throughput analysis of myelin, providing deeper insight into the impact of myelin degradation in different contexts. Birefringence microscopy (BRM) is an emerging technology which enables widefield (camera-based), label-free imaging for structural imaging of individual myelinated axons for analysis of myelin pathology. In this thesis, I present technical advancements that optimize BRM for high-throughput and multiscale structural imaging of myelin. I develop new imaging and analysis methods to enhance the quantitative capabilities of BRM, and identify key sample preparation protocols required for reliable, high-resolution imaging of individual myelinated axons. These optimizations establish BRM as a scalable tool for analysis of myelin integrity.
Building on this, I validate BRM for identifying myelin pathology in two rhesus monkey models of myelin damage: (1) circumscribed cortical injury and (2) age-related cognitive decline. I also implement deep learning tools to aid in the automated quantification of myelin pathology across large brain regions. In both models, BRM enables robust detection of myelin defects and their spatial distribution, which are compared to behavioral and functional metrics. Finally, in the cortical injury model, I evaluate the efficacy of treatment with mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for promoting myelin repair, demonstrating BRM’s ability to detect treatment-driven changes in myelin structure. Together, these investigations highlight BRM as a powerful tool for scalable, high-resolution analysis of myelin damage and repair, with broad applicability to studies of neurodegeneration, injury, and aging
Systems and methods for matrix-vector multiplication
Get PDFA patent filed on multiples techniques to implement efficient and scalable optical matrix-vector multiplication.Othe
Regulation of vascular smooth muscle: calponin 3 contributes to phorbol ester-induced cell contraction and is critical for cell proliferation and migration
No full text2025Under physiological conditions, vascular smooth muscle cells (VSMCs) exhibit a contractile phenotype, which maintains vascular tone through contraction. In response to vascular injury, VSMCs switch to a synthetic phenotype, contributing to tissue repair through proliferation and migration. While the Ca2+-calmodulin-myosin light chain kinase pathway is the best-studied mechanism regulating vascular smooth muscle (VSM) contraction, the regulation of actin filaments (F-actin) in this process is not fully understood. Apart from cross-bridge cycling, cytoskeletal actin remodeling is also essential for VSM contraction, yet the underlying mechanisms remain unclear. Calponin 3 (CNN3), an actin-binding protein, is expressed in both non-muscle and smooth muscle tissues, whereas its function has been minimally investigated in smooth muscle. The known functions of CNN3 in other cell types are closely associated with its regulation of F-actin. This study elucidates the roles of CNN3 in regulating VSMC contraction, proliferation, and migration, processes that are contingent upon F-actin.
This study reveals that CNN3, though containing binding sites for ERK and PKC, does not interact with either protein in contractile VSMCs and has no significant effect on ERK phosphorylation, suggesting it does not function as an adaptor protein in phospho-ERK-mediated VSM contraction. During DPBA-induced VSM contraction, the binding of CNN3 to F-actin increases after 5 minutes but subsequently decreases after 10 minutes, suggesting its biphasic role in regulating the availability of F-actin. The interactions of CNN3 with three actin isoforms—alpha-smooth muscle actin (α-SMA), beta-cytoplasmic actin (β-actin), and gamma-cytoplasmic actin (γ-actin)—are characterized here. In resting VSM, CNN3 binds to all three actin isoforms. Following DPBA-induced VSM contraction, the interactions of CNN3 with all three actin isoforms undergo significant changes, with isoform-specific changes observed across different cell compartments. These findings suggest that CNN3 acts as a stabilizer of contractile actin filaments and as a regulator of cytoskeletal actin, facilitating actin cytoskeleton remodeling during VSM contraction. Furthermore, this study shows that CNN3 knockdown disrupts VSMC proliferation and migration, highlighting its role in vascular injury repair.
Characterizing CNN3’s biological functions in contractile and synthetic VSMCs broadens our knowledge of its functions in these cells and provides insights into the mechanisms underlying VSMC contraction, proliferation, and migration, thereby advancing therapeutic strategies by identifying potential targets for vascular diseases associated with impaired or abnormal VSMC functions.2027-05-16T00:00:00
Power, politics, and finance: how multilateral development banks shape ASEAN’s energy transition - insights from Viet Nam and Indonesia
Get PDFThis thesis examines the effectiveness of multilateral development banks (MDBs) in shaping ASEAN’s energy transition through climate finance, focusing on Viet Nam and Indonesia between 2016 and 2023. Using a mixed-methods approach that integrates project-level data analysis with qualitative policy review, the study evaluates how the Asian Development Bank (ADB), Asian Infrastructure Investment Bank (AIIB), and the World Bank Group (WBG) mobilize financial and technical resources in two of ASEAN’s largest economies. The study finds that although Indonesia received more funding, MDB financial commitments contributed a greater share to Viet Nam’s climate finance needs, GDP, and renewable energy (RE) targets.Indonesia had a higher share of technical assistance projects, reflecting the country’s complex regulatory environment. The findings highlight the
importance of institutional capacity, and streamlined regulatory and policy frameworks in shaping MDB effectiveness. Regional initiatives such as the ASEAN Catalytic Green Finance Facility (ACGF) illustrate MDBs’ potential to catalyze coordinated efforts in ASEAN’s energy transition. The study concludes that MDB success depends not only on the scale of financial contributions, but also on how well MDBs navigate national and regional policy environments to accelerate the energy transition
Investigating the components of heterotypic immunity associated with protection against coronavirus related disease
Get PDF2025A few highly pathogenic coronaviruses (CoVs) have emerged in the human population in the past twenty-five years and have impacted the world on a global scale. Several demographic and clinical factors are associated with protection against severe disease from these pathogenic human CoV infections. In the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recent infection with a “common cold” causing human endemic CoV (eCoV) is associated with protection against severe coronavirus disease 2019 (COVID-19). Yet, the cross-reactive immune components providing this heterotypic immunity between heterologous coronaviruses have not been fully elucidated. We hypothesize that heterotypic immune protection is not mediated by neutralizing antibodies (nAbs) because of the diversity in spike protein receptor binding domains within the CoV family, but by alternative adaptive immune factors that target more conserved CoV regions. To test this hypothesis, we identified individuals from Boston Medical Center (BMC) with prior infections or vaccinations to SARS-CoV-2 or the eCoVs (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) and measured both homologous and heterologous CoV directed immune responses. First, in a study of risk factors of SARS-CoV-2 reinfection, SARS-CoV-2 antibody responses were similar between those with or without a SARS-CoV-2 reinfection and nAbs were not associated with long-term homotypic CoV protection. To explore heterotypic immunity, we classified individuals with or without a presumed or documented recent eCoV infection in a cohort of SARS-CoV-2 naïve individuals. Cross-reactive T cell and nAb responses against SARS-CoV-2 were similar between individuals regardless of recent eCoV infection history. Meanwhile, individuals with a presumed or documented recent eCoV infection had higher and correlative levels of Fc receptor (FcR) binding antibodies against eCoV spikes (S) and SARS-CoV-2 S2 subunit. Lastly to investigate the extent of coronavirus heterotypic immunity, we investigated immune components associated with SARS-CoV-2 mediated protection against subsequent symptomatic eCoV infections. Cross-reactive replication and transcription complex (RTC)-specific CD8+ T cells were associated with protection against symptomatic eCoV infections in individuals with a previous SARS-CoV-2 infection, while other eCoV-responsive T cells and nAbs were not predictive of heterotypic immune protection. In aggregate, nAbs were not associated with long-term protection against homologous or heterologous CoV infections and associated disease, but instead, antibody Fc effector functions and CD8+ T cells were associated with protective roles. These findings indicate that eliciting diverse immune functions along with nAbs in a future pan-CoV vaccine will be important to protect against disease from current and novel human CoVs
SMAD signaling in early foregut development and the basal cell program: mechanisms driving lung competence and airway maintenance
No full text2025During foregut development, several domains are rapidly specified into organs that are diverse in terms of cellular composition and function, including the trachea and lungs. These respiratory airways and alveolar regions are lined with an epithelium that conducts the critical functions of gas exchange, host defense, filtration and hydration. While the respiratory epithelium is essential to human health, airway and alveolar disfunction contribute to a multitude of chronic diseases that are major contributors to death and disability worldwide. Though animal models continue to progress our understanding of respiratory epithelial development, mature cell function and disease, in-vitro culture of human cell and tissue types can broaden our investigative abilities, enabling precise chemical and physical environmental modulation. In these studies, I utilized cutting edge in-vitro technology to investigate both the early stages of human respiratory epithelial development as well as mature airway stem cell function. First, I leveraged the induced pluripotent stem cell (iPSC) directed differentiation platform to enhance our understanding of the molecular mechanisms that control early embryonic development of the gut tube endoderm, with a particular emphasis on the signals that define the presumptive lung domain. Using multifactorial design of experiment (DOE), I observed a sensitive concentration dependent role of bone morphogenic protein (BMP) on priming the foregut to a respiratory fate. RNA sequencing of iPSC derived foregut patterned with decreasing levels of BMP signaling revealed dose dependent patterning of the foregut in an anterior to posterior manner from pharynx to lung to liver. Using in-vivo and ex-vivo animal models of early development, I validated the specific anterior-posterior priming of liver, lung and pharyngeal pouch fates within iPSCs and confirmed the central role of BMP in driving this process. Second, I sought to gain insight into the molecular program of the airway basal cell (BC), the primary stem cell of the airway epithelium, with a focus on BC heterogeneity. I employed lentiviral barcoding technology on primary human BCs to understand how the transcriptional profile of BC subpopulations informs stem cell function. Barcoding uncovered significant heterogeneity in both proliferation and differentiation ability of uniquely labeled BC clones that did not correlate with their starting gene expression profile. Analysis revealed a subset of BC clones generated a large pool of daughter cells, including basal and differentiated cells. This multipotent group of clones was used to identify the most stem BCs which were enriched for key regulators of TGF-β, Notch, and Wnt signaling pathways, including Follistatin (FST), delta-like noncanonical notch ligand 2 (DLK2) and Dickkopf Wnt Signaling Pathway Inhibitor 3 (DKK3), as well as downstream targets of the Salvador-Warts-Hippo (SWH) signaling pathway, connective tissue growth factor (CTGF) and cysteine-rich angiogenic inducer 61 (CYR61). Modulation of Hippo pathway kinases large tumor suppressor kinase (LATS1/2) resulted in augmented stem cell ability ex vivo and increased expression of BC stemness markers. In summary, these studies reveal important insights into respiratory development and stem cell function that can help generate more effective iPSC derived respiratory cell types and lead to a better understanding of pathological airway remodeling in the context of disease.2027-11-24T00:00:00