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Studies On The Structural Basis Of Oxygenic Photosynthesis, David Flesher Jan 2025

Studies On The Structural Basis Of Oxygenic Photosynthesis, David Flesher

Yale Graduate School of Arts and Sciences Dissertations

Oxygenic photosynthesis — performed on all seven continents by green plants, algae, and cyanobacteria — supports the global biome through its ability to capture and store light energy. This is achieved through a series of protein complexes collectively known as the photosynthetic apparatus. During my PhD research, I’ve investigated the structural basis for how these protein complexes capture this light energy and transduce it to redox energy. My thesis work, summarized in this dissertation, can be grouped in two broad research themes: (i) structural studies on Nature’s water oxidation reaction, explored in Part I of this dissertation; and (ii) the …

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Cell State Dependent Strategies For Resolving Fundamental Properties Of Ligands Via Receptor Processes, Andrew Goetz Jan 2025

Cell State Dependent Strategies For Resolving Fundamental Properties Of Ligands Via Receptor Processes, Andrew Goetz

Yale Graduate School of Arts and Sciences Dissertations

Ligands may carry information through features such as their concentration, identity, and spatial distribution. Cells that can resolve these properties gain access to additional dimensions of information which may be beneficial as certain ligand properties possess unique features (e.g., ligand identity does not disperse with distance the way concentration does). Cells can accomplish this, at least in part, through the use of signaling cascades initiated by membrane receptors which bind to the ligand and activate downstream processes. The properties of these signaling cascades depend on the "state" of the cell (a property encompassing important cell features like protein levels and …

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Livy's Historiography Of Roman Colonization, Talia Boylan Jan 2025

Livy's Historiography Of Roman Colonization, Talia Boylan

Yale Graduate School of Arts and Sciences Dissertations

Many early modern and enlightenment readers of Livy’s Ab urbe condita approached that work as a trove of local, colonial histories rather than an account of Rome’s rise to power— the interpretation favored by modern scholars of Livy as well as, on occasion, by Livy himself (e.g., in Praef. 1). This dissertation recuperates the localized mode of reading employed by pre-modern readers of Livy by treating his notices concerning colonies as self-contained nuggets of Italian history embedded within the imperial edifice of the Ab urbe condita. It explores how Livy worked to accommodate the colonial history they contain to the …

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Coordinated Wnt And Shh Signaling In Hair Follicle Mesenchyme Development And Regeneration, Yiqun Jiang Jan 2025

Coordinated Wnt And Shh Signaling In Hair Follicle Mesenchyme Development And Regeneration, Yiqun Jiang

Yale Graduate School of Arts and Sciences Dissertations

Developmental morphogenesis requires cells to balance proliferation with differentiation, often regulated by multiple signaling pathways. While most studies consider these pathways as additive, less is known about how they interact to regulate fate transitions. In this dissertation, I use the hair follicle dermal condensate (DC), the first differentiated mesenchymal population of the skin with the ability to instruct new hair growth, to study morphogens interact to regulate the dermal mesenchyme.Wnt and SHH are necessary and sufficient for DC formation, during which cell cycle exit with molecular DC gene expression occur simultaneously. Interestingly, high Wnt alone is sufficient to induce cell …

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Smart Synthesis: Harnessing Electrochemistry To Enhance Catalytic Water Treatment, Aidan Francis Meese Jan 2025

Smart Synthesis: Harnessing Electrochemistry To Enhance Catalytic Water Treatment, Aidan Francis Meese

Yale Graduate School of Arts and Sciences Dissertations

Catalytic water treatment technologies hold great promise for degrading even the most recalcitrant contaminants of emerging concern (CECs). Heterogeneous catalytic processes are especially appealing, providing the benefits of easy catalyst recovery and reduced risk of secondary pollution. However, heterogeneous reactions often suffer from mass transfer limitations, and the development of catalyst materials that are sufficiently active, selective, and stable under the conditions necessary for pollutant degradation remains challenging. Furthermore, synthesis of catalyst materials, particularly those with desirable catalytic properties and novel architectures, are often time- and energy-intensive and involve expensive materials and/or equipment. In this work, we address these challenges …

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Nanoporous Inp And Its Application In Short-Wave Infrared Vertical-Cavity Surface Emitting Lasers, Chenziyi Mi Jan 2025

Nanoporous Inp And Its Application In Short-Wave Infrared Vertical-Cavity Surface Emitting Lasers, Chenziyi Mi

Yale Graduate School of Arts and Sciences Dissertations

The Short-Wave Infrared (SWIR) range is a crucial wavelength window with a wide range of applications. Just to name a few, it covers the important telecommunication bands, provides advantages in bio-sensing and there are emerging applications recently such as noninvasive glucose monitoring, eye-safe 3D sensing and Si photonics. The development of SWIR vertical cavity surface emitting lasers (VCSELs) has been ongoing for more than 30 years but has not yet led to commercialization. The main reason is that it hasn't been easy to build highly reflective distributed Bragg reflectors (DBRs). Unlike the GaAs systems, materials lattice-matched to InP suffers from …

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Understanding The Formation Of Ultra-Diffuse Galaxies Through Systematic Observations, Zili Shen Jan 2025

Understanding The Formation Of Ultra-Diffuse Galaxies Through Systematic Observations, Zili Shen

Yale Graduate School of Arts and Sciences Dissertations

Ultra-Diffuse Galaxies (UDGs) are low-mass, large-sized galaxies that challenge traditional galaxy formation theories. Understanding how UDGs formed is crucial because each formation pathway can constrain different physical processes relevant to galaxy formation. The proposed formation pathways include early quenching, stellar feedback, and mergers, each generating predictions about the halo mass, the stellar population, and the Globular Cluster (GC) population of the galaxy. In this thesis, we develop observational techniques to distinguish between these key pathways. First, we found that UDGs can form in the absence of dark matter (DM) in a high speed merger of progenitor dwarf galaxies. Using a …

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Application Of Peptide-Based Organocatalysts In Asymmetric Catalysis, Tyler Myers Jan 2025

Application Of Peptide-Based Organocatalysts In Asymmetric Catalysis, Tyler Myers

Yale Graduate School of Arts and Sciences Dissertations

This dissertation outlines our efforts in advancing small-molecule, peptide-based organocatalysts for applications in asymmetric catalysis. The catalytic systems developed span a wide range of reactivities, including transition-metal-catalyzed, Brønsted basic, Brønsted acidic, and Lewis basic transformations. Chapter 1 details the development of an enantioselective copper-catalyzed aromatic Finkelstein reaction, mediated by a guanidinylated peptide ligand for the remote desymmetrization of diarylmethanes (up to 95:5 er). Furthermore, by leveraging the reactivity differences of aryl iodides and aryl bromides in transition-metal catalysis, the resulting enriched aryl iodide products could be chemoselectively modified, allowing access to a diverse library of diarylmethane analogs from a common …

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Streamlining Drug Discovery With The Aid Of Artificial Intelligence And Physics-Based Modeling, Anastasia Saar Jan 2025

Streamlining Drug Discovery With The Aid Of Artificial Intelligence And Physics-Based Modeling, Anastasia Saar

Yale Graduate School of Arts and Sciences Dissertations

The drug discovery pipeline is both expensive and prone to high attrition rates with many compounds failing in late-stage clinical trials. Computer-aided drug design (CADD) has emerged as a pivotal part of the pipeline to mitigate these challenges by enabling earlier and more cost-effective assessment of compound viability. This work focuses on two major aspects of CADD: absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions and free energy calculations. First, neural network models are developed for the prediction of aqueous solubility and cytotoxicity, two key contributors to late-stage drug attrition. Ensemble models of graph convolutional networks (GCNs) and graph attention …

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Development Of The Human Brain Networks During Infancy, Huili Sun Jan 2025

Development Of The Human Brain Networks During Infancy, Huili Sun

Yale Graduate School of Arts and Sciences Dissertations

In early infancy, the human brain undergoes rapid network construction and remodeling. Advances in neuroimaging have made non-invasive, in-vivo observation of these brain changes possible during the perinatal period. However, how the brain develops to support dynamic activity and cognitive function remains unclear. In this thesis, I leverage the network control theory to model brain controllability - the capacity to drive activity changes - and examine its role in neurodevelopment. I first outline the developmental trajectories of controllability during the perinatal period and link them to synaptogenesis with cross-species models. Next, I introduce a machine-learning framework to explore how white …

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A Dimensional Approach To Assessing The Effects Of Early-Life Stress On Mental Health Across Development, Emily Meryl Cohodes Jan 2025

A Dimensional Approach To Assessing The Effects Of Early-Life Stress On Mental Health Across Development, Emily Meryl Cohodes

Yale Graduate School of Arts and Sciences Dissertations

Decades of research inform our understanding of the pernicious effects of exposure to stress for individuals across the lifespan. This research underscores that exposure to stressful contexts places individuals at increased risk for developing cognitive, social, emotional, and physical health problems. However, exposure to stress does not have a universal effect on all individuals across development, likely due in part to the extreme heterogeneity in experiential, environmental, and temporal aspects of stress. Recent advances in the study of the psychobiological effects of stress have focused on better understanding how heterogeneity in exposure may account for heterogeneity in developmental and clinical …

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Approaches To Strongly-Coupled Field Theory, Joseph Dominicus Lap Jan 2025

Approaches To Strongly-Coupled Field Theory, Joseph Dominicus Lap

Yale Graduate School of Arts and Sciences Dissertations

Roughly a microsecond after the big-bang, the universe was too hot and dense to form the protons or neutrons of quotidian matter. The process in which a hot soup of quarks and gluons coalesced into standard matter was strongly-coupled and dynamical, making it difficult to analyze with standard techniques such as perturbative QFT and lattice simulations. This thesis showcases various attempts at better understanding this enigmatic phenomenon: effective field theory (Phys.Lett.B 23), CFT approaches to quantum information theory (JHEP 24, JHEP 25), and Energy-Energy Correlators (in progress).

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Causal Inference For Environmental And Text-Based Interventions, Megan Ayers Jan 2025

Causal Inference For Environmental And Text-Based Interventions, Megan Ayers

Yale Graduate School of Arts and Sciences Dissertations

Causal inference provides statistical tools for generating empirical evidence about causal relationships. In conventional settings, randomized experiments can enable estimation of causal effects with simple methods and under weak assumptions, but many pressing causal questions concern complex systems where standard approaches break down. This dissertation presents advances and insights for such cases, first in the context of carbon markets and conservation programs, and then in settings where text serves as treatment. In the first chapter, we develop a generalized causal inference framework for analyzing forest carbon protocols. Recent work has questioned the credibility of forest carbon offsets as an environmental …

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An Ecological Approach For Understanding The Influence Of Threats In Youth’S Social Environments, May Isabella Conley Jan 2025

An Ecological Approach For Understanding The Influence Of Threats In Youth’S Social Environments, May Isabella Conley

Yale Graduate School of Arts and Sciences Dissertations

A central question motivating developmental research for decades has been how threats in youth’s social environments influence development. In particular, researchers have focused on understanding how threats in different contexts in youth’s social environments increase risk for adverse outcomes and why some youth exposed to threats appear more susceptible to adverse outcomes than others. Increasingly, researchers have identified cognitive and neurobiological factors that are thought to contribute to youth’s susceptibility to threats. Despite these advances, our understanding of the influence of threats on development remains incomplete due to a few critical limitations. Notably, while foundational ecological theories emphasize youth’s social …

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Serving Subjects - Oratorical Self-Representation In Deliberative Settings In Aristotle, Quintilian, Christian Weise, And Adam Müller, Marc Petersdorff Jan 2025

Serving Subjects - Oratorical Self-Representation In Deliberative Settings In Aristotle, Quintilian, Christian Weise, And Adam Müller, Marc Petersdorff

Yale Graduate School of Arts and Sciences Dissertations

In this dissertation, I address the following question: how does the tradition of rhetoric answer the question of how a subject constitutes itself that can only act by constituting another subject that will act in its stead? For this purpose, I focus on the subject of oratorical self-representation in four theories of rhetoric to each of which one more or less self-contained chapter is dedicated. The first two are prominent examples from antiquity: Aristotle's Rhetoric and Quintilian's Institution Oratories. The other two come from German-speaking traditions: Christian Weise's Politischer Redner and Adam Müller's Zwölf Reden über die Beredsamkeit und deren …

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Satellite Galaxy Kinematics: A Competitive And Complementary Probe Of The Galaxy-Halo Connection And Cosmology, Kaustav Mitra Jan 2025

Satellite Galaxy Kinematics: A Competitive And Complementary Probe Of The Galaxy-Halo Connection And Cosmology, Kaustav Mitra

Yale Graduate School of Arts and Sciences Dissertations

Most cosmological analyses of galaxy surveys under-utilize the data from the smallest scales. Firstly, analytical calculations become challenging in the fully non-linear regime. Moreover, the small scales are inherently plagued by several systematic uncertainties, such as the effects of baryons. Interestingly, analyses that have delved into the non-linear regimes of structure formation, mostly using galaxy clustering or weak gravitational lensing, often show an ongoing tension with the probes of early Universe physics, such as the cosmic microwave background, about the exact values of some of the cosmological parameters. This begs the following questions: (a) Can we think of a new …

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The Roles Of Terrestrial Weathering And Marine Bioturbation In Shaping Earth’S Surface Habitability Across Time, Brian Beaty Jan 2025

The Roles Of Terrestrial Weathering And Marine Bioturbation In Shaping Earth’S Surface Habitability Across Time, Brian Beaty

Yale Graduate School of Arts and Sciences Dissertations

The existence of life on Earth for over 3.8 billion years implies continuously habitable conditions despite major changes to the planet’s climate and surface geochemistry. In this thesis, I explore two Earth surface processes – terrestrial weathering and marine bioturbation – and their roles in shaping environmental habitability across various timescales. Weathering has long been recognized as a fundamental component of the Earth system. On multi-million-year timescales, it is the primary source for limiting nutrients to the biosphere and primary sink for atmospheric CO2. This concept underlies recent interest in artificially accelerating global weathering rates to mitigate near-future warming. However, …

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Two Systems For User Control On The Modern Web, Caleb Malchik Jan 2025

Two Systems For User Control On The Modern Web, Caleb Malchik

Yale Graduate School of Arts and Sciences Dissertations

Providers of web services and content are compelled to offer value in order to attract users, but they are also increasingly incentivized to abuse their users in order to maximize revenue. Interfaces that monitor, distract, manipulate, and addict users are commonplace, and means of resistance are largely individualized and dependent on technical proficiency. This dissertation advocates a collective approach to empowering users in their relationship to the web services that they use, centered on an organizational form known as the data co-op. We describe two software systems that pair naturally with data co-ops and are designed to improve users’ control …

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Exploring The Dynamical Properties Of Resolved Stellar Satellites And Streams, Juan Guerra Jan 2025

Exploring The Dynamical Properties Of Resolved Stellar Satellites And Streams, Juan Guerra

Yale Graduate School of Arts and Sciences Dissertations

The ΛCDM model for cosmology accurately predicts the large scale structure of our universe. However, at smaller scales (≤ 100 Mpc) observations are at tension with what ΛCDM predicts. Dwarf galaxies which exhibit scale radii on the order of pc to kpc and stellar streams which span sizes of up to several 100 kpc have the potential to shed light into these discrepancies between observations and theory. One particular misconception comes from the distribution of dark matter in the inner regions of dwarf galaxies. ΛCDM dark matter only simulations predict the steeply rising density profiles, while observations of several systems …

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Transition Metal-Catalyzed N–H Functionalization For The Synthesis Of Nitrogen Heterocycles, Jenna Cailin Cordial Molas Jan 2025

Transition Metal-Catalyzed N–H Functionalization For The Synthesis Of Nitrogen Heterocycles, Jenna Cailin Cordial Molas

Yale Graduate School of Arts and Sciences Dissertations

Nitrogen heterocycles are privileged scaffolds found in 82% of FDA approved pharmaceuticals approved from 2013 – 2023. Thus, modular and efficient methods to synthesize these motifs are valuable for drug discovery and development. Chapters 1 and 2 will discuss the use of Cp*Rh(III)-catalyzed N–H functionalization to synthesize two types of non-aromatic nitrogen heterocycles. Chapter 3 discusses ongoing work for a Cu(I)-catalyzed three-component synthesis of piperazines. Chapter 1 describes a three-component synthesis of piperazinones from readily available amino amides, aldehydes, and diazo compounds. This method proceeds by a new mode of reactivity: imine directed Cp*Rh(III)-catalyzed N–H functionalization/annulation. This method represents the …

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Unraveling The Phenotypic Plasticity In Glioblastoma, Chunxiao Ren Jan 2025

Unraveling The Phenotypic Plasticity In Glioblastoma, Chunxiao Ren

Yale Graduate School of Arts and Sciences Dissertations

Cell plasticity enables cancer cells to transition between distinct phenotypic states, driving heterogeneity and therapeutic resistance. Here, I present the RACE (Rapid Analysis of Cell phenotypic Extremes) assay, a longitudinal in vitro experimental model designed to functionally isolate and enrich fast- and slow-migrating glioblastoma (GBM) cell subpopulations in response to mechanical input imposed by an extracellular matrix (ECM)-mimicking nanofabricated platform with pro-migratory property. I tracked these phenotypically distinct subpopulations and characterized their dynamic evolution through bulk and single-cell transcriptomic profiling. I found that fast- and slow-migrating cells corresponded to mesenchymal- and proneural-like transcriptional programs, respectively, and were regulated by a …

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Molecular Mechanisms Of Kras Regulation And Resistance In Pancreatic Ductal Adenocarcinoma, Xiangyu Ge Jan 2025

Molecular Mechanisms Of Kras Regulation And Resistance In Pancreatic Ductal Adenocarcinoma, Xiangyu Ge

Yale Graduate School of Arts and Sciences Dissertations

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive human malignancies, with a five-year survival rate of less than 13%. Oncogenic KRAS mutations occur in over 90% of cases and drive tumor initiation and progression, making KRAS a desirable therapeutic target. Despite the development of direct KRAS inhibitors, clinical efficacy has been modest due to rapid adaptive resistance. This thesis primarily investigates the molecular mechanisms by which PDAC cells adapt to KRAS inhibition, while also uncovering co-vulnerabilities that can be therapeutically exploited. Chapter 1 provides a comprehensive literature review of KRAS biology in PDAC, summarizing historical and contemporary findings …

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Characterizing And Modeling Spectral State Dynamics In Human Cortex, Heraclitos Maximos Lefcochilos-Fogelquist Jan 2025

Characterizing And Modeling Spectral State Dynamics In Human Cortex, Heraclitos Maximos Lefcochilos-Fogelquist

Yale Graduate School of Arts and Sciences Dissertations

There is increasing evidence that the large-scale spectral dynamics of human cortex can exhibit non-Gaussian features and marked variation over a range of timescales in resting state. Robust documentation and characterization of such complex phenomena, however, remains a challenge and is comparatively sparse, given the paradigmatic complexity of the human brain. Here, we adopt a methodological approach which can account for dynamic changes in spectral signals of electrophysiological data by explicitly using a measure of spectral variation over time, for which we can generate single-variable time courses, enabling robust characterization of the real-time activity of spectral modes across various timescales. …

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Vaccine-Induced Immunity: Insights Into Sars-Cov-2 And Orthopoxvirus, Valter Monteiro Jan 2025

Vaccine-Induced Immunity: Insights Into Sars-Cov-2 And Orthopoxvirus, Valter Monteiro

Yale Graduate School of Arts and Sciences Dissertations

Emerging infectious diseases like SARS-CoV-2 and re-emergent pathogens such asmpox (formally known as monkeypox) have posed substantial challenges to global health, often due to immune escape and antigenic variability. My research addresses these challenges by evaluating and designing vaccine strategies to enhance immune responses and cross-protection, focusing on SARS-CoV-2 variants and members of the Orthopoxvirus family. The central aim of my research is to understand and overcome limitations in immune responses to antigenically variable pathogens. My studies focus on humoral responses to SARS-CoV-2 variants through targeted booster regimens, exploring cross-protective immunity in Orthopoxvirus vaccines, and testing new mRNA vaccines to …

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Acquisition Of Hydrogen To Earth-Like Planets By The Solar Wind Radiation: A Possible Way To Get Water Within The Snowline During Planetary Formation, Qinting Jiang Jan 2025

Acquisition Of Hydrogen To Earth-Like Planets By The Solar Wind Radiation: A Possible Way To Get Water Within The Snowline During Planetary Formation, Qinting Jiang

Yale Graduate School of Arts and Sciences Dissertations

Volatile delivery of terrestrial planets within the snowline is one of the key issues in planetary science. The solar wind has been considered a significant contributor to the volatile acquired by dust within the snowline and of airless planetary bodies surfaces. This thesis explores the effects of solar wind implantation on planetary materials through a series of experimental and theoretical studies, focusing on three interrelated aspects: volatile acquisition, lattice damage mechanical weakening dust grains, and volatile isotopic evolution of the irradiated mineral grains. First, we performed hydrogen implantation experiments on olivine, orthopyroxene, and quartz to investigate the distribution and concentration …

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Fine Particulate Air Pollution Exposure Burden And Sociodemographic Health Disparities In The United States: Impacts From Energy Transitions And Temporal Variation In Mortality Risk, Rory Stewart Jan 2025

Fine Particulate Air Pollution Exposure Burden And Sociodemographic Health Disparities In The United States: Impacts From Energy Transitions And Temporal Variation In Mortality Risk, Rory Stewart

Yale Graduate School of Arts and Sciences Dissertations

Climate change, the defining environmental crisis of our time, has been shown to impact concentration, distribution, and composition of tropospheric air pollutants, including particulate matter. Economic patterns greatly shape the generation of particulate matter as well as greenhouse gases that enhance climatic changes. Substantial evidence shows that exposure to fine particulates, particulate matter with aerodynamic diameter <2.5 µm (PM2.5), contributes to premature mortality and morbidity. These detrimental health outcomes have been shown to be experienced unequally across population groups, with disparities in the level of exposure and in the magnitude of health response for marginalized populations that have higher vulnerability to air pollution exposure. It is also possible that these health responses are not static, but dynamic over time due to changes in population health and composition of air pollution exposures, warranting deeper investigation into the directionality and shape of these health responses. Modeling potential future energy scenarios by using existing knowledge on health responses to air pollutants allows researchers and policymakers to understand how changes to air pollution can impact population health before policies are implemented. Thus, inclusion of appropriate modelling techniques and analyses of energy policy impacts is essential to understanding health impacts from climate mitigation and adaptation across population groups within the United States. This dissertation contributes to the growing knowledge base on climate mitigation, health co-benefits from air pollution concentration changes and health response changes across time to air pollution exposures. Chapter two presents work investigating whether energy policies that aim to reduce greenhouse gas emissions have a secondary impact of reducing health burden in the United States (U.S.) and if any changes to mortality and hospitalizations differ across subpopulations. I explored four future sector-specific energy policy scenarios (electrification of ports and marine shipping, low long-term natural gas pricing, high electric vehicle uptake, and innovations in building energy efficiency) and a business-as-usual scenario to determine how changes to ambient PM2.5 levels impact health within the continental U.S. by region, race/ethnicity, urbanicity, and income. I also investigated how methodological assumptions impact findings. I found projected avoided premature mortalities from energy transition policies range from 67,011 (95% CI: 45,692, 82,397) to 81,003 (55,286, 99,532) individuals in 2050 and 11,577 (1,332, 19,918) to 13,552 (1,560, 23,303) avoided cardiorespiratory hospitalizations in 2050, showing substantial health co-benefits from greenhouse gas mitigation policy implementation. These benefits vary by region and subpopulation, with Black, suburban, and less wealthy Americans experiencing the highest percent reduction in mortalities across all energy policy scenarios. Analysis into how population assumption specificity (such as using race-specific incidence rates instead of total population rates) influences the results proved that more specific population assumptions can make substantial differences to overall health projections. This research demonstrates the vast health benefits of climate mitigation strategies and how they differ across subpopulations, with some environmental justice populations benefiting more relative to the overall population. In chapter three, I investigated how PM2.5-mortality associations vary over time (2001-2016) in North Carolina and Michigan, while considering how temporality of these associations varies by sociodemographic variables. Results indicate that the direction of PM2.5– mortality health effects varies by location. The odds ratio (OR) for mortality per 10?g/m3 PM2.5 differed across time from 2001-2008 to 2009-2016, increasing by 0.28% in Michigan and decreasing 0.78% in North Carolina. Non-linear models show steadily increasing PM2.5-mortality odds over time for Michigan but an “S” shape for North Carolina. I also found suggestive evidence of widening disparities in PM2.5-mortality odds over time by age, race/ethnicity, urbanicity, sex, and education, although the magnitude of those changes varies across subpopulations and state. This research shows that mortality impacts of PM2.5 are changing over time, with different trends by location and subpopulation, potentially exacerbating environmental justice. This dissertation research underscores the importance of analysis to determine sociodemographic population health disparities when modeling co-benefits of energy and air pollution policies as overall estimates may obscure important differences across subpopulations. Better projections on local health effects on vulnerable communities can enhance equity considerations for climate mitigation actions, as well as provide a more holistic analysis on benefits of cost to implement versus avoided exposure and health costs. Further, this research shows that concentration-response functions may vary temporally and that such trends vary across location. This suggests that applications of historical concentration-response estimates may be obscuring the actual health impact on populations through over- or underestimates of health responses to a certain level of exposure. Improvements in the methodological assumptions of exposure and health response by introducing temporal variation provide researchers with a more accurate representation of the association between air pollution and health, which should be more widely considered in epidemiologic research. These results can inform policymakers and public health professionals in evaluating which communities are at highest risk from particulate exposures in the present day and into the future, especially in relation to temporal trends and projected changes in emissions, particulate composition, and population vulnerability.

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Chemosensory Variation Within And Across Bacterial Species, Jeremy Philippe Moore Jan 2025

Chemosensory Variation Within And Across Bacterial Species, Jeremy Philippe Moore

Yale Graduate School of Arts and Sciences Dissertations

Bacteria use a highly conserved sensory pathway to navigate chemical gradients. In particular, the chemotactic signaling pathway of Escherichia coli is one of the best-characterized systems in biology. However, despite decades of study, there are still open questions about bacterial chemotaxis, including how clusters of receptors cooperatively amplify signals, how variability in the composition of these arrays affects behavioral diversity, and how findings in E. coli generalize to diverse motile behaviors across bacteria. In this thesis, we explore diversity in chemosensory capabilities within and across bacteria species. First, we characterize the distribution of sensitivities to various chemical attractants in populations …

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Epicurus’S Ethics: Pleasure, Deliberation, And The Goal, Max Duboff Jan 2025

Epicurus’S Ethics: Pleasure, Deliberation, And The Goal, Max Duboff

Yale Graduate School of Arts and Sciences Dissertations

Although Epicurus was a highly systematic thinker, most discussion of his ethics has had too narrow a focus. To address this problem, I propose a unified account of pleasure, the absence of pain, and deliberation in Epicurus's ethics. I explain three puzzles which have plagued Epicureanism since Cicero and even before: why the absence of pain is called pleasure; why the absence of pain is the greatest good; and how the absence of pain governs deliberation, including about death. I develop a new view of Epicurean pleasure, and I argue against the standard framing of Epicurus's ethics as a "hedonistic …

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Mental Health Disparities From Climate Change: Age Differences And Structural Drivers Across California, Elizabeth Choa Jan 2025

Mental Health Disparities From Climate Change: Age Differences And Structural Drivers Across California, Elizabeth Choa

Yale Graduate School of Arts and Sciences Dissertations

Background: The health impacts of climate change are shaped by a complex interplay of geopolitical, ecological, and socioeconomic forces. Climate events impose substantial personal and societal costs, draining resources and deepening existing vulnerabilities within communities. Yet few studies examine how these dynamics affect groups often overlooked in climate–health discourse, including LGBTQ+ individuals, informal caregivers, and older adults. Objective: To examine how individual, community, and structural-level factors influence both climate vulnerability (defined as susceptibility to adverse health impacts) and climate resilience (the capacity to adapt to and withstand climate-related stressors). Focusing on diverse adult populations in California, this dissertation aims to …

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Investigations Of Allosteric Mechanisms In Proteins, Brandon C. Allen Jan 2025

Investigations Of Allosteric Mechanisms In Proteins, Brandon C. Allen

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines how allosteric communication governs the dual catalytic and immunomodulatory functions of the macrophage migration inhibitory factor (MIF) superfamily, with an emphasis on D-dopachrome tautomerase (MIF-2). Despite limited primary sequence identity, MIF and MIF-2 share a conserved trimeric fold centered on a solvent-accessible channel that connects their catalytic N-terminal proline to distant receptor-binding loops. Experimental work using NMR spin relaxation, site-directed mutagenesis, and in vivo inflammatory assays suggest that single-residue mutations near this channel can dramatically alter tautomerase activity of MIF-2 and its ability to recruit neutrophils in murine lung models, thereby cementing the link between local perturbations …

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