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Disentangling Sequence Constraints On The Cofilin N-Terminal Phosphorylation Site, Joel Andrew Sexton Apr 2023

Disentangling Sequence Constraints On The Cofilin N-Terminal Phosphorylation Site, Joel Andrew Sexton

Yale Graduate School of Arts and Sciences Dissertations

Eukaryotic cells require cofilin, also known as actin depolymerizing factor (ADF), to regulate the severing and rapid reorganization of actin filaments during processes such as cell division and migration. Cofilin severing activity is facilitated by a binding interaction between actin and the cofilin N-terminus. The cofilin N-terminus contains a phosphorylation site that reversibly inhibits actin severing when phosphorylated by members of the LIM kinase (LIMK) family. These two functions of the N-terminus, actin severing and phospho-regulation, converge to promote strict evolutionary conservation of a Ser-Gly-Val/Ile/Met/Thr motif, but how the N-terminal motif conforms and contributes to these two requirements has remained …

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The Role Of Laminin In A Model Of Maternal Antiviral Immune Activation During Early Placental Development, Emily Kay Condiff Apr 2023

The Role Of Laminin In A Model Of Maternal Antiviral Immune Activation During Early Placental Development, Emily Kay Condiff

Yale Graduate School of Arts and Sciences Dissertations

During pregnancy, the maternal immune system must strike a delicate balance between immune tolerance to prevent rejection of the allogeneic fetus and immune activation to support tissue remodeling and anti-pathogen responses. From the first days of pregnancy and implantation to the development of the mature placenta, fetal trophoblasts rapidly invade the maternal uterine decidua and facilitate tissue reorganization through closely regulated mechanisms of maternal-fetal crosstalk. The extracellular matrix, and particularly the basement membrane protein laminin, is an essential mediator of this process. In this thesis, I describe a model of γδ T cells responding to viral inflammation and causing changes …

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Essays On Political Economy And Gender, Antonia Paredes-Haz Apr 2023

Essays On Political Economy And Gender, Antonia Paredes-Haz

Yale Graduate School of Arts and Sciences Dissertations

Chapter 1: Gender quotas and strategic voters: Experimental evidence from Chile’s constitutional convention Citizens’ perceptions of certain groups influence voting behavior and policy choices worldwide, frequently reducing the representation of historically disadvantaged people. Can laws limiting the group identity of elected officials undo these effects? And if so, how does this impact legislator competence and how legislatures represent policy preferences of different groups? I examine these issues in the context of Chile’s constitutional conventional election, which was the first election to mandate gender parity in both candidate lists and elected officials without limiting voter choice. I induce experimental variation in …

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Essays On Decision Making Under Uncertainty, Masaki Miyashita Apr 2023

Essays On Decision Making Under Uncertainty, Masaki Miyashita

Yale Graduate School of Arts and Sciences Dissertations

This dissertation studies several economic questions related to decision making under uncertainty. In the first chapter, I consider the question of to what extent an external observer can infer the underlying information structure by observing an equilibrium action distribution in an incomplete information game. I investigate this issue in a general linear-quadratic-Gaussian framework. A simple class of canonical information structures is offered and proves rich enough to rationalize any possible equilibrium action distribution that can arise under an arbitrary information structure. I show that the class is parsimonious in the sense that the relevant parameters can be uniquely pinned down …

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Spatiotemporal Regulation Of Atypical B Cell Memory, Wenzhi Song Apr 2023

Spatiotemporal Regulation Of Atypical B Cell Memory, Wenzhi Song

Yale Graduate School of Arts and Sciences Dissertations

The immune system functions as the major defender against pathogenic challenges but can also cause damage to host tissues. Humoral immunity, mediated by diverse B cell subsets, is a crucial component of immunological memory and forms the basis of long-lasting immunological protection induced by most existing vaccines. On the flip side, B cell response is a key link in the cascade of events leading to autoimmunity and immunopathology. Atypical memory B cells (also known as age-associated B cells, hereafter ABCs) is a recently described population of B cells strongly associated with pathological immune functions, both in patients with autoimmune diseases …

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Children's Intuitive Theories Of Group Collaboration, Emory Richardson Apr 2023

Children's Intuitive Theories Of Group Collaboration, Emory Richardson

Yale Graduate School of Arts and Sciences Dissertations

Cumulative culture has amplified human knowledge far beyond what any individual learner could teach themselves or even be taught in a single lifetime: a doctor can learn to drive a car without having to literally reinvent the wheel. In some cases, complex artifacts can be produced through the accumulation of incremental improvements over time; but frequently, they’re a product of more or less direct collaboration. But collaboration comes with costs of its own. This thesis is about the cognitive capacities individuals need for collaborative learning to be worth the trouble. I first describe a set of interrelated obstacles to the …

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The Shape Of Things: Reading Culture Through Form In The Wilhelmine And Weimar Republic, Sophie Duvernoy Apr 2023

The Shape Of Things: Reading Culture Through Form In The Wilhelmine And Weimar Republic, Sophie Duvernoy

Yale Graduate School of Arts and Sciences Dissertations

This dissertation explores the historical transformation of the concept of form in Germany between 1850 and 1930 into a dynamic term that intellectually enabled the project of liberal cultural critique. It describes how form was reconceived from a static shaping force with Platonic overtones into a mobile, dynamic means of structuration that allowed for internal difference and change. The dynamization of form allowed it to become a central term in the renewal of epistemology, and in turn, allowed philosophy to move into the study of culture and its material products. The project is based around three key figures – the …

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Host Immunity And Receptor Expression Determine Rna Virus Pathogenesis, Madison Scott Strine Apr 2023

Host Immunity And Receptor Expression Determine Rna Virus Pathogenesis, Madison Scott Strine

Yale Graduate School of Arts and Sciences Dissertations

Identifying host factors essential for viral infections has the potential to reveal novel mechanisms of viral pathogenesis and immune escape. Here, we use two mucosal positive-sense RNA viruses – murine norovirus (MNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – as probes to investigate mechanisms of viral pathogenesis at mucosal barrier surfaces. Among noroviruses, murine norovirus (MNV) is a model for human norovirus and a tractable system to elucidate fundamental mechanisms of viral tropism and immune evasion. The strain MNVCR6 infects rare chemosensory epithelial cells called tuft cells, which are dispensable for the canonical non-persistent strain MNVCW3. Herein, we …

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Delineating Novel Checkpoints In Metabolic Syndromes, Jonathan Sun Apr 2023

Delineating Novel Checkpoints In Metabolic Syndromes, Jonathan Sun

Yale Graduate School of Arts and Sciences Dissertations

The global rise in obesity and overnutrition has rapidly increased diagnosedmetabolic syndromes, including fatty liver disease and hypercholesterolemia. This growing burden of metabolic diseases elicits an immense health and economic burden on society, as metabolic syndromes are significant risk factors for co-morbidities such as cancer and heart failures, leading to an attributable cost of $147 billion in US healthcare spending. Given this, it is of high importance to uncover the dynamic metabolic programs that drive the progression of these metabolic syndromes toward end-stage diseases. Metabolic rewiring during overnutrition can regulate the expression of feedback loops, referred hereupon as metabolic checkpoints, …

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Piezo-Brillouin Electro-Optomechanics With High-Overtone Bulk Acoustic Resonators, Taekwan Yoon Apr 2023

Piezo-Brillouin Electro-Optomechanics With High-Overtone Bulk Acoustic Resonators, Taekwan Yoon

Yale Graduate School of Arts and Sciences Dissertations

Bulk acoustic resonators support robust, long-lived mechanical modes, capable of coupling to various quantum systems. In separate works, such devices have achieved strong coupling to both superconducting qubits, via piezoelectricity, and optical cavities, via Brillouin interactions. In this thesis, we discuss piezoelectric and Brillouin interactions between phonons and microwave/optical photons, as well as microwave and bulk acoustic resonators that enable the interactions. Based on the understanding of these elements, we then present a novel hybrid microwave/optical platform that exploits resonantly enhanced Brillouin interactions and piezoelectric couplings to efficiently access phonons within a variety bulk crystalline materials (quartz, CaF2, Si, etc) …

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Helicobacter Pylori Catabolism Of Host Glutathione: An Emerging Mechanism Of Nutritional Virulence, Maia Joi Baskerville Apr 2023

Helicobacter Pylori Catabolism Of Host Glutathione: An Emerging Mechanism Of Nutritional Virulence, Maia Joi Baskerville

Yale Graduate School of Arts and Sciences Dissertations

Mammalian cells synthesize the antioxidant glutathione (GSH) to shield cellular biomolecules from oxidative damage. Certain bacteria, including the gastric pathogen Helicobacter pylori, can perturb host GSH homeostasis. H. pylori infection significantly decreases GSH levels in host tissues, which has been attributed to the accumulation of reactive oxygen species in infected cells. However, the precise mechanism of H. pylori-induced GSH depletion remains unknown, and tools for studying this process during infection are limited. We developed an isotope-tracing approach to quantitatively monitor host-derived GSH in H. pylori-infected cells by mass spectrometry. Using this method, we determined that H. pylori catabolizes reduced GSH …

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Robotic Fabrics Enabled By Functional Fibers And Responsive Materials, Trevor Luke Buckner Apr 2023

Robotic Fabrics Enabled By Functional Fibers And Responsive Materials, Trevor Luke Buckner

Yale Graduate School of Arts and Sciences Dissertations

The burgeoning field of soft robotics brings with it a wave of new and nontraditional materials to the robotics repertoire. New advances are being made using elastomers, foams, and gels as the core robotic substrate, giving rise to entirely new avenues of robot capability. Now more than ever, machines can be designed with extreme flexure, stretch, and even volume change as key functions, opening up a design space that rigid machinery cannot easily occupy. In this dissertation, I build upon the use of atypical materials, introducing fabrics as a new soft robotics platform. Fabrics are thin, have a fiber-based structure, …

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Realism By Rail: Art And Mobilities In Late Imperial Russia, Stephen Tyler Urchick Apr 2023

Realism By Rail: Art And Mobilities In Late Imperial Russia, Stephen Tyler Urchick

Yale Graduate School of Arts and Sciences Dissertations

This dissertation is the first in English to consider how artists primarily from Russia’s Partnership for Traveling Art Exhibitions, known as the Wanderers, wandered. It breaks with decades of scholarship portraying these painters as pleinarist populists who went to the people, or bourgeois professionals who stayed home. Although the Wanderers rarely accompanied their group’s eponymous Traveling Exhibition as it toured by rail, the artists remained exceptionally mobile over their careers in both the literal and extended notions of this word. How did these artists exploit the accelerations of the late nineteenth century to advance their ambitions, reproduce and circulate their …

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Antecedents And Consequences Of Racial Group Status Threat Among White Americans, Xanni Brown Apr 2023

Antecedents And Consequences Of Racial Group Status Threat Among White Americans, Xanni Brown

Yale Graduate School of Arts and Sciences Dissertations

The United States is becoming increasingly racially diverse, with non-Hispanic White Americans expected to comprise less than 50% of the population beginning sometime between 2040 and 2050. The prospect of this racial demographic shift has been shown to cause feelings of threat among White Americans, as well as negative intergroup outcomes like increased racial bias and decreased support for integration. This work examines racial group status threat in the U.S., with an eye toward mitigating its negative consequences. Chapter 1 presents a theoretical framework for predicting the antecedents of potential consequences of racial group status threat, arguing that the US …

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Essays On The Industrial Organization Of The Digital Economy, Michael Rolland Sullivan Apr 2023

Essays On The Industrial Organization Of The Digital Economy, Michael Rolland Sullivan

Yale Graduate School of Arts and Sciences Dissertations

Recent years have witnessed a surge in the significance of digital platforms and online retailers. The analysis of digital firms and the industries in which they compete is useful for both furthering general economic knowledge and for informing policy. First, digital firms’ activities incidentally generate digitized data that facilitate the empirical analysis of economic concepts applying to settings traditional and digital alike. Examples of such concepts include network externalities, pass-through of tariffs in vertical relationships, and consumer search. In addition, digital firms differ from traditional firms in ways that matter for the effects of regulation; this makes an understanding of …

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Necroptotic Cell Death Sensing Directly Promotes Fibroblast And Macrophage Inflammatory Effector Responses, Lindsey Demaree Hughes Apr 2023

Necroptotic Cell Death Sensing Directly Promotes Fibroblast And Macrophage Inflammatory Effector Responses, Lindsey Demaree Hughes

Yale Graduate School of Arts and Sciences Dissertations

Programmed cell death is carried out by a wide array of molecularly executed pathways. We postulated that the ensuing tissue effector response to cellular corpses reflects this diversity in cell death modalities. Importantly, the demise of a cell does not immediately coincide with the termination of its capacity to relay information to the surrounding tissue. We have previously described that apoptotic cell death in the lung, in the context of helminth infection and an IL-4-rich environment, is sensed by macrophages to direct the resolution of inflammation and induction of a tissue repair gene expression program. In organs like the gut, …

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Essays On Leadership, Domestic Politics, And Diplomacy, Michael Goldfien Apr 2023

Essays On Leadership, Domestic Politics, And Diplomacy, Michael Goldfien

Yale Graduate School of Arts and Sciences Dissertations

This dissertation explores leadership and the politics of diplomacy at the international and domestic levels. How do leaders shape and intervene in their domestic environments to gain diplomatic advantages on the international stage? And how does political accountability constrain leaders on matters of cooperation? The dissertation includes three chapters that address these questions. The first chapter argues that regime type determines whether hawkish or dovish leaders are more likely to achieve a rapprochement with international rivals. Using game theory and quantitative and qualitative empirics, it shows that doves are more likely to achieve a rapprochement when they lead autocracies rather …

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Socially Responsible Operations: Essays On Public Sector Management, Yu Shi Apr 2023

Socially Responsible Operations: Essays On Public Sector Management, Yu Shi

Yale Graduate School of Arts and Sciences Dissertations

This dissertation studies a range of topics in social responsibility and the operations of public sector. The three essays presented in this dissertation are intended to provide normative recommendations to better inform public-policy decisions, through the examination of private-public sector interactions. Chapter 1 focuses on the enforcement of environmental/labor regulations and highlights the role of self-inspection by the regulated entity. Chapters 2 and 3 focus on the management of the Australian blood bank. The chapters identify a causal relationship between blood age and hospital demand, and propose novel remedies to improve the blood bank's supply chain. Chapter 1, "Competing to …

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Neutral-Current Neutral Pion Production Measurement In Microboone Using Wirecell, Giacomo Scanavini Apr 2023

Neutral-Current Neutral Pion Production Measurement In Microboone Using Wirecell, Giacomo Scanavini

Yale Graduate School of Arts and Sciences Dissertations

This dissertation presents the first-ever measurements of the inclusive flux-averaged differential cross sections for neutral-current neutral pion production in $\pi^0$ momentum and cos$\theta$ on argon, as well as exclusive cross section measurements based on proton multiplicity. The NC$\pi^0$ channel is a significant source of photon background in long-baseline neutrino oscillation appearance searches and in NC$\Delta$ single-gamma production rate in MicroBooNE. The lack of previous measurements in the sub-GeV to few GeV neutrino energy region, specifically on argon, makes this investigation a priority.The measurements were conducted using the MicroBooNE detector, which is a Liquid Argon Time Projection Chamber exposed to the …

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First Measurement Of Inclusive Muon Neutrino Charged Current Triple-Differential Cross Section On Argon, London Cooper-Troendle Apr 2023

First Measurement Of Inclusive Muon Neutrino Charged Current Triple-Differential Cross Section On Argon, London Cooper-Troendle

Yale Graduate School of Arts and Sciences Dissertations

The field of accelerator neutrino experiments is entering an era of precision oscillation measurements in which many of the remaining unknown neutrino measurements will be determined. The upcoming DUNE and Hyper-K experiments aim to determine the neutrino mass hierarchy and degree of Charge-Parity (CP) violation in the neutrino sector, providing potential insight on the matter-antimatter imbalance observed in the universe. However, these experiments require highly accurate measurements, and neutrino cross section modeling uncertainties may limit their capabilities. Cross section measurements at current-generation experiments can aid the development of neutrino interaction models to reduce these uncertainties. This is especially true for …

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Increasing Gene Targeting Efficiency Through T-Dna Amplification In Plants, Lauren Dickinson Apr 2023

Increasing Gene Targeting Efficiency Through T-Dna Amplification In Plants, Lauren Dickinson

Yale Graduate School of Arts and Sciences Dissertations

In gene targeting, a double strand DNA break is created in a gene ofinterest, and the break is repaired via homologous recombination using an exogenous DNA donor template (DT) harboring a desired modification flanked by sequences homologous to the target locus. If the cell undergoes homologous repair using the template, the desired modification can be copied onto the gene of interest. This is a highly worthwhile process, given that virtually any modification could potentially be made to an endogenous target. However, in plants, the process of gene targeting is extremely inefficient, often to the point that it is impossible, or …

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Improved Computational Strategies To Investigate Mechanisms Of Immune Response In The Tumor And Wound Healing Microenvironments From Single-Cell Data, Kathryn Helen Bridges Apr 2023

Improved Computational Strategies To Investigate Mechanisms Of Immune Response In The Tumor And Wound Healing Microenvironments From Single-Cell Data, Kathryn Helen Bridges

Yale Graduate School of Arts and Sciences Dissertations

Advances in single-cell RNA-sequencing (scRNA-seq) technology enable unbiased, whole transcriptome profiling of tissues, which have revolutionized systems-level studies of these complex microenvironments. Computational analyses of scRNA-seq data have the potential to provide a tissue-level snapshot of cell types, their associated cell states, and a map of their interactions with other cells in the tissue. However, choosing the optimal approach to reconstruct biologically interpretable cell communities from the sparse single-cell transcriptomes collected in scRNA-seq data, especially in the context of dynamic biologically processes, remains a challenge. This is especially true when analyzing dynamic immune processes, which include many cell types, cell …

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Magical Realism In The Middle Ages: The Marvelous Merlin Of Arthurian Legend, Aaron Richard Kestle Apr 2023

Magical Realism In The Middle Ages: The Marvelous Merlin Of Arthurian Legend, Aaron Richard Kestle

Yale Graduate School of Arts and Sciences Dissertations

The figure of Merlin conjures the image of the enchanter par excellence. He is a magician and a prophet; he changes shape in the blink of an eye; and he reads and records the omens of the kings of Britain. Thus, Merlin is the locus around which the magical and the marvelous proliferate in Arthurian legend. These marvelous qualities are linked to many sources: a long-standing tradition of popular magic and divination, contemporary Christian beliefs, and even autochthonous Brythonic culture and literature. Yet, these magical events – which have inspired clear disbelief and rejection among skeptical readers both medieval and …

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Essays On Macroeconomic Policy With Heterogeneous Agents, And Digital Assets, Antzelos Kyriazis Apr 2023

Essays On Macroeconomic Policy With Heterogeneous Agents, And Digital Assets, Antzelos Kyriazis

Yale Graduate School of Arts and Sciences Dissertations

This dissertation has three chapters. In the first chapter, I build a three-agent preferred-habitat NewKeynesian (PHANK) model. I show that the fiscal multiplier decreases in the presence of countercyclical QE policies after a fiscal expansion since countercyclical QE implies that the central bank sells government bonds, leading to higher expected returns on these bonds, which in turn incentivizes the bondholders to save more. However, since bondholders save more, they consume less, and as a result, consumption inequality between the savers and the non-savers falls, but wealth inequality increases. The qualitative results are similar in a medium-scale heterogeneous agents New Keynesian …

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Essays On Civil Procedure: Remedies, Federal Courts, And Marginalized Groups, Portia Pedro Apr 2023

Essays On Civil Procedure: Remedies, Federal Courts, And Marginalized Groups, Portia Pedro

Yale Graduate School of Arts and Sciences Dissertations

This dissertation is a series of essays on the processes that judges use to make procedural decisions and the ways in which judges use procedure to navigate the tensions between law and equity, standards and rules, finality and fairness, and states and marginalized groups. It explores the procedure of procedure—how procedure develops and what hinders or furthers procedural decisionmaking. Some of these essays describe the ways in which racial subordination and the subordination of other marginalized groups manifest in civil procedure, remedies, and federal courts. The dissertation challenges the dominant understanding of these three areas of law as neutral and …

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The Making Of Pasolini's Poetic Cinema, Sarah Atkinson Apr 2023

The Making Of Pasolini's Poetic Cinema, Sarah Atkinson

Yale Graduate School of Arts and Sciences Dissertations

This dissertation is a study of how Pier Paolo Pasolini pioneered representations of otherness through a new kind of mimesis of the gaze. For the poet-filmmaker, cinema offered a liberating way to represent plural subjectivities through expressive modes that transcend verbal language. Central to his theory of poetic cinema is free indirect discourse, a literary technique wherein a narrator temporarily enters a character’s frame of mind and adopts their distinct point of view. When adapted to film, it becomes a strategy for representing alternative perspectives which allows the audience to experience concrete social difference and highlights nuances that may otherwise …

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The Role Of O-Glcnac Transferase In Ventromedial Hypothalamic Control Of Energy Balance, Qi Wang Apr 2023

The Role Of O-Glcnac Transferase In Ventromedial Hypothalamic Control Of Energy Balance, Qi Wang

Yale Graduate School of Arts and Sciences Dissertations

The central nervous system plays a vital role in the homeostatic control of body weight and metabolism. Among brain nuclei, the ventromedial hypothalamus (VMH) is an important hypothalamic nucleus known to regulate body weight, energy balance, and counterregulatory response. However, the pathways for VMH neurons to regulate lipid metabolism and the mechanisms by which VMH neurons sense nutrients and hormones remain obscure. O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of stress, nutrients, and hormones, regulating a variety of cellular activities. Here we report that mice with VMH neuron-specific OGT deletion exhibit rapid development …

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Sonic Virtuality: Imagining Voices In Late Medieval English Lyric, Melissa Tu Apr 2023

Sonic Virtuality: Imagining Voices In Late Medieval English Lyric, Melissa Tu

Yale Graduate School of Arts and Sciences Dissertations

This dissertation explores a textual effect in late medieval English religious poetry, which the project terms “sonic virtuality”: a form of sensory stimulation where instincts of bodily sensation are activated regardless of the performative circumstances under which the poem is encountered. This effect allows the poems to catalyze for their audiences exceptionally vivid imaginative encounters with the poetic personas who appear in them. The project focuses especially on devotional lyrics written, copied, and circulated in medieval England during the fourteenth and fifteenth centuries, focusing on deictic ambiguities surrounding the lyrics’ uses of the first-person pronoun I. Studies of first-person voices …

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Towards Microwave-To-Optical Transduction Of Quantum Microwave Signals, Mingrui Xu Apr 2023

Towards Microwave-To-Optical Transduction Of Quantum Microwave Signals, Mingrui Xu

Yale Graduate School of Arts and Sciences Dissertations

A quantum network combining superconducting processors and low-loss optical fibers has thepotential to revolutionize the world of information technology. However, the large frequency gap between superconducting qubits (∼ 7 GHz) and telecommunication fibers (∼ 200 THz) present a significant challenge that requires the development of microwave-to-optical (M2O) frequency transducers. For a M2O transducer to successfully transmit quantum signals, two stringent criteria need to be met: near-unity efficiency and near-ground state added noise. Despite encouraging progress in the past decade, quantum signal transduction remains elusive with many challenges to be addressed. In this thesis, we focus on M2O transducers based on …

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Molecular Mechanisms Of Microbial Adaptation To The Host, Daniel G. Dumitrescu Apr 2023

Molecular Mechanisms Of Microbial Adaptation To The Host, Daniel G. Dumitrescu

Yale Graduate School of Arts and Sciences Dissertations

All host-associated microorganisms require mechanisms to adapt to stress encountered in the host. In particular, host immunity generates reactive oxygen species (ROS) as a measure to regulate microbial expansion in the gut and to kill invading pathogens. ROS are broadly toxic to cellular biomolecules, and consequently both microorganisms and the host employ molecular mechanisms to contend with their harmful properties. Accordingly, all life forms rely on low- molecular-weight (LMW) thiols, a family of ubiquitous small molecule antioxidants, to maintain intracellular redox homeostasis and resist oxidative damage caused by ROS. Chapter 1 reviews the molecular and biological functions of LMW thiols, …

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