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2022

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Robot Tool Use: Learning, Transferring, Reasoning, And Applying Knowledge About Robots Using Human Tools, Meiying Qin Oct 2022

Robot Tool Use: Learning, Transferring, Reasoning, And Applying Knowledge About Robots Using Human Tools, Meiying Qin

Yale Graduate School of Arts and Sciences Dissertations

Using human tools can significantly benefit robots in many application domains. It will endow a home robot with the ability to carry out everyday household activities such as cleaning. It will enable an industrial robot to work in manufacturing or maintenance using human tools such as screwdrivers. It will allow a robot to perform experiments using existing human lab tools in a chemistry lab. Such ability would allow robots to solve problems that they were unable to without tools. However, robot tool use is a challenging task. Tool use was initially considered to be the ability that distinguishes human beings …

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Neoantigen-Driven B Cell And Cd4 T Cell Collaboration Promotes Anti-Tumor Cd8 T Cell Responses In Lung Adenocarcinoma, Can Cui Oct 2022

Neoantigen-Driven B Cell And Cd4 T Cell Collaboration Promotes Anti-Tumor Cd8 T Cell Responses In Lung Adenocarcinoma, Can Cui

Yale Graduate School of Arts and Sciences Dissertations

Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for ~1.8 million deaths annually. Lung adenocarcinoma (LUAD) is the most common form of non-small cell lung cancer (NSCLC; 40% of cases) and is most frequently associated with mutations in KRAS proto-oncogene (30% of cases). Traditionally, therapeutic options for KRAS-mutant LUAD have been limited, but the successful application of immune checkpoint blockade (ICB) targeting the PD-1 pathway has changed the therapeutic landscape. The success of PD-1-blockade therapy has also changed the perception that LUAD is a non-immunogenic cancer type because anti-PD-1/PD-L1 treatment potentiates the function of previously activated T …

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Lesion-Informed Design And Characterization Of A Multi-Drug Compartment, Topical Nanofibrous Scaffold For Treatment Of Cutaneous Leishmaniasis, Rebecca Byler Oct 2022

Lesion-Informed Design And Characterization Of A Multi-Drug Compartment, Topical Nanofibrous Scaffold For Treatment Of Cutaneous Leishmaniasis, Rebecca Byler

Yale Graduate School of Arts and Sciences Dissertations

Cutaneous leishmaniasis (CL) is a debilitating and disfiguring parasitic disease that predominantly manifests clinically as ulcerative skin lesions. Despite extensive global transmission, frontline treatments for CL have remained unchanged for decades due to underfunding and being overlooked scientifically. Consequently, available treatment options for CL demonstrate toxicity and varied efficacy. There exists the possibility of improving CL treatment options by developing new topical therapeutics. However, development is impeded by limited physiological and pharmacological knowledge of the CL lesion site. This work provides an improved understanding of the altered skin structure and barrier function both during acute CL infection and as a …

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Paleoenvironmental Context Of Early Stone Age Archaeology: An Analysis Of The Gona Fauna Between ~3 And 1 Ma., Amanda Christie Leiss Oct 2022

Paleoenvironmental Context Of Early Stone Age Archaeology: An Analysis Of The Gona Fauna Between ~3 And 1 Ma., Amanda Christie Leiss

Yale Graduate School of Arts and Sciences Dissertations

The advent of tool-making has long been associated with expanding grasslands in Africa. My dissertation reconstructs paleoenvironments at Gona, in the Afar region of Ethiopia, between ~3–1 Ma (1) to make inferences about how hominins were utilizing the paleo-landscape and interacting with mammalian communities and (2) to investigate whether the environment was influential in the development of stone tools. This time period spans the origin of our genus Homo and the evolution of Homo erectus, and it provides evidence of increased behavioral complexity (stone tools), brain expansion, and the acquisition of large nutrient-rich food sources (animal carcasses). Because of the …

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The Resurgence Of The Nuu-Chah-Nulth First Nations In The Clayoquot Sound Bio-Cultural Landscape: A Case Study Of Iisaak Forest Resources, Ltd., Cintra Cady Agee Oct 2022

The Resurgence Of The Nuu-Chah-Nulth First Nations In The Clayoquot Sound Bio-Cultural Landscape: A Case Study Of Iisaak Forest Resources, Ltd., Cintra Cady Agee

Yale Graduate School of Arts and Sciences Dissertations

The Central Region Nuu-chah-nulth First Nations (NCN) are an alliance of five First Nations: the Ahousaht, the Tla-o-qui-aht, the Hesquiaht, the Toquaht, and the Ucluelet. Their traditional territories cover the central west coast of Vancouver Island, British Columbia (BC)—known as Clayoquot Sound. Industrial logging concessionaires had clearcut much of the ‘old-growth’ forests in Clayoquot. These were public lands, and multiple forest values important to multiple stakeholders had been reduced. In 1984, the NCN obtained a logging injunction for Meares Island in Clayoquot Sound. The NCN publicly protested for additional curbs on logging in their traditional territories. In the early 1990s, …

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The Role Of Estrogen Signaling In Sexually Dimorphic Adipose Expansion, Rocío Del Mar Saavedra-Peña Oct 2022

The Role Of Estrogen Signaling In Sexually Dimorphic Adipose Expansion, Rocío Del Mar Saavedra-Peña

Yale Graduate School of Arts and Sciences Dissertations

In obesity, white adipose tissue (WAT) distribution differs between the sexes, with men preferentially accumulating visceral WAT (VWAT) and females exhibiting subcutaneous WAT (SWAT) accumulation bias. Obesogenic adipocyte hyperplasia (increase in adipocyte number) contributes to the sexually dimorphic pattern of fat distribution in mice driven by cues in the tissue microenvironment, with females displaying hyperplasia in both VWAT and SWAT, while males have VWAT-specific hyperplasia, implicating a role for sex hormones in this process during obesity. Sex hormones play a pivotal role in physiology and disease. Estrogen, the female sex hormone, has been long implicated in having protective roles against …

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Biobehavioral Markers Of Social-Emotional Functioning, Erica Ho Oct 2022

Biobehavioral Markers Of Social-Emotional Functioning, Erica Ho

Yale Graduate School of Arts and Sciences Dissertations

Difficulties with social and emotional functioning characterize most major psychiatric disorders and exert outsize influence on treatment prognosis and quality of life, evincing a pressing public health concern that necessitates closer investigation. In recognition of the diverse pathways through which social contexts interact with social-emotional functioning and psychopathology, the three studies that form this dissertation deliberately span a range of topics, methods, and populations, with the goal of characterizing individual differences in the perception of social-emotional signals across a range of increasingly complex social settings. Study 1 (presented in Chapter 2) uses functional magnetic resonance imaging in an adult community …

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Translational Systems Metabolism In Health And Disease, Brooks Phillip Leitner Oct 2022

Translational Systems Metabolism In Health And Disease, Brooks Phillip Leitner

Yale Graduate School of Arts and Sciences Dissertations

The breakdown, synthesis, and interconversion of macronutrients is essential to sustaining life and driving pathological mechanisms rooted in disease. With attempts to combat the metabolic underpinnings of disease, it has become clear that focus on individual metabolites, proteins, or genes cannot fully explain the complexity of dysregulated metabolism in systemic conditions such as obesity, cancer, and sepsis. With the advent of accessible Omics techniques and hordes of open access data it has become possible to study metabolism as a whole—at the level of gene transcription, translation, and metabolism. A major goal of this PhD thesis was to integrate isotope tracing …

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Antinomies Of Organizing, Mie Inouye Oct 2022

Antinomies Of Organizing, Mie Inouye

Yale Graduate School of Arts and Sciences Dissertations

AbstractAntinomies of Organizing This dissertation theorizes a problem that attends all attempts to form or deepen democracy, namely, the problem of democratic transitions. People are shaped as political subjects by their participation in the institutions that govern their lives; their analyses of society, their self-understandings, and their political capacities are determined in large part by their participation in the state, the family, the workplace, and the market. When these institutions are oppressive, they may undermine participants’ capacities to engage in political action, to recognize and identify the sources of their oppression, and to self-govern. They may also undermine their sense …

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Strategic Organizing, Dangerous Rhetoric, And Philanthropic Decision-Making In The U.S. New Right, Alexandra Jane Dibranco Oct 2022

Strategic Organizing, Dangerous Rhetoric, And Philanthropic Decision-Making In The U.S. New Right, Alexandra Jane Dibranco

Yale Graduate School of Arts and Sciences Dissertations

While rightist politics have drawn increased scholarly attention in recent years, the study of movements on the right lacks the depth and nuance afforded to movements on the left. This dissertation investigates organizing, communication, and funding strategy by the New Right in the United States. The papers in this dissertation address misconceptions about rightist movements that limit scholarship, including calling attention to their heterogeneity, historical embeddedness, and leadership dynamics. The first paper in the dissertation addresses the perception of the Christian Right as monolithic, demonstrating the strategic organizing and ideological/theological work involved since the 1960s in bringing disparate and hostile …

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A Rapid Rig-I Signaling Relay Mediates An Efficient Antiviral Response, Daniel Thoresen Oct 2022

A Rapid Rig-I Signaling Relay Mediates An Efficient Antiviral Response, Daniel Thoresen

Yale Graduate School of Arts and Sciences Dissertations

RIG-I is our first line of defense against RNA viruses, serving as a patternrecognition receptor (PRR) that identifies molecular features common among dsRNA and ssRNA viral pathogens. RIG-I is maintained in an inactive conformation as it samples the cellular space for pathogenic RNAs. Upon encounter with the triphosphorylated terminus of blunt-ended viral RNA duplexes, the receptor changes conformation and releases a pair of signaling domains (CARDs) that are selectively modified and interact with an adapter protein (MAVS), thereby triggering a signaling cascade that stimulates transcription of type I interferon. While the molecular mechanisms of RIG-I recognition of viral pathogen-associated molecular …

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Polymeric Nanoparticles For The Local Delivery Of Small Molecule Inhibitors: Applications Toward Glioblastoma And Airway Delivery, Alexander Danels Josowitz Oct 2022

Polymeric Nanoparticles For The Local Delivery Of Small Molecule Inhibitors: Applications Toward Glioblastoma And Airway Delivery, Alexander Danels Josowitz

Yale Graduate School of Arts and Sciences Dissertations

Techniques such as polymeric nanoparticle formulation and nontraditional drug delivery modalities have been developed to address complex delivery challenges associated with aggressive diseases. In this dissertation, polymeric nanoparticle formulations are demonstrated to encapsulate small molecule drugs and coupled with direct local delivery methods to avoid the weaknesses associated with systemic delivery towards two different applications. Firstly, glioblastoma (GBM) is the most deadly and common brain cancer and little progress has been made in improving the standard of care for nearly 17 years. Current therapies suffer from dose limiting toxicities, low penetration into the brain, and tumors resistant to chemotherapies that …

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Host Redox Signaling During Helicobacter Pylori Infection, Yekaterina Kovalyova Oct 2022

Host Redox Signaling During Helicobacter Pylori Infection, Yekaterina Kovalyova

Yale Graduate School of Arts and Sciences Dissertations

Helicobacter pylori is a gastric pathogen that chronically infects up to half of the global population and is the strongest risk factor for gastric cancer. Host cells infected with H. pylori are exposed to oxidative stress characterized by the continuous production of reactive oxygen species (ROS). While the correlation between H. pylori-induced chronic oxidative stress and disease has been well-documented, the molecular oxidation events that contribute to pathogenesis are largely unknown. The main intracellular targets of ROS are proteins, particularly those with redox-sensitive cysteine residues. Oxidation of reactive cysteines, termed redox signaling, can alter protein behavior and modulate important cellular …

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Decoding Immunometabolism In Inflammatory Macrophages, Zheng Wei Oct 2022

Decoding Immunometabolism In Inflammatory Macrophages, Zheng Wei

Yale Graduate School of Arts and Sciences Dissertations

The mammalian innate immune system uses a variety of pattern recognition receptors (PRRs) to recognize foreign pathogen-associated molecular patterns (PAMPs) and host damage-associated molecular patterns (DAMPs) and transduce the upstream signals from the cell membrane and intracellular receptors to core downstream immunometabolic signaling outcomes, including the secretion of proinflammatory cytokines and the production of critical reactive oxygen species (ROS), reactive carbonyl species (RCS), and reactive nitrogen species (RNS). Orchestration and resolution of these inflammatory outcomes are indispensable to healthy innate immune function. Correspondingly, their dysregulation is associated with various inflammatory diseases and an impaired ability to resolve bacterial and viral …

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The Role Of Type I Ifns In Fasting Metabolism, Kavita Israni-Winger Oct 2022

The Role Of Type I Ifns In Fasting Metabolism, Kavita Israni-Winger

Yale Graduate School of Arts and Sciences Dissertations

The immune system has a versatility of functions beyond its response to foreign pathogens. This is the case not only in inflammatory perturbations but in sterile challenges as well. Here we present a role for the family of immune cytokines, type I IFNs, in maintaining homeostasis and mediating adaptation during prolonged food deprivation. We demonstrate that through glucocorticoid mediated upregulation of endogenous retroviral elements (ERVs), cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway is activated and upregulates unique subsets of type I IFNs. These IFNs are necessary for metabolic adaptation that ensures survival of the organism when no food is …

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Mechanisms Of Protein Quality Control At The Nuclear Envelope And During Nuclear Pore Complex Biogenesis, Sarah M. Prophet Oct 2022

Mechanisms Of Protein Quality Control At The Nuclear Envelope And During Nuclear Pore Complex Biogenesis, Sarah M. Prophet

Yale Graduate School of Arts and Sciences Dissertations

Collapse of protein quality control (PQC) is a defining feature of numerous neurological diseases. Work described within this thesis argues that DYT1 dystonia, a neurological movement disorder of unclear etiology, arises due to a PQC defect. While it is clear that mutations in the AAA+ ATPase TorsinA cause this disease, it is not known why loss of this protein function causes DYT1 dystonia. In cells lacking Torsin function, nuclear pore complexes (NPCs) fail to be properly assembled. Instead, nuclear envelope (NE) herniations form that sequester abundant molecular chaperones. Ubiquitylated proteins, that in healthy cells are rapidly degraded, become sequestered with …

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Robots That Tutor In Complex And Dynamic Environments, Nicole Salomons Oct 2022

Robots That Tutor In Complex And Dynamic Environments, Nicole Salomons

Yale Graduate School of Arts and Sciences Dissertations

Robots have shown great promise in being effective tutors for both children andadults. For instance, they have been shown to be successful in math tutoring for children [203], interruptions training for adults with Autism Spectrum Disorder [204], and assisting the elderly while exercising [87]. Yet, despite the great potential of tutoring robots, most studies have focused on providing short-term tutoring either in a laboratory or a school while the researcher is present. For robots to be more broadly successful, users need to be able to practice skills on a more prolonged basis and in the wild. This requires robotic systems …

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The Ambassadors: Indigenous Democracy And American Monarchy After The War Of 1812, Zachary Conn Oct 2022

The Ambassadors: Indigenous Democracy And American Monarchy After The War Of 1812, Zachary Conn

Yale Graduate School of Arts and Sciences Dissertations

This dissertation investigates sites of state activity in the early United States which have received far less attention from historians than executive mansions, legislative halls, courtrooms, military outposts, or overseas embassies: the numerous embassies the federal government maintained on, or adjacent to, lands belonging to North America’s sovereign Indigenous polities. At the helm of each of these embassies, known as Indian agencies, sat a presidentially appointed ambassador known as the Indian agent. I argue that Indian agents were monarchical officers within a republican system, compelled to follow diplomatic scripts originating in the centuries of contact between European monarchies and Indigenous …

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The Role Of Xenobiotic Metabolizing Enzymes In Liver And Colon Carcinogenesis, Yewei Wang Oct 2022

The Role Of Xenobiotic Metabolizing Enzymes In Liver And Colon Carcinogenesis, Yewei Wang

Yale Graduate School of Arts and Sciences Dissertations

Both liver and colon cancers comprise the heterogeneous complex array of disorders, ranking the most common malignancies worldwide [1-3]. In 2022, the estimated 41,260 new cases of liver cancers and 106,180 new cases of colon cancers diagnosed in the United States, with 30,520 and 52,580 estimated deaths of corresponding cancers [4, 5]. A combination of surgery, chemotherapy, and/or radiotherapy is currently used to treat these cancers, and the five-year survival rate remains low for most of them [1-5]. This high lethality makes liver and colon cancers a major public health issue [6-11]. Despite extensive efforts over decades to characterize the …

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Influence Of Odor Plume Properties On Behavioral Decisions And Odor Representations In The Mouse Olfactory Bulb, Ankita Gumaste Oct 2022

Influence Of Odor Plume Properties On Behavioral Decisions And Odor Representations In The Mouse Olfactory Bulb, Ankita Gumaste

Yale Graduate School of Arts and Sciences Dissertations

Animal survival in the wild is largely dependent on their ability to locate food sources, find mates, and avoid predators — tasks which are all heavily reliant on their sense of smell. However, to be adept at these behaviors, animals must navigate a complex odor landscape where odors cues can be released in many forms, including odor trails and airborne odor plumes. Odor plumes result when an odor is carried by ambient wind, where it’s structure changes with distance from the odor source, providing potential navigational cues to searching animals. Odor plumes can adopt a variety of structures depending on …

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Immunology, Immunopathology, And Immunopharmacology Of Covid-19, Tianyang Mao Oct 2022

Immunology, Immunopathology, And Immunopharmacology Of Covid-19, Tianyang Mao

Yale Graduate School of Arts and Sciences Dissertations

Respiratory viruses represent a continuous and growing threat to humanity. This is exemplified by the ongoing global COVID-19 pandemic, which is caused by a newly emerged coronavirus SARS-CoV-2. The immune system provides a formidable barrier to viral pathogens, while dysregulated immunity leads to deleterious infection outcomes. Understanding the involvement of immune responses in viral infections will provide crucial insights into disease pathogenesis and shed light on potential targets for therapeutic interventions. In this thesis, we interrogate the components of the immune response that control SARS-CoV-2 and contribute to its pathogenesis. Based on these insights, we develop distinct immunopharmacological strategies to …

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Quantitative Analysis Of Dynamic Functional Connectivity In The Brain, David O'Connor Oct 2022

Quantitative Analysis Of Dynamic Functional Connectivity In The Brain, David O'Connor

Yale Graduate School of Arts and Sciences Dissertations

Functional magnetic resonance imaging (fMRI) is a key tool in translational neuroscience. It has been used to investigate the neurobiological phenomena which underpin traits, behaviors and disorders. However, it’s utilization far from perfect. The field struggles with statistical false positives, model overfitting, and poor generalizability. These issues have greatly impeded translation. The causes are multi-factorial, including, but not limited to; the use of small, homogeneous sample sizes, uncertainty about which brain states contribute to successful brain behavior models, and an unclear relationship between the fMRI blood oxygenation level dependent (BOLD) signal and underlying neural activity. Solutions to these issues are …

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Bachahs, Murats, And ShāKhs: The Culture Of Same-Sex Desire In Afghanistan, Ali Abdi Oct 2022

Bachahs, Murats, And ShāKhs: The Culture Of Same-Sex Desire In Afghanistan, Ali Abdi

Yale Graduate School of Arts and Sciences Dissertations

This dissertation is an introduction to the culture of same-sex desire in Afghanistan and aims at understanding how (non-normative) gender and sexuality materialize in everyday social relations in Kabul. I conducted ethnographic fieldwork in Kabul (and, for a much shorter period, in Bamyan and Mazar-i-Sharif) between 2016 and 2021. The main population with whom I worked were a group of male-born, non-masculine dancers and sex-workers who used murat for self-identification, a term they had borrowed from the argot of hijras/khwaja siras in Pakistan. By examining the formation of the queer subjectivity of murats, I suggest that the sex/gender world in …

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Inspired Filth: Working Blue In Vaudeville America, William Davenport Mercer Oct 2022

Inspired Filth: Working Blue In Vaudeville America, William Davenport Mercer

Scholarly Works

No abstract provided.

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The Stream Of The Moment: Music Streaming, Modes Of Listening, And The Curated “Song”, Tatiana Rose Daub Koike Oct 2022

The Stream Of The Moment: Music Streaming, Modes Of Listening, And The Curated “Song”, Tatiana Rose Daub Koike

Yale Graduate School of Arts and Sciences Dissertations

People today largely agree that music streaming is significantly changing the ways we experience music. But what often goes unnoticed is the question of how, exactly, such changes occur. What are the processes that are embedded in a media form that can bring about such broad-scale changes to listening practice? What are some methodological tools we can use to understand these causes and effects? My dissertation seeks to address these questions by exploring how music streaming mediates cultures of musical listening. I will stage a complex relationship between musical ontology, the listening experience, and sonic technologies that forms a perspective …

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Bistable Neural Dynamics Underlying Cognition And Spontaneous Activity: Computational Modeling And Empirical Analysis, Daming Li Oct 2022

Bistable Neural Dynamics Underlying Cognition And Spontaneous Activity: Computational Modeling And Empirical Analysis, Daming Li

Yale Graduate School of Arts and Sciences Dissertations

Characterizing the spatiotemporal patterns of neural dynamics is crucial to understanding many brain functions and psychiatric disorders. A commonly observed dynamic pattern is bistability, where the neurons switch between a high and a low firing state over the course of time. However, the origin of bistable dynamics and its role in cognitive functions and spontaneous activity remain unclear. In this thesis, we combined empirical data analysis and dynamical systems modeling approaches to quantitatively study brain dynamics. Statistical analysis allowed discovering various patterns of interest hidden in the experimental data, while dynamical systems modeling allowed us to causally test different hypotheses …

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Microglia Maintain Homeostatic Conditions In The Developing Rostral Migratory Stream, Sarah Jane Meller Oct 2022

Microglia Maintain Homeostatic Conditions In The Developing Rostral Migratory Stream, Sarah Jane Meller

Yale Graduate School of Arts and Sciences Dissertations

Microglia are brain-resident immune cells responsible for both maintaining homeostatic conditions necessary for normal neurodevelopment as well as orchestrating the brain’s response to environmental insults. Research into how the immune system and nervous system concomitantly develop and interact will not only improve our understanding of normal neurodevelopment but may provide insights into therapy after brain injury. The innate immune function of microglia phagocytosis is now understood to be involved in the developmental events of neurogenesis and synaptic pruning. However, microglia are also the first-line responders to environmental insults such as infection, trauma or toxins. Thus, if these environmental insults occur …

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Analyzing The Trophic Structure Of Ancient Communities, Jack Oliver Shaw Oct 2022

Analyzing The Trophic Structure Of Ancient Communities, Jack Oliver Shaw

Yale Graduate School of Arts and Sciences Dissertations

Since the proliferation of animal life during the Cambrian (ca. 541-485 million years ago), the biosphere has changed considerably, including long-term trends towards increasing taxonomic and functional diversity within and across ecosystems. Whether and how long-term trends in the evolution of life affected the Earth system is an active area of research, in part because the function and dynamics of ecosystems cannot be inferred by simply summing up the effect of all individuals present. Instead, the effect of diversity on ecosystem-level properties is modulated by the network of links between individuals, including trophic (e.g., predator-prey) and non-trophic (e.g., symbiosis and …

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The Role Of Gene Regulatory Mechanisms In Brain Evolution And Neuropsychiatric Disease, Sydney Keaton Muchnik Oct 2022

The Role Of Gene Regulatory Mechanisms In Brain Evolution And Neuropsychiatric Disease, Sydney Keaton Muchnik

Yale Graduate School of Arts and Sciences Dissertations

The human brain is widely acknowledged to be one of the most complex, mysterious, and intriguing structures on earth. Crucial to expanding our understanding of this fascinating organ is exploring the evolutionary processes that culminated in the development of the human brain, but also understanding what happens when the development or function of the brain are altered, as in the case of neurodevelopmental or neuropsychiatric diseases. While some interesting examples of human-specific protein coding genes with roles in brain development or disease have been identified,1–3 it has been hypothesized that changes in non-coding, regulatory regions have played a primary role …

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Interactions Between Statistical Prediction And Episodic Memory, Brynn Elizabeth Sherman Oct 2022

Interactions Between Statistical Prediction And Episodic Memory, Brynn Elizabeth Sherman

Yale Graduate School of Arts and Sciences Dissertations

Every day is a new day, but much of our experience is richly structured and predictable. From the scenery of our walks to the stereotyped nature of conversation, the vast majority of our experiences are ones that we've encountered before. Human memory is thus shaped by the predictable, structured nature of experiences. Our memories contain not only details about unique experiences (episodic memory), such as your tenth birthday, but also commonalities extracted across experience (statistical learning), such as what tends to happen at a birthday party. Notably, these two kinds of memory require opposing computations: episodic memories are formed rapidly …

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