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Does Soil Carbon Support Climate Resilient Agricultural Systems? Searching For Evidence And Developing New Measurement Tools, Daniel Kane Apr 2022

Does Soil Carbon Support Climate Resilient Agricultural Systems? Searching For Evidence And Developing New Measurement Tools, Daniel Kane

Yale Graduate School of Arts and Sciences Dissertations

2022Increasing soil organic carbon (SOC) is frequently promoted as a “win-win” strategy for agricultural management in the face of a changing climate. This framing is based on the notion that building SOC both reduces yield losses/variability by improving soil water dynamics, and that building SOC can contribute to climate change mitigation by reducing atmospheric carbon. While this framing may be useful, relationships between SOC and such outcomes are often poorly described and not quantitative. That is, it’s unclear how much of an improvement to SOC is needed to reduce yield losses, whether or not that effect translates across soil types …

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Stresses Within The Actin Meshwork Control The Turnover Of Fimbrin During Clathrin-Mediated Endocytosis, Xiaobai Li Apr 2022

Stresses Within The Actin Meshwork Control The Turnover Of Fimbrin During Clathrin-Mediated Endocytosis, Xiaobai Li

Yale Graduate School of Arts and Sciences Dissertations

In this dissertation, I investigated the molecular mechanism of clathrin-mediated endocytosis (CME) in fission yeast with a sparse labeling strategy to track endocytic proteins at the single molecule level. CME is involved in a variety of biological processes, such as nutrient internalization and receptor recycling. CME is also a well-conserved biological process from yeast to mammalian cells. During clathrin-mediated endocytosis, about 60 different endocytic proteins are recruited to the endocytic site in a highly reproducible order. During the endocytic event, endocytic proteins assemble into endocytic structures, contributing to membrane invagination and endocytic vesicle formation. Based on the single molecule endocytic …

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Modulating Innate Immunity Via Cd40-Based Myeloid Targeting Can Overcome Anti-Pd1 Therapy Resistance, Irina Krykbaeva Apr 2022

Modulating Innate Immunity Via Cd40-Based Myeloid Targeting Can Overcome Anti-Pd1 Therapy Resistance, Irina Krykbaeva

Yale Graduate School of Arts and Sciences Dissertations

Melanoma is the most aggressive skin cancer and is estimated to have caused 7180 deaths in the United States in 2021. Immune checkpoint inhibitors have revolutionized melanoma treatment over the past decade and dual therapy with anti-PD-1 and anti-CTLA4 inhibitors is currently the standard of care for advanced melanoma. Despite the success of this treatment regimen, resistance remains a significant clinical challenge. Many tumors either do not respond to checkpoint inhibition or develop resistance and ultimately patients experience disease progression. Options for these patients are limited and there is a critical need for new therapies to adequately treat anti-PD1 non-responders. …

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Essays In Financial Economics, Canyao Liu Apr 2022

Essays In Financial Economics, Canyao Liu

Yale Graduate School of Arts and Sciences Dissertations

In my dissertation, I dive into three specific areas in financial economics. Chapter 1 of my Ph.D. dissertation studies how the boom in off-exchange trading at the market close affects the close price discovery. In recent years, investment banks like Goldman Sachs have started a "guaranteed close" business where investors looking to buy or sell shares of a certain stock can get a guarantee from the bank to execute their orders at the close price set on the primary exchange. Using the TAQ data and a quasi-experimental shock from NYSE fee cut, we find that when the fraction of trades …

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An Intellectual History Of Black Literary Discourse 1910-1956, Shayne Mcgregor Apr 2022

An Intellectual History Of Black Literary Discourse 1910-1956, Shayne Mcgregor

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines the first forty-six years of black literary discourse in the American twentieth century. Beginning with Benjamin Brawley’s The Negro in Literature and Art (1910), I begin the dissertation by identifying black literary discourse’s original goal. In the parlance of the time, the goal of black literary discourse was to solve the “Negro Problem.” I then discuss how further into the twentieth century other critics and artists like James Weldon Johnson and Sterling Brown expanded on Brawley’s ideas in ways that attempted to get at the underlying philosophical thought that underpinned the Problem. By the 1930s a competing …

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Investigating The Impact Of Maternal Antiviral Responses On Pregnancy And Fetal Development, Alice Lu-Culligan Apr 2022

Investigating The Impact Of Maternal Antiviral Responses On Pregnancy And Fetal Development, Alice Lu-Culligan

Yale Graduate School of Arts and Sciences Dissertations

The maternal-fetal interface during pregnancy is an underexplored environment rich in immunological factors that must propel developmental processes while simultaneously providing protection from invading pathogens such as viruses. Almost half of all cells in the maternal decidua in pregnancy are leukocytes, which are required for successful pregnancy, and the placenta has increasingly become recognized as an immunological organ. Viral infections during pregnancy are associated with significant mortality and morbidity, both for the pregnant female and the developing fetus. Notably, impacts on fetal development have typically been attributed to direct viral damage to cells and tissues during the course of infection, …

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4pi Single-Molecule Switching Nanoscopy For Live-Cell Imaging, Kevin Hu Apr 2022

4pi Single-Molecule Switching Nanoscopy For Live-Cell Imaging, Kevin Hu

Yale Graduate School of Arts and Sciences Dissertations

plays a critical role in cell biology due to its ability tovisualize molecules of interest inside living cells with high specificity and contrast. However, diffraction of light limits spatial resolution to ~250 nm. Super-resolution microscopy bypasses this physical limit to achieve resolutions of ~10 nm, which is nearly the size of many biological macromolecules. Notably, 4Pi single-molecule switching nanoscopy achieves this resolution in all three spatial dimensions, finally making it possible to resolve specific proteins within convoluted structures like the Golgi. However, the current implementation is only compatible with dead or fixed cell samples, restricting experimental design. To explore the …

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Light Microscopy Of Proteins In Their Ultrastructural Context, Ons M'Saad Apr 2022

Light Microscopy Of Proteins In Their Ultrastructural Context, Ons M'Saad

Yale Graduate School of Arts and Sciences Dissertations

Fluorescence light microscopy is an essential tool in biomedical research. In immunofluorescence, fluorophore-conjugated antibodies are used to detect specific proteins of interest in a fixed biological sample. With recently developed nanoscopy techniques, whole cells can be imaged at an isotropic spatial resolution of ~10 nm, revealing accurate protein distributions on the nanoscale. However, most localized proteins are imaged against a dark background, which forbids seeing the overall subcellular compartments (ultrastructural context) that encompass them. Electron microscopy (EM), on the other hand, offers a complete cellular overview on the scale of a few nanometers. However, EM fails to reliably detect specific …

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Network Approaches To The Study Of Genomic Variation In Cancer, Hussein Mohsen Apr 2022

Network Approaches To The Study Of Genomic Variation In Cancer, Hussein Mohsen

Yale Graduate School of Arts and Sciences Dissertations

Advances in genomic sequencing technologies opened the door for a wider study of cancer etiology. By analyzing datasets with thousands of exomes (or genomes), researchers gained a better understanding of the genomic alterations that confer a selective advantage towards cancerous growth. A predominant narrative in the field has been based on a dichotomy of alterations that confer a strong selective advantage, called cancer drivers, and the bulk of other alterations assumed to have a neutral effect, called passengers. Yet, a series of studies questioned this narrative and assigned potential roles to passengers, be it in terms of facilitating tumorigenesis or …

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The Role Of Metabolism In Embryonic Development: Mitochondria Determine The Fate Of The Spemann-Mangold Organizer, Alexandra Elizaberth Maccoll Garfinkel Apr 2022

The Role Of Metabolism In Embryonic Development: Mitochondria Determine The Fate Of The Spemann-Mangold Organizer, Alexandra Elizaberth Maccoll Garfinkel

Yale Graduate School of Arts and Sciences Dissertations

Carbon metabolism is critical for complex multicellular life. Therefore, mitochondria, and the aerobic metabolism that they perform, have long been a focus of developmental biologists. The discovery of the Spemann-Mangold Organizer, a powerful embryonic patterning center in the dorsal region of the vertebrate embryo, first inspired the idea that embryonic patterning and aerobic metabolism may be connected almost 100 years ago. However, the advent of modern molecular genetics overshadowed this work, and metabolism in development has only recently resurfaced as a focus in the field. A permissive role for mitochondria has been well studied in development. However, it remains unclear …

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Religion And Contested Cultural Heritage: The Rotunda And Hagia Sophia As Church, Mosque, And Museum, Stephanie Machabee Apr 2022

Religion And Contested Cultural Heritage: The Rotunda And Hagia Sophia As Church, Mosque, And Museum, Stephanie Machabee

Yale Graduate School of Arts and Sciences Dissertations

This project uses the fourth-century Rotunda in Thessaloniki, Greece and the sixth-century Hagia Sophia in Istanbul, Turkey as case study sites for exploring conflicts over religious heritage. These two sites have a shared history of repurposing, from pre-Christian sites, to churches, to mosques, to museums, and to hybrid religious/heritage spaces today. These transformations are the outcome of shifting political powers and changing religious priorities over the centuries. As a result of these complex histories, the Rotunda and Hagia Sophia are notable examples of “dissonant heritage” (Tunbridge and Ashworth 1996). That is, they are loci of competing narratives and public representations …

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Structural Analysis Of Complex Bacterial Secretion Systems, Donghyun Park Apr 2022

Structural Analysis Of Complex Bacterial Secretion Systems, Donghyun Park

Yale Graduate School of Arts and Sciences Dissertations

From the moment Anton van Leeuwenhoek saw bacteria for the first time to the modern era of the ‘resolution revolution’ by the Nobel prize-winning method single particle cryo-electron microscopy (EM), advances in microscopy have led to visual observations that enhance our understanding of life at a wide range of scales, from millimeters to angstroms. The increasingly popular imaging technique cryo-electron tomography (cryo-ET) is uniquely suited for visualizing protein complexes and cellular features at high resolution in their native environment. This technology presents great potential for visualizing host-pathogen interactions. The work within this dissertation utilizes cutting-edge cryo-ET technologies to visualize different …

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Fern Ecophysiology: Linking Photosynthesis, Water Relations, And Stomatal Dynamics In Ferns, Kyra Alexandra Prats Apr 2022

Fern Ecophysiology: Linking Photosynthesis, Water Relations, And Stomatal Dynamics In Ferns, Kyra Alexandra Prats

Yale Graduate School of Arts and Sciences Dissertations

Ferns are the second-most diverse major clade of green, vascular plants, and yet, they have been historically excluded from ecophysiology, ecology, and evolution studies. Ferns were once the dominant vegetation making up forested ecosystems, and while the fern lineage predates seed plants (gymnosperms and angiosperms), the majority of extant ferns diversified alongside and even after angiosperms, the flowering plants. The theory that ferns were literally overtopped by angiosperms includes the hypothesis that over evolutionary time ferns had to adapt to new ecological niches that are less desirable, such as shaded understories or bright and dry tree canopies growing on branches …

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Targeted Nucleic Acid Delivery To The Endothelium, Melanie Reschke Apr 2022

Targeted Nucleic Acid Delivery To The Endothelium, Melanie Reschke

Yale Graduate School of Arts and Sciences Dissertations

The human endothelium extends throughout nearly all tissues in the body, and has an estimated total surface area of up to seven thousand square meters [1]. This expansive monolayer of endothelial cells (ECs) serves as the interface between materials circulating in the bloodstream and the internal tissues of the body. Even in its quiescent state, the endothelium is actively signaling and reacting in order to support the basic functions of the vascular system – transporting oxygen, nutrients, and waste. A closer look reveals that the cells that make up this endothelial lining are diverse in their phenotypes and functions, dependent …

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Somewhere Toward Freedom: Sherman's March And The History Of Emancipation, Bennett Parten Apr 2022

Somewhere Toward Freedom: Sherman's March And The History Of Emancipation, Bennett Parten

Yale Graduate School of Arts and Sciences Dissertations

When William Tecumseh Sherman’s army marched through Georgia in the last full year of the American Civil War, it didn’t march alone. As many, if not more, than 20,000 freed refugees from slavery marched along at the army’s rear. This dissertation tells their story. It argues that Sherman’s fateful March to the Sea represented not just an important military campaign, but quite possibly the largest emancipation event in American history. It also follows the refugee experience on to the shores of Georgia and South Carolina, showing how the army’s arrival in Savannah and this emerging refugee crisis shaped some of …

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Witnessing The Evolution Of Rna, Xavier Portillo Apr 2022

Witnessing The Evolution Of Rna, Xavier Portillo

Yale Graduate School of Arts and Sciences Dissertations

The RNA World theory postulates that at a certain point around 4 billion years ago during an RNA World period, a molecule, possibly RNA, developed the ability to self-replicate via polymerization. The theory also suggests that all extant life evolved from this initial RNA-based predecessor. No geological evidence from this RNA World period remains, and a self-replicating RNA polymerase has yet to be discovered or created. However, there is ample evidence from extant life pointing to an RNA-based predecessor. For example, the ribosome is a ribozyme, RNA functions as precursor signaling molecules, riboswitches regulate transcription and translation, and many more. …

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Insights Into The Allosteric Regulation And Exploitation Of The Mapk Phosphatases As Therapeutic Targets, Shanelle Rashida Shillingford Apr 2022

Insights Into The Allosteric Regulation And Exploitation Of The Mapk Phosphatases As Therapeutic Targets, Shanelle Rashida Shillingford

Yale Graduate School of Arts and Sciences Dissertations

Protein tyrosine phosphatases (PTPs), while important regulatory enzymes, have proven a challenge to elucidate their mechanisms of actions, distinct functions, as well as their potential inhibition. These enzymes, responsible for the removal of phosphate groups from tyrosine residues, share high domain and sequence homology and a charged active site. Two factors that increase the difficulty in using small molecules, either as activators or inhibitors, to investigate their functions in cells. A subclass of the PTPs is the mitogen-activated protein kinases (MAPKs) phosphatases (MKPs), responsible for the dephosphorylation and inactivation of the three groups of MAPKs: ERK, p38 MAPK, and JNK. …

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Deep Risk Prediction And Embedding Of Patient Data: Application To Acute Gastrointestinal Bleeding, Dennis Shung Apr 2022

Deep Risk Prediction And Embedding Of Patient Data: Application To Acute Gastrointestinal Bleeding, Dennis Shung

Yale Graduate School of Arts and Sciences Dissertations

Acute gastrointestinal bleeding is a common and costly condition, accounting for over 2.2 million hospital days and 19.2 billion dollars of medical charges annually. Risk stratification is a critical part of initial assessment of patients with acute gastrointestinal bleeding. Although all national and international guidelines recommend the use of risk-assessment scoring systems, they are not commonly used in practice, have sub-optimal performance, may be applied incorrectly, and are not easily updated. With the advent of widespread electronic health record adoption, longitudinal clinical data captured during the clinical encounter is now available. However, this data is often noisy, sparse, and heterogeneous. …

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Resonant Integrated Nonlinear Photonics For The Development Of Compact And Stable Soliton Microcombs, Joshua Brian Surya Apr 2022

Resonant Integrated Nonlinear Photonics For The Development Of Compact And Stable Soliton Microcombs, Joshua Brian Surya

Yale Graduate School of Arts and Sciences Dissertations

Nonlinear nanophotonic devices are crucial building blocks of a fully integrated photonic system. They enable high-speed, high-throughput and customizable transfer of information, with applications ranging from biology to cutting edge quantum information technologies. A particularly important nanophotonics component is the micro-resonator. Not only do micro-resonators confine light and allow an effective increased length of interaction with a desired material platform, they are also highly compact. Through the amplification of light-matter interaction, nonlinear phenomena such as soliton comb generation, record breaking second and third harmonic generation as well as electro-optic frequency conversion have been observed on an integrated on-chip platform. The …

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Computational Studies Of Packing And Jamming In Biological Systems, John Durkin Treado Apr 2022

Computational Studies Of Packing And Jamming In Biological Systems, John Durkin Treado

Yale Graduate School of Arts and Sciences Dissertations

The application of coarse-grained computational models to the study of physical systems has explodedin recent years, in part due to the relative simplicity of such models compared to the drastic complexity that can be found in the natural world. These models have been of particular use to the study of biological systems, as living things are typically highly complex and live far from thermodynamic equilibrium. In this thesis, I will present several coarse-grained computational models of different biological systems with the aim of identifying the role physical constraints, in particular those of packing and jamming, play in different biological systems. …

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Uncovering Hidden Diversity In Plants, Xing Wu Apr 2022

Uncovering Hidden Diversity In Plants, Xing Wu

Yale Graduate School of Arts and Sciences Dissertations

One of the greatest challenges to human civilization in the 21st century will be to provide global food security to a growing population while reducing the environmental footprint of agriculture. Despite increasing demand, the fundamental issue of limited genetic diversity in domesticated crops provides windows of opportunity for emerging pandemics and the insufficient ability of modern crops to respond to a changing global environment. The wild relatives of crop plants, with large reservoirs of untapped genetic diversity, offer great potential to improve the resilience of elite cultivars. Utilizing this diversity requires advanced technologies to comprehensively identify genetic diversity and understand …

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On The Evolutionary Ecology Of Microbial Metabolic Niche Construction, Jean Celestin Charles Vila Apr 2022

On The Evolutionary Ecology Of Microbial Metabolic Niche Construction, Jean Celestin Charles Vila

Yale Graduate School of Arts and Sciences Dissertations

All organisms construct the shared environment in which they live. This is especially notable in micro-organisms as they secrete and uptake a diverse range of metabolites depending on their genotype and environment. Over the past few decades, systems biologists have developed computational tools to predict the nutrient uptake and secretions of microbes across environments, using metabolic networks inferred from whole-genome sequencing. These tools provide an opportunity to quantify eco-evolutionary dynamics at the genomic level, by combining genome-scale metabolic models mapping genotype to phenotype, with consumer-resource models predicting population dynamics from phenotype. By leveraging these new computational approaches and combining them …

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Structural Origins Of The Stiffness And Work Contributions Of The Human Foot, Ali Yawar Apr 2022

Structural Origins Of The Stiffness And Work Contributions Of The Human Foot, Ali Yawar

Yale Graduate School of Arts and Sciences Dissertations

Human foot mechanics have been extensively studied over the last century to understand human evolution and treat foot pathologies.Much of this understanding has centered on the foot's longitudinal arch that runs from heel to toe, especially its role in making human feet stiff enough to withstand many times our bodyweight during walking and running. But numerous studies on foot biomechanics, orthopedic surgical reconstructions, and human evolution point to substantial gaps in the understanding based on the longitudinal arch alone. In this thesis, I present two new findings related to foot stiffness and how it produces the mechanical power needed for …

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Efferent Modulation Of Spontaneous Activity In Developing Sensory Systems, Yixiang Wang Apr 2022

Efferent Modulation Of Spontaneous Activity In Developing Sensory Systems, Yixiang Wang

Yale Graduate School of Arts and Sciences Dissertations

Patterned spontaneous activity plays an instructive role in developing sensory systems. Before hearing onset, inner support cells release ATP and induce spontaneous firing of neighboring inner hair cells. This periphery-initiated spontaneous activity propagates throughout the auditory hierarchy via the afferent pathway, coordinating neural activity in distinct tonotopic zones in the central auditory system. Similarly, spontaneous retinal waves initiated in the retina by starburst amacrine cells (stage II) or bipolar cells (stage III) were observed throughout the visual system via the retinotopic visual afferent circuits. Deciphering the underlying mechanisms of patterned spontaneous activity is critical to elucidate its instructive role in …

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Dissecting The Contributions Of Langerhans Cells To Skin Wound Healing And The Angiogenic Niche, Renee R. Wasko Apr 2022

Dissecting The Contributions Of Langerhans Cells To Skin Wound Healing And The Angiogenic Niche, Renee R. Wasko

Yale Graduate School of Arts and Sciences Dissertations

Mammalian skin is complex, heterogeneous, and essential for survival. It is the primary barrier that protects us from physical, microbial, and chemical hazards, and must therefore be highly regenerative. When skin is wounded, healing occurs through a series of temporally-overlapping and tightly regulated stages of inflammation, proliferation, and remodeling. Angiogenesis, the growth of new blood vessels from pre-existing vessels, occurs during the proliferative phase of repair and is essential for the formation of new, healthy tissue. Blood vessels are a vital source of oxygen, nutrients, and immune cells, and failure of these vessels to regenerate after injury results in chronic, …

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Towards Understanding The Mechanism Of Wolbachia-Induced Cytoplasmic Incompatibility, Mengwen Zhang Apr 2022

Towards Understanding The Mechanism Of Wolbachia-Induced Cytoplasmic Incompatibility, Mengwen Zhang

Yale Graduate School of Arts and Sciences Dissertations

Wolbachia is a vertically transmitted intracellular bacterium that infects a large number of arthropods and filarial nematodes. Many strains of Wolbachia manipulate host reproduction through cytoplasmic incompatibility (CI). In its simplest form, CI is a phenomenon where male host infected with Wolbachia cannot produce viable offspring with uninfected females; this apparent sterility is restored when the male host mates with Wolbachia-infected females—a phenomenon called rescue. Since Wolbachia is transmitted through the female germline, CI helps Wolbachia propagate in the host population. These properties of CI have been utilized in Wolbachia-based methods to control mosquito-borne diseases such as Dengue and Zika …

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Bosonic Quantum Simulation In Circuit Quantum Electrodynamics, Christopher Shen Wang Apr 2022

Bosonic Quantum Simulation In Circuit Quantum Electrodynamics, Christopher Shen Wang

Yale Graduate School of Arts and Sciences Dissertations

The development of controllable quantum machines is largely motivated by a desire to simulate quantum systems beyond the capabilities of classical computers. Investigating intrinsically multi-level model bosonic systems, using conventional quantum processors based on two-level qubits is inefficient and incurs a potentially prohibitive mapping overhead in the current "near-term intermediate-scale quantum" (NISQ) era. This motivates the development of hybrid quantum processors that contain multiple types of degrees of freedom, such that one can leverage an optimal one-to-one mapping between the model system and simulator. Circuit quantum electrodynamics (cQED) has emerged as a leading platform for quantum information processing owing to …

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Genetic Covariance Analysis Reveals Heterogeneous Etiologic Sharing Of Complex Traits: Theory, Methodology And Applications, Yiliang Zhang Apr 2022

Genetic Covariance Analysis Reveals Heterogeneous Etiologic Sharing Of Complex Traits: Theory, Methodology And Applications, Yiliang Zhang

Yale Graduate School of Arts and Sciences Dissertations

Over the past fifteen years, genome-wide association studies (GWAS) have identified tens of thousands of single-nucleotide polymorphisms (SNPs) associated with complex human traits and diseases. Besides the success in finding risk loci, the estimation of genetic covariance based on collected GWAS data also provides insights into the genetic basis of complex traits/diseases. Genetic covariance is the covariance of genetic effects contributing to two phenotypes. Methods based on linear mixed model (LMM) in conjunction with the restricted maximum likelihood (REML) algorithm have been developed to estimate these two quantities of significant genetic interests. However, methods based on LMM have only gained …

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Modulation Of T Cells To Promote An Anti-Tumor Response: Activation And Inhibition Of T Cells For Efficacy In T-Cell Lymphomas And Melanoma, Samuel Robert Kerr Apr 2022

Modulation Of T Cells To Promote An Anti-Tumor Response: Activation And Inhibition Of T Cells For Efficacy In T-Cell Lymphomas And Melanoma, Samuel Robert Kerr

Yale Graduate School of Arts and Sciences Dissertations

Cancer is the leading cause of premature death in the United States and other developed countries. Current decreases in cancer mortality rates are largely being driven by immunotherapies, which leverage an understanding of T cell activation and inhibition to produce an anti-tumor response. T-cell-based therapies may help decrease mortality rates even further. CAR T cell therapies and T cell activators like bispecific T-cell engagers and dendritic cell vaccines have increased survival in patients otherwise out of treatment options. While these therapies have been successful for niche patient populations, applying these therapies to wider patient populations has been difficult. In a …

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Dissecting The Impact Of Clonal Hematopoiesis On Age-Related Disease, Seyedeh Maryam Zekavat Apr 2022

Dissecting The Impact Of Clonal Hematopoiesis On Age-Related Disease, Seyedeh Maryam Zekavat

Yale Graduate School of Arts and Sciences Dissertations

Aging is the strongest risk factor for a number of diseases. Despite current risk prediction, prevention, and therapeutic strategies, age-related diseases including coronary artery disease (CAD), cancer, and now COVID-19, are the leading causes of death in the US and worldwide. The aging hematopoietic system is characterized by increased prevalence of acquired somatic variants predisposing to clonal expansion. Carriers of somatic mutations predisposing to clonal expansion in hematopoietic stem cells (clonal hematopoiesis of indeterminate potential, CHIP) are at increased risk for not only hematologic cancer but also atherosclerosis. Other classes of somatic variation besides CHIP, including larger somatic structural variants …

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