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Essays On Structural Transformation, Satoshi Matsuzawa Oct 2022

Essays On Structural Transformation, Satoshi Matsuzawa

Yale Graduate School of Arts and Sciences Dissertations

This thesis revolves around the research question of what policies contributed to Japan's economic growth, especially concerning the transition from an agrarian to an industrialized economy.Identifying such policies would help today's emerging economies accelerate the process of structural transformation. To answer this question, we first identify key policy areas and conduct a more in-depth investigation of selected policies. Our analysis to detect key policy areas consists of two parts.The first is a literature review on economic growth and industrial policy. A literature review on empirical analysis of Japan's economic growth using a growth accounting framework is in Chapter 1, and …

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Single-Cell Transcriptome Analysis Of Embryonic Cortex In Wild Type And Chd8+/− Mice, Kristina Yim Oct 2022

Single-Cell Transcriptome Analysis Of Embryonic Cortex In Wild Type And Chd8+/− Mice, Kristina Yim

Yale Graduate School of Arts and Sciences Dissertations

Over one hundred risk genes have been identified that, when disrupted, contribute to increased likelihood of an autism diagnosis. Studies have shown that expression of these risk genes converge in co-expression networks in human mid-fetal cortex. However, knowledge of these networks and the neurodevelopmental mechanisms they regulate remains limited. Several studies have focused on one risk gene in particular, the chromatin remodeler CHD8. Decreased CHD8 expression due to a gene disrupting variant is hypothesized to affect autism-associated transcriptional networks in the developing brain, thereby contributing to autism risk. In this work, we used single-cell RNA-sequencing to characterize gene expression during …

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Strategies For Targeting Dna Damage Repair And Overcoming Drug Resistance In Idh Mutant Cancers, Jonathan Dow Oct 2022

Strategies For Targeting Dna Damage Repair And Overcoming Drug Resistance In Idh Mutant Cancers, Jonathan Dow

Yale Graduate School of Arts and Sciences Dissertations

The identification and exploitation of DNA repair defects has enabled major advances in treating specific cancers. One such defect was discovered in cancers with isocitrate dehydrogenase 1/2 (IDH1/2) mutations, which confer neomorphic production of the oncometabolite 2-hydroxyglutarate (2-HG). Specifically, 2-HG production disrupts homology-directed repair (HDR) by inducing global histone hypermethylation, via histone demethylase inhibition, masking dynamic epigenetic signaling required for HDR. This HDR deficiency underlies subsequent findings of increased IDH mutant sensitivity to radiation, chemotherapy and DNA damage repair inhibitors, initially focusing on poly(ADP)-ribose polymerase (PARP) inhibitors. The discovery of IDH mutant HDR deficiency, and resulting vulnerabilities, has sparked new …

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Epigenetic Regulation Of Stem Cell Fate Decisions By Dna N(6)-Methyladenine, Raman Venkat Nelakanti Oct 2022

Epigenetic Regulation Of Stem Cell Fate Decisions By Dna N(6)-Methyladenine, Raman Venkat Nelakanti

Yale Graduate School of Arts and Sciences Dissertations

Stem cells are the parental cells from which all other cells of the organism originate. Their diverse functions range from producing an embryo from a single-celled zygote and replenishing cells that are lost during adulthood. Over the past decades, there has been growing interest in understanding how stem cells regulate their cell fate decisions, whether to self-renew or differentiate into daughter cell types. One mechanism controlling these decisions is epigenetic regulation, which involves stable changes to gene expression that do not change the DNA sequence. Studying the epigenetic pathways that regulate stem cells will provide a better understanding of development, …

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Leveraging Eqtls To Understand Genetic Etiology Of Human Diseases, Wei Liu Oct 2022

Leveraging Eqtls To Understand Genetic Etiology Of Human Diseases, Wei Liu

Yale Graduate School of Arts and Sciences Dissertations

For the last two decades, genome-wide association studies (GWAS) have been applied to identify trait-associated genetic variants in thousands of traits and diseases. This method has guided the identification of disease-causing genes and further benefited the downstream clinical treatment and drug target identification. However, due to the study design, data limitations, and lack of result interpretability in GWAS, more and more downstream analysis and integration studies with other data types have been put forward. For example, epigenomic data such as DNase hypersensitivity, histone modifications, DNA methylation, chromatin organization and interaction have helped researchers to better identify disease-associated genetic variants. The …

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Molecular And Cellular Analyses Of Thermotactic Behavioral Strategies In Caenorhabditis Elegans, Agustin Almoril-Porras Oct 2022

Molecular And Cellular Analyses Of Thermotactic Behavioral Strategies In Caenorhabditis Elegans, Agustin Almoril-Porras

Yale Graduate School of Arts and Sciences Dissertations

Animals must be able to flexibly deploy distinct behavioral strategies that allow them to fulfill specific goals in a shifting environment. I used the thermotaxis behavior of the nematode Caenorhabditis elegans as a paradigm to study the deployment and transition between two complementary behavioral strategies, gradient migration and isothermal tracking. I performed reverse and forward genetic screens to examine the contribution of known and novel molecules that regulate the execution of these two strategies. I found a novel allele of the gap junction gene inx-1/Innexin and demonstrated that it is required to terminate isotherm-oriented forward runs. Mutants for this gene …

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Synthetic Studies Of Colibactin, A Carcinogenic Gut Microbiome Metabolite, Kevin Mark Wernke Oct 2022

Synthetic Studies Of Colibactin, A Carcinogenic Gut Microbiome Metabolite, Kevin Mark Wernke

Yale Graduate School of Arts and Sciences Dissertations

The human microbiota is now understood to be intimately linked to host physiology. Recent studies indicate that microbiota species which possess a biosynthetic gene cluster – termed clb – contribute to the development and progression of colorectal cancer. Bacteria possessing the clb gene cluster are correlated to colorectal cancer (CRC) in humans, initiate colonic tumor and polyp formation in murine models, and induce DNA interstrand cross-links in cell models. Furthermore, clb+ bacteria induce a unique mutational signature which has been detected in a number of human tumor samples. Early studies by Oswald and co-workers established that the final product of …

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Molecular Mechanisms That Promote Fitness Of A Mammalian Gut Symbiotic Bacterium, Weiwei Han Oct 2022

Molecular Mechanisms That Promote Fitness Of A Mammalian Gut Symbiotic Bacterium, Weiwei Han

Yale Graduate School of Arts and Sciences Dissertations

The mammalian gut is densely populated with trillions of microbes, collectively termed the gut microbiota. The gut microbiota is critical to the health of the host. Therefore, it is critical to understand how beneficial microbes persist in the gut. This dissertation presents molecular mechanisms by which conserved genetic factors promote gut colonization by the abundant human gut symbiotic bacteria from the Bacteroides genus. Bacteroides species have an extraordinary ability to utilize various complex polysaccharides available in the gut. I have identified the global regulon of a transcriptional regulator, BT4338, necessary for the utilization of polysaccharides and intestinal colonization by B. …

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A Peak Through The Noise: Capturing Biological Heterogeneity In Aging With Our Machine Learning Toolkit, Kyra Thrush Oct 2022

A Peak Through The Noise: Capturing Biological Heterogeneity In Aging With Our Machine Learning Toolkit, Kyra Thrush

Yale Graduate School of Arts and Sciences Dissertations

Despite significant investment of resources for its study, Alzheimer’s Disease (AD) is an incurable disease with incredibly high prevalence in the older adult population. The confusion surrounding the recent approval of Aduhelm (Aducanumab) has highlighted a fraught history of inconsistent clinical trial results, difficult risk/ benefit analyses, and the desperate need for hope for an ever-increasing number of patients and their families. The primary motivation of this work is to directly characterize and embrace the heterogeneity of Alzheimer’s disease with the intent of future subtyping of patients in a data-driven manner. In this project we use extant postmortem multi-omics data …

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Ancient Andean Archipelagos: Human Interaction And Social Innovation At Chawin Punta And Kunturay In The East-Central Highlands Of Pasco, Peru, Nicholas E. Brown Oct 2022

Ancient Andean Archipelagos: Human Interaction And Social Innovation At Chawin Punta And Kunturay In The East-Central Highlands Of Pasco, Peru, Nicholas E. Brown

Yale Graduate School of Arts and Sciences Dissertations

This dissertation studies the dynamic relationship between interaction and innovation in ancient Peru, where archipelagos of social movement developed among groups of people living in distant regions of the Central Andes and Amazon. The earliest development of these archipelagic societies can be traced to the rise of the Chavín phenomenon in the 2nd and 1st millennia B.C.E., when monumental platforms and plazas were built across the Andes to accommodate large gatherings of people for new kinds of civic and ceremonial events. Although the people who gathered at Chavin monuments had different cultural backgrounds and geographic origins, their collective experiences forged …

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Integrated Lithium Niobate Nonlinear Photonics, Juanjuan Lu Oct 2022

Integrated Lithium Niobate Nonlinear Photonics, Juanjuan Lu

Yale Graduate School of Arts and Sciences Dissertations

Integrated silicon photonics, as a post-Moore technology, has been intensively studied and proven to be particularly advantageous due to its compatibility to the CMOS processing technology and feasibility of dense integration. The rapid progress of various low-loss photonic platforms has also opened up new possibilities of nonlinear sciences at nanoscale due to high optical confinement and enhanced light-matter interactions assisted by the high-Q microcavities. However, as a centrosymmetric material, silicon lacks intrinsic second-order (χ(2)) nonlinearity, which fundamentally limits its performance in terms of electro-optic modulation, second harmonic generation, parametric down conversion process, etc. Possessing significant χ(2)&χ(3) nonlinearities, broad transparency window …

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Novel High-Resolution Instrumentation To Characterize Electrified Nano-Jets For Space Propulsion: The Case Of Emi-Fap (1-Ethyl-3-Methylimidazolium Tris(Pentafluoroethyl)Trifluorophosphate) At Variable Current And Temperature, Luis Javier Perez Lorenzo Oct 2022

Novel High-Resolution Instrumentation To Characterize Electrified Nano-Jets For Space Propulsion: The Case Of Emi-Fap (1-Ethyl-3-Methylimidazolium Tris(Pentafluoroethyl)Trifluorophosphate) At Variable Current And Temperature, Luis Javier Perez Lorenzo

Yale Graduate School of Arts and Sciences Dissertations

A series of electrified nanojets of the ionic liquid EMI-FAP (1-Ethyl-3-methylimidazoliumtris(pentafluoroethyl)trifluorophosphate) are investigated at various liquid flowrates (60- 1000pl/s), and emitter temperatures (25-75C). Time of flight (TOF) and energy analysis in vacuum are used in series to determine jet parameters at the point of breakup, and propulsive properties. At each experimental condition, the jet velocity Uj , diameter dj , electrical potential Vj and energy dissipated ΔV are obtained at the jet breakup point. Additionally, the following propulsive parameters of the spray are measured: specific impulse Isp , propulsive efficiency ηprop and thrust T. These measurements provide an insight into …

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Expanding The Repertoire And Applications Of Single-Domain Antibodies, Feimei Liu Oct 2022

Expanding The Repertoire And Applications Of Single-Domain Antibodies, Feimei Liu

Yale Graduate School of Arts and Sciences Dissertations

Camelid single-domain antibody fragments (“nanobodies”), first described in the late 1980s, have proven particularly useful as both research tools and therapeutic agents. Tremendous progress has been made over the past three decades to understand these 15-kDa immunoglobulin domains derived from camelid heavy chain antibodies, from their structure, evolution, and biochemical properties to their various applications as a versatile binding moiety. Commercialization of nanobodies exploded in 2001, as a growing body of literature revealed salient features of nanobodies, including favorable solubility, stability, high-affinity, and deep penetration of its structure to active sites of enzymes. The approval of the first nanobody-based therapeutic, …

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Elf4 Transcriptionally Regulates The Inflammatory Capacity Of Cd4 T Cells, Molly Lynn Bucklin Oct 2022

Elf4 Transcriptionally Regulates The Inflammatory Capacity Of Cd4 T Cells, Molly Lynn Bucklin

Yale Graduate School of Arts and Sciences Dissertations

Inborn errors of immunity provide a unique lens through which broader biological and immunological mechanisms can be elucidated. While inborn errors of immunity constitute a range of manifestations, monogenic autoinflammatory diseases offer insights into the regulation of classically protective inflammation. Inflammation is mediated by many different cell types and complex factors that must carefully regulate initiation, duration, and magnitude of a given response. Autoinflammation occurs when there is no clear trigger and often results in a sustained and potentially pathogenic response. We have discovered a novel monogenic disease, Deficiency of ELF4 X-Linked (DEX), caused by the deficiency of the transcription …

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Human Plscr1 Is A Host Restriction Factor Against Sars-Cov-2, Weiqian Jiang Oct 2022

Human Plscr1 Is A Host Restriction Factor Against Sars-Cov-2, Weiqian Jiang

Yale Graduate School of Arts and Sciences Dissertations

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to a range of clinical outcomes, varying from asymptomatic to severe disease. One of our body’s early immune responses against viruses involves the activation of the interferon (IFN) signaling pathway, which mobilizes a diverse set of proteins that defends the host against the invading pathogen. The importance of the IFN response to combatting SARS-CoV-2 infection has been demonstrated by studies showing that patients with genetic deficiencies interfering with the IFN pathway or neutralizing autoantibodies against type I IFNs are predisposed to developing severe COVID-19 disease. Additional studies have shown …

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Attention Neural Network For Cardiac Strain Analysis In 3d Echocardiography, Shawn Ahn Oct 2022

Attention Neural Network For Cardiac Strain Analysis In 3d Echocardiography, Shawn Ahn

Yale Graduate School of Arts and Sciences Dissertations

Coronary artery disease remains the leading cause of death around the world. Acute myocardial infarction (MI) causes regional dysfunction which places remote areas of the heart at a mechanical disadvantage resulting in long term adverse left ventricular (LV) remodeling and complicated congestive heart failure (CHF). Stress echocardiography is currently the clinically established, cost-effective 2D imaging technique for detecting and characterizing myocardial injury by imaging the left ventricle at rest and after either exercise or pharmacologically-induced stress to reveal ischemia and/or infarct. However, the inherent limitations of a 2D echocardiography make it difficult to characterize the whole 3D volume of ischemic/infarct …

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Theory And Applications Of Attribution For Interpretable Language Technology, Yiding Hao Oct 2022

Theory And Applications Of Attribution For Interpretable Language Technology, Yiding Hao

Yale Graduate School of Arts and Sciences Dissertations

Attribution methods (Lipovetsky and Conklin, 2001; Štrumbelj et al., 2009; Simonyan et al., 2014; Zeiler and Fergus, 2014; Bach et al., 2015; Ribeiro et al., 2016; Shrikumar et al., 2017a; Murdoch et al., 2018; Sundararajan et al., 2017; Sundararajan and Najmi, 2020, inter alia) are a family of local interpretability techniques that measure the “contribution” of input features towards an individual model output. In natural language processing (NLP), attribution methods are often used to identify input tokens (e.g., Li et al., 2016, 2017; Arras et al., 2017b; Jumelet et al., 2019) or neural network units (e.g., Lakretz et al., 2019; …

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Pro-Life Science: The Production And Circulation Of Reproductive Knowledge In North American Anti-Abortion Movements, 1968-2003, Megann Licskai Oct 2022

Pro-Life Science: The Production And Circulation Of Reproductive Knowledge In North American Anti-Abortion Movements, 1968-2003, Megann Licskai

Yale Graduate School of Arts and Sciences Dissertations

My work shows the inextricability of what I call “pro-life science” from religious, moral, and violent anti-abortion activism. While activists tried to distinguish their scientific pro-life work from “other” kinds of activism, these research programs were built on and then reinforced the movements pro-life scientists tried to distance themselves from. This project spans the three turbulent decades of pro-life activism that bridges the liberalization of American abortion laws to twenty-first century abortion restrictions. The dissertation begins in the years preceding Roe v. Wade, as anti-abortion activists created pro-life reproductive health centers. After the 1973 decision to legalize abortion in the …

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Patterns Of Acute Liver Injury And Post-Acute Liver Sequelae Of Covid-19, Basile Njei Oct 2022

Patterns Of Acute Liver Injury And Post-Acute Liver Sequelae Of Covid-19, Basile Njei

Yale Graduate School of Arts and Sciences Dissertations

Background: Emerging data suggests severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may indirectly or directly cause acute liver injury (ALI) in patients with Coronavirus disease 2019 (COVID-19). In severe SARS-CoV-2 infection, activation of lung epithelial immune cells can lead to massive release of cytokines that can affect other organs, including the liver. Additionally, SARS-CoV-2 can induce local inflammation in the liver, either by activating liver-resident immune cells or by directly infecting cholangiocytes and hepatocytes after binding to angiotensin converting enzyme 2 (ACE2) receptors. This has raised the possibility of a predominantly biliary epithelial direct SARS-CoV-2-mediated damage as opposed to hepatocyte …

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Energy Dissipation Bounds In Fundamental Biological Processes, Samuel Bryant Oct 2022

Energy Dissipation Bounds In Fundamental Biological Processes, Samuel Bryant

Yale Graduate School of Arts and Sciences Dissertations

Biological processes consume energy to drive changes in their internal and external environments. From an abstract perspective, we can think of these energetic costs as arising from the dissipation associated with breaking time-reversal symmetry. Here we explore some new quantitative energetic bounds for specific classes of biological functions dictating exactly how much dissipation is necessary to perform the function. In particular, we examine the role of time-reversal symmetry breaking in the control of thermodynamic systems and the energetic cost of communicating information under physical constraints. The new principles we present are relevant to understanding the energetic budget of processes as …

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Nickel Catalyzed Cross-Coupling And Cross-Electrophile Coupling Reactions For The Construction Of New C-C Bonds, Emily Lucille Barth Oct 2022

Nickel Catalyzed Cross-Coupling And Cross-Electrophile Coupling Reactions For The Construction Of New C-C Bonds, Emily Lucille Barth

Yale Graduate School of Arts and Sciences Dissertations

This thesis summarizes work towards the development of new methods for the construction of C-C bonds through Ni-catalyzed cross-coupling reactions of nontraditional electrophiles and dual-catalytic cross-electrophile coupling reactions. Chapter 1 presents an introduction to Ni-catalyzed cross-coupling and cross-electrophile coupling reactions. Chapter 2 details the development and mechanistic study of a new Ni precatalyst for Suzuki-Miyaura cross-coupling reactions involving aryl carbonates. Chapter 3 describes a Ni/Co dual-catalytic strategy for cross-electrophile coupling and provides an exploration of the scope of the method, including its compatibility with pharmaceutically relevant substrates. Chapter 4 describes progress toward the development of a Ni/Ti dual catalytic cross-electrophile …

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Cavity-Enhanced Lithium Niobate Microwave-To-Optical Conversion, Yuntao Xu Oct 2022

Cavity-Enhanced Lithium Niobate Microwave-To-Optical Conversion, Yuntao Xu

Yale Graduate School of Arts and Sciences Dissertations

With superconducting circuits emerging as a promising platform for quantum computation and optical photons being the most suitable long-haul quantum information carrier, efficient bidirectional conversion between microwave and optical photons at the quantum level is in critical demand. Through high-efficiency microwave-to-optical interface, a hybrid system where quantum information is processed by superconducting circuits and distributed with photonic circuits is one of the most promising schemes to implement large-scale quantum networks. Among various approaches to realize coherent microwave-to-conversion, the cavity electro-optic (EO) system utilizes the Pockels nonlinearity to realize direct conversion between GHz microwave and optical photons without introducing an intermediate …

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Metabolic Abnormalities In Post-9/11 Veterans Of The United States And The Role Of Blast Exposure, Psychological And Somatic Conditions, Dora Lendvai Oct 2022

Metabolic Abnormalities In Post-9/11 Veterans Of The United States And The Role Of Blast Exposure, Psychological And Somatic Conditions, Dora Lendvai

Yale Graduate School of Arts and Sciences Dissertations

Metabolic abnormalities – including overweight/obesity, glucose dysregulation and insulin resistance (IR) – are an emerging health concern in military Veterans of the United States (US) who served since the 2001 terrorist attacks (post-9/11 Veterans). There are unique risk factors for overweight/obesity in this young Veteran population, including military-service related exposures (such as blast exposure [BE] and combat trauma), changes in lifestyle after military service, and the presence of psychological (e.g., posttraumatic stress disorder [PTSD] and mood disorders) or somatic (e.g., sleep disorders and pain) conditions that can impact metabolic health overtime. The aims of this dissertation study were: 1) to …

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Control Of Synaptic Cargo Delivery By Microtubule End Resident Proteins, Jun Hyun Park Oct 2022

Control Of Synaptic Cargo Delivery By Microtubule End Resident Proteins, Jun Hyun Park

Yale Graduate School of Arts and Sciences Dissertations

Neuron, a cell type that comprises the nervous system, requires unique polarized transport for its function. The neuronal polarity stems from the inherent biochemical asymmetry of the microtubule polymer which has GTP-bound tubulin enriched, dynamic plus end and more stable minus end on each pole. In most neurons, an axon has microtubule orientation where its plus end faces away from the cell body (plus-end out) while a dendrite has either mixed or plus end facing towards the cell body (minus-end out). Since microtubule orientation largely dictates the types of cargoes entering each neurite, microtubule polarity essentially defines the identity of …

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Precipitation Efficiency In Climate Change, Ryan Li Oct 2022

Precipitation Efficiency In Climate Change, Ryan Li

Yale Graduate School of Arts and Sciences Dissertations

This thesis examines precipitation efficiency, from its definition, measurements in observations and models, to its role in global climate change. Precipitation Efficiency (PE) is the ratio of surface precipitation to cloud condensation and an essential parameter in the atmospheric circulation and hydrological cycle. However, what sets its current range and whether this range will change in future climates is poorly understood. Recent developments of satellite observations and high-resolution models expand the horizon for PE research, enabling deeper exploration into this fundamental characteristic of the atmosphere. Although first studies of PE traces to the mid-20th century, the work that brought the …

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Gas-Phase Control Of Heteroatom Placement And Structure In Carbon Nanotube Synthesis, Eric Phillip Johnson Oct 2022

Gas-Phase Control Of Heteroatom Placement And Structure In Carbon Nanotube Synthesis, Eric Phillip Johnson

Yale Graduate School of Arts and Sciences Dissertations

Carbon nanotubes (CNTs) have exceptional electronic properties that give rise to promising use as sensors, interconnects, and semiconductor materials. However, functionalizing carbon nanotubes with covalent modifications to enable sensing applications, or selecting desirable semiconductive tubes via liquid treatment, both dominates the environmental impact of CNTs and suffers limitations in control and product quality. In this thesis, I explored alternative approaches to functionalization and chirality direction that leverage exotic gas-phase precursors or vapor-phase treatments. In the first part of this work, I leveraged oxygen-bearing, short-chained alkynes. Briefly, terminal alkyne precursors polymerize on a metal nanoparticle catalyst to form carbon nanotubes, and …

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Banking Regulation In Denmark: Overview, Thomson Reuters: Reuters Oct 2022

Banking Regulation In Denmark: Overview, Thomson Reuters: Reuters

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No abstract provided.

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Annual Update On Sdr Trading Operations (2022), International Monetary Fund (Imf) Oct 2022

Annual Update On Sdr Trading Operations (2022), International Monetary Fund (Imf)

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No abstract provided.

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Argentina Product Exports And Imports To China, World Bank/World Bank Group Sep 2022

Argentina Product Exports And Imports To China, World Bank/World Bank Group

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No abstract provided.

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Ypfs Lessons Learned Oral History Project: An Interview With Fabrizio López-Gallo, Mercedes Cardona Sep 2022

Ypfs Lessons Learned Oral History Project: An Interview With Fabrizio López-Gallo, Mercedes Cardona

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No abstract provided.

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