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Dna-Origami-Based Fluorescence Brightness Standards For Convenient And Fast Protein Counting In Live Cells, Nathan David Williams Apr 2021

Dna-Origami-Based Fluorescence Brightness Standards For Convenient And Fast Protein Counting In Live Cells, Nathan David Williams

Yale Graduate School of Arts and Sciences Dissertations

Fluorescence microscopy has been one of the most discovery-rich methods in biology. In the digital age, the discipline is becoming increasingly quantitative. Virtually all biological laboratories have access to fluorescence microscopes, but abilities to quantify biomolecule copy numbers are limited by the complexity and sophistication associated with current quantification methods. Here, we present DNA-origami-based fluorescence brightness standards for counting 5–300 copies of proteins in bacterial and mammalian cells, tagged with fluorescent proteins or membrane-permeable organic dyes. Compared to conventional quantification techniques, our brightness standards are robust, straightforward to use, and compatible with nearly all fluorescence imaging applications, thereby providing a …

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Statistical Methods For Gene-Environment Interactions, Yaqing Xu Apr 2021

Statistical Methods For Gene-Environment Interactions, Yaqing Xu

Yale Graduate School of Arts and Sciences Dissertations

Despite significant main effects of genetic and environmental risk factors have been found, the interactions between them can play critical roles and demonstrate important implications in medical genetics and epidemiology. Although many important gene-environment (G-E) interactions have been identified, the existing findings are still insufficient and there exists a strong need to develop statistical methods for analyzing G-E interactions. In this dissertation, we propose four statistical methodologies and computational algorithms for detecting G-E interactions and one application to imaging data. Extensive simulation studies are conducted in comparison with multiple advanced alternatives. In the analyses of The Cancer Genome Atlas datasets …

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Competition In Global Value Chains, Lucas Zavala Apr 2021

Competition In Global Value Chains, Lucas Zavala

Yale Graduate School of Arts and Sciences Dissertations

I show that exporter market power prevents farmers from benefiting from international trade. Using microdata from Ecuador, I link exporters to the farmers who supply them across the universe of cash crops. I document that farmers earn significantly less when they sell crops in export markets that are highly concentrated. I propose a model in which farmers choose a crop to produce and an exporter to supply. Exporter market power is driven by two key elasticities, which govern heterogeneity in farmer costs of switching crops and switching exporters. I develop a method to estimate them using exporter responses to international …

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Assisted Network Analysis In Cancer Genomics, Huangdi Yi Apr 2021

Assisted Network Analysis In Cancer Genomics, Huangdi Yi

Yale Graduate School of Arts and Sciences Dissertations

Cancer is a molecular disease. In the past two decades, we have witnessed a surge of high- throughput profiling in cancer research and corresponding development of high-dimensional statistical techniques. In this dissertation, the focus is on gene expression, which has played a uniquely important role in cancer research. Compared to some other types of molecular measurements, for example DNA changes, gene expressions are “closer” to cancer outcomes. In addition, processed gene expression data have good statistical properties, in particular, continuity. In the “early” cancer gene expression data analysis, attention has been on marginal properties such as mean and variance. Genes …

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Experiments With 87rb: Towards Co-Trapping 88sr19f And 87rb, Yuqi Zhu Apr 2021

Experiments With 87rb: Towards Co-Trapping 88sr19f And 87rb, Yuqi Zhu

Yale Graduate School of Arts and Sciences Dissertations

Polar molecules can interact via the anisotropic and long-range electric dipole-dipole interaction owing to their large permanent electric dipole moments. Being able to study them in the ultracold temperature regime and at high density would allow us to study strongly correlated physics, and expand the toolbox for quantum computation. In order to reduce the temperature of SrF beyond the sub-Doppler temperature ($\sim10$ $\mu$K) achieved with laser cooling by polarization gradients, we hope to implement sympathetic cooling of SrF and Rb. Pursuing this direction requires advancements in experimental capabilities. This thesis describes the experimental efforts towards co-trapping SrF and Rb, which …

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Mechanisms By Which Metaflammation And Adiponectin Regulates Glucose And Lipid Metabolism, Xiruo Li Apr 2021

Mechanisms By Which Metaflammation And Adiponectin Regulates Glucose And Lipid Metabolism, Xiruo Li

Yale Graduate School of Arts and Sciences Dissertations

Obesity and Type 2 Diabetes mellitus (T2DM) are among the most serious global health problems as they are increasing in prevalence and related to many chronic diseases, including cardiovascular and cerebrovascular diseases, cancer and other metabolic disorders. Obesity increases the risk for T2DM through the development of low-grade inflammation and insulin resistance. Specifically, studies have shown that enhanced inflammation in adipose tissue is an essential player in the progression of insulin resistance and T2DM in obese individuals. However, how immune cells sense nutritional status and contribute to whole-body metabolism are largely unknown. In addition, most of the currently available therapies …

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Morphogenesis Of Class Iv Neurons In Drosophila Melanogaster, Olivier Trottier Apr 2021

Morphogenesis Of Class Iv Neurons In Drosophila Melanogaster, Olivier Trottier

Yale Graduate School of Arts and Sciences Dissertations

The establishment of the neuron's morphology is essential to its function. The class IV neurons of the Drosophila melanogaster larva are two-dimensional sensory neurons that develop a complex dendritic arbor sensitive to mechanical stimuli. The fully-developed dendritic tree results from a multitude of stochastic processes including dendritic tip growth, branching and self-avoidance. However, it is yet unknown how the microscopic dendritic growth processes produce the macroscopic morphology of the class IV neurons. In this study, we aim to bridge this gap by formulating multi-scale models of neuronal dendritic morphogenesis. We begin by analyzing the tip dynamics and branching process of …

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Interdisciplinary Machine Learning Methods For Particle Physics, Mariel Pettee Apr 2021

Interdisciplinary Machine Learning Methods For Particle Physics, Mariel Pettee

Yale Graduate School of Arts and Sciences Dissertations

Following the discovery of a Higgs boson-like particle in the summer of 2012 at the Large Hadron Collider (LHC) at CERN, the high-energy particle physics community has prioritized its thorough study. As part of a comprehensive plan to investigate the many combinations of production and decay of the Standard Model Higgs boson, this thesis describes a continued search for this particle produced in association with a leptonically-decaying vector boson (i.e. a W or Z boson) and decaying into a pair of tau leptons. In Run 1 at the LHC, ATLAS researchers were able to set an upper constraint on the …

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Hearing The Tonality In Microtonality, Michael Bruschi Apr 2021

Hearing The Tonality In Microtonality, Michael Bruschi

Yale Graduate School of Arts and Sciences Dissertations

In the late 1970s and 1980s, composer-pianist Easley Blackwood wrote a series of microtonal compositions exploring the tonal and modal behavior of a dozen non–twelve-tone equal temperaments, ranging from 13 to 24 tones per octave. This dissertation investigates a central paradox of Blackwood’s microtonal music: that despite being full of intervals most Western listeners have never heard before, it still seems to “make sense” in nontrivial ways. Much of this has to do with the music’s idiosyncratic approach to tonality, which I define as a regime of culturally conditioned expectations that guides one’s attentional processing of music’s gravitational qualities over …

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Intuitive And Accurate Material Appearance Design And Editing, Weiqi Shi Apr 2021

Intuitive And Accurate Material Appearance Design And Editing, Weiqi Shi

Yale Graduate School of Arts and Sciences Dissertations

Creating and editing high-quality materials for photorealistic rendering can be a difficult task due to the diversity and complexity of material appearance. Material design is the process by which artists specify the reflectance properties of a surface, such as its diffuse color and specular roughness. Even with the support of commercial software packages, material design can be a time-consuming trial-and-error task due to the counter-intuitive nature of the complex reflectance models. Moreover, many material design tasks require the physical realization of virtually designed materials as the final step, which makes the process even more challenging due to rendering artifacts and …

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Motive-Directed Meter, Daniel Nathan Cox Apr 2021

Motive-Directed Meter, Daniel Nathan Cox

Yale Graduate School of Arts and Sciences Dissertations

This dissertation isolates, defines, and explores the phenomenon of Motive-Directed Meter (MDM), which has hitherto received little scholarly attention. MDM is a listening experience evoked by music that is temporally regular enough to encourage metric listening and prediction, but irregular enough to frustrate these behaviors. MDM arises when recurring musical motives suggest parallel metric hearings, but shifting durational spans make metrical parallelism difficult to achieve. Listeners are therefore caught in a state of expectational limbo, urged to continually revise predictions that are recurrently thwarted. To approach this phenomenon, Chapter 1 describes the model of musical meter that undergirds this project, …

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Analyzing The Role Of Er Membrane Biogenesis In Mitotic Fidelity, Holly Elizabeth Merta Apr 2021

Analyzing The Role Of Er Membrane Biogenesis In Mitotic Fidelity, Holly Elizabeth Merta

Yale Graduate School of Arts and Sciences Dissertations

In cell division, chromosomes align and attach to the mitotic spindle with high fidelity in order to limit missegregation of chromosomes that form individual nuclei, termed micronuclei. During cell division, membrane-bound organelles are cleared to the periphery of the cell; lack of clearance of membranes from chromosomes leads to chromosome missegregation. Cells regulate the biogenesis of their membranes throughout the cell cycle. Cancer cells frequently have upregulation of membrane lipid synthesis and micronuclei, but a connection between membrane biogenesis and chromosome missegregation leading to formation of micronuclei has not been established. In my thesis work, I show that the protein …

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Co-Transcriptional Splicing In Murine Erythroblasts, Kirsten Reimer Apr 2021

Co-Transcriptional Splicing In Murine Erythroblasts, Kirsten Reimer

Yale Graduate School of Arts and Sciences Dissertations

Eukaryotic genes contain non-coding sequences called introns. The removal ofintrons from pre-mRNAs, termed splicing, is carried out by the spliceosome, a multi-megadalton molecular complex of proteins and RNAs. Splicing occurs cotranscriptionally across multiple cell types and species. The Neugebauer lab has developed single molecule nascent RNA sequencing methods—including single molecule intron tracking (SMIT) and long-read sequencing (LRS) of nascentRNA— to visualize the precursors, intermediates, and products of transcription and splicing in budding and fission yeasts. Using these methods, the lab was able to estimate the kinetics of single intron removal in both yeasts by relating the 30 end of nascent …

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Improving Risk Factor Identification Of Human Complex Traits In Omics Data, Weimiao Wu Apr 2021

Improving Risk Factor Identification Of Human Complex Traits In Omics Data, Weimiao Wu

Yale Graduate School of Arts and Sciences Dissertations

With recent advances in various high throughput technologies, the rise of omics data offers a promise of personalized health care with its potential to expand both the depth and the width of the identification of risk factors that are associated with human complex traits. In genomics, the introduction of repeated measures and the increased sequencing depth provides an opportunity for deeper investigation of disease dynamics for patients. In transcriptomics, high throughput single-cell assays provide cellular level gene expression depicting cell-to-cell heterogeneity. The cell-level resolution of gene expression data brought the opportunities to promote our understanding of cell function, disease pathogenesis, …

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Diffusion-Based Approaches To Visualization And Exploration Of High-Dimensional Data, Scott Anthony Gigante Apr 2021

Diffusion-Based Approaches To Visualization And Exploration Of High-Dimensional Data, Scott Anthony Gigante

Yale Graduate School of Arts and Sciences Dissertations

In recent years, modern technologies have enabled the collection of exponentially larger quantities of data in the biomedical domain and elsewhere. In particular, the advent of single-cell genomics has allowed for the collection of datasets containing hundreds of thousands of cells measured in tens of thousands of dimensions. This rapid expansion of common datasets beyond the possibility of manual annotation brings forth the need for large-scale exploratory data analysis. In this thesis, we will explore the problem of dimensionality reduction for visualization of high-dimensional datasets. Visualization of high-dimensional data is an essential task in exploratory data analysis, as the low-dimensional …

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Stretching The Limits In Thermoplastic Forming Of Bulk Metallic Glasses, Rodrigo Miguel Ojeda Mota Apr 2021

Stretching The Limits In Thermoplastic Forming Of Bulk Metallic Glasses, Rodrigo Miguel Ojeda Mota

Yale Graduate School of Arts and Sciences Dissertations

Metallic glasses (MG) suggest that superb mechanical properties can be paired with plastic-like processing. Their high strength and elasticity are often paired with fracture toughness. Their supercooled liquid region gives rise to plastic-like processing and suggests parts and shapes that can otherwise not be obtained for crystalline metals. However, current processing techniques only allow for limited options in terms of geometry, thicknesses uniformity, and shape complexity. In the first part of my thesis, I introduce the form-giving aspect of metallic glass thermoforming, by introducing stretch blow molding, to expand the geometries that can be fabricated with metallic glasses. For this …

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Latent Factor Analysis Of High-Dimensional Brain Imaging Data, Siyuan Gao Apr 2021

Latent Factor Analysis Of High-Dimensional Brain Imaging Data, Siyuan Gao

Yale Graduate School of Arts and Sciences Dissertations

Recent advances in neuroimaging study, especially functional magnetic resonance imaging (fMRI), has become an important tool in understanding the human brain. Human cognitive functions can be mapped with the brain functional organization through the high-resolution fMRI scans. However, the high-dimensional data with the increasing number of scanning tasks and subjects pose a challenge to existing methods that wasn’t optimized for high-dimensional imaging data. In this thesis, I develop advanced data-driven methods to help utilize more available sources of information in order to reveal more robust brain-behavior relationship. In the first chapter, I provide an overview of the current related research …

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Analyzing The Effect Of Fuel Nitrogen On Soot Formation, Matthew Jacob Montgomery Apr 2021

Analyzing The Effect Of Fuel Nitrogen On Soot Formation, Matthew Jacob Montgomery

Yale Graduate School of Arts and Sciences Dissertations

In modern-day life, energy is primarily supplied by the combustion of carbon-containing fuels. As global economic and population growth occurs, the demand for energy, and consequently the amount of energy supplied by carbon-containing fuels, is predicted to increase. Despite overwhelming use of carbon-containing fuels, there are various human health, climate, and environmental issues related to combustion emissions like carbon dioxide (CO2) and soot. To alleviate our dependence on fossil fuels while concomitantly minimizing the negative impacts of these pollutants, research into renewable fuels, engine geometries, and burning strategies is needed alongside advancements in renewable energy technologies. One strategy to reduce …

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Polybrominated Diphenyl Ethers, Thyroid Hormones, And Risk Of Papillary Thyroid Cancer, Huang Huang Apr 2021

Polybrominated Diphenyl Ethers, Thyroid Hormones, And Risk Of Papillary Thyroid Cancer, Huang Huang

Yale Graduate School of Arts and Sciences Dissertations

Thyroid cancer is the most common cancer of the endocrine system. The incidence of thyroid cancer has increased worldwide for decades in the general populations and in the US military personnel. Although emerging evidence indicates that exposure to polybrominated diphenyl ethers (PBDEs) is related to disruption of thyroid hormone homeostasis, the association between exposure to PBDEs and risk of thyroid cancer is still unclear. Additionally, mutations in genes coding for enzymes involved in regulation, metabolism, or functional activation of PBDEs and thyroid hormones could modify the PBDEs and thyroid hormones related risk of thyroid carcinogenesis. Using data from a nested …

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Rethinking Aesthetic Humanism: Schiller After Agamben And Rancière, Thiti Owlarn Apr 2021

Rethinking Aesthetic Humanism: Schiller After Agamben And Rancière, Thiti Owlarn

Yale Graduate School of Arts and Sciences Dissertations

Since de Man, aesthetic humanism is often thought of as an ideology that valorizes the arts and their capacity to improve humanity. This study argues that something more important is at stake in Schiller’s aesthetics. Following Rancière, I argue that aesthetic experience is inherently meaning-disruptive and therefore not utilizable as means to an end. The fact that the aesthetic has this means-without-end structure allows us to reconceive of humanity, like Agamben, not as a rational animal or an end-setting subject, but as a figure of surplus potential, a life that gives itself form without being reducible to a specific way …

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African Bargaining Power: On The Origins Of Strong Investment Deals With China, Christina Seyfried Apr 2021

African Bargaining Power: On The Origins Of Strong Investment Deals With China, Christina Seyfried

Yale Graduate School of Arts and Sciences Dissertations

This project investigates how African governments strategize around private Chinese capital. How much bargaining power do individual African countries have with private Chinese investors? What factors influence countries’ strategies around this type of investment? Under what conditions do governments ask private Chinese investors to contribute to developing local content (ownership and employment)? How do these Chinese investors react to stricter regulations? And finally, and most importantly, is there more to gain for some African partners in this relatively new relationship with China?Most development scholars accept what I call a “Weak Bargaining Power Narrative” about the African region – that due …

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The Preexistence Of The Soul In The Early English Enlightenment: 1640-1740, Clay Paul Greene Apr 2021

The Preexistence Of The Soul In The Early English Enlightenment: 1640-1740, Clay Paul Greene

Yale Graduate School of Arts and Sciences Dissertations

This dissertation assesses the English revival of the metaphysical Platonic doctrine of the soul’s preexistence against the backdrop of the philosophical, cultural, and religious changes that defined seventeenth-century intellectual life. The reemerged doctrine of preexistence was the last important gasp of strict metaphysical dualism, and through the writings of its defenders, the idea became incorporated into the primary philosophical innovations of modernity, scientific materialism, democratic equality, and what Charles Taylor calls exclusive humanism. But preexistence did not persist in seventeenth-century life only in philosophical argument, but in literary creations and ideas with practical human import. Between 1640 and 1740, Henry …

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Prototypical Arm Motions From Human Demonstration For Upper-Limb Prosthetic Device Control, Yuri Gloumakov Apr 2021

Prototypical Arm Motions From Human Demonstration For Upper-Limb Prosthetic Device Control, Yuri Gloumakov

Yale Graduate School of Arts and Sciences Dissertations

Controlling a complex upper limb prosthesis, akin to a healthy arm, is still an open challenge due to the inadequate number of inputs available to amputees. Designs have therefore largely focused on a limited number of controllable degrees of freedom, developing a complex hand and grasp functionality rather than the wrist. This thesis investigates joint coordination based on human demonstrations that aims to vastly simplify the controls of wrist, elbow-wrist, and shoulder-elbow wrist devices.The wide range of motions performed by the human arm during daily tasks makes it desirable to find representative subsets to reduce the dimensionality of these movements …

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Hardware Architectures For Post-Quantum Cryptography, Wen Wang Apr 2021

Hardware Architectures For Post-Quantum Cryptography, Wen Wang

Yale Graduate School of Arts and Sciences Dissertations

The rapid development of quantum computers poses severe threats to many commonly-used cryptographic algorithms that are embedded in different hardware devices to ensure the security and privacy of data and communication. Seeking for new solutions that are potentially resistant against attacks from quantum computers, a new research field called Post-Quantum Cryptography (PQC) has emerged, that is, cryptosystems deployed in classical computers conjectured to be secure against attacks utilizing large-scale quantum computers. In order to secure data during storage or communication, and many other applications in the future, this dissertation focuses on the design, implementation, and evaluation of efficient PQC schemes …

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Environmental Assessments Of Capital-Intensive Product Systems, Travis Reed Miller Apr 2021

Environmental Assessments Of Capital-Intensive Product Systems, Travis Reed Miller

Yale Graduate School of Arts and Sciences Dissertations

The UN Sustainable Development Goals (SDGs) set out a bold vision to advance global society on multiple dimensions by the year 2030. The 17 SDGs tackle key issues of human wellbeing in part by building infrastructure, industrializing, and growing economies. The SDGs simultaneously aim to prevent climate change and conserve the natural environment. There are synergies between many of the goals, but clear tradeoffs as well. Investments in capital assets like buildings, roads, equipment, vehicles, and information technology come at an environmental cost. Innovative strategies are needed to grapple with these tradeoffs and optimize paths toward sustainable development. Innovative tools …

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Computational Studies Of The Protocol-Dependent Mechanical Properties Of Granular Materials, Philip Wang Apr 2021

Computational Studies Of The Protocol-Dependent Mechanical Properties Of Granular Materials, Philip Wang

Yale Graduate School of Arts and Sciences Dissertations

Dry granular materials are collections of macroscopic-sized grainsthat interact via purely repulsive and dissipative contact forces. In this thesis, we describe discrete element method (DEM) simulations to characterize the structural and mechanical properties of jammed packings of spherical particles. Many previous studies have shown that the bulk modulus of jammed sphere packings depends only weakly on the pressure during isotropic compression, whereas the ensemble-averaged shear modulus $\langle G \rangle$ increases as a power-law in pressure $P$ at large pressures. However, the origin of the power-law scaling of the shear modulus with pressure is not well-understood. In particular, why is the …

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Surveilling The Distinctive Vascular And Metabolic Features Of Tumor Progression And Response To Therapy, John James Walsh Apr 2021

Surveilling The Distinctive Vascular And Metabolic Features Of Tumor Progression And Response To Therapy, John James Walsh

Yale Graduate School of Arts and Sciences Dissertations

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment with surgical resection, radiotherapy and temozolomide chemotherapy, prognosis is dismal with median survival around 15 months. GBMs are highly infiltrative tumors that invade into surrounding brain tissue, which makes defining the extent of tumor spread difficult and recurrence common. Radiological identification of GBMs with magnetic resonance imaging (MRI), using transvers (T2) or longitudinal (T1) relaxation contrasts, is a mainstay in the initial diagnosis as well as tracking therapeutic response in GBM. However, there is extreme variability in the structural appearance, size, metabolism, and genetic landscape …

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Mechanisms Of Resource Competition With Intraspecific Variation, Erica Marie Holdridge Apr 2021

Mechanisms Of Resource Competition With Intraspecific Variation, Erica Marie Holdridge

Yale Graduate School of Arts and Sciences Dissertations

Intraspecific trait variation occurs in nearly all species and is found in a variety of traits, including morphological, behavioral, and physiological traits. Unlike fields such as evolutionary biology and behavioral ecology which have long recognized the importance of intraspecific trait variation (ITV), community ecologists have historically viewed ITV as “noise” that obscures broader population- and community-level patterns of interest. However, recent work has demonstrated that ITV can profoundly affect ecological interactions and processes through a variety of mechanisms (other earlier paper, Bolnick et al. 2011). Of particular interest is the effect of ITV on competition and coexistence. Empirical work has …

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Electrocatalytic Oxygen Reduction Using Molecular Iron Porphyrins: Detailing The Role Of Electrostatics In Small Molecule Activation, Daniel James Martin Apr 2021

Electrocatalytic Oxygen Reduction Using Molecular Iron Porphyrins: Detailing The Role Of Electrostatics In Small Molecule Activation, Daniel James Martin

Yale Graduate School of Arts and Sciences Dissertations

Energy storage and conversion are key facets of sustainable energy science. Fuel cells, for instance, allow us to convert chemical and electrical energies while minimizing energy loss in the form of heat. The oxygen reduction reaction—which involves combining O2, protons, and electrons to make water—is one such reaction common to many types of fuel cells but is hard to perform both rapidly and efficiently. Typically there are trade-offs, and faster catalysis is only achieved at lower efficiencies. Overcoming these tradeoffs is a long withstanding goal in electrocatalysis and would be broadly impactful for the optimization of energy-relevant reactions. The atomistic …

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Exoplanet Measurement To The Extreme: Novel Methods Of Instrumentation And Data Extraction For Radial-Velocity Spectrographs, Ryan Richard Petersburg Apr 2021

Exoplanet Measurement To The Extreme: Novel Methods Of Instrumentation And Data Extraction For Radial-Velocity Spectrographs, Ryan Richard Petersburg

Yale Graduate School of Arts and Sciences Dissertations

The current generation of radial-velocity spectrographs are at the precipice of discovering the first Earth-like exoplanets orbiting in the habitable zones of nearby stars. Such detections require Doppler precision of approximately 10 cm/s, an order of magnitude better than the typical best-case measurement from the previous generation of instruments. Therefore, the radial-velocity community requires research and innovation from all angles to push our technology over the brink. This thesis presents multiple contributions to this field---ranging from the development of precision laser equipment to the implementation of advanced statistical data analysis algorithms---all in support of the EXtreme PREcision Spectrograph (EXPRES) with …

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