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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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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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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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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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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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Metformin And Statin’S Effect On Prostate Cancer Risk In Diabetics With Benign Prostatic Hyperplasia, Kevin Mugno Apr 2021

Metformin And Statin’S Effect On Prostate Cancer Risk In Diabetics With Benign Prostatic Hyperplasia, Kevin Mugno

Yale School of Medicine Physician Associate Program Theses

Prostate cancer, a leading cause of cancer mortality, is associated with benign prostatic hyperplasia. Additionally, individuals with type 2 diabetes have a diminished prostate cancer risk. Metformin and statins are routinely used in the management of diabetes; however, it is unclear whether the combination of metformin and statins can reduce the incidence of prostate cancer in men with a concurrent diagnosis of type 2 diabetes and benign prostatic hyperplasia. This study will determine whether combination treatment of metformin and statins lowers the incidence of prostate cancer in patients with benign prostatic hyperplasia and type 2 diabetes. Using a retrospective cohort …

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Culturally-Adapted Cognitive Behavioral Therapy For Bilingual Latinx With Depressive Symptoms, Leanne Gonzalez Apr 2021

Culturally-Adapted Cognitive Behavioral Therapy For Bilingual Latinx With Depressive Symptoms, Leanne Gonzalez

Yale School of Medicine Physician Associate Program Theses

The prevalence of depression is particularly high in the Latinx population, and this population is associated with lower rates of depression diagnosis and treatment. One intervention that has shown to be effective in treating mild to moderate depression is cognitive behavioral therapy. Though the effects of culturally adapted therapy, language being the most common adaptation, have been studied, the difference in outcomes for bilingual, bicultural speakers has not been examined. In this randomized control trial, we will compare the effectiveness of Spanish language cognitive behavioral therapy to that of English language therapy in bilingual, foreign-born, Latinx patients with depressive symptoms. …

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Vitamin E Alpha-Tocopherols To Prevent Recurrent Stroke In Patients With A Minor Neurovascular Event, Veronica Guirguis Apr 2021

Vitamin E Alpha-Tocopherols To Prevent Recurrent Stroke In Patients With A Minor Neurovascular Event, Veronica Guirguis

Yale School of Medicine Physician Associate Program Theses

Minor ischemic strokes and transient ischemic attacks involve impaired perfusion to corresponding brain regions leading to neurological deficits that may or may not resolve after the event. Adults suffering one of these minor neurovascular events have high odds of a recurrent stroke within the first 90 days, mitigated but not prevented by standard treatment of clopidogrel and aspirin. Vitamin E alpha-tocopherols have been shown to reduce platelet aggregation, potentiate aspirin, and reduce ischemic damage. This study will assess the efficacy of vitamin E alpha-tocopherol, in addition to the standard treatment, on stroke recurrence in adults with a minor neurovascular event …

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The Role Of O-Glcnac Transferase In Liver Fibrosis, Bichen Zhang Apr 2021

The Role Of O-Glcnac Transferase In Liver Fibrosis, Bichen Zhang

Yale Graduate School of Arts and Sciences Dissertations

The liver is a key metabolic tissue that is constantly challenged with various insults. Liver fibrosis is the common pathway for chronic liver injury, yet the treatment for liver fibrosis remains experimental. O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) is a nutrient- and stress-sensing post-translational modification that regulates a variety of cellular events. Here I report that O-GlcNAc transferase (OGT) protects hepatocytes against necroptosis and initiation of liver fibrosis. Liver-specific OGT knockout (OGT-LKO) mice show fast-developed liver fibrosis and inflammation. The deletion of OGT induces global transcriptome changes in hepatocytes. OGT-deficient hepatocytes undergo excessive necroptosis and show elevated expression of key genes in …

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Delving Into Survival Of Colorectal Cancer - Long-Term Survival, Younger Populations, And Prediction Models, En Cheng Apr 2021

Delving Into Survival Of Colorectal Cancer - Long-Term Survival, Younger Populations, And Prediction Models, En Cheng

Yale Graduate School of Arts and Sciences Dissertations

Colorectal cancer (CRC) is one of most common cancers in the United States and is a longstanding health threat to men and women. Although survival rates after CRC diagnosis have markedly increased since 1975, likely due to advances in early screening and treatment, there are three important aspects demanding further investigation: 1) the long-term survival and causes of death after CRC diagnosis, 2) the differences of survival of early-onset CRC (defined as age <50 years) compared to CRC diagnosed at older ages, and 3) the development of novel comprehensive prediction models for personalized survival estimates. In this dissertation, I delve into the above research areas that may advance our knowledge in CRC survival.In Chapter 1, I investigated long-term survival rates and causes of death among men and women diagnosed with colorectal cancer in three cohorts of U.S. health professionals - Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study. After over three decades of follow-up, among male CRC survivors, the 30-year cumulative overall mortality rate was 93.2%, and cancer-specific mortality rate was 37.0%. Due to longer follow-up of women, we observed 86.5% for 35-year cumulative overall mortality rate, and 39.6% for cancer-specific mortality rate. Regarding causes of death, given that cancer-specific mortality rate increased by <4% between 10 to 30- or 35-year following diagnosis (among men, from 35.2% to 37.0%; among women, from 35.8% to 39.6%), CRC patients surviving more than 10 years after diagnosis are unlikely to die from that malignancy and other diseases should receive more attention in treatment of survivors beyond 10 years. This is good news for CRC patients. In Chapter 2, given that the incidence rate of early-onset CRC rapidly increased by 19.7% from 2012 to 2017, it is of great importance to look into survival after diagnosis of early-onset CRC. Using the National Cancer Database, I assessed the survival differences of early-onset CRC and later-onset CRC (defined as ages 51-55 years in this study), and explore the heterogeneity of survival within early-onset CRC. Early-onset CRC patients experienced a modestly inferior overall survival for all years in unadjusted analysis, compared to later-onset CRC. However, following adjustment for other predictors for mortality, most notably disease stage, early-onset CRC patients had a lower risk of death compared to subjects diagnosed between ages 51-55 (adjusted hazard ratio: 0.95 [95% CI, 0.93-0.96]). The survival advantage appeared greatest for patients diagnosed at ages 35-39 and stages I-II, and was absent among those diagnosed at 25 years or younger and stages III-IV. The survival advantage of early-onset CRC for younger patients should be interpreted cautiously, given that the advantage has small magnitude and is heterogeneous by age and stage. Further study is needed to understand the underlying heterogeneity of survival within early-onset patients by age and stage. In Chapter 3, I specially focused on developing novel prediction models for colon cancer. Although CRC is a term that combines colon cancer and rectal cancer, colon cancer accounts for >70% of CRC. Using a cohort derived from a large multiple-center randomized trial CALGB 89803, I developed visual nomograms of prediction models by clinical, pathologic, diet, and …

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Genetically Encoded Biomaterials: Design, Characterization, And Applications For Functionalizing Biological Therapeutics, Koen Vanderschuren Apr 2021

Genetically Encoded Biomaterials: Design, Characterization, And Applications For Functionalizing Biological Therapeutics, Koen Vanderschuren

Yale Graduate School of Arts and Sciences Dissertations

Engineering of the translation apparatus has permitted site-specific incorporation of nonstandard amino acids (nsAAs) into proteins, thereby expanding the genetic code of organisms. Recent work in genome engineering has enabled whole genome recoding, in which codons removed from the genetic code can be repurposed as new sense codons dedicated for incorporation of nsAAs. This work describes our vision of how synthetic biology and genetic code expansion will allow the development of genetically encoded biomaterials -- a new class of biomaterials that marries the sequence-defined production, fidelity and processivity of ribosomal protein expression, with the vast molecular and structural diversity of …

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Identification Of Tumor Immune Regulatory Factors Using High Throughput Crispr Screening, Adan Hughett Codina Apr 2021

Identification Of Tumor Immune Regulatory Factors Using High Throughput Crispr Screening, Adan Hughett Codina

Yale Graduate School of Arts and Sciences Dissertations

Cancer is a broad umbrella term that covers hundreds of diseases, each with their own unique molecular pathologies and genetic legions. The field of cancer biology has strived to uncover the significance of this vast array of mutations, hoping to translate basic science into clinically meaningful biomarkers, useful for diagnosis, prognosis, and in recent years treatment. This process has only become more relevant with the adoption of targeted molecular medicine, whether it be tyrosine kinase inhibitors (TKIs) or immune therapies targeting checkpoint blockade molecules.Immune therapies in particular, have the potential to revolutionize cancer management. Therapies such as checkpoint blockade inhibitors …

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Tracking Single Cell Lineages In Saccharomyces Cerevisiae, Guste Urbonaite Apr 2021

Tracking Single Cell Lineages In Saccharomyces Cerevisiae, Guste Urbonaite

Yale Graduate School of Arts and Sciences Dissertations

The ability to measure the number of gene-specific mRNA molecules in individual mammalian cells has transformed the transcriptomics field. Among the key technologies enabling single-cell mRNA sequencing has been Droplet Sequencing (Drop-Seq). While this method works efficiently for mammalian cells, its direct application to yeast cells has been problematic due to cell-type specific differences such as size, doublet formation rate, and cell wall. Here we introduce yeast DropSeq, a single-cell RNA sequencing method for the study of transcriptomics in yeast. I modified and optimized the original Drop-Seq method to address the issues that emerged from smaller cell sizes and the …

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Insights Into The Biogenesis Of Stress-Induced Readthrough Transcripts, Nicolle Alexandra Rosa Mercado Apr 2021

Insights Into The Biogenesis Of Stress-Induced Readthrough Transcripts, Nicolle Alexandra Rosa Mercado

Yale Graduate School of Arts and Sciences Dissertations

Readthrough transcription, defined as transcription extending beyond the annotated termination site of genes, is induced by cellular stress and results in the production of thousands of long noncoding RNAs called DoGs (downstream-of-gene transcripts). The localization and induction patterns of these transcripts have been extensively characterized in different cellular contexts. However, the mechanisms that lead to DoG production upon cellular stress remain unknown. To gain a better understanding of the mechanisms that lead to DoG production, I investigated the transcriptional and proteomic landscapes that accompany the induction of these RNAs in human cells exposed to hyperosmotic stress.In collaboration with Dr. Matthew …

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Genetic Dissection Of Local And Systemic Responses In States Of Perturbed Iron Balance, Xiuqi Li Apr 2021

Genetic Dissection Of Local And Systemic Responses In States Of Perturbed Iron Balance, Xiuqi Li

Yale Graduate School of Arts and Sciences Dissertations

Iron balance is essential for health. Iron deficiency can impair multiple biological processes and, when severe, restrict red blood cell production, resulting in iron deficiency anemia. Excess iron, on the other hand, can catalyze the generation of harmful reactive oxygen species, leading to tissue damage and organ failure. Because at least 1 billion people worldwide exhibit altered iron balance, understanding iron pathophysiology has broad implications for global health. In this thesis, I use genetic approaches in mouse models and tissue culture systems to dissect local and systemic responses in states of perturbed iron balance. The first part of this thesis …

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Neurite Placement And Synapse Formation In Layered Neuropils, Titas Sengupta Apr 2021

Neurite Placement And Synapse Formation In Layered Neuropils, Titas Sengupta

Yale Graduate School of Arts and Sciences Dissertations

A fundamental design principle of nervous systems is the grouping of neuronal contacts into layers within nerve bundles. The layered arrangement of neurites requires nanoscale precision in their placement within bundles, and this precision, which cannot be exclusively explained by simple tip-directed outgrowth dynamics, underpins synaptic specificity and circuit architecture. For my thesis work, I implemented novel dynamic imaging methods and analyses and constructed fluorescent labeling tools to document the specific placement of single neurites during the assembly of the C. elegans nerve ring. We uncover a zippering mechanism that controls precise placement of neurites onto specific layer subdomains. Through …

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Time As A Bridge From Brain To Behavior, Maxwell Shinn Apr 2021

Time As A Bridge From Brain To Behavior, Maxwell Shinn

Yale Graduate School of Arts and Sciences Dissertations

Time has mystified philosophers, artists, and scientists for centuries, but only recently has it become possible to study the neurobiology of time. Time is critical for cognition, and the mechanisms through which it impacts neural processes, such as those for decision-making, are starting to be better understood. Standard mathematical models for decision-making are not suited to studying stimuli or strategies which change over time, so we construct a generalization of a standard model as well as an efficient computational framework, providing insight at both the behavioral and the neural level. We use this framework to understand behavior and single-neuron recordings …

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Analysis Of The Regulation Of Transcriptional Noise In Nf-Κb-Induced Transcription, Victor Louis Bass Apr 2021

Analysis Of The Regulation Of Transcriptional Noise In Nf-Κb-Induced Transcription, Victor Louis Bass

Yale Graduate School of Arts and Sciences Dissertations

Transcriptional noise can regulate biological processes including the immune response and reactivation of latent HIV, both of which depend on the transcription factor NF-κB. To better understand the molecular mechanisms that can alter this noise, we quantified transcripts in single cells and assayed events at gene promoters to inform a mathematical model of transcriptional bursting. Initially, we compared transcriptional noise from different HIV integrations to test the effect of basal chromatin environment on noise in response to stimulation of NF-κB by the inflammatory cytokine TNF. We then characterized basal and TNF-induced transcription of endogenous NF-κB targets to test whether the …

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Improvements In Pulmonary Tissue Engineering: Toward Functional Tracheal And Lung Replacements, Allison M. Greaney Apr 2021

Improvements In Pulmonary Tissue Engineering: Toward Functional Tracheal And Lung Replacements, Allison M. Greaney

Yale Graduate School of Arts and Sciences Dissertations

Tissue engineering offers a uniquely powerful solution for the regeneration of damaged or diseased tissues, in the form of personalized living replacements. Building such replacements, however, requires a deep appreciation for the biological, chemical, and engineering aspects that govern their function. Currently, the generation of biomimetic trachea and lung replacements is hampered by incomplete recapitulation of certain of these critical aspects, which have been addressed through the work in this thesis. In Chapter 2, I reviewed all reported clinical applications of engineered tracheal grafts to replace long-segment, circumferential damage from 1898 to 2018. From these reports, I identified the current …

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Uncovering Novel Roles For Glia In Neurodegenerative Diseases, Leon Lall Tejwani Apr 2021

Uncovering Novel Roles For Glia In Neurodegenerative Diseases, Leon Lall Tejwani

Yale Graduate School of Arts and Sciences Dissertations

The complexity of the central nervous system poses a tremendous challenge for understanding the intricate interplay between the myriad cell types that comprise the brain and spinal cord. Understanding these interactions becomes especially challenging when examining dynamic processes, such as aging or disease. In genetic disorders, an additional layer of complexity emerges when multiple cell types express the disease-causing or disease-associated proteins, as this expression can contribute to pathophysiology through primary, cell autonomous effects and secondary, non-cell autonomous mechanisms. Identifying these cell type-specific changes and interpreting them in the overall context of the disease have remained difficult, especially in the …

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Characterization Of Structures And Biosyntheses Of Ecologically Important Secondary Metabolites In Escherichia Coli And Xenorhabdus Species, Jhe-Hao Li Apr 2021

Characterization Of Structures And Biosyntheses Of Ecologically Important Secondary Metabolites In Escherichia Coli And Xenorhabdus Species, Jhe-Hao Li

Yale Graduate School of Arts and Sciences Dissertations

Gut microbes both compete for shared resources among neighboring species as well as promote synergistic interactions with the host in order to thrive in their extraordinarily complex environment. Bacterial secondary metabolites mediate these different types of interactions between the producer and its environment. Small molecule therapeutics, such as antibiotics, can elicit production of different secondary metabolites and may contribute to a dysregulated microbiota. In identifying novel bacterial-derived metabolites, we aim to understand the molecular mechanisms by which bacteria interact with the environment, which may serve as future biomarkers or therapeutics for microbiome-targeted intervention. To this end, my work is concerned …

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High-Throughput Experimental Strategies: The Highway To New Complex Alloys And Understanding Complex Phenomena, Sebastian Alexander Kube Apr 2021

High-Throughput Experimental Strategies: The Highway To New Complex Alloys And Understanding Complex Phenomena, Sebastian Alexander Kube

Yale Graduate School of Arts and Sciences Dissertations

Metallurgical research is struggling to build a satisfactory understanding of various complex alloy classes and phenomena. For many of these problems, such as glass formation, single phase solid solution formation, or supercooled melt viscosities, computational approaches are overwhelmed. Experiments, by contrast, can directly evaluate real materials systems to generate valuable data. Unfortunately, experiments remain costly and time consuming, severely restricting the progress of materials discovery. This dissertation pushes to overcome this obstacle through a comprehensive high-throughput research strategy: The experimental approach is centered around combinatorial co-sputtering and rapid characterization, investigating hundreds of alloys at a time while maintaining highest sample …

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Building Mouse Models For Tumor Immunology: Ninja In Kras-Driven Lung Adenocarcinoma, Brittany Fitzgerald Apr 2021

Building Mouse Models For Tumor Immunology: Ninja In Kras-Driven Lung Adenocarcinoma, Brittany Fitzgerald

Yale Graduate School of Arts and Sciences Dissertations

Genetically engineered mouse models of tumor immunology frequently require the addition of exogenous neoantigens to trigger immune responses, often within lentiviral vectors that introduce confounding variables. Mouse models with inducible neoantigens avoid some of these problems but have been historically difficult to generate because of leaky expression of antigens in the thymus, resulting in central tolerance in developing CD8 and CD4 T cells. We developed the iNversion INducible Joined neoAntigen (NINJA) mouse model that uses RNA splicing, DNA recombination, and three levels of regulation to prevent neoantigen leakiness and bypass central and peripheral tolerance. We describe the development of these …

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Investigations Of Novel Mechanisms Of Epigenetic Regulation On Chromatin, William J. Lu-Culligan Apr 2021

Investigations Of Novel Mechanisms Of Epigenetic Regulation On Chromatin, William J. Lu-Culligan

Yale Graduate School of Arts and Sciences Dissertations

The epigenetic regulation of gene expression, mediated by chromatin, is a critical component of eukaryotic cellular function. Chromatin regulates gene expression through a variety of mechanisms including histone post-translational modifications, chromatin remodeling, and recruitment of non-coding RNAs. Together, the chromatin states enable cells to organize the genome and efficiently carry out cellular functions. Given the implications of chromatin regulation in normal, developmental, and disease states, an understanding of the mechanisms of chromatin regulation is of critical importance. In this dissertation, I describe three projects towards furthering the field’s understanding of the mechanisms of chromatin regulation.First, I propose Kacme, a novel …

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Biogeochemical Controls On Greenhouse Gas Dynamics In Streams And Rivers, Kelly S. Aho Apr 2021

Biogeochemical Controls On Greenhouse Gas Dynamics In Streams And Rivers, Kelly S. Aho

Yale Graduate School of Arts and Sciences Dissertations

Streams and rivers are biogeochemical “hot spots”, simultaneously processing and transporting both terrestrially and locally fixed carbon and nitrogen. The greenhouse gases carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) are (by)products of some of these biogeochemical processes, making streams and rivers significant natural sources of greenhouse gases to the atmosphere. The magnitude of greenhouse gas emissions from streams and rivers is highly uncertain, in part, because of the numerous controls on greenhouse gas production and export across spatial and temporal scales. This dissertation examines biological, physical, and chemical controls on greenhouse gas dynamics in nested streams and rivers, …

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Allyl-Palladium Catalyzed Dehydrogenation Of Carbonyl Compounds And Total Synthesis Of (+)-Granatumine A And Clovan-2,9-Dione, Yizhou Zhao Apr 2021

Allyl-Palladium Catalyzed Dehydrogenation Of Carbonyl Compounds And Total Synthesis Of (+)-Granatumine A And Clovan-2,9-Dione, Yizhou Zhao

Yale Graduate School of Arts and Sciences Dissertations

Methodology development was motivated by the synthesis of natural products and various biologically active compounds. The direct dehydrogenation of ketones and carboxylic acids are particularly attractive because the corresponding unsaturated products are highly versatile intermediates in organic synthesis and the step-economic approaches may find broad utility in drug discovery. In addition to advance methodologies, computational tools such as DFT calculation and machine learning techniques are also incorporated in retrosynthetic analysis to accelerate the small molecule synthesis process. This thesis herein describes two dehydrogenation methodologies that can be readily applied to the synthesis of pharmaceutically relevant compounds, and two natural product …

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Development Of Mechanically Complex Dna Nanodevices And A Diverse Dna Origami Toolkit For Cryo-Em Imaging, John Taylor Powell Apr 2021

Development Of Mechanically Complex Dna Nanodevices And A Diverse Dna Origami Toolkit For Cryo-Em Imaging, John Taylor Powell

Yale Graduate School of Arts and Sciences Dissertations

Mechanically interlocked supramolecular assemblies are appealing building blocks for creating functional nanodevices. Here we describe the multi-step assembly of massive DNA origami rotaxanes that are capable of programmable structural switching. We validated the topology and structural integrity of these rotaxanes by analyzing the intermediate and final products of various assembly routes using electrophoresis and electron microscopy. Additionally, we explore the use of various other DNA origami nanodevices as support structures for improved cryoEM imaging of proteins of interest. Namely, we demonstrate progress toward several DNA nanodevice-based solutions to artifacts stemming from air-water interface interactions and other freezing effects.

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Appropriate Transgressions: Parody And Decorum In Ancient Greece And Rome, Niek Janssen Apr 2021

Appropriate Transgressions: Parody And Decorum In Ancient Greece And Rome, Niek Janssen

Yale Graduate School of Arts and Sciences Dissertations

Through the close analysis of Greek and Roman parodies and writings about parody, this dissertation seeks to defamiliarize the process by which readers identify one text (or genre, image, action, body, and so on) as a parody of another. Parody differs from other modes of adaptation in that it introduces an incongruity that was not present in the original. To read a text as parody, then, is to claim that the parodying text lacks the decorous integrity, the appropriate fitting-together as a whole, possessed by its model. At the same time, however, parodies are not simply failed, incongruous imitations. The …

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