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Leveraging Individual Differences To Gain Insight Into The Developing Functional Connectome, Corey Horien Oct 2022

Leveraging Individual Differences To Gain Insight Into The Developing Functional Connectome, Corey Horien

Yale Graduate School of Arts and Sciences Dissertations

Studying individual differences in functional connectomes provides a powerful framework to tackle questions in developmental human neuroscience. In this work, I use such a framework to study a multitude of factors, ranging from data quality control issues to building predictive models of clinically relevant phenotypes in neurodiverse youth. The first empirical chapter explores how factors related to the reliability of functional connections, namely the amount of scan data, in-scanner head motion, and the spatiotemporal resolution of data acquisition affect the detection of individual differences. In the second empirical chapter, I demonstrate that individual differences in connectomes are stable in developing …

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Elements Of The Ubiquitin Ligase Doa10 Regulating Protein Ubiquitylation And Er Membrane Extraction, Adrian Mehrtash Oct 2022

Elements Of The Ubiquitin Ligase Doa10 Regulating Protein Ubiquitylation And Er Membrane Extraction, Adrian Mehrtash

Yale Graduate School of Arts and Sciences Dissertations

In endoplasmic reticulum-associated degradation (ERAD), misfolded proteins at the endoplasmic reticulum (ER) are degraded by the proteasome after undergoing ubiquitylation. In yeast, Doa10 (MARCHF6/TEB4 in humans) is a conserved membrane-embedded E3 ubiquitin ligase that functions with the E2 ubiquitin-conjugating enzymes Ubc6 and Ubc7. These E2s use a sequential E2 mechanism where Ubc6 attaches a single ubiquitin molecule to a lysine, serine, or threonine residue of a substrate that is subsequently elongated by Ubc7 to form a poly-ubiquitin chain. How the Doa10 complex mediates non-canonical and sequential poly-ubiquitylation of its substrates is unclear. I determine the conserved 16-residue C-terminal element (CTE) …

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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Understanding Distinct Roles Of Egfr Family Mutations In Different Cancers, Chun Hu Oct 2022

Understanding Distinct Roles Of Egfr Family Mutations In Different Cancers, Chun Hu

Yale Graduate School of Arts and Sciences Dissertations

The epidermal growth factor receptor (EGFR) is frequently mutated in human cancer and is an important therapeutic target. EGFR inhibitors have been successful in lung cancer, where mutations in the intracellular tyrosine kinase domain activate the receptor, but not in glioblastoma multiform (GBM), where mutations occur exclusively in the extracellular region. In this dissertation, I show that common extracellular GBM mutations prevent EGFR from discriminating between its activating ligands. Different growth factor ligands stabilize distinct EGFR dimer structures that signal with different kinetics to specify or bias outcome. EGF itself induces strong symmetric dimers that signal transiently to promote proliferation. …

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Biobehavioral Markers Of Social-Emotional Functioning, Erica Ho

Yale Graduate School of Arts and Sciences Dissertations

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

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

Translational Systems Metabolism In Health And Disease, Brooks Phillip Leitner

Yale Graduate School of Arts and Sciences Dissertations

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

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Insights To Fundamental Proton-Coupled Electron Transfer (Pcet) Processes Of Aqueous Titanium Dioxide And Gold Nanoparticle Colloids, Noreen Elizabeth Gentry Oct 2022

Insights To Fundamental Proton-Coupled Electron Transfer (Pcet) Processes Of Aqueous Titanium Dioxide And Gold Nanoparticle Colloids, Noreen Elizabeth Gentry

Yale Graduate School of Arts and Sciences Dissertations

Nanoparticles have wide utility due to their large reactive surface areas and their unique optical, electronic, and chemical properties relative to bulk materials. Titanium dioxide (TiO2) is a widely used photocatalyst and redox mediator due to its earth abundance, chemical stability, and ability to hold and transport multiple redox equivalents. In contrast, gold is an expensive coinage metal that is inert at the bulk scale; and yet, gold nanoparticles (AuNPs) exemplify the nano paradigm through their unique reactivity and vibrant colors. Despite their differences, catalysis with TiO2 NPs and AuNPs has traditionally been described using only electron transfer (ET) processes. …

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Antinomies Of Organizing, Mie Inouye Oct 2022

Antinomies Of Organizing, Mie Inouye

Yale Graduate School of Arts and Sciences Dissertations

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

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Host Redox Signaling During Helicobacter Pylori Infection, Yekaterina Kovalyova

Yale Graduate School of Arts and Sciences Dissertations

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

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Development Of An Anionic Glycosylation Strategy To Form Α- Or Β-Linked 2-Deoxy-O-Glycosides, Kevin Hoang Oct 2022

Development Of An Anionic Glycosylation Strategy To Form Α- Or Β-Linked 2-Deoxy-O-Glycosides, Kevin Hoang

Yale Graduate School of Arts and Sciences Dissertations

In this thesis, I describe the development of an anionic glycosylation strategy toform 2-deoxy-O-glycosides (referred to as “2-deoxyglycosides” hereafter) with control of anomeric stereochemistry. Control over glycosidic bond stereochemistry is a central challenge in carbohydrate chemistry, and decades of research have yielded reliable and general methods to synthesize α- or β-linked 2-oxygenated glycosides. However, methods for the direct stereocontrolled synthesis of 2-deoxyglycosides are lacking. This is problematic because 2-deoxyglycosides are present in a variety of natural products and medicinal agents, including the calicheamicins, ivermectin, and vancomycin. These glycosides are formed in nature as specific α- or β-anomers, and the composition …

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Identifying Riboregulatory Elements In Long, Single-Stranded, Positive-Sense Rna Viral Genomes, Nicholas Cornell Huston Oct 2022

Identifying Riboregulatory Elements In Long, Single-Stranded, Positive-Sense Rna Viral Genomes, Nicholas Cornell Huston

Yale Graduate School of Arts and Sciences Dissertations

Single-stranded, positive-sense RNA viruses are a class of pathogens that pose a serious danger to human health. As a group, they have been the focus of research exploring how they infect, evade, and hijack host cellular machinery to propagate. Though these studies have primarily focused on viral proteins, the past two decades have seen a resurgence of interest in the RNA genomes themselves. This is because RNA viral genomes contain functional RNA structures that expand their functional repertoire. While studies of viral RNA structure were originally restricted to 5’ and 3’ viral termini, recent methodological advancements have facilitated the search …

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Elucidating Extracellular Signal-Regulated Kinase (Erk) Dynamics With Fret-Based Biosensors, Archer Hamidzadeh Oct 2022

Elucidating Extracellular Signal-Regulated Kinase (Erk) Dynamics With Fret-Based Biosensors, Archer Hamidzadeh

Yale Graduate School of Arts and Sciences Dissertations

Proper cell functions are dependent on the precise regulation of signal transduction pathways to relay specific external environmental cues into the cell for processing and yielding a specific response. Dysregulation of signaling function or localization is a hallmark of numerous diseases including neurodegenerative, autoimmune, and immunological disorders and most human cancers. Given that signaling pathways are large networks of nodes capable of interacting in complex manners, a notable question that arises for many studying the intricacies of signaling regulation is: “How is signaling tightly controlled in different subcellular compartments?” Here we examine and elucidate mechanisms that begin to answer this …

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Synthetic Studies Of (–)-Gukulenin A, Joshua Benjamin Combs Oct 2022

Synthetic Studies Of (–)-Gukulenin A, Joshua Benjamin Combs

Yale Graduate School of Arts and Sciences Dissertations

In this thesis, I describe our progress towards the synthesis of the cytotoxic tetraterpenoid (–)-gukulenin A (1). (–)-Gukulenin A (1) is a challenging target for synthesis due to its congested syn-syn-quaternary cyclopentanes, tri-substituted and tetra- substituted α-tropolone moieties, and central ethyl-keto bridging subunit. (–)-Gukulenin A (1) has produced a dose-dependent reduction in the size of grafted human ovarian cancer tumors (A2780) in a murine model. Although the mechanism of action is unknown, it has been established that (–)-gukulenin A (1) associated cell death is reliant upon the activation of procaspases-3, -8, and -9. Access to dimeric gukulenin A (1) derivatives …

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Lipid Transfer Proteins At Membrane Contact Sites Between The Endoplasmic Reticulum And Mitochondria, Andres Guillen Samander Oct 2022

Lipid Transfer Proteins At Membrane Contact Sites Between The Endoplasmic Reticulum And Mitochondria, Andres Guillen Samander

Yale Graduate School of Arts and Sciences Dissertations

The Endoplasmic Reticulum (ER) is a subcellular compartment distributed throughout the entire cytosol which plays a variety of functions in cell physiology, including synthesis of most membrane lipids. From the ER, lipids can be transported to other membranous organelles. This process can occur via two mechanisms: vesicular trafficking, in which lipids are transported as part of the membrane of vesicular carriers, and protein-mediated lipid transfer, in which lipids are carried between two membranes within the hydrophobic pocket of a protein. Many of these proteins act at membrane contact sites, where the short distance between two organelles enhances the efficiency and …

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Formation Of Fused Ring Junction N-Heterocycles Via Cp*Rh(Iii) Imidoyl C–H Activation And Application To Rna Targeting, Andrew Douglas Streit Oct 2022

Formation Of Fused Ring Junction N-Heterocycles Via Cp*Rh(Iii) Imidoyl C–H Activation And Application To Rna Targeting, Andrew Douglas Streit

Yale Graduate School of Arts and Sciences Dissertations

Nitrogen heterocycles are present in almost two-thirds of U.S. FDA approved pharmaceuticals, garnering interest in the ability to rapidly access these structures displaying different functional groups. The first two chapters of this dissertation will discuss develop-ment of Cp*Rh(III)-catalyzed C–H activation to rapidly access two different classes of 5.6-fused nitrogen heterocycles. The third chapter describes the application of these heterocycles to the validation of a novel whole transcriptome RNA screen.Chapter 1 describes a three component reaction for the rapid assembly of pyra-zolopyrimidines from commercially available aminopyrazoles, aldehydes, and sulfoxo-nium ylides. The method was optimized for setup without the use of an …

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Electrons On The Move In Proteins: Microbial Cytochrome Nanowires In Extracellular Electron Transfer And As Functional Materials, Catharine Cerise Shipps Oct 2022

Electrons On The Move In Proteins: Microbial Cytochrome Nanowires In Extracellular Electron Transfer And As Functional Materials, Catharine Cerise Shipps

Yale Graduate School of Arts and Sciences Dissertations

Proteins are commonly known to transfer electrons over distances limited to a few nanometers. However, many biological processes require electron transport over far longer distances. For example, some soil and sediment bacteria transport electrons over hundreds of micrometers to even centimeters. In particular, Geobacter sulfurreducens uses extracellular electron transfer (EET) to move respiratory electrons from the cytoplasm to external electron acceptors such as minerals or external electrodes in biofilm growth. These terminal acceptors are mere microns to as far as thousands of times the length of a cell away in biofilms. The exact mechanisms for the EET pathway and the …

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Elucidating The Mechanisms Of Water And Ion Transport Under Nanoconfinement, Cody Lee Ritt Oct 2022

Elucidating The Mechanisms Of Water And Ion Transport Under Nanoconfinement, Cody Lee Ritt

Yale Graduate School of Arts and Sciences Dissertations

Water scarcity is among the most prominent humanitarian crises of our time. Achieving equitable access to safe drinking water for all humankind necessitates the treatment of unconventional and underutilized sources. Pressure-driven desalination technologies are particularly well-suited for augmenting global water supplies due to their energy efficiency. In these technologies, the membrane is the critical component driving process efficacy and requires material breakthroughs to achieve paradigm-shifting performance. Attempts to improve conventional membrane materials and investigations into numerous novel materials have failed to produce the next generation of desalination membranes due to our limited understanding of the mechanisms that govern water and …

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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Investigation Of Various Organocatalytic Modes In Asymmetric Transformations: Controlling Different Elements Of Chirality, Sooyun Choi Oct 2022

Investigation Of Various Organocatalytic Modes In Asymmetric Transformations: Controlling Different Elements Of Chirality, Sooyun Choi

Yale Graduate School of Arts and Sciences Dissertations

The ubiquity of stereogenic elements both found in nature and encountered in our daily lives has necessitated the control of chirality in chemical synthesis. This dissertation describes the study of Brønsted acidic, Lewis basic and anion-binding catalysis, all moderated within organic chiral scaffolds to control different elements of chirality, including diastereoisomerism, point chirality and atropisomerism.In Chapter 2, BINOL and peptidic phosphoric acids were evaluated in the development of an atroposelective catalytic cyclodehydration to afford 1,2,4-triazoles, obtained with up to 88:12 er. The enantioenriched products obtained via chiral phosphoric acid catalysis were recrystallized and isolated as enantiopure samples, demonstrating the first …

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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The Evolution Of The Surface Lithium Cycle Through Earth’S History, Boriana Kalderon-Asael Oct 2022

The Evolution Of The Surface Lithium Cycle Through Earth’S History, Boriana Kalderon-Asael

Yale Graduate School of Arts and Sciences Dissertations

In order to sustain habitability on our planet – Earth, a fine balance between the inputs and outputs of atmospheric carbon dioxide must be maintained. New steady states have emerged throughout the Earth’s history as the nature is dynamic. Yet, the carbon cycle seems to have been stabilized by the silicon cycle and the two cycles evolved concertedly together, contributing to the long-term stability of the Earth’s climate. Explicitly, silicate weathering, occurring both in terrestrial and marine environments, provides negative feedback to fluctuations in atmospheric carbon dioxide concentrations. Direct observations not being available, we often resort to geochemical proxies and …

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Impact And Cost-Effectiveness Of Human Papillomavirus Vaccination Policies In The United States Uniformed Armed Forces, Noel Dickens Oct 2022

Impact And Cost-Effectiveness Of Human Papillomavirus Vaccination Policies In The United States Uniformed Armed Forces, Noel Dickens

Yale Graduate School of Arts and Sciences Dissertations

Background. Virtually all cervical cancers and cases of recurrent respiratory papillomatosis (RRP) are caused by human papillomavirus (HPV) as well as a large proportion of anal, penile, oropharyngeal, vulvar, and vaginal cancers and anogenital warts (AGW). Vaccination with the nonvalent HPV vaccine (9vHPV) is proven to prevent a significant proportion of HPV-associated diseases. Adoption of large-scale HPV vaccination programs by US public institutions requires careful consideration of the cost to benefit ratio of each program through economic evaluations. US Uniformed Armed Forces (USUAF) HPV vaccination policy would benefit from economic evaluations that consider the unique population and institutional characteristics of …

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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Sooting Tendencies And Soot Formation Pathways Of Alternative Fuels And Compounds, Junqing Zhu Oct 2022

Sooting Tendencies And Soot Formation Pathways Of Alternative Fuels And Compounds, Junqing Zhu

Yale Graduate School of Arts and Sciences Dissertations

In the modern age, human activities depend more and more on energy. Fossil fuels and the related combustion process play important roles in supplying global energy. However, fossil fuels emit CO2 and pollutants into the atmosphere when they combust. CO2 leads to global warming with a single half-life of more than hundreds of years in the atmosphere. In order to contain the rise of the average global temperature, net emissions of CO2 must approach zero. However, given the high energy density of liquid fuels relative to other energy carriers, such as batteries, liquid fuels are likely to remain the dominant …

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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