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Tucked In: Weighted Blankets To Improve Sleep In Intensive Care Unit Patients, Jaime Conway Apr 2021

Tucked In: Weighted Blankets To Improve Sleep In Intensive Care Unit Patients, Jaime Conway

Yale School of Medicine Physician Associate Program Theses

Sleep deprivation is ubiquitous in hospital settings and deleterious to patients’ health. Specifically, sleep deprivation has been reported to play a role in multiorgan dysfunction, leads to poor critical illness outcomes, and can be considered a risk factor for delirium, a highly prevalent disease in intensive care units with even greater implications. To date, there are no evidence-based pharmacological interventions for sleep deprivation, and have even resulted in more adverse effects. However, non-pharmacological solutions have had limited efficacy, displaying a need for novel therapeutic options. In this randomized control trial, we will investigate and compare mean lengths of total sleep …

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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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Training Pediatricians To Support Families Of Lesbian, Gay, Bisexual, Transgender, And Queer Youth, Siena Tice Apr 2021

Training Pediatricians To Support Families Of Lesbian, Gay, Bisexual, Transgender, And Queer Youth, Siena Tice

Yale School of Medicine Physician Associate Program Theses

Lesbian, gay, bisexual, transgender, and queer youth have an increased risk of mental health disorders. Family support of the child’s sexual orientation or gender identity can mitigate this increased risk when families are provided the proper tools. Pediatricians have the potential to strengthen the parent/child relationship, but few pediatricians receive training in how to guide parents appropriately and accurately. In this randomized controlled trial, we test whether receiving the Family Acceptance Project training increases pediatricians’ self-efficacy in engaging parents to support their lesbian, gay, bisexual, transgender, or queer child. We will utilize a waitlist control arm to examine the change …

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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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After The Negotiations: Understanding Multilateral Nuclear Arms Control, Stephen Herzog Apr 2021

After The Negotiations: Understanding Multilateral Nuclear Arms Control, Stephen Herzog

Yale Graduate School of Arts and Sciences Dissertations

Why do advanced nuclear states agree to legally forswear nuclear weapons? Many international relations studies have explored why states seek to develop nuclear weapons. Yet, the literature does not address why states would participate in multilateral nuclear arms control treaties that tie their hands against doing so. This gap in the existing scholarship matters because nuclear weapons are one of few tools that can effectively guarantee a state's sovereignty and national survival. My dissertation disaggregates the process of entering multilateral nuclear arms control treaties into two phases. Previous studies have discussed either treaty signature or ratification, overlooking the often lengthy …

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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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Attributing Discrimination To Implicit Bias: Consequences For Perceived Accountability And Punishment, Natalie Daumeyer Apr 2021

Attributing Discrimination To Implicit Bias: Consequences For Perceived Accountability And Punishment, Natalie Daumeyer

Yale Graduate School of Arts and Sciences Dissertations

The term implicit bias is becoming more popular among the general public. Although researchers have spent decades studying implicit bias and its effects on behavior, little is known about how laypeople make sense of discrimination that is attributed to implicit bias. In this dissertation, I explore how attributing discrimination to implicit bias shapes the extent to which people hold perpetrators accountable and support punishing them for their discriminatory behavior attributed to implicit, compared to explicit bias. I begin in Chapter 1 by reviewing the limited literature that has attempted to address this topic, discussing how implicit bias attributions relate to …

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Infant Fmri: A Model System For Cognitive Neuroscience, Cameron Thomas Ellis Apr 2021

Infant Fmri: A Model System For Cognitive Neuroscience, Cameron Thomas Ellis

Yale Graduate School of Arts and Sciences Dissertations

Studying the infant mind and brain promises to benefit three distinct fields of science in critical ways. In developmental science, understanding infancy is necessary for appreciating the foundations of the human life and determining what changes with development. In cognitive science, revelations about infant cognitive capacities can constrain theories by limiting the possible explanations of how those capacities emerge. In neuroscience, infants offer the unique possibility to study large-scale neural change in humans, while also revealing principles that underlie the optimization of neural circuitry. Yet, there are limits on the kinds of questions that can be asked by the methods …

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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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Bulk Metallic Glasses Structure And Properties Investigated By Scanning Probe Microscopy, Zheng Chen Apr 2021

Bulk Metallic Glasses Structure And Properties Investigated By Scanning Probe Microscopy, Zheng Chen

Yale Graduate School of Arts and Sciences Dissertations

Bulk metallic glasses (BMGs) have been intensively investigated because of their special mechanical properties as amorphous materials and their unique glass transition state. However, the atomic structural origin of their properties has not been unequivocally understood. To explain their properties, structural models of BMGs have been proposed but not yet confirmed due to the relatively macro-scale of characterization and properties measurements. Scanning probe microscopy, as one of the most advanced techniques to characterize nano to sub-nano features, possesses the potential of direct observation on the atomic structure once given a clean atomically flat surface of BMG. In this thesis, novel …

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The Ed.Trauma Study: Evaluating The Discordance Of Trauma Readmission And Unanticipated Mortality In The Assessment Of Hospital Quality, Cheryl K. Zogg Apr 2021

The Ed.Trauma Study: Evaluating The Discordance Of Trauma Readmission And Unanticipated Mortality In The Assessment Of Hospital Quality, Cheryl K. Zogg

Yale Graduate School of Arts and Sciences Dissertations

Trauma is a common, high-risk, and high-cost condition that uniquely affects the health of older adults. Through this dissertation, we built on existing efforts to expand external benchmarking in trauma from a historical focus on in-hospital mortality to include a broader array of additional, long-term quality-metrics. To do so we: (1) assessed the distributions of proposed quality-metrics and ascertained their correlations with the current benchmarking standard (in-hospital mortality), (2) considered the utility of implementing proposed quality-metrics as a combined composite score and analyzed associations between hospital quality and important hospital-level risk-factors when trauma quality for older adults was defined based …

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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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Three Essays On Political Responses To Opioid Use In The United States, Lilla Orr Apr 2021

Three Essays On Political Responses To Opioid Use In The United States, Lilla Orr

Yale Graduate School of Arts and Sciences Dissertations

In the first two decades of the 21st century, opioid use in the United States has grown to unprecedented levels. Approximately half of the U.S. adult population has been prescribed an opioid based pain reliever, 1.7 million people have an opioid use disorder, and nearly 50,000 people die of opioid related overdoses each year. Public attitudes and drug policy have transformed in the wake of this staggering loss of life. These changes are often attributed to the racial, socioeconomic, and geographic profile of those most affected by the overdose and addiction epidemic, as well as the perceived culpability of physicians, …

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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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Urban Inequalities: Measuring, Forecasting, And Understanding Human Health Implications, Bhartendu Pandey Apr 2021

Urban Inequalities: Measuring, Forecasting, And Understanding Human Health Implications, Bhartendu Pandey

Yale Graduate School of Arts and Sciences Dissertations

Urbanization, inequality, and human health are three of the biggest challenges facing society. Demographic projections from the United Nations suggest that the number of people living in urban areas will increase by ~200,000 every day, on average, between now and the middle of this century. A recent report suggests that inequality is rising in countries where 70% of the global population lives. The COVID-19 pandemic has amplified the significance of these challenges and points to an intricate interlacing between urban areas, inequality, and human health. This research is motivated by a pursuit to understanding how. It examines a central proposition …

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Entangled Revolutions: Cuba, Nicaragua, And The United States In The Cold War Caribbean, 1979-1990, Emily Snyder Apr 2021

Entangled Revolutions: Cuba, Nicaragua, And The United States In The Cold War Caribbean, 1979-1990, Emily Snyder

Yale Graduate School of Arts and Sciences Dissertations

“Entangled Revolutions” examines Cuba and Nicaragua’s revolutionary relationship with a sustained lens on institutions, ideology, gender, and local and international frames. My analysis first demonstrates how each revolution’s relationship with the other demanded, and produced, profound domestic and international effects. Nicaragua relied on Cuba for material support and technical expertise; Cuba looked to Nicaragua as a source of revolutionary radicalization. The United States crafted public diplomacy campaigns alongside the Contra insurgency in Nicaragua as it attempted to prevent “another Cuba.” Second, Cuban and Nicaraguan experiences of collaboration were heavily gendered. Though both revolutionary states sought to impose gendered logics on …

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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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Where Do We Go When We Go Off-The-Grid?, Andrey Tolstoy Apr 2021

Where Do We Go When We Go Off-The-Grid?, Andrey Tolstoy

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines how the idea of going off-the-grid has affected the epistemology of documentary film, particularly three of its variants: romantic ethnography, observational cinema, and the essay film. The grid is understood to be a graphic design that is fundamental to modern cultural techniques, especially those involving the organization of objects and data, administration and governance. The grid as an organizational principle has been a definitive feature of modernity, particularly in so-called “disciplinary societies,” where its use intensified as a system of social control during industrialization and increasing urbanization. The expansion of the grid has resulted in a certain …

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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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Fraternité, Liberté, Égalité: Sophie De Grouchy, Moral Republicanism, And The History Of Liberalism, 1785-1815, Kathleen Theodora Mccrudden Apr 2021

Fraternité, Liberté, Égalité: Sophie De Grouchy, Moral Republicanism, And The History Of Liberalism, 1785-1815, Kathleen Theodora Mccrudden

Yale Graduate School of Arts and Sciences Dissertations

This thesis explores the political thought and activities of Sophie de Grouchy (1763-1822), author of Letters on Sympathy (1798) and wife of the philosophe and French Revolutionary the marquis de Condorcet. The chapters proceed chronologically and thematically. I begin by forwarding a new and earlier date for the drafting of Grouchy’s major treatise, Letters on Sympathy, and thus an original interpretation of this text. I argue that the central tenets of Grouchy’s philosophy, in particular her key argument that founds a knowledge of natural rights on the proper combination of sympathy and reason, were developed in response to her interest …

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Genomic Analysis Of 11,555 Probands Provides A Framework For Congenital Heart Disease Genetics, Michael Sierant Apr 2021

Genomic Analysis Of 11,555 Probands Provides A Framework For Congenital Heart Disease Genetics, Michael Sierant

Yale Graduate School of Arts and Sciences Dissertations

This dissertation presents the results from a genomic analysis of 11,555 congenital heart disease (CHD) probands with deep clinical phenotyping using a custom Molecular Inversion Probe Sequencing (MIPS) gene panel in order to further elucidate the genetic etiology of human CHD. CHD is a structural defect in the heart arising during development and afflicting ~1% of live newborns. CHD is a phenotypically complex and genetically heterogenous disease that frequently presents with congenital extracardiac abnormalities (EC) and neurodevelopmental deficits (NDD). The etiology for a majority of CHD cases is unknown and genotype-phenotype correlation is rare. Although hundreds of genes have been …

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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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Emiral Patronage: George Of Antioch, The Martorana, And The Arab-Christians Of Norman Sicily, Ariel Fein Apr 2021

Emiral Patronage: George Of Antioch, The Martorana, And The Arab-Christians Of Norman Sicily, Ariel Fein

Yale Graduate School of Arts and Sciences Dissertations

Twelfth-century Latin panegyrist Peter of Eboli famously described the multicultural atmosphere of twelfth-century Palermo, Sicily as a “fortunate city, endowed with a trilingual people.” In his words, he captured the intense cultural and religious interaction of the capital city of the Norman Kingdom of Sicily (1072-1194). The arts of Norman Sicily offer an unprecedented mixture of Byzantine, Islamic, and Romanesque visual forms which exemplify this distinctive syncretic environment. Scholars have overwhelmingly investigated this visual culture through the lens of royal patronage, attending to the celebrated royal foundations of the Cappella Palatina, Cefalù, and Monreale, as well as the products of …

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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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