Digital Commons Network^™

Parenting Experiences And Outcomes Among Former Adolescent Mothers: A Mixed Methods Study, Serena Flaherty

Yale Graduate School of Arts and Sciences Dissertations

Adverse outcomes for adolescent mothers and their children are significant, often resulting in long-term health inequities. Women who have a first child in adolescence face concurrent demands of parenting and complex developmental demands. Supportive interventions, such as early home visiting programs (EHV), promote positive and nurturing parenting. Minding the Baby® (MTB) is an EHV program designed to improve parenting outcomes among young mothers living in medically underserved communities. The MTB intervention (from pregnancy through the child’s second birthday) was tested through two 2-group randomized controlled trials (RCT; 2002-2016). In the MTB early school-age (ESA) follow-up study (2016-2018), researchers described associations …

Analyzing The Trophic Structure Of Ancient Communities, Jack Oliver Shaw

Yale Graduate School of Arts and Sciences Dissertations

Since the proliferation of animal life during the Cambrian (ca. 541-485 million years ago), the biosphere has changed considerably, including long-term trends towards increasing taxonomic and functional diversity within and across ecosystems. Whether and how long-term trends in the evolution of life affected the Earth system is an active area of research, in part because the function and dynamics of ecosystems cannot be inferred by simply summing up the effect of all individuals present. Instead, the effect of diversity on ecosystem-level properties is modulated by the network of links between individuals, including trophic (e.g., predator-prey) and non-trophic (e.g., symbiosis and …

The Role Of Gene Regulatory Mechanisms In Brain Evolution And Neuropsychiatric Disease, Sydney Keaton Muchnik

Yale Graduate School of Arts and Sciences Dissertations

The human brain is widely acknowledged to be one of the most complex, mysterious, and intriguing structures on earth. Crucial to expanding our understanding of this fascinating organ is exploring the evolutionary processes that culminated in the development of the human brain, but also understanding what happens when the development or function of the brain are altered, as in the case of neurodevelopmental or neuropsychiatric diseases. While some interesting examples of human-specific protein coding genes with roles in brain development or disease have been identified,1–3 it has been hypothesized that changes in non-coding, regulatory regions have played a primary role …

Interactions Between Statistical Prediction And Episodic Memory, Brynn Elizabeth Sherman

Yale Graduate School of Arts and Sciences Dissertations

Every day is a new day, but much of our experience is richly structured and predictable. From the scenery of our walks to the stereotyped nature of conversation, the vast majority of our experiences are ones that we've encountered before. Human memory is thus shaped by the predictable, structured nature of experiences. Our memories contain not only details about unique experiences (episodic memory), such as your tenth birthday, but also commonalities extracted across experience (statistical learning), such as what tends to happen at a birthday party. Notably, these two kinds of memory require opposing computations: episodic memories are formed rapidly …

Graphene Formation Via Catalytic Chemical Vapor Deposition: Environmental Implications Of Synthetic Design, Nina Zoran Janković

Yale Graduate School of Arts and Sciences Dissertations

Nanotechnology’s perceived maturity motivated the assessment of the environmental impacts of the industry in anticipation of the large-scale production of engineered nanomaterial (ENM). However, the relatively early evaluation of ENM risks posed the challenge of discerning relevant use and release scenarios of emerging materials. Further, early evaluation of nanomaterial production efficiencies estimated that nanomaterial syntheses have exceptionally high waste-to-product ratios compared to other materials (e.g., bulk and fine chemicals and pharmaceuticals). Identifying industrially relevant ENMs and their specific synthetic constraints offers an opportunity to influence the manufacturing process to minimize environmental impacts. The first part of this dissertation (Chapter 2) …

Identification Of Genetic Implications In Psychiatric Disorders, Jiawei Wang

Yale Graduate School of Arts and Sciences Dissertations

Posttraumatic stress disorder (PTSD) affects approximately 8% of the general population, with higher rates in those exposed to extreme stress, including combat veterans or victims of sexual assault. Despite extensive study of the neurobiological correlates of PTSD, little is known about its molecular substrates. In Chapter 1, differential gene expression and network analyses of 4 prefrontal cortex (PFC) postmortem subregions of male and female PTSD subjects demonstrates extensive remodeling of the transcriptomic landscape. The data revealed a highly connected down-regulated set of interneuron transcripts in the most significant gene network associated with PTSD and integration of this data with genotype …

Enhancing The Creative Process In Digital Prototyping, Zeyu Wang

Yale Graduate School of Arts and Sciences Dissertations

Despite advances in computer-aided design (CAD) systems and video editing software, digital content creation for design, storytelling, and interactive experiences remains a challenging problem. This dissertation introduces a series of studies, techniques, and systems along three thrusts that engage creators more directly and enhance the user experience in authoring digital content. First, we present a drawing dataset and spatiotemporal analysis that provide insight into how people draw by comparing tracing, freehand drawing, and computer-generated approximations. We found a high degree of similarity in stroke placement and types of strokes used over time, which informs methods for customized stroke treatment and …

Investigating A Locomotor Neuron That Makes A Potential Sensory Cilium Lying Over The C. Elegans Egg-Laying Apparatus, Designing An Accessible System For Neuron Identifications, And Advancing Imaging And Modeling In The Egg-Laying System, Nakeirah Tm Christie

Yale Graduate School of Arts and Sciences Dissertations

The neural circuit for Caenorhabditis elegans egg laying has been studied intensively for decades, yet its known components cannot account for how egg laying and locomotion behaviors are coordinated. In my graduate work within the Koelle lab, I worked to further complete that model circuit. The first half of this dissertation covers my work on the PVP neurons. I discovered that the PVP neuron pair, which has previously been implicated in locomotion, makes previously-undescribed branches that terminate in large wing-shaped endings directly over the egg-laying apparatus. The PVP wing structures occur only in hermaphrodites and develop during the L4 larval …

Short Linear Motif Specificity In Mitogen-Activated Protein Kinase Signaling, Jaylissa M. Torres Robles

Yale Graduate School of Arts and Sciences Dissertations

Mitogen-activated protein kinases (MAPKs) are critical components of complex signal transduction networks that control cell physiology in response to a broad range of stimuli. Alterations to MAPK signaling networks drive many diseases, including cancer, immunological, developmental, neurological, cardiovascular, and metabolic disorders. Despite their high sequence similarity, the three major mammalian MAPK subfamilies (ERK, JNK, and p38) are activated in response to different stimuli and mediate distinct cellular responses. Each MAPK must engage in highly specific interactions with unique substrates, regulators, and activators to achieve appropriate cellular responses. Short linear motifs (known as “D-sites”) found in MAPK interacting partners are thought …

Essays On Structural Transformation, Satoshi Matsuzawa

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

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

Yale Graduate School of Arts and Sciences Dissertations

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

Energy Dissipation Bounds In Fundamental Biological Processes, Samuel Bryant

Yale Graduate School of Arts and Sciences Dissertations

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

A Protocol For Coupling Volumetrically Dynamic In Vitro Experiments To Numerical Physiology Simulation For A Hybrid Cardiovascular Model, Abraham Umo, Ethan Kung

Publications

Objective: The Physiology Simulation Coupled Experiment (PSCOPE) is a hybrid modeling framework that enables a physical fluid experiment to operate in the context of a closed-loop computational simulation of cardiovascular physiology. Previous PSCOPE methods coupled rigid experiments to a lumped parameter network (LPN) of physiology but are incompatible with volumetrically dynamic experiments where fluid volume varies periodically. We address this limitation by introducing a method capable of coupling rigid, multi-branch, and volumetrically dynamic in-vitro experiments to an LPN. Methods: Our proposed method utilizes an iterative weighted-averaging algorithm to identify the unique solution waveforms for a given PSCOPE model. We confirm …

2023 Western Australian Crop Sowing Guide, B. Shackley, B. Paynter, J. Bucat, M. Seymour, H. Dhammu

Bulletins 4000 -

Welcome to the 2023 edition of the Crop Sowing Guide for WA, which introduces 31 new variety releases: two wheat, seven barley (one as feed only and six currently under malt evaluation), 15 canola, three hay-only oat and four lentil varieties.

The Crop Sowing Guide for WA has been compiled by officers in the Department of Primary Industries and Regional Development. It provides information to support variety decisions for each of the major crops for the upcoming season.

In this edition, the canola NVT series are now identified by GRDC/NVT as ‘Low-Med Rainfall’ and ‘Med–High Rainfall’ to reflect the environments …

Societal Perceptions Surrounding Child Maltreatment And Mental Health, Olivia K. Smith

Selected Honors Theses

Child maltreatment, mental illness, and criminal behavior are all commonly known topics and a wide variety of research has been conducted to investigate the implications of all three concepts. Even though there is quality research on each of these topics, the awareness of important facts and theories in these areas may not be known to the general public. This study surveyed university students on their knowledge of the characteristics and risk factors of victims of child maltreatment, in addition to their perceptions of people with mental illness. Items included in the study were comprised of items from Taylor and Dear’s …

Educating Providers Regarding The Black Women’S Health Study Breast Cancer Risk Calculator In A Rural Primary Care Setting: A Quality Improvement Project, Shelby Ashton Holliday

Doctoral Projects

Breast cancer risk (BC) prediction algorithms can allow referrals for identified high-risk individuals for further tests like mammography. Unfortunately, there is not yet a reliable method for predicting Black women's risk of developing BC in the United States (U.S.). Compared to White women, Black women in the U.S. are at an increased risk of developing BC at a younger age and experiencing a worse prognosis (Palmer et al., 2021). Race-based tumor inequalities and other social and health factors contribute to BC disparities. These disparities include limited access to care, inadequate health education, financial constraints, and poor patient-provider relations (Wheeler et …

Implementing A Staff Education Module For Early Identification Of Depression In Intellectually Disabled Individuals, Charlie Crafton

Doctoral Projects

Depression in a normally developed individual can be easy to identify. Sadness and other mood changes are easily noticed. Even in children, symptoms such as mood swings and crankiness, and the loss of interest in things they used to enjoy can be easily recognized by family, teachers, and other caregivers. What makes depression so hard to diagnose in individuals with conditions such as Autism or other intellectual disabilities is the patient’s inability to communicate. Providers must rely on their behavior for diagnostic purposes. This can be difficult for those diagnosed with Autism because the core symptoms of Autism may overlap …

Otherfathering And Black Men’S Mental Health: A Primer For Counselors, Michael D. Hannon

Department of Counseling Scholarship and Creative Works

No counseling research exists about how otherfathering affects Black men’s wellness. Black otherfathering has been primarily studied in schools as one of many expectations for Black male teachers. A review of research about the relationship between fathering, otherfathering, and mental health in Black men is presented and concludes with a rationale for more research about Black otherfathering as a potential protective factor for Black men’s mental health.