18525 research outputs found
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Leveraging large-scale biobank data to investigate the landscape of congenital anomalies and to discover their genetic risk factors
No full textCongenital anomalies (CAs) affect 3-6% of live births and are the leading cause of infant morbidity and mortality. Large-scale genomic biobanks provide an opportunity to better understand the genetic drivers of CAs and reduce their public health burden. We utilized two electronic health record (EHR) linked biobanks, BioVU and the electronic medical records and genomics (eMERGE) consortium biobank, to investigate four CA populations: individuals with at least one CA, multiple congenital anomalies (MCA), congenital heart defects (CHDs), and craniofacial anomalies (CFAs). First, we developed a portable and accurate method for identifying individuals with MCAs in the EHR utilizing a novel approach removing distinctions between minor and major anomalies. We conducted genome wide association studies (GWAS) in all four CA populations. Initially, an analysis restricted to absorption, distribution, metabolism, and excretion (ADME) genes, which are crucial for teratogenic drug processing, revealed no significant SNP associations with CA, MCA, CFA, or CHD status. Expanding the analyses to all SNPs genome-wide identified serval significantly associated (p<1.0x10-6) SNPs within genes important for fetal development, such as PARD3B, involved in cell polarity. Transcriptome-wide association studies (TWAS) identified genes crucial for development whose genetically predicted gene expression (GPGE) were associated with CA status. The GPGE of NMNAT1, which is already associated in a Mendelian fashion with one MCA syndrome, was significantly associated with MCA status. Both eMERGE and BioVU CFA populations had a significant association with the GPGE of GLI2, which is involved with cardiomyogenesis. Our work demonstrates the value of utilizing big data resources for identifying genetic drivers of CAs and highlights the complex, shared nature of CAs. We plan to extend these analyses to additional biobanks
Exploring the Black Parental Imaginary: A Critical Mixed Methods Exploration of How and Why Black Parents (Re)Imagine Black Education Through Homeschooling
No full textScholars compellingly argue the many ways public schooling in the US was never designed to foster Black children’s thriving. As such, Black parents wrestle with the extraordinary challenge of either hoping ongoing school reforms will result in better educational opportunities and experiences for their children or fully removing them from schools altogether, and in doing so, take full responsibility for imagining and designing an educational experience that ensures Black children’s wellbeing. Wellbeing can take many forms which may include Black youth’s pride in their racial identity, public and private regard for being Black. This mixed methods dissertation utilizes large-scale nationally representative survey data, interviews, and ethnography to explore the motivations and visions of Black parents who have turned to homeschooling as an act of resistance against anti-Black schooling structures that reproduce racialized harm
Life on a String: Examining the Mathematical and Playful Lives of Basketball Players
No full textThis dissertation explores basketball court as a pro-Black play space through a qualitative study of one collegiate women’s basketball team: the Stephenson Owls. Drawing on situative and sociocultural theories of identity, the study examines how space, play, and mathematics were defined enacted, and valued by the players themselves. Through participant observations, interviews, and video-based conversations with players, I investigate how the team creates a pro-Black space marked by joy and creativity; how play manifests in both traditional and transgressive forms; and how mathematical thinking is embedded in players’ practices. Findings reveal the multitude of ways in which players navigate and re-author dominant narratives about athleticism, Blackness, and mathematical competence. The study contributes to theorizations of identity in STEM and sport by centering players’ perspectives, and it argues for taking Black play seriously as a generative and mathematically rich practice. In doing so, it challenges deficit framings in education and contributes to scholarship that imagines expansive possibilities for who is and can be mathematical
Characterization of Senescence and SASP in Zebrafish Retina Regeneration
No full textRegeneration of the retina is critical for the restoration of vision after loss of retinal neurons, however most mammals lack the ability to regenerate the retina after damage. Zebrafish have innate regenerative potential, making them ideal candidates for studying and understanding retina regeneration. Senescence is a biological process that can exist as both a damage response and a response to cellular aging. After acute NMDA damage, senescent immune cells are detectable within 2-3 days post injury, but are then cleared as retina regeneration concludes. The transient appearance and clearance of senescent cells is crucial because premature clearance of senescent cells inhibits regeneration. To determine the function of senescent cells during regeneration, we analyzed their secretomes and identified a conserved 31 factor gene signature that includes many regulators of inflammation and pro-regenerative factors. Among these, depletion of the chromatin modifier npm1a was found to inhibit regeneration. Lastly, depletion of the alternative splicing factor ptbp1a was found to induce senescence and enhance retina regeneration. Together, this thesis demonstrates a crucial role for senescence in the modulation of inflammation and stemness
Jordan's 1970 Civil War: The Limits of U.S. Intervention in the Middle East
No full textHistory Department Honors ThesisCollege of Arts and ScienceDepartment of Histor
Neurophysiological Reward Responsiveness, Exposure to Stressors, and Depressive Symptoms Across the Perinatal Period
No full textPerinatal depression (i.e., depression during pregnancy and following childbirth) is associated with negative outcomes for both mothers and their offspring. There is an urgent need to identify underlying processes associated with perinatal depression to reduce burden. Outside of the perinatal period, alterations in positive valence systems function, particularly reward responsiveness, have been associated with depression. Electroencephalography can be used to derive time domain and time-frequency domain measures of reward responsiveness across the perinatal period, including the reward positivity (RewP) and delta and theta power, respectively. Exposure to life stressors is also an established predictor of depression and has been found to impact and interact with reward responsiveness, such that the combination of greater exposure to stressors and reduced reward responsiveness has been associated with depression. Additionally, biological changes unique to the perinatal period appear to directly influence reward responsiveness, making the perinatal period a unique life stage to examine dynamic relations between reward responsiveness and depression. Although research supports the conceptualization that blunted reward responsiveness precedes depression onset, a recent study in youth found bidirectional associations between reward responsiveness and depression across time. Associations between changes in reward responsiveness and depression, as well as interactive effects with stress, have not been examined in the perinatal period and may inform understanding of underlying mechanism of perinatal depression. The present study examined bidirectional associations between reward responsiveness (i.e., RewP, delta, and theta) and depression across the perinatal period using random-intercept cross-lagged panel models as well as interactive effects with lifetime stressor exposure through linear regressions in a sample of 117 pregnant adults. Results provide partial support that reduced reward responsiveness as measured by RewP predicts depressive symptoms during pregnancy, and that this association does not appear to be reciprocal across the perinatal period. Lifetime stressor exposure did not significantly interact with depressive symptoms in predicting reward responsiveness, nor with reward responsiveness in predicting depressive symptoms. This work highlights important future directions for the further exploration of these associations during the perinatal period and contributes to the larger literature examining underlying mechanisms of depression
UNDERSTANDING ACCRETION ACTIVITY IN YOUNG STARS USING SDSS-V BOSS SPECTRA
No full textDefended on Fall 2024Stellar spectra are a valuable tool for understanding young pre-main sequence stars. Some spectral lines, such as Li I, can be a direct indicator of stellar youth while other lines, e.g., H or Ca II, can be used as a tracer of either disk accretion or magnetic activity that is also heightened in young stars. In our research, we used low resolution optical spectra collected from the fifth iteration of Sloan Digital Sky Survey (SDSS-V) to develop techniques to perform a spectroscopic identification of YSOs and to analyze their properties. We present a data-driven pipeline, LineForest, that autonomously measures the equivalent width of 52 different lines in the optical spectra, including Li I, Balmer series, Paschen series, and a number of lines that can be seen in emission due to accretion. Using these lines, we construct a classifier that, to date, has confirmed the youth of 18,000 stars, including 5500 classical T Tauri stars (CTTSs). Through modeling the decrement of the lines in the Balmer series, we estimate the properties of the accretion stream of these CTTSs, such as the temperature of the accretion flow and its surface density. Using the veiling measurements, we further explore the accretion properties of these stars. We particularly analyzed how veiling correlates with other physical properties, such as H equivalent width, age, and effective temperature, to gain insights into the accretion mechanisms. We compared these results with existing theoretical models to evaluate their consistency.College of Arts & ScienceDepartment of Physics & Astronom
Translational Informatics Approaches for Studying Cytochrome P450-Mediated Drug Interactions and Their Genetic Influences
No full textDrug-drug interactions (DDIs) involving cytochrome P450 (CYP) enzymes can alter drug metabolism, potentially leading to serious adverse drug events (SADEs). While pharmacokinetic mechanisms of CYP-mediated DDIs are relatively well understood, identifying clinically relevant ADE signals remains challenging, particularly given the limitations of pre-marketing clinical trials, spontaneous reporting biases, and the complexity of real-world clinical data. Furthermore, genetic variations in CYP enzymes significantly contribute to individual susceptibility to ADEs. Despite their clinical importance, drug-gene interactions (DGIs) remain understudied, leaving significant gaps in our ability to predict and prevent ADEs influenced by genetic factors. To address these gaps, this dissertation developed a comprehensive translational informatics framework integrating multiple data sources and advanced computational approaches: (1) Generating and prioritizing CYP-mediated DDI-SADE hypotheses through statistical disproportionality analyses and novel ranking algorithms applied to spontaneous reporting systems, followed by rigorous validation using electronic health record (EHR) databases. (2) Systematically mining biomedical literature to uncover previously unrecognized CYP-mediated DDI-SADE signals using advanced transformer-based natural language processing (NLP) models, and subsequently validating these signals through large-scale real-world EHR analyses. (3) Translating validated DDI-SADE signals into genetically informed DGI-SADE hypotheses by integrating comprehensive pharmacogenomic analyses leveraging genetic data linked to biobanks, systematically exploring CYP enzyme polymorphisms and their contributions to variability in ADE risks. Collectively, this dissertation enhances the current understanding of CYP-mediated drug interactions and genetic influences on drug safety, providing a broadly applicable computational framework for pharmacovigilance and personalized medication management through pharmacogenomic insights
Disruptive Innovation to Marketing Impact: Communicating AI-Driven Financial Crime Detection in a Lean Startup Context
No full textLeadership and Learning in Organizations capstone projectThis capstone examined the communication needs of an early-stage startup specializing in financial crime detection, with particular attention to the externally facing materials designed to engage prospective customers and investors. The study aimed to identify opportunities to enhance both the effectiveness of external communications and the internal processes that support their development. Strengthening these dimensions was intended to improve stakeholders’ objective understanding of the company’s products, more clearly convey the value proposition, and build trust in the brand, ultimately facilitating the adoption of the firm’s disruptive innovation
Constructing an Ekklēsia Trabajadora del Pueblo: Lessons and Insights from the Faithful Labor Organizing of Latine-Immigrant Workers
No full textThrough the methods of theological studies, ethnography, and interdisciplinary research, this study investigates how centering the lived faith and organizing experiences of working-class Latine-immigrant workers yields an expansive notion of the church as “the people of God” and a bottom-up, relational, community-rooted, and liberationist ecclesiology. Despite some significant moves in contemporary ecclesiologies towards more communal and people-centered understandings of the church in relation to God, much ecclesiological work, in theory and practice, has remained focused on the formal, institutional, and often hierarchical aspects of the church. As such, the church as the people of God is mostly seen as a worshipping and organizational entity within a specific church sanctuary and/or denomination—led by its clerical power structure—with both theology and power flowing from the top-down or from within official church settings to the outside world. The locus theologicus—both the sources of theology and the locations where theology happens and is contextualized—is then largely confined to institutional church structures, official doctrines, teachers, and traditions. Theology and power at the extra-ecclesial level—the alternative theological expressions and ethical practices involving the agency of Christians outside of formal church settings in the collective struggle for survival, dignity, and meaning-making in lo cotidiano (daily living)—are largely ignored. Shifting the focus to material-spiritual practices in working-class organizing contexts uncovers grassroots theological reflection and ethical praxis at work. I define this as the Ekklēsia Trabajadora del Pueblo—the working-class majority church as a broader assembly of people of faith that challenges institutional forms of the church to reclaim its liberationist roots and mission