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    Dream Jobs, Road Maps, and Support Systems: Persistence of Racially Minoritized Youth in STEM Education

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    This dissertation seeks to understand attrition of racially underrepresented minority (URM) youth from STEM pathways. URM youth aspire to STEM careers at the same rate as White peers, but Black and Latinx students leave STEM disciplines at nearly twice the rate of White students. As a result, the STEM workforce does not reflect national demographics. Literature reveals key socioenvironmental factors in the exosystem (STEM coursework, qualified STEM teachers), the mesosystem (mentorship opportunities, family and peer support), and the microsystem (STEM interest, math self-efficacy, STEM outcome expectations and choice goals, and math achievement) that contribute to low persistence of URM youth in STEM education and careers. However, few studies investigate this problem in a pre-college population, analyze interaction across levels of the system, and emphasize marginalized students’ lived experiences through phenomenological approaches. Utilizing Social Cognitive Career Theory and Phenomenological Variant of Ecological Systems Theory, this study examines socioenvironmental experiences that shape persistence in a year-long after-school algebra-for-engineering program, interest in STEM careers, and postsecondary plans. Interviews from three cohorts (n = 25) between 2021 and 2024 in a large urban district revealed students’ experiences in school-based math and science coursework, students’ plans for postsecondary STEM pathways, and patterns between mesosystem factors in relation to microsystem factors resulting in differential persistence in an algebra-for-engineering program. Interviews revealed an accumulation of weak math and science school experiences yet overall high math self-efficacy, STEM interest, and strong family support. Most students described ambitions to attend college and focus on “getting good grades” at present, yet participant postsecondary plans ranged considerably between firm, burgeoning, and vague. High-persisting students differed most starkly from low-persisting students regarding mentorship opportunities (namely pragmatic support), STEM identities (consolidated identities across home, school, and extracurriculars), and coordinated school-based postsecondary planning. Students with these supportive mesosystem factors clustered at two of nine schools. Low-persisting students described weak bonds with teachers, limited peer support, haphazard curriculum, and delayed or absent advising. This study explores how those postsecondary goals develop, pointing to modifiable socio-environmental factors relevant to urban program developers, school administrators, and policy makers interested in supporting flourishing STEM ecosystems

    Oral History Interview with Rebecca S. Dresser

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    This interview with Rebecca Dresser, JD, is part of “Moral Histories: Voices and Stories from the Founding Figures of Bioethics,” an oral history project of the Johns Hopkins Berman Institute of Bioethics. She is Daniel Noyes Kirby Professor Emeritus of Law and Professor of Ethics in Medicine at Washington University in St. Louis, Missouri. As a legal scholar and bioethicist, her areas of expertise include end-of-life care, biomedical research protocols, genetics, assisted reproduction, and the ethics of using animals in scientific research. She has written five books and dozens of articles for scholarly and public audiences. From 2002-2009, she was a member of the President’s Council on Bioethics during the Bush administration. Professor Dresser discusses her early life, including the experience of losing her father to melanoma, her early educational interest in psychology and sociology, and her law school experience at Harvard in the late 1970s. Rebecca Dresser discussed her introduction to bioethics as a field, and subsequent career transitions, as she navigated differences between being tenured in medical or law schools and the challenges of balancing joint law and medical ethics positions. Dresser explains how she became involved in animal research ethics, her involvement with the Institutional Animal Care and Use Committee, and the regulatory challenges in this field. She emphasized the importance of including women in research and the impact of the Dobbs v. Jackson Women’s Health Organization decision on reproductive rights, noting the shift from privacy to liberty as a constitutional basis for such decisions. She recounts her service on the President's Commission on Bioethics under George W. Bush and what that experience taught her about bioethics and politics. Dresser discusses her cancer diagnosis and treatment journey as a patient and as a bioethicist. A few years after her remission, she gathered other bioethicists who had experienced cancer and edited a book, Malignant (2012), that emphasizes the value of personal knowledge in the field of bioethics.</p

    From Zero-Tolerance to Zero Options: The Criminalization of Marginalized Youth in Education

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    This dissertation, "From Zero-Tolerance to Zero Options: The Criminalization of Marginalized Youth in Education," critically examines the systemic inequities in urban educational settings that disproportionately funnel marginalized students, especially BIPOC and low socioeconomic status (SES) youth, into transfer schools and, ultimately, the school-to-prison pipeline. Utilizing Bronfenbrenner's ecological systems theory (EST) as a conceptual framework, this study interrogates how nested societal, systemic, and interpersonal factors create cycles of punitive discipline and student pushout. Through comprehensive literature synthesis and analysis, this research explores foundational factors including racial bias, the pervasive myth of meritocracy, disproportionate disciplinary practices, cyclical fear between students and school adults, and the criminal justice system's intersection with education. It emphasizes the detrimental impacts these elements have on students' educational experiences, self-concept development, and long-term life trajectories. The research also highlights the psychological and neurobiological consequences of chronic stress and hyper-vigilance induced by discriminatory practices, cultural mismatches, and pervasive negative stereotyping within educational settings. Qualitative data from students in transfer schools reveal their lived experiences, underscoring their perception of institutional rejection and mischaracterization, and the emotional toll this systemic disenfranchisement imposes. The dissertation argues for educational reform that prioritizes empathy, cultural responsiveness, and systemic accountability to dismantle the cyclical oppression of marginalized youth, thus advocating for practices that foster genuine opportunities and meaningful engagement rather than punitive exclusion

    Multistage Neural Networks for High Dimensional Function Approximation

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    Multistage Neural Networks (MSNNs) have demonstrated promising accuracy for low-dimensional function approximation problems with a compact, interpretable structure. This thesis investigates the application of MSNNs to high-dimensional scientific problems, particularly in the context of solving partial differential equations (PDEs). We analyze the scaling behavior of MSNNs in dimensions ranging from 1 to 4 using a benchmark problem (Poisson’s equation). Additionally, we implement a sparse FFT, which replicates the accuracy of full FFT with better performance in high-dimensional use cases. Our findings provide new insights into how MSNNs balance memory constraints with approximation accuracy, and we propose improved heuristics for adaptive stagewise scaling factors. This work extends MSNNs as a viable tool for high-dimensional scientific machine learning

    GDE2 Maintains TDP-43 Localization and Function by Regulating Neuronal Wnt Signaling

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    Alzheimer’s disease (AD) and AD-related dementias (ADRDs) such as Amyotrophic lateral sclerosis (ALS) and Frontotemporal dementia (FTD) are the most common forms of neurodegeneration. Studies over the last decade revealed that nuclear exclusion of the DNA/RNA-binding protein TDP-43 drives neurodegeneration by altering the splicing and expression of genes important for neuronal health. Diverse processes have been implicated to influence TDP-43 mislocalization, including disrupted nucleocytoplasmic transport (NCT). How these changes are initiated in disease is unknown. Glycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein that cleaves the glycosylphosphatidylinositol (GPI) anchor that tethers some proteins to the outer leaflet of the plasma membrane. In development, GDE2 plays important roles in cortical and spinal neurogenesis and oligodendrocyte maturation. The expression of GDE2 persists in the adult nervous system, and recent studies identified unique roles for GDE2 in maintaining neuronal survival that are separate from its developmental functions. Notably, GDE2 exhibits abnormal trafficking and reduced function in AD, ALS, and ALS/FTD patient neurons. Specifically in ALS and ALS/FTD patient tissues, GDE2 accumulation correlates precisely with TDP-43 abnormalities. Using genetic ablation of GDE2 in mice to model its loss of function, our lab has found that GDE2 loss leads to complex behavioral and cognitive changes in aged animals, some of which are associated with neurodegenerative diseases. On the cellular level, GDE2 ablation leads to age-progressive neurodegeneration in the cortex, preceded by TDP-43 abnormalities. Thes findings suggest that the erosion of GDE2 physiological function contributes to common pathologies underlying AD and ADRDs. In this study, we find that GDE2 is widely expressed in the adult mouse brain. Specifically in the cortex, GDE2 ablation leads to aberrant neuronal Wnt signaling activation that drives NCT defects and TDP-43 mislocalization. Further, GDE2 deficits are evident in human neuronal cell models of ALS, which display erroneous Wnt activation that, when inhibited, partially rescued the TDP-43 molecular function. We also show preliminary data supporting that the GPI-anchored protein, Glypican-6, mediates neuronal Wnt regulation by GDE2. These findings provide insights into the mechanisms underlying disease pathogenesis and highlight Wnt pathway activation as an unappreciated mechanism contributing to TDP-43 abnormalities in disease

    THE MOLECULAR MECHANISM FOR TERRA RECRUITMENT AND ANNEALING TO TELOMERES

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    Telomeric repeat containing RNA (TERRA) is a noncoding RNA that is transcribed from telomeres. Previous study showed that TERRA trans anneals by invading into the telomeric duplex to form an R-loop in mammalian cells. Here, we elucidate the molecular mechanism underlying TERRA recruitment and invasion into telomeres in the context of shelterin proteins, RAD51 and RNase H using single molecule (sm) assays. We demonstrate that TERRA trans annealing into telomeric DNA exhibits dynamic movement that is stabilized by TRF2. TERRA annealing to the telomeric duplex results in the formation of a stable triplex structure which differs from a conventional R-loop. We identified that the presence of a sub-telomeric DNA and a telomeric overhang in the form of a G-quadruplex significantly enhances TERRA annealing to telomeric duplex. We also demonstrate that RAD51-TERRA complex invades telomere duplex more efficiently than TERRA alone. Additionally, TRF2 increases TERRA affinity to telomeric duplex and protects it from RNase H digestion. In contrast, TRF1 represses TERRA annealing to telomeric duplex and fails to provide protection against RNase H digestion. Our findings provide an in-depth molecular mechanism underpinning TERRA recruitment and annealing to the telomere

    Kinetic Controlled Assembly of Nanoparticles for Delivery of Therapeutics

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    This thesis develops a kinetic-controlled nanoparticle assembly method that integrates flash nanocomplexation (FNC) with flash nanoprecipitation (FNP) to encapsulate diverse therapeutics based on their structural properties. Using this approach, nanoparticles loaded with anti-TNFα, semaglutide, and small-molecule drugs achieve high loading capacity and encapsulation efficiency. Their controlled release and therapeutic efficacy are demonstrated in mouse models of inflammatory bowel disease, hepatocellular carcinoma, and Parkinson’s disease. This study highlights the advantages and translational potential of this novel assembly process

    From Hope to Harm: Addressing Ethical Issues with Device Abandonment

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    In 2010, Rita Leggett enrolled in a clinical trial for a novel Brain-Computer Interface (BCI) device. Leading up to the study, Leggett had struggled for decades with debilitating epilepsy that prevented her from living an otherwise normal life. The BCI offered a potential solution: the implant could detect incoming seizures and alert her in time to take preemptive medication. Her life changed significantly, and she described feeling transformed. All was well until the company running the trial declared bankruptcy and requested that Leggett “return” her implant. This case exemplifies an overlooked ethical issue in BCI research: undue psychological harms associated with device abandonment. While much attention has been paid to the risks of implantation, comparatively little has been said about the harms of losing a device after it has meaningfully improved a participant’s life. This paper argues that such abandonment directly violates the principle of nonmaleficence. If the loss of regained function leads to a lower level of well-being than before the intervention—or to a perceived loss of self—then device removal cannot be treated as a mere logistical or financial concern. Instead, it should be recognized as a significant ethical risk, especially in trials involving neurotechnologies that impact autonomy, agency, or identity. Using the Leggett case as a starting point, I explore how BCI device abandonment creates unique ethical harms for neurological patients and argue that these harms may outweigh those associated with never receiving the intervention at all. This paper calls for trial design and regulatory oversight to account for the risk of abandonment by including safeguards such as long-term device access plans, post-trial obligations, and mechanisms to prevent participants from being left worse off than they were prior to enrollment

    PLASMODIUM VIVAX MALARIA IN A LOW ENDEMIC REGION OF PERU: EPIDEMIOLOGY OF ASYMPTOMATIC PARASITEMIA, TRENDS IN ANTIBODIES TO THE P. VIVAX DUFFY BINDING PROTEIN-II (PV DBP-II) AND IMPACT OF MALARIA ZERO PROGRAM

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    Introduction Malaria poses a significant public health threat, especially P. vivax as the most prevalent Plasmodium species in the Americas. Asymptomatic, submicroscopic infections pose challenges for control programs based on active case surveillance, but serology can detect exposure and assess changes in transmission intensity. Objectives of this study were: 1) To assess the prevalence and incidence of asymptomatic parasitemia and associated risk factors in a low-endemic region of Loreto; 2) To evaluate trends of seropositivity against Pv DBP-II and their association with parasitemia; and 3) To evaluate the impact of Malaria Zero Program (MZP) on malaria incidence in the Loreto region between 2016 and 2019. Methods Between 2019 and 2022 we conducted a four-assessment, open cohort in Padrecocha, Loreto, and collected blood samples for malaria diagnosis plus a population survey. Serum/plasma samples were used for Pv DBP-II serology testing. We identified factors associated with being malaria positive at any of the four study assessments. We also estimated changes in malaria incidence in Loreto before MZP (2016-7) and after the implementation of MZP (2018-9), using surveillance data. Results The prevalence and incidence of asymptomatic vivax parasitemia were found to be 2.9% and 3.4%, respectively. Asymptomatic vivax parasitemia at any assessment was associated to being female, malaria episodes in the last year, being close to a water source during sunset/dawn and spraying the house with insecticide (ORs: 2.89-5.71). Pv DBP-II antibody seropositivity was low and had a significant decreasing trend across assessments both among participants with/without parasitemia (p<0.010). Loreto exhibited a substantial reduction in malaria incidence during MZP (IRR=0.27), after adjustment for climate variability. Discussion The overall low prevalence and incidence of vivax parasitemia and the predominance of submicroscopic, asymptomatic cases highlight the need for more sensitive diagnostic methods and active surveillance, especially in elimination scenarios. The low Pv DBP-II seropositivity may result from reduced exposure to malaria during the study period and limited booster effects after infections. The reduction in malaria incidence in Loreto during the MZP indicates that current control measures can be highly effective, regardless of climatic variability

    Computational Modeling of Nanomaterials and Chemical Processes for Energy and Sustainability Applications

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    With increasing energy demands and the need for countries to reduce CO2 emissions, there is a significant need to innovate at many levels and in many different industries, from small electronic devices and nanomaterials to large-scale chemical processes. Computational research is an essential cornerstone of innovation in these fields, providing meaningful support for studying systems ranging from individual atoms and electrons to plant-scale chemical processes. This work spans multiple systems within this range, including nanomaterials composed of lead chalcogenide quantum dots and other layered materials and a carbon utilization process to produce medium-chain-length polyhydroxyalkanoates. Nanomaterials have shown considerable promise for use in applications related to semiconductors and energy. However, the syntheses of these materials require further development to obtain materials with desired electronic and optical properties. Previous work has focused on combining self-assembly and directed attachment of colloidal quantum dots at fluid interfaces to form two-dimensional quantum dot superlattices. We use Molecular Dynamics simulations to study the atomic behavior behind the oriented attachment of multiple colloidal lead sulfide quantum dots. We have utilized a semi-empirical force field, the Simple Molecular Reactive Force Field, that allows access to orders-of-magnitude-larger system sizes while retaining accurate system behaviors on an atomic scale. This potential enables us to provide simulations of epitaxial bridge formation between multiple quantum dots and observe how different nanocrystal positions and orientations in solution can affect disorder in the epitaxially-connected structure. Transition metal dichalcogenide and other layered materials are exciting candidates for photovoltaic devices, photosensors, and solar cell technologies with improved capabilities. Computational techniques like Density Functional Theory allow the study of these materials at the atomic level, allowing us to understand how various material parameters can impact the consequent performance of said material. We utilize a codebase for calculating thermoelectric coefficients to gauge the thermoelectric performance of 2D materials composed of transition metal dichalcogenides. Scaling up from the atomic scale to more large-scale studies, we use simulation to evaluate the economic and environmental considerations regarding a specific carbon utilization process. We use techno-economic assessment to evaluate an integrated electrocatalytic and biocatalytic carbon dioxide utilization process

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