American Society for Eighteenth-Century Studies

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    IMPROVING MULTIDISCIPLINARY CARE FOR METASTATIC BREAST CANCER PATIENTS THROUGH QUALITY IMPROVEMENT AND EVIDENCE-BASED PRACTICE

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    Breast cancer remains the most diagnosed form of cancer in the United States. In 2024, an estimated 310,720 women were projected to receive this life-altering diagnosis, with approximately 6% of these new cases being metastatic breast cancer (MBC), the most advanced stage of the disease. [1] As of 2020, an estimated 167,518 women in the U.S. were living with MBC, a number that was expected to steadily increase to 246,194 by 2030. [2] The Hope at Hopkins program is a multidisciplinary care (MDC) program established to specifically support the physical, psychological, social, and emotional needs of patients with MBC. This dissertation utilizes a quality improvement (QI) and evidence-based practice (EBP)-focused approach to improving the performance of the Hope at Hopkins program to better support its patient population. Through a retrospective analysis of patient-reported outcomes collected from a preliminary cohort of MBC patients, this dissertation assessed the health status, needs and concerns of patients with MBC and identified particularly vulnerable populations within the cohort. A scoping review yielded insights into the multitude of QI efforts and evidence-based practices used in other comprehensive or MDC clinics to improve performance. Finally, integrating these insights, a strategic plan was developed for Version 2.0 of the Hope at Hopkins program. An initial evaluation of Version 2.0 showed marked improvements across numerous performance metrics, including time to navigate the program, time to recommendation letter, number of patients receiving a recommendation letter, and number of patients completing a clinic evaluation survey. While there remains no cure for MBC, it is treatable, and advances in treatment have made it possible to live longer with the disease. The insights gained from this research contribute to promoting impactful and sustainable MDC programs that holistically support a patient’s physical, emotional, psychological, spiritual, and financial needs. Strengthening MDC programs to better deliver comprehensive care is vital to improving outcomes and health-related quality of life for patients with MBC and ensuring the delivery of patient-centered care

    INVESTIGATIONS ON HIGH VALENT IRON CORROLAZINE COMPLEXES: SYNTHESIS, CHARACTERISATION AND REACTIVITY

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    Heme enzymes utilize a heme cofactor which contain iron bound porphyrin in the active site to facilitate several important chemical transformations in biology. Most common species that is responsible for enabling these enzymes to achieve their function is reactive high valent iron oxo porphyrin -radical cation. This intermediate is often fleeting requiring synthetic analogs necessary to study their spectroscopic and reactivity properties. This dissertation features synthesis, characterization and reactivity studies on iron corrolazine complexes to generate high valent iron oxo corrolazine species particularly providing insights on factors controlling their reactivity. An overview to high-valent iron-oxo found in heme enzymes, as well as a background on the synthetic metalloporphyrinoid analogues using iron metal and the factors controlling their reactivity properties have been discussed in Chapter 1. Chapter 2 describes the generation and characterization of a series of 6-coordinate iron (IV)-oxo porphyrinoid-π-cation-radical complexes, FeIV(O)(X)(TBP8Cz+•) using the ring contracted corrolazine ligand framework. This work demonstrate that the PCET reactivity of a Cpd-I analog is driven by the redox potential of Cpd-I rather than basicity and it provide the first evidence showing axial ligation inhibits the PCET reactivity of a Cpd-I analog. Chapter 3 describes the isolation of first high valent Fe(IV)(X) (where X = Cl, triflate) corrolazine complexes. The reactivity of these complexes with O-atom donors were investigated. Utilizing an array of spectroscopic techniques (XAS, variable field Mossbauer, IR, LDI-MS), the new complex has been proposed to be hosting O-atom at one of the meso N atoms in the corrolazine ring. The OAT reactivity of this complex has been explored using PPh3 as the substrate. Chapter 4 summarizes the optimized synthetic conditions to stabilize an Fe(IV)(OH) in corrolazine ligand. This involves characterization by oxidation and reduction titration UV-vis experiments, Mossbauer and DFT studies on the electronic structure of Fe(IV)(OH) corrolazine. Chapter 5 reports the synthetic strategy to modify the remote ligand sites on iron corrolazine complex. Synthesis and isolation of monoprotonated and tri protonated iron corrolazine by crystal structure has been described in this chapter

    PREDICTION OF SPATIALLY RESOLVED CHROMATIN ACCESSIBILITY USING SPATIAL TRANSCRIPTOMICS DATA

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    Integrating spatial transcriptomics and epigenomics from the same tissue provides deeper insights into the mechanisms underlying gene regulation. However, current spatial multi-omics datasets remain limited in number and are often affected by high levels of noise, presenting significant challenges for downstream analysis. In this study, we propose a novel method based on a big data regression framework to predict spatial epigenomics from spatial transcriptomics data. Our approach effectively recovers and enhances the signals in raw chromatin accessibility data, thereby increasing the number and improving the quality of available spatial multi-omics datasets

    Enabling Rapid Reconfigurability of FPGA Accelerators in Embedded Software Defined Radios

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    Software Defined Radios (SDRs) are ubiquitous in modern wireless communications, offering flexibility and reconfigurability across various protocols, such as IEEE 802.11 and 4G LTE. Industry-standard SDR platforms such as the Ettus USRP and Xilinx RFSoC provide considerable wireless capabilities by combining FPGA- and software-based digital signal processing (DSP). However, the high cost of these SDR platforms can make them impractical for student or hobbyist use. In contrast, common entry-level SDRs typically lack FPGAs entirely. The software-only processing approach reduces cost, but limits both their maximum processing capability and their usefulness as educational tools for FPGA-based DSP. This thesis leverages the Analog Devices Pluto SDR and the AntSDR E200, which both contain a Xilinx Zynq-7000 System-on-Chip (SoC), to create an accessible and versatile platform for FPGA-based implementation of SDR systems. By integrating Xilinx PYNQ, an embedded Linux framework for simplifying hardware/software co-design on Zynq SoCs, this research provides an environment for developing hardware-accelerated signal processing functions. PYNQ provides a Python interface and Linux kernel drivers for memory-mapped peripherals and direct memory access, so developers can focus on FPGA implementation of DSP algorithms and avoid the overhead of Linux integration. The Pluto-PYNQ system is both a tool for learning FPGA signal processing and a platform for practical SDR application development. The products of this thesis include the creation of the Pluto-PYNQ Linux image, a framework for building DSP overlays, and an example FM-radio accelerator. The open-source SDR community benefits from this research through the creation of a low-cost, educationally valuable SDR platform, and the Pluto-PYNQ can be used in advanced collegiate coursework to develop and demonstrate DSP functionality on real over-the-air radio frequency signals

    Computationally Probing Atomic Motion Within Crystalline Systems: Defect Migration in Perovskites and Schwoebel Barriers to Admolecule Diffusion on Titanium Dioxide Surfaces

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    Computational studies of atomic motion in crystalline systems provide critical insights into defect dynamics and surface growth mechanisms, enabling the optimization of materials for energy applications. In metal halide perovskites, the defect tolerance essential to their photovoltaic performance is attributed to self-regulation of free charge carriers via Schottky defect formation. Chapter 2 investigates CsPbBr3, an all-inorganic perovskite, using Nudged Elastic Band Density Functional Theory (NEB-DFT) to quantify migration and activation energies of Br interstitials (Br_i). Calculated migration energies (0.53–0.80 eV) align with the experimentally observed 0.52 eV value. Similarly, titanium dioxide (TiO2) thin films, crucial in photocatalysis and electronics, require precise control of surface morphology influenced by the Ehrlich-Schwoebel barrier. Chapter 3 combines atomic force microscopy (AFM) and ab initio simulations to determine Schwoebel barriers on anatase TiO2, advancing understanding of growth kinetics and enabling tailorable material properties. Together, these computational approaches further link atomic-scale processes with material properties for tunable synthetic control

    CHARACTERIZATION AND BIOLOGICAL EVALUATION OF ABSORBABLE POLYMERS

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    The use of absorbable polymers in medical devices has garnered increasing interest due to their applications in sutures, cardiovascular devices, orthopedic fixation devices, and surgical mesh. However, evaluating these polymers presents significant challenges as their materials properties and the identity and quantity of degradation products continuously change over time. This project investigates the impact of polymer degradation on biological responses throughout the device degradation process and seeks to correlate polymer material properties and degradation products with biological responses. The chosen polymer, PLGA 50:50, was degraded at 37°C and 45°C to simulate biologically relevant and accelerated conditions, respectively. Section 1 introduces the concept of absorbable polymers and their growing role in the biomedical field. It discusses various degradation mechanisms, current advantages and disadvantages, and existing assessment methods. Section 2 details the synthesis of PLGA 50:50 and its characterization throughout the degradation process. Mass loss and pH changes of the supernatant were recorded at each timepoint. Changes in surface morphology were studied using scanning electron microscopy (SEM), while contact angle and protein absorption were also investigated. These characterizations support the premise that PLGA 50:50 undergoes bulk erosion during hydrolytic degradation, which can interfere with metabolic processes in the endothelial lining. Section 3 examines the biocompatibility of the two monomers that can be formed during the degradation processes. Human Coronary Artery Endothelial Cells were exposed to increasing concentrations of lactic acid and glycolic acid. In vitro assays were used to determine cell viability and permeability relative to the untreated cell controls, assessing the biocompatibility of these degradation products. In conclusion, while lactic and glycolic acid monomers are naturally metabolized by the body, the acidic environment produced by these degradants can negatively affect cells. This suggests the need for more stringent standards in the approval and research of medical devices utilizing absorbable polymers

    THESE FRAGILE YEARS: THE ACCELERATING DISCORD OF NOW

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    Does the decadent American way of life come at a cost? Our prosperity seems normal, but in the grand scheme of time, it’s not. The formerly obscured toll of our lifestyles has risen in scientific importance. While powerful forces enforce current norms, some people bring change. Enlightenment about topics like climate change, biodiversity loss, and the loneliness of modernity is at the heart of my work. “These Fragile Years: The Accelerating Discord of Now” is a collection of essays and articles that give voice to anxieties and their antidotes

    PRACTICES AND POLICIES USED IN MANAGEMENT OF CUBA AND AUSTRALIA’S CORAL REEFS CAN WE SAVE THEM?

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    Climate change is rapidly and significantly impacting the planet and the ocean in harmful ways. (Environment U.N., 2017). (NOAA, 2019). (NASA, 2024). (Nature Conservancy, n.d.). The Earth’s average surface temperature in 2024 was the warmest on record, according to an analysis led by NASA scientists. (2024). Coral reefs are experiencing negative climate impacts more quickly and more severely than the ocean in total. Our research addresses global coral threats like ocean warming, acidification, and extreme storms, plus local threats like overfishing, marine migration, invasive species, pollution, and excess nutrients. We have shown how coral reef threats, management practices, and resilience in Cuba and Australia impact the health and restoration of coral reefs. We focused this Capstone project on these elements of reef management: threats, practices, and resilience. Coral reefs provide value to our society as a home and food source for 25% of marine life. (Loiacono, 2024). Coral reefs support industry in terms of fishing, tourism, and recreation. Water sports are enhanced by the mystery, bounty, and beauty of coral reefs. (Loiacono, 2024). Currently, 30 - 50% of coral reefs have been destroyed globally. Climate change and local threats greatly weaken coral reefs leading to damage, disease, and death. (Environment U.N., 2017). (NOAA, 2019). (NASA, 2024). (Nature Conservancy, n.d.). Reef management practices provide options to preserve, recover, and save these amazing coral reef ecosystems. Local management priorities for Cuba and Australia include Marine Protected Areas (MPAs), multi-purpose objective setting, bioscience solutions, and ecological role management. These significant actions can provide value to other coral areas. Climate action is a topic for further research

    The epigenome as a mediator of genetic and environmental contributions to the heritability of normal phenotypes and disease

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    Despite increasingly large cohort sizes and the advent of whole genome sequencing, genome-wide association studies continue to report limited genetic contributions for many common heritable diseases and phenotypes. This seemingly paradoxical result suggests the existence of an additional, non-genetic source of this missing heritability. DNA methylation, a stable epigenetic modification that is inherited across cell division and sensitive to environmental exposures, serves as a strong candidate to explain at least a portion of this missing disease heritability. The aim of this thesis is to concurrently analyze the genome, methylome, and transcriptome in order to understand their relationship to one another as well as to investigate the manner in which they interface with epigenetic inheritance and the heritability of common diseases. To do so, we designed novel experimental and computational pipelines that apply genomic mediation analyses, long-read sequencing, and highly controlled environmental exposures within genetically diverse mouse populations to identify genetic and epigenetic mechanisms contributing to the etiologies of common, complex diseases. Utilizing these approaches, we discovered novel candidate genes associated with diet-induced obesity, schizophrenia, and bipolar disorder, highlighting the potential of DNA methylation to enhance diagnostic, therapeutic, and preventative approaches to disease mitigation. Furthermore, we identified and characterized widespread non-Mendelian intergenerational epigenetic inheritance patterns in mice, underscoring the critical role of the epigenome in the study of heritability. Taken together, the results of this thesis indicate that DNA methylation can serve as a mediator of both genetic and environmental contributions to the heritability of normal phenotypes and disease states

    Oral history interview of Dr. Alisa Griffin

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    In this interview, Dr. Warren Hayman asks Dr. Alisa Griffin to share her experiences in the Hopkins Dunbar Health Professions Program. Specifically, Dr. Griffin reflects on the pre-academy summer program and how she benefited from social components like community building and of physically working in scientific labs. She shares how the program gave her a better idea of what was possible for her and other young people in Baltimore, what inspired her to be a teacher, and how the folks she encountered in the program continue to show up for her and she considers them family. Alisa graduated from Dunbar High School in 1991 and then attended Clark Atlanta University. After completing degrees in biology and molecular genetics, she earned a PhD in cell biology and signal transduction. Today, Dr. Griffin works at Spelman College as a senior laboratory educator and teaches several courses, some on the African Diaspora and biology

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