American Society for Eighteenth-Century Studies

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    Chapter 12: Music Copyright and Libraries

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    Libraries play a broad range of functional roles in managing music collections, including acquiring and providing access to music and recordings for entertainment, education, or performance purposes; administering and preserving performances; and maintaining archival records of our musical heritage. Fulfilling these roles requires librarians to understand music copyright and the complicated system of music licensing that has developed in the United States

    POLICY CHANGES NECESSARY FOR STATES IN THE PJM INTERCONNECTION REGION TO ACHIEVE CLIMATE GOALS BY 2030

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    The transition to a sustainable energy future is a pressing global imperative, and regional electricity markets play a pivotal role in achieving climate goals. This paper explores the necessary policy changes and investments required by PJM Interconnection, one of the largest electricity markets in North America, and state regulators to align with its ambitious climate objectives by 2030. This study assesses the challenges, benefits, and opportunities associated with a focus on renewable energy integration, grid modernization, electrification of transportation, and energy efficiency. Drawing from extensive research and case studies, the paper presents policy recommendations aimed at streamlining regulatory processes, fostering financial incentives, promoting technological innovation, and increasing public and utility engagement. Notably, PJM and FERC must collaborate to reduce the backlog of energy projects waiting in the interconnection queue. While FERC Order 2023 and the establishment of a queue scoping tool by PJM are much needed steps in the right direction, the implementation of these instruments is crucial to achieving PJM’s climate goals. PJM must also focus on easing the renewable energy procurement process through improvements in their market design. Lastly, PJM needs to reduce barriers to entry and encourage participation in their stakeholder structure to incorporate the suggestions of new clean energy developers in the interconnection. These findings emphasize the critical role of regulatory changes in shaping PJM’s transition to a low-carbon energy landscape, highlighting the economic, environmental, and societal benefits that can be realized through timely and informed decision-making. As governments, industries, and communities seek pathways to sustainable development, the insights provided in this paper contribute to the broader discourse on achieving climate objectives through effective policies, governance, and investments

    THE PAST AS PROLOGUE?: A COMPARISON OF INSURANCE MARKET INSTABILITY AFTER NATURAL DISASTERS IN FLORIDA AND CALIFORNIA

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    Climate change is causing a rapid increase in the frequency and severity of natural disasters, including hurricanes and wildfires. Adapting to the impacts of more frequent and severe disasters will be a significant challenge in the coming decades. Homeowners’ insurance offers significant adaptive capacity to individual homeowners and the communities they make up. However, climate change has the potential to overwhelm the insurance industry’s ability to reduce risk for homeowners. Two states that are already experiencing these climate impacts are Florida and California. Florida, because of its unique geography, has always been at heightened risk for hurricanes, and has experienced decades of insurance market instability as a result. After a period of consecutive years of severe wildfires, California is beginning to show signs of potential instability in its insurance market. This paper sets out to examine the extent to which California is headed down the same path of market instability paved by Florida. To do that, the homeowners insurance market in the two states are compared across five metrics: loss ratios, premium rate increases, cancelation rates, the size of the residual market, and population growth. This paper finds that the ingredients for significant market instability are present in California, held in check only by the relatively low risk exposure in terms of the population of wildfire-prone counties. Intervention to stabilize the insurance market may be needed, but policymakers must do so carefully. Mitigation efforts to reduce the likelihood and severity of damage in the event of a disaster is one policy that could have a stabilizing effect on the insurance market

    International Human Rights Law Clinic Report, 2022-2023

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    The Johns Hopkins University School of Advanced International Studies (SAIS) International Human Rights Law Clinic is a capstone course which allows students to undertake a year-long project involving research, interviews, travel, and an opportunity to engage deeply in an intensive, interactive exercise. Each year, the class studies the ways in which a different country adjusts its internal legal regime to address a serious human rights challenge. In the 2022-23 academic year, the class investigated the impact of the massive influx of Venezuelan migrants in Peru. International law governing migration is relatively well-developed, but attention to and compliance with that body of law around the world, especially in crisis situations, are at best inconsistent. This report summarizes the class’s study of Peru’s experience in confronting an immigration crisis without historical parallel. We attempted to analyze the applicable laws and policies as they exist on paper, but also to explore how they are applied in practice in the face of unexpected pressures.Johns Hopkins University, School of Advanced International Studies (SAIS

    THE LIVING CORPSE: THE LIVING INTERIOR, ANESTHESIA, AND THE TRANSFORMATION OF THE SURGICAL PATIENT IN BRITAIN AND AMERICA IN THE NINETEENTH CENTURY

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    Access to the interior of the living body had always been difficult in medicine. Physicians longed for the opportunity to explore it but the emotionality and mobility of the patient during surgery had weighed on their conscience. Central to this experience was pain, and consciousness was the agent that allowed the perception of it. It would not be until the middle of the nineteenth century that such an opportunity had finally, allowed surgeons that access—to the Living Interior of the human body. Anesthesia negated pain by disconnecting consciousness from the lived experience of surgery. This had silenced patients and provided surgeons access to the Living Interior unrestricted by time and emotionality. Surgeons perceived the unconscious patient laid out on the surgical table much like how cadavers laid upon the dissection table under their knife and scrutiny. Anesthesia, they thought, blurred the line between the living and the dead, and this had aided in the objectification of the patient. They perceived the anesthetized patient as dead, still and unmoving, much like a corpse; yet alive. The anesthetized patient I contend, was transformed into a Living Corpse. And this reduction of the patient during surgery in the nineteenth century in America and Britain had a profound effect on the relationship between physicians and the surgical body ever since. In order investigate the effect that inhalation anesthesia had on surgery in the mid-19th century, I focused on physicians and surgeons practicing at the time of its discovery. I explored their academic letters, autobiographies, and published reflections on the state of their craft

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    UNDERSTANDING ADVERSE EVENTS, BARRIERS, AND FACILITATORS TO DEPRESCRIBING AMONG HOSPITALIZED OLDER ADULTS

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    Background: Older adults with multiple chronic illnesses and polypharmacy, the administration of five or more medications, are particularly vulnerable to adverse drug reactions (ADRs), which often increase the risk of unplanned healthcare utilization such as Emergency Department (ED) visits and hospital readmissions. Deprescribing is the process wherein a healthcare provider withdraws/reduces medication doses to improve outcomes and address polypharmacy. Benefits of deprescribing have been demonstrated in primary care and nursing home settings; however, the evidence for deprescribing is lacking for hospitalized older adults and those undergoing surgery. Objective: To understand barriers, facilitators, and preferences for deprescribing among patients and providers before surgery and to examine 90-day ED visits or hospital readmissions during a deprescribing intervention. Methods: This study used a multi-method design guided by the integration of the Framework of Treatment Discontinuation, the Framework for Minimizing Inappropriate Medication Use, and the Theoretical Domains framework. The qualitative portion included 16 participants (eight Primary Care Providers (PCPs) and eight patients), who were interviewed individually by phone. The quantitative portion was a secondary analysis of a deprescribing trial, Shed-MEDS (NIA R01AG053264) with 283 participants. Results: Qualitative interviews revealed that providers and patients are generally open to deprescribing for surgery since discontinuing and/or withholding medication(s) is commonplace before surgery. Additionally, patient’s trust in their providers and the involvement via shared decision-making with the shared goal of improving health and/or functional status provided hope for both. Conversely, contextual factors lack of deprescribing resources (i.e., guidelines) hindered deprescribing. Secondary analysis of the Shed-MEDS trial data revealed no statistically significant difference in the time to first ED visit/readmission between the intervention and control group. Additionally, higher comorbidities were associated with a higher hazard of unplanned healthcare utilization. Conversely, higher pre-hospital drug burden index score and the presence of financial burden due to medication costs were associated with a lower hazard of unplanned healthcare utilization. Conclusion: This study results underline the importance of shared decision-making between providers and patients and provide evidence that deprescribing before surgery is accepted, feasible, and safe

    Works and Methods on miRNA Localization and Evolution

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    Much of the current research in the field of miRNA expression lacks a basis in miRNA localization, which is an integral part of understanding the role of miRNA in disease. This work provides information on miRNA localization in pathology and evolution, which can provide important context for and information for future research in the field. Expression microdissection (xMD) is a technique for isolating specific cell types. It is a possible method of understanding miRNA localization, however existing experimental protocols required optimization. The first project was a series of modifications undertaken to leverage xMD for miRNA experiments. Changes were made to both the staining and xMD methods, and were validated with qPCR. Epithelium micro dissected from tissue obtained with the optimized xMD has between a 2-14 fold increase of epithelial specific miRNAs, and a 20-390 fold decreases of non-epithelial cell miRNAs, indicating the utility of xMD for use with qPCR. An endothelial cell specific miRNA, miR-126, is known to be expressed in Ciona robusta, a species that does not have endothelial cells. This leads to questions on the order of miRNA and cell type evolution. The second project is a reconstruction of the evolutionary history of miR-126, and its host gene (EGFL7/8). These analyses showed that C. robusta, EGFL7/8 was lost, while miR-126 was retained. RISH used on C. robusta, determined that miR-126 was only expressed in granular amebocytes. The results show that miR-126 essential activity predates endothelial cells, and it is a cell specific miRNA, giving evidence of miRNAs influencing the creation of diverse cell types. An understanding of the histology of C. robusta was required to complete the previous work. The comprehensive works on Ciona histology are out of date with modern histology presentation. The third project discussed is an updated histological atlas of C. robusta. This atlas uses standard histologic stains on all major organs, allowing others to use C. robusta in their labs. The works of this dissertation discussed the optimization of a miRNA localization technique, the application of miRNA localization, and the creation of a histological atlas of a model organism for vertebrate evolution

    PROGRAMMABLE M13 HYPERPHAGE DISPLAY OF DIVERSE ANIMAL TOXIN LIBRARIES TO DISCOVER MEMBRANE PROTEIN TARGETED THERAPEUTICS

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    Animal toxins and cysteine-reinforced miniproteins present underexplored landscapes for drug discovery due to their unique structural attributes, potent bioactivity, and selective targeting. Recognizing the value of these compounds for therapeutic strategies, we developed a high-throughput strategy for large-scale screening of these miniproteins. To meet the urgent requirement for large-scale screening of cysteine-reinforced miniproteins, we devised a high-throughput strategy targeting the discovery of innovative drug candidates. Central to this strategy is the construction of two distinct libraries: the 'Animal Toxin' library, assembled from Uniprot database resources, and the 'Metavenome' library, developed to expand the former through sequence homologous proteins within an extensive Metagenomic database. Using programmable phage display integrated with high-throughput oligonucleotide library synthesis, we encoded these libraries with chosen polypeptides, thereby representing a substantial fraction of the cysteine-rich toxins universe for protein-protein interaction studies. We optimized our phage display using a programmable hyperphage technique for M13 phage display. Our hyperphage system enables the fusion of ligands with all five copies of the P3 protein expressed on the phage surface. This polyvalent display system not only enhances binding avidity but also amplifies the sensitivity to detect lower affinity interactions. Moreover, we have coupled single-round screening with next-generation sequencing (NGS) to evaluate the binding of all library members simultaneously. This innovative combination allows for rapid and efficient identification of potential ligands for target membrane proteins and can even detect interactions with very rare members of a library that might otherwise be outcompeted in a typical multiple-round panning process of traditional phage display. As an initial demonstration of the utility of our platform, we focused on two distinct receptors, epidermal growth factor receptor (EGFR) and Mas-related G-protein coupled receptor member X4 (MrgprX4), which are implicated in cellular growth processes and pain/itch signaling, respectively. We rediscovered known ligands, identified novel binders, and provided insights into potential binding modalities of these ligands. Our findings demonstrate the potential of our libraries in discovering bioactive ligands and the prospects of these binders as scaffolds for novel therapeutics. Altogether, our platform offers a promising approach for membrane protein-targeted drug discovery and exploring the structural diversity of cysteine-rich miniproteins

    BAYESIAN NON-PARAMETRIC MODEL FOR CELL TYPE CHARACTERIZATION USING SINGLE-CELL DATA

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    Single-cell sequencing technology enables the measurement of RNA molecules at the single-cell level, which makes it possible to explore the cell-to-cell heterogeneity based on individual cells' transcriptome profile. However, the high noise level from both the technical and biological sides hinders the goal of distinguishing diverse cell types and characterizing the underlying true distribution of gene expressions for each type of cells. In this dissertation, we propose single-cell Bayesian non-parametrics (scBNP), an unsupervised generative method that explicitly models the uncertainty in raw gene expression counts and characterizes cell types for scRNA-seq data via small sets of marker genes. Our method adopts zero-inflated Dirichlet Mixture Process as the prior of marker gene parameters, and uses Gibbs sampling and variational Bayesian approaches to approximate the parameters in the distribution of gene expression counts for each cell. Such method simultaneously automates both the cell grouping and marker gene selection process with no need for labeled data. To take advantage of the prior biological knowledge provided by the fast-growing single-cell comprehensive reference resources, we also develop a semi-supervised learning variant of scBNP, which assumes the number of cell types is pre-defined based on the prior belief. To evaluate scBNP, we conducted a series of comparative experiments with existing state-of-art methods in single-cell analysis. First, we demonstrate the high robustness and stability of scBNP to the underlying distribution of data. Next, we illustrate the capacity of scBNP in capturing genuine biological heterogeneity across cells and characterizing cell types. Finally, we show that scBNP corrects cell-depth shift and distinguishes cell types across tissues via modeling cross-cell variations due to measurement bias through a cell-specific latent variable

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