Since their rise over half a century ago, community archives have filled in the gaps that mainstream archives have knowingly or unknowingly left, preserving the history of typically marginalized groups on their own terms. But it is only in the past decade or two that scholars have begun seriously contending with community archives, a timeline that perhaps not coincidentally overlaps with the archival profession’s increased focus on its own role in perpetuating power relations and systems of oppression. How has the so-called traditional archival community conceived of its relationship to both power and community archives, and what potential do community archives hold to help the archival field rectify its history of exclusion? Through a review of trends in the current literature on the topic, this paper will explore community archives as an alternative to traditional archival practice. Ultimately, this paper will argue for a reconceptualization of community archives as part of the archival continuum rather than as traditional or mainstream archives’ binary opposite. If archives and archival professionals want to begin to grapple with their legacy of power and exclusion, rethinking how we conceptualize archival working taking place outside of the academy and traditional heritage sector is a promising place to begin.

While architectural and algorithmic innovations have prolonged the viability of conventional semiconductor devices, diminishing returns are eventually inevitable. Emerging technologies often present alternative and more promising paths forward, but their adoption is not without challenges. Developing advanced fabrication processes is both costly and slow, and many existing circuit, digital logic, and microarchitecture solutions are, at best, suboptimal for these technologies due to fundamental differences in device physics.

This dissertation advocates for superconductor electronics, promising for applications ranging from classical computing acceleration to integrated quantum and sensing systems, and introduces practical co-optimizations that exploit the technology's strengths while circumnavigating its limitations. The objective is to examine and exploit the opportunities created by the absence of resistance and the intrinsic characteristics of Josephson junctions at various levels of the computing stack, rather than blindly force-fitting established abstractions.

To this end, the presented research focuses on four aspects critical to the development of a computer system: logic, design automation, fanout, and memory. In each case, the overarching goal is to maximize the utility of every Josephson junction. For the first three aspects, this means optimizing logic density, while for memory, the focus is on demonstrating how leveraging inexpensive data movement can improve both circuit complexity and energy efficiency.

Macrophages are a critical cell within the innate immune system capable of performing phagocytosis. This process allows macrophages to clear bacteria, viruses, and aged or mutated cells from the body. The ability of a macrophage to phagocytose is shown to be altered within the tumor microenvironment. Macrophages adopt an anti-phagocytic phenotype and demonstrate an altered metabolic state. Previous research has focused on identifying the end-state result of these changes. However, it has not been demonstrated what initiates this process and how it is propagated through tumor associated macrophages (TAMs). The work in this thesis demonstrates a new approach to studying macrophages and their ability to phagocytose using chemical biology techniques. We implement many tools to profile proteins present at baseline and when activated in human macrophages. Then, we expand our focus on macrophages isolated from human tumors, mouse tumors, and in vitro co-culture experiments. Widespread changes within macrophages are observed and documented to elucidate their response to inflammatory signaling and changes which occur following phagocytosis of cancerous cells.

In chapter 1, the research is centered around understanding the protein content of human monocyte-derived macrophages. This work was part of manuscript which was published in the Royal Society of Chemistry’s (RSC) journal of Chemical Biology. Previous work performing proteomic analyses of human macrophages utilized immortalized cell models or combined input from multiple donors. Additionally, the work was performed prior to major advances in mass spectrometry (MS) technology which improved coverage with lower sample input. As a result, we recognized a need for an improved analysis of proteins within human macrophages. We optimized a strategy to isolate monocytes from donated patient blood and derive them into functional macrophages. We then analyzed how these macrophages changed in response to stimuli with the inflammatory cytokine interferon gamma. This research serves as an important resource to inform future experiments within our own lab and broadly across those researching human macrophages.

In chapter 2, we used flow cytometry and surface proteomics to characterize macrophage surface proteins to better understand how TAMs become dysregulated. Our initial experiments isolated TAMs from within resected human tumors for Hepatocellular Carcinomas (HCC) and Pancreatic Ductal Adenocarcinomas (PDAC) and found on their surface the presence of Epithelial Cell Adhesion Molecule (EpCAM). This finding was surprising as macrophages do not express this protein. By applying the chemical biology tool stable isotope labeling of amino acids in cell culture (SILAC), we showed that human macrophages acquire and redeploy surface proteins, like EpCAM, from the target cell they phagocytose. We demonstrated that many of these acquired proteins are nutrient transporters which remain functional following redeployment. This causes changes in the ability of macrophages to uptake nutrients, directly impacting their function and ability to phagocytose. Collectively, our findings demonstrate a novel phenomenon which occurs during macrophage phagocytosis. Through these two projects, the goal was to provide insight into the proteome of human macrophages. We plan to continue exploring the mechanism of target protein acquisition following phagocytosis and analyze further how it alters macrophages. The research in both generated a large amount of data that can serve as resource for the broader community. The hope is by understanding further how TAMs develop, we can identify new targets to improve cancer therapies.

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