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    EVALUATING PHOSPHATIDYLINOSITIDE AS LIPID BIOMARKERS FOR HYPERGLYCEMIA-RELATED TRIPLE-NEGATIVE BREAST CANCER AGGRESSIVENESS
    ([Bloomington, Ind.] : Indiana University, 2025-10) Kile, Aaron; Wells, Clark
    Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, marked by limited treatment options and poor patient outcomes. Clinical and epidemiological studies suggest that systemic metabolic conditions, particularly high blood glucose associated with Type 2 Diabetes, may worsen TNBC progression. However, there are no current biomarker for detecting TNBC, especially in hyperglycemic patients. This thesis investigates how elevated glucose levels influence TNBC behavior and whether lipid signaling molecules at the cell membrane, known as phosphatidylinositol lipids (PIs), can serve as biomarkers of disease progression. To address this, we combined functional assays that measure key cancer traits, including cell migration, attachment to the extracellular matrix (ECM), and cell accumulation, with lipidomic analyses of cell membranes under normal and high-glucose conditions. Our findings demonstrate that hyperglycemia enhances aggressive traits in TNBC cells, promoting increased movement and growth, but no effect on ECM attachment. In parallel, lipid profiling revealed alterations in PI molecules that regulate growth and survival pathways, with differences observed across cell models. These results highlight a direct connection between metabolic stress and cancer progression. By linking systemic metabolic dysregulation to cell signaling in TNBC, this work identifies PI4P, PI(4,5)P2 and PIP3 lipids as potential biomarkers and points toward new strategies for risk stratification and therapeutic intervention.
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    THE CRISIS OF LOCAL JOURNALISM: DEATH BY A THOUSAND PAPER CUTS
    ([Bloomington, Ind.] : Indiana University, 2025-10) Paladhi, Arijit; Peifer, Jason
    The decline of local journalism in the United States represents a critical threat to democratic governance. Nearly one-fifth of Americans live in news deserts – which are communities with limited or no access to reliable local news. Predicated on this threat, we draw upon the political economy of media, public goods theory, and media pluralism frameworks to establish journalism as a public good characterized by positive externalities. However, the market mechanisms in place today have either consistently failed to adequately provide these externalities or been superseded by neoliberal capitalism's thirst for pillaging profit at any cost. To that end, this dissertation’s empirical analysis proceeds through two major studies. First, the theoretical analysis demonstrates how the confluence of technological disruption from digital platforms and these neoliberal deregulatory policies created conditions enabling aggressive financialized ownership – which we call greedy money models – to extract value from struggling newspapers while undermining their democratic functions. Using a stacked difference-in-differences design, we examine how private-equity-and-hedge-fund acquisitions of local newspapers affect electoral competitiveness in affected communities. Contrary to expectations of simple democratic decline, the findings reveal a surprising pattern: elections become substantially less competitive while simultaneously experiencing increases in voter turnout, declines in incumbent win rates, and increased candidate entry. These effects peak one year after acquisition before partially dissipating, suggesting immediate disruption to local political equilibrium followed by a degree of gradual adjustment. Second, we incorporate machine learning algorithms to identify counties that share similar socioeconomic profiles to news deserts. Addressing significant class imbalance in the data through various resampling techniques, the analysis finds that Random Forest combined with SMOTEENN is the strongest performer. The most significant predictor is the interaction between population density and GDP, highlighting how economic vulnerability intersects with demographic factors. Crucially, we incorporated neighboring counties' socioeconomic characteristics, which can help tease out how the formation of news deserts operates as a regional contagion rather than isolated local failures. These findings challenge conventional narratives about media ownership and democratic health. Rather than straightforward erosion, private equity acquisition triggers complex political reorganization in local communities. The temporal dynamics and spatial dependencies suggest specific intervention windows and the need for regional rather than purely local policy responses. Ultimately, this work demonstrates that the crisis of local journalism operates through patterns that, once understood, offer opportunities for intervention.
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    Compiler Support for an RMI Implementation using NexusJava
    (1997-12) Breg, Fabian; Gannon, Dennis
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    Dead Code Elimination Using Program-Based Regular Tree Grammars
    (1997-11) Liu, Yanhong; Stoller, Scott