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Privacy Protection Amplified: Leveraging Agent-Based Simulation
No full textPrivacy protection is inherently complex and challenging, especially with the rise of interdependent data sharing. This dissertation addresses the intricate nature of privacy risks by developing agent-based models to simulate user behavior in sensitive contexts, focusing on genomic data sharing and health data auditing. In the first part, we model the social dynamics of genomic data sharing using a game-theoretic framework. Our analysis highlights how individual decisions can produce network effects and negative externalities, leading to multiple Nash equilibria and potential tragedies of the commons. In the second part, we design a reinforcement learning–based auditing policy for online data sharing and access platforms, such as the NIH’s All of Us program. By integrating agent-based modeling with deep reinforcement learning over a dynamic bipartite graph of users and workspaces, our approach learns effective auditing strategies that leverage peer effects. Together, these contributions advance our understanding of interdependent privacy and provide a new simulation-based paradigm for designing privacy-preserving systems
QTL Mapping with Collaborative Cross Mice Identifies FFAR3 as a Target for ILC2 Anti-Inflammatory Reprogramming
No full textPulmonary group 2 innate lymphoid cells (ILC2s) are key drivers of Type 2 inflammation in diseases like asthma, yet the molecular mechanisms regulating their function remain incompletely described. Using the genetically diverse Collaborative Cross (CC) mouse panel, we mapped a quantitative trait locus (QTL) that governs ILC2 prevalence in the lung after aeroallergen exposure. The broader effect of this QTL is to create a large population of ILC2s in the lung that are resistant to activation and have diminished Type 2 effector function. We implicate free-fatty acid receptor 3 (Ffar3) as a gene responsible for this QTL effect, and we demonstrate that FFAR3 signaling reprograms ILC2s to an anti-inflammatory state by promoting their survival, reducing Type 2 cytokine production, and enhancing IL-10 expression. This reprogramming is mediated by epidermal growth factor receptor (EGFR) upregulation on ILC2s. We showed that FFAR3’s anti-inflammatory effect is conserved in human ILC2s, making it a potential therapeutic target for Type 2 inflammation
Mass Spectrometry-Based Approaches to Improve Small Molecule Annotation and Analysis
No full textMass spectrometry (MS)-based untargeted metabolomics studies aim to profile small molecules (<~1000 Da) to more fully understand their roles and impacts in various biological processes. However, due to the prevalence of isomers, isobars, and common fragmentation patterns, confidently identifying specific species proves to be a notable challenge. Ion mobility (IM) is a size-dependent gas phase separation technique that, when coupled with liquid chromatography (LC) pre-MS, can improve the separation of complex biological samples. Additionally, IM-derived values, the collision cross section (CCS), can be used in conjunction with retention time, accurate mass, and possible fragmentation data to better identify analytes. As LC-IM-MS workflows continue to be used, it is imperative to assess the impact of pre-mobility parameters, such as LC solvent composition and electrospray ionization (ESI) source parameters, on CCS to maintain the high reproducibility of these values in small molecule analysis. For a variety of drug and drug-like molecules, CCS values were measured in various solvent compositions, ESI gas temperatures, and in-source activation energies. Taken together, this dissertation summarizes efforts and recommendations toward the continued improvement in identification of small molecules using LC-IM-MS
Navigating the Cross and Crossing the Sea: Collaborative Knowledge-Production, Visual Literacies, and Racial Formations Across the Spanish Empire
No full textThis dissertation titled “Navigating the Cross and Crossing the Sea: Collaborative Knowledge-Production, Visual Literacies, and Racial Formations Across the Spanish Empire” puts indigenous codices, Spanish manuscripts—some translated from Portuguese and others integrating Chinese vocabularies—transcontinental correspondence, cartographic representations, illustrations, original archival research, and published literary works into conversation with each other to illuminate how colonial knowledge-production intersected each other in Spanish America and Spanish Asia during the Early Modern Period. The project underscores the interconnectedness of the early modern world and challenges the conventional narratives of colonial history by highlighting the collaborative and contested nature of knowledge creation and dissemination. This work contributes to the historical understanding and enriches the appreciation of the cultural, political, and intellectual exchanges that shaped the modern world. It is a testament to the impact of visual and written culture in bridging diverse civilizations under the expansive umbrella of the Spanish Empire, revealing a world where boundaries were both drawn and blurred through the acts of seeing, writing, and mapping
Protein-Protein Interactions Required for CagA Recruitment and Secretion by the Helicobacter pylori Cag Type IV Secretion System
No full textHelicobacter pylori strains that contain the cag pathogenicity island (PAI) utilize the Cag type IV secretion system (T4SS) to deliver a bacterial effector protein (CagA) and non-protein substrates into human gastric cells. The Cag T4SS outer membrane core complex (OMCC) contains multiple copies of five proteins, two of which are species-specific proteins. Additional species-specific proteins encoded by the cag PAI are required for Cag T4SS activity, but their localization within the Cag T4SS is undefined. By using optimized mass spectrometric methods and modifications of a previously described OMCC immunopurification method, we have identified four cag PAI-encoded proteins (CagW, CagL, CagI, and CagH) that co-purify with the Cag T4SS OMCC. Analysis of immunopurified samples by size exclusion chromatography revealed that CagW, CagL, CagI and CagH co-elute with OMCC components. These four Cag proteins are copurified with the OMCC in immunopurifications from a Δcag3 mutant strain (lacking peripheral OMCC components), but not from a ΔcagX mutant strain (defective in OMCC assembly). Mutant strains with deletions of cagW, cagL, cagI, or cagH lacked T4SS activity but retained the ability to assemble OMCCs. Furthermore, by targeting several different Cag proteins and adding crosslinkers to the bacteria prior to immunopurification, we improved our ability to isolate multiple Cag proteins, providing further insight into protein-protein interactions among cag PAI-encoded proteins. We also generated H. pylori strains that produce CagA N-terminal fusion proteins (APEX2-CagA, GFP-CagA) and found that these fusion proteins retained the ability to interact with the Cag T4SS OMCC. In summary, the experiments described in my dissertation provide new insights into protein-protein interactions relevant to the structural organization of the Cag T4SS
Selling Pleasure, Teaching Pleasure: Frontline Service Work in Adult Retail
No full textThis dissertation examines how frontline workers in adult retail establishments—commonly referred to as "sex shops"—make meaning of their labor in a stigmatized industry at the intersection of commerce and sexuality education. Drawing on 21 in-depth interviews with workers and analysis of over 1,000 job reviews written by frontline adult retail workers, I explore how workers navigate the conditions of adult retail labor while framing their work as educational, healing, pleasurable, and purposeful. This research contributes to the sociology of work by analyzing how service workers in “spicy retail” mobilize their identities and experiences to perform emotional labor under conditions of stigma and precarity. Across four analytic chapters, I trace how workers enter adult retail through pathways shaped by sexual subcultures, biographical experiences, financial instability, and identity. On the job, identity is also “working,” and participants’ narratives reveal that they are leveraging their gender, sexuality, trauma histories, and neurodivergence in customer service interactions. Finally, I analyze how workers find meaning in their labor by framing it as a low-barrier form of public health, a site of personal and collective healing, and a space where joy, humor, and pleasure coalesce. In foregrounding the voices of frontline workers, this dissertation expands scholarship on sexualized labor and emotional labor. By showing how workers make sense of their labor in terms of care, I show that adult retail work—and sex industry labor such as this—is not just worthy of sociological attention—it is a key site for understanding how workers strive for meaning in the contemporary occupational landscape in the United States
Dissecting Gene Regulatory Dynamics and Mechanisms with Single Cell Imaging Techniques
No full textCells must be able to rapidly and specifically respond to stress to survive. In order to control RNA and protein levels in response to a signal, transcription must be tightly controlled as well. Since transcription is a highly dynamic process, studying pathways at a fine spatiotemporal resolution is essential to fully understanding signaling-induced regulation. We utilize the Saccharomyces cerevisiae Hog1 osmotic stress response pathway as a model for inducible signal response, investigating the role and dynamics of the highly conserved Spt-Ada-Gcn5-Acetyltransferase (SAGA) transcriptional cofactor complex in responsive gene regulation. As part of our larger investigation, we developed a software tool called TrueSpot to facilitate fully automated and accurate signal quantification from large batches of RNA fluorescent in situ hybridization (RNA-FISH) imaging data. We then applied TrueSpot to preliminary RNA-FISH studies of osmosensitive gene transcription profiles over time in cells with Gcn5, a catalytic subunit of SAGA, knocked out or depleted. We confirmed that perturbation of Gcn5 delayed and dampened the transcriptional response of upregulated osmosensitive genes
Privacy Preservation in Pervasive Computing Environments
No full textWith the widespread adoption of location-based services it is vital to emphasize location privacy to prevent unexpected and unwanted location disclosure. However, privacy preservation often introduces challenges such as increased computational complexity, communication overhead, or reduced data precision. To address these challenges, this work explores novel protocols in secure multi-party computation (SMPC) to enable accurate and efficient solutions within the domains of location sharing, traffic aggregation, contact tracing, and crowdsensing without sacrificing privacy. In location sharing, the protocols are developed for kNN, range and point queries ensuring location privacy is maintained. In traffic aggregation secure multiparty computation is developed to aggregate near future traffic data in a privacy preserving manner. In contact tracing, privacy-preserving mechanisms are developed to detect potential exposure events without revealing users' movement patterns. In crowdsensing applications, protocols are developed to safeguard location privacy from the task assignment phase through payment for task completion, ensuring participant location privacy throughout the process. In addition to privacy preserving protocols, this work looks at the privacy of servers through the use of novel distributed architecture and protocols for firewall evaluation and management. Lastly, this work looks at the current state of privacy preservation in pervasive environments and the potential of these techniques in future technologies for preserving users’ privacy
Goodness of Fit: Teachers’ Boundary Work at the Intersection of Data Science and Mathematics Education
No full textSchool mathematics in the U.S. is shaped by competing and contradictory goals that reflect broader tensions around the purpose of public education: whether it should serve democratic or socioeconomic aims. These tensions have created a landscape in which mathematics often functions as a sorting mechanism and gatekeeper, positioning students in hierarchies of academic and social value. Despite ongoing reform efforts, mathematics instruction continues to be shaped by these logics of efficiency, standardization, and quantification. In this context, data science has been increasingly positioned as a modern, relevant alternative to traditional mathematics. However, data science is not a neutral alternative and carries its own epistemologies, histories, and risks. This dissertation takes up the question of how teachers make sense of and integrate data practices in ways that they see as relevant, meaningful, and equitable within the structural and ideological constraints of school mathematics.
This qualitative study examines how four secondary mathematics teachers navigated the everyday instructional and ideological work of integrating data practices. Data include professional development sessions, classroom video and artifacts, lesson plans, and interviews. Findings illustrate how teachers worked to use data to recontextualize mathematics – positioning data as a means to surface inquiry, contextualize mathematical ideas, and connect to students’ lived experiences. Their lesson designs reflected different orientations to disciplinary integration, using data to either situate, serve, or reshape mathematical goals. In classrooms, teachers engaged in boundary work that revealed tensions between mathematical precision and interpretive judgment. These tensions created moments of both constraint and possibility as teachers attempted to hold space for student reasoning within the dominant logics of school mathematics. Across their decisions, teachers’ pedagogical commitments shaped what kinds of participation and meaning-making were possible, and reflected broader efforts to design mathematics instruction that was relevant, meaningful, and humanizing.
This dissertation offers design principles for integrating data and mathematics that attend to disciplinary tensions, support interpretive reasoning, and center equity. It contributes to theory-building in data science education by situating teacher learning within the sociohistorical and political landscape of mathematics education
The Functional Nano-Organization of Distinct Forms of Neurotransmission
No full textWithin the single micron of the synapse action potential dependent and independent neurotransmission concurrently signal. However, the molecular mechanisms that mediate and regulate the specificity and diversity of this synaptic signaling is lacking. In this dissertation a synaptic nano-organization composed of neurotransmitter release machinery, molecular platforms, scaffolding proteins, and liquid complexes that support the discrete signaling of evoked and spontaneous neurotransmission are outlined. First, the use of the molecularly specific small molecule, Artemisinin, reveals the concentric post-synaptic center surround organization of evoked and spontaneous neurotransmission at GABAergic synapses. Subsequently, the pharmacological disruption of liquid-liquid phase separation uncovers how pre-synaptic active zone liquid condensates facilitate evoked release at both glutamatergic and GABAergic synapses at nanoscale. Lastly, chronic clinically relevant genetic manipulations provide mechanistic insight into rare developmental and epileptic encephalopathies, while simultaneously illuminating the dynamic relationship between SNARE mediated release machinery and the structure of the synapse in dually regulating basal neurotransmission. The described robust nano-organization supports unique functional roles for each discrete mode of release at both excitatory glutamatergic and inhibitory GABAergic synapses. This work proposes a fundamental design principle, that the single synapse is a highly ordered and compartmentalized unit whereby the functional nano-segregation of distinct forms of neurotransmission shapes synaptic efficacy. The elucidation of basic synaptic physiology is essential to both uncovering mechanisms underlying neurological diseases and designing their treatment