Dartmouth Institute for Health Policy and Clinical Practice
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“I Would Like, If I May, To Take You, On a Strange Journey:” Camp in Queer Film From 1975-2022 as a Reflection of the Cultural Context
Get PDFMicroglial Dynamics and Mechanisms Underlying the Phagocytosis of Dying Oligodendrocytes
Get PDFMyelin is a complex multilamellar structure, generated by oligodendrocytes, that ensheaths axons and is a vital component for neural processing. Degeneration of both oligodendrocytes and their myelin sheaths is a common pathological feature associated with aging and neurodegenerative diseases. Efficient removal of the cellular and myelin debris is crucial for remyelination and prevention of further degeneration. Microglia, the primary phagocytes of the CNS, are thought to play a key role in this process. To investigate the cellular dynamics underlying microglia-mediated clearance of degenerating oligodendrocytes and myelin sheaths, at the single cell level, we developed a novel model for inducible cortical demyelination called oligodendrocyte 2Phatal. This model activates a non-inflammatory stereotyped degeneration cascade, leading to remyelination by local oligodendrocyte precursor cells. Using this model of single-cell demyelination, I observed microglia engaging with both the targeted oligodendrocyte and its myelin sheaths followed by a stereotyped and efficient removal of both. Following the removal of the myelin sheath, I observed rapid remyelination, suggesting that efficient clearance of the myelin debris plays a vital role in successful remyelination. Deletion of the fractalkine receptor, CX3CR1, delayed microglia engagement with the targeted oligodendrocyte but did not affect the clearance of myelin sheaths. Surprisingly, the deletion of the phosphatidylserine receptor, MERTK, had no impact on the clearance of either the targeted oligodendrocyte or the myelin sheaths. These new findings reveal the underlying cellular dynamics involved in myelin debris clearance and repair and highlight the role of CX3CR1 signaling in the efficient removal of dying oligodendrocytes
Toward the Integration of Behavioral Sensing and Artificial Intelligence
Get PDFThe integration of behavioral sensing and Artificial Intelligence (AI) has increasingly proven invaluable across various domains, offering profound insights into human behavior, enhancing mental health monitoring, and optimizing workplace productivity. This thesis presents five pivotal studies that employ smartphone, wearable, and laptop-based sensing to explore and push the boundaries of what these technologies can achieve in real-world settings. This body of work explores the innovative and practical applications of AI and behavioral sensing to capture and analyze data for diverse purposes. The first part of the thesis comprises longitudinal studies on behavioral sensing, providing a detailed, long-term view of how significant events, such as the COVID-19 pandemic and professional promotions, impact mental health and productivity among college students and information workers. The \textit{College Experience Study} spans five years, tracking two cohorts of students through their entire college experience, offering a rare longitudinal perspective on student behavior and mental health during global disruptions. The second study provides a year-long observation of information workers, focusing on physiological and behavioral changes post-promotion, highlighting how career advancements influence personal well-being and professional duty. The second part of the thesis expands the application of behavioral sensing with novel methods and integration with AI technologies. This section introduces a pioneering approach to mental health assessment through the \textit{MoodCapture Study}, which utilizes passively captured smartphone images to detect depression symptoms. Additionally, we explore the enhancement of personal productivity and well-being through AI-driven tools, including Large Language Models (LLM) powered personalized productivity agents and the MindScape mobile application for contextual AI-driven journaling. These tools leverage real-time behavioral data to provide adaptive, user-specific support, demonstrating the effectiveness of integrating advanced AI with behavioral sensing in creating responsive and user-centric applications. Overall, our work highlights significant advancements in AI and behavioral sensing, providing practical applications and implications for improving mental health, enhancing educational experiences, and boosting workplace productivity. Each study contributes to a broader understanding of the dynamic interaction between technology and human behavior, laying the groundwork for future innovations that could lead to more efficient, healthy, and productive lifestyles
Patterned Magnetic And Plasmonic Nanostructures In Microfluidics For Extracellular Vesicle Screening And Drug Loading
No full textExtracellular vesicles (EVs), once dismissed as shuttles for cellular waste, have emerged as vital nanoscale biomolecules, facilitating intercellular communication through transfer of host-cell specific molecular cargo. Tumor-derived EVs, released by cancer cells, hold potential as diagnostic biomolecules due to their links to cancer cells, abundance within biofluids, and potential for direct extraction and detection. More broadly, EVs from a wide array of cellular origins have been explored as therapeutic carriers, stemming from their innate function as cargo carriers, high biocompatibility, and their ability to evade immune detection. However, harnessing EVs for diagnostic or therapeutic applications necessitates efficient isolation, purification, and manipulation directly from biofluids, presenting challenges given their minuscule size and micro-nano scale physics. Consequently, the tangible use of EVs in clinical settings has remained limited, with technological progress primarily constrained to research pursuits.
This thesis outlines the development of four technologies: (1) microtransfer patterned magnetic microchips for rapid EV isolation, (2) laser-patterned magnetic microchips for on-chip EV patterning, (3) a photothermal engineering system enabling integrated capture and cargo loading within EVs, and (4) patterned plasmonic nanostructures with applications in EV biosensing. Firstly, we describe a novel magnetic microchip architecture with patterned flow-invasive micromagnets, enhancing traditional immunomagnetic sorting while enabling precise profiling of EVs. Secondly, we detail an advancement to magnetic microchip fabrication that promotes scalability, a necessity for clinical implementation. Thirdly, we introduce a novel photothermal engineering system that enables cargo loading within patient derived EVs and highlight promising results concerning loading of the small molecule, nucleic acid, and protein cargo. Lastly, we discuss the development progress of an exosome assay that utilizes patterned plasmonic nanostructures to facilitate exosome detection within a standard microwell-plate format. Technology development within each contribution spans from enabling micro/nanoscale phenomena, through material/device engineering and concludes with application driven technology validation. Collectively, this thesis presents a step towards the realization of EV-centered diagnostic and therapeutic clinical workflows, whereby we can harness the innate biological properties and functions of EVs within molecular diagnostics and personalized medicine
“I Know A Place Where You Don’t Need Protection, Even If It’s Only in My Imagination:” 21st Century Queer Politics and Cultural Positions Through Pop Music
Get PDFFrom Madonna to Britney Spears to Beyoncé, women have dominated and defined pop music for decades. Pop music is a vital part of American culture; it is both shaped by and capable of shaping the broader sociopolitical landscape. Thus, women in pop can utilize the deep relationship between music and culture to convey a stance on the role of women in American society. However, queer women in pop music are somewhat scarce, even in 2024 when acceptance of queerness is relatively high. As such, the queer women and queer themes that are present in pop necessitate nuanced analysis to understand the various positionings of queer women in American culture. In order to address these positions, this paper will analyze several musicians, their artistry, and their lyrics to look for political messaging and influences. The analysis has found that these positionings are diverse in their relationships with gender, queerness, and political thought. They are also shaped by a myriad of sociopolitical contexts that have been subject to rapid change as the United States has evolved its thinking on queerness. In a period where right-wing attacks against the queer community are increasingly frequent and dangerous, the political standpoints and goals of the community are at a crucial crossroads. The strategy decisions and positions taken now will influence the environment that future generations of queer people will have to face. The entire queer community has a part to play in these decisions. Queer women in pop music can have enormous influence and can thus be powerful drivers of regression, stagnation, or revolution
Shifting Forms: Queer Placemaking Amidst Neoliberalism In New York City Through Art
Get PDFThis project explicates how queer people produce space for themselves through art in New York City amidst the prevalent neoliberal frameworks that have existed since the 1980s. Drawing on semi-structured interviews with queer artists and nonprofit workers, participant observation in art spaces, and close reading of art compiled through archival work, I explore sites of presentation (places in which art is displayed) and modes of presentation (how specific artists decide to present their art). I analyze museums and nonprofit spaces, and engage with queer artists that create what I consider to be site-specific art. I zoom in on spatial art interventions by artists Frederick Weston, Sharon Hayes, and REPOhistory to show how queer artists relate to their personal histories as well as collective histories within the urban, subverting perspectives within human and urban geographies that neglect the personal in favor of larger-scale patterns. I argue that the nonprofit space is an overlooked site of presentation—functioning as what I call an intimate semi-public—that stands in contrast to the neoliberal flattening within the institutional art world. Using a “both-and” approach, the benefits of these organizations can be embraced alongside radical grassroots initiatives. Bringing together analytics from queer phenomenology, art theory, and queer affect theory, I root these art interventions in critical theories of the production of space
Liquid Metal Printing of Ultrathin Conductive Metal Oxides
Get PDFWidegap metal oxides are critical semiconducting materials in solar power generation, transparent electronics and displays. Ultrathin versions of these materials are poised to be at the forefront of next generation technology due to their high transparency, flexibility, and the capacity to advantageously use backchannel sensitivity and quantum confinement. Liquid metal printing is a novel deposition technique that fundamentally yields ultrathin oxide materials by exfoliating the self-limited oxide that exists on molten metals at low temperatures. Our work involves the invention of novel liquid metal printing techniques to deposit semiconducting 2D metal oxides with precise electrostatic properties. We investigate the electronic behavior of single and multilayer stacks of InOx, GaOx and ITO materials primarily by integrating them into switching devices. Their optoelectronic and morphological properties are characterized through the use of UV-Vis, XPS, XRD and TEM in order to explain the link between their physical and electronic structure. 2D liquid metal printed oxides have demonstrated a number of advantageous traits such as high mobility and transparency, beneficial responses to heterojunction stacking, and flexibility. The formation of the oxide skin is also examined through the lens of the relevant theory. We generate models from the experimental data and governing oxidation equations in order to predict the synthesis parameters of desirable materials. The overarching aim of our work in the field of liquid metal printing is to discover fundamental characteristics of 2D oxides which could lead to the development of high-performance flexible transparent electronic materials and low-cost, rapid production of metal oxide switching devices
Machine Learning for Graph Algorithms and Representations
Get PDFThis thesis explores a variety of common graph theoretic problems from a machine learning perspective. The topics covered include fundamental network problems such as distance approximation, distance sensitivity, community detection, cross-network alignment, and graph embedding dimension reduction. These projects are unified by the theme of machine learning on graphs, graph embeddings, and representations of graphs
Establishment of Bacteroides in the gut and its role in the cystic fibrosis gut-lung axis
No full textIn the quest to understand the complex interplay between the gut microbiota and cystic fibrosis (CF), a disease characterized by chronic upper respiratory complications and an exacerbated proinflammatory response, our lab engaged in a collaborative study with Dartmouth-Hitchcock Medical Center (DHMC) to characterize the gut microbiota of pediatric CF patients. Initial analyses established a connection between gut microbial composition and respiratory health, particularly highlighting a scarcity of Bacteroides species compared to healthy controls. In following investigations, we utilized random forest models to understand how stool microbiota may influence clinical outcomes of these pediatric CF patients, including: age, upper respiratory infections, and proinflammatory biomarkers like NLR. We identified specific bacterial genera including Faecalibacterium, Butyricoccus, and Bacteroides as significant indicators of upper respiratory infection frequencies within the first two years of life.
A deeper dive into the functional role of Bacteroides revealed their capacity to suppress IL-8 production, attenuating inflammation in CFTR−/− intestinal epithelial cells. This anti-inflammatory action was further evidenced in a CF mouse model, where Bacteroides supplementation yielded a local increase in propionate levels and a significant reduction in systemic pro-inflammatory cytokines, showcasing the potential of gut microbiota manipulation in managing CF-related inflammation.
A pivotal element of our study was the examination of microbiota biogeography within the gut, assessing how spatial distribution across various gut regions, particularly the colon\u27s luminal and mucosal surfaces, influences microbial diversity and immune gene expression. Our findings indicate that while Bacteroides supplementation post-antibiotic treatment successfully colonizes the gastrointestinal tract, it primarily establishes in the luminal colon and by itself does not drive huge differences in alpha or beta diversity, as measured by 16s RNA amplicon sequencing. Gavage with Bacteroides further showed the highest response by the host in the small intestine, where the most regulated pathways are those regulating the adaptive immune system.
This thesis underscores the therapeutic promise of tailored gut microbiota management, highlighting how microbial biogeography informs the modulation of systemic inflammation in CF. The nuanced understanding of these spatial microbial patterns, and their interplay with host immune responses, charts a course for innovative, microbe-centered interventions, leveraging the gut-lung axis to ameliorate the burdens of this chronic disease
