Dartmouth Institute for Health Policy and Clinical Practice
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Exploitation to Liberation: Care Worker Kinship in New York City
No full textThis project aims to identify the relationship between power and care in the home health industry and how who has the power (the worker or another entity) can drastically transform the embodied effect of care—either as overwhelming or emancipatory. Focusing on Home Health Aides (HHAs) in New York City, I apply geographies of care and labor geography to analyze how home health workers organize across disparate workplaces to regain their agency over their labor and care relationships. Through this research, I found that HHAs use kinships and care webs to mobilize and organize against care agency and patient surveillance and state failures. I conclude that HHAs depend on each other to mobilize using principles of inter-community solidarity and kinship to regain agency over their spatial productions. In this praxis of care, HHAs offer a unique insight into how care and power intersect, transforming the act of caring either into subjugation or liberation
OBSERVATIONS OF SEA ICE THERMAL STRAIN AND MOTION AT GEOPHYSICALLY RELEVANT SCALES
No full textOngoing and unprecedented Arctic sea ice change as a result of anthropogenic climate change impacts life in the Arctic and beyond. The sea ice cover is becoming less expansive, thinner, younger, and more dynamic. Quantifying processes and properties that differ between old versus young and thick versus thin ice is central understanding the sea ice cover, improving climate change predictions, and developing strategies to adapt and mitigate the adverse effects of sea ice loss. Therefore, we seek to better understand how a key inherent ice property, the thermal strain coefficient, changes as ice types change, and observe how sea ice motion and deformation are changing over time.
We conduct studies on the thermal strain of natural sea ice using in situ and remote sensing techniques, over km+ scales – a significant development from prior laboratory-based studies. We evaluate the thermal-strain relationship of first-year, multiyear, and freshwater ice. We find that thermal strain varies considerably from that expected in laboratory studies likely due to unique combinations of physical processes in situ such as thermal gradients, surface fractures, and brine exchange. We unify contradicting laboratory findings with these results. A potentially profound finding is that FYI (increasingly more common) behaves differently from MYI. Differing behavior between ice types and thicknesses are considered as they relate to Arctic sea ice decline, motion and deformation.
Current sea ice motion-extracting tools are unable to test hypotheses about thermal fracture effects on basin wide motion, which would require high resolution and wide spatial coverage. Available algorithms produce high quality maps, however with resolutions too coarse to resolve much of the important ice deformation. The need for higher resolution sea ice motion analysis is widely recognized and there are many new algorithms under development for this purpose. Therefore, we aim to consolidate efforts by creating a “community challenge problem” that addresses a lack of validation and intercomparison between proposed methods. We release a standardized dataset that includes all necessary input imagery and a validation process using ground truth data from extensive drifting buoy networks. The provided documentation is intended to enable interdisciplinary contributions to the challenge problem
Properties and Interactions of the CcoP Subunit of Cytochrome cbb3 Oxidase
No full textPseudomonas aeruginosa (Pa) is a pathogenic bacterium known for its antibiotic resistance and ability to survive in low-oxygen environments through biofilm formation. Central to its aerobic respiration under such conditions is cytochrome cbb3 oxidase, a terminal enzyme usually receiving electrons from c type cytochromes. This thesis investigates the molecular basis of electron transfer to cytochrome cbb3 oxidase, focusing on the CcoP subunit, which contains two heme c groups and is proposed to be the primary electron entry site. CcoP isoforms (CcoP1 and CcoP2) from Pa and its non-pathogenic relative Pseudomonas stutzeri (Ps) were expressed, purified, and analyzed using spectroscopic methods and binding assays. Ps CcoP1 and CcoP2 displayed high structural similarity with minor redox differences that may influence donor interactions. In Pa CcoP2, spectroscopic and structural characterizations revealed a deviation from canonical Methionine (Met) coordination in the oxidized state, consistent with a longer-than-usual distance between the C-terminal heme iron and the sulfur atom of M186 noticed in cryo-EM structure. Mutagenesis near M186 partially restored Met coordination and reduced nitric oxide (NO) binding, indicating that local structural features influence ligand stability. These results underscore the importance of axial ligand identity in electron transfer: stable Met ligation raises the heme’s reduction potential, promoting electron entry into CcoP. Conversely, unstable Met or alternative ligands may facilitate electron transfer from CcoP to downstream subunits. Furthermore, NO binding studies provide insight into Met stability and Pa’s survival under nitrosative stress. Biolayer interferometry suggested strong binding between Ps CcoP isoforms and ii i cytochrome c4 (cyt c4), with enzymatic assays further supporting cyt c4 as a physiological electron donor in Ps. However, the observed viability of Ps strains lacking cyt c4 suggested the existence of alternative redox partners, which were subsequently investigated through in-vivo pull-down assays. Recent cryo-EM analysis of the Pa cytochrome bc1–cbb3 super-complex revealed the presence of both cyt c4 and a fragment likely from cytochrome c5 (cyt c5). A truncated Pa cyt c5 was expressed, purified, and shown by NMR to bind Pa CcoP2 with higher affinity than cyt c4, suggesting its potential role in bridging electron flow to cbb₃ oxidase in Pa respiration
Single-Cell Transcriptomics Reveal the Heterogeneous Landscape of Epithelial Identity During Zebrafish Pancreatic Tumorigenesis
No full textWhile the majority of human pancreatic cancers are classified as ductal adenocarcinomas, the cell of origin of these tumors remains uncertain and many tumors are comprised of dedifferentiated cell types, making it imperative to understand the full spectrum of neoplastic differentiation and how it is regulated. The central focus of this dissertation is the utilization of a zebrafish model of pancreatic cancer driven by tissuespecific expression of UAS:mKO2-KRASG12D under the regulation of a Ptf1a:Gal4-VP16 transcriptional driver to elucidate mechanisms of tumorigenesis and differentiation. Transgenic zebrafish generate heterogenous tumors comprised histologically of mixed acinar and ductal elements, providing the opportunity to interrogate specific transcriptional and epigenetic modifiers responsible for regulating neoplastic pancreatic cellular differentiation. Single-cell RNA sequencing of these tumors has confirmed neoplastic cell populations expressing exclusively acinar and ductal markers, as well as distinct clusters expressing markers of both cell lineages and additional progenitor-like cells. Screening a panel of 21 unique chromatin modifiers and chromatin readers for differential expression in these distinct cell clusters reveals hdac9b to be upregulated in the progenitor-like population enriched for ductal features [1]. Pseudo-time trajectory inferences support an acinar cell-of-origin for these hdac9b-expressing progenitor-like cells. Treatment of fish with the class IIA HDAC inhibitor TMP195 supports a functional role of HDAC activity in regulating neoplastic cell differentiation through activation of pancreatic progenitor gene expression and repression of the acinar cell state (Graphical Abstract). This work further shows that neoplastic gene signatures from zebrafish are conserved in premalignancy and progenitor-like populations in murine tissue and have a high correlation with human transcriptional subtype signatures. The human ortholog, HDAC9, is a strong predictor of overall survival in PDAC patients with classical tumors. These findings are described in detail in Chapter 2 and may lead to new strategies for therapeutic manipulation of neoplastic cell differentiation. Additional methods and attempts at pancreatic cancer modeling in zebrafish are outlined in Chapter 3
PIP fabrication and Keogram analysis: Preparation for the GNEISS mission to study sheetlike auroral arcs
No full textThe upcoming Geophysical Non-Equilibrium Ionospheric System Science Rocket (GNEISS) mission aims to investigate the structure and dynamics of the auroral ionosphere by deploying a fully instrumented multipoint, multiplatform payload suite into the Alaskan ionosphere in March 2026. This project supports GNEISS through the fabrication of Petite Ion Probes (PIPs) and analysis of auroral keograms derived from all-sky imagery. PIPs are used to measure ion flux and are mounted on both main and subpayloads to provide spatial insight into electron precipitation patterns. We detail the step-by-step assembly process for PIP stacks using gold-coated mesh and screens and report improvements in fabrication methods that reduced mechanical wrinkling. Additionally, keogram analysis was performed on March 2025 auroral data to develop magnetic field-aligned expectations for GNEISS, correlating observed structures with reconnection signatures. These efforts inform both instrument readiness and scientific planning.https://digitalcommons.dartmouth.edu/wetterhahn_2025/1003/thumbnail.jp
Postglacial Erosional Response of a Permafrost Landscape across Decadal to Millenial Timescales, Aklavik Range, Arctic Canada
No full textRapid warming and permafrost thaw across Arctic landscapes are projected to drastically accelerate local erosion rates and sediment fluxes to downstream systems and the communities that rely on them. However, interpreting this signal of change first requires disentangling the relative contributions of postglacial landscape responses, periglacial processes, and modern warming to observed changes in erosion. To explore this problem, we combine a suite of geochronometers to examine erosion and deposition rates over timescales of 102–107 years across a periglacial alluvial fan and catchment system on the former margin of the Laurentide Ice Sheet in the Aklavik Range of Northwest Territories, Canada. We use low-temperature thermochronology (apatite fission-track and apatite/zircon (U-Th)/He) to constrain the background (~25 Ma) erosion rate of the Aklavik Range at ~0.09 mm/yr. Cosmogenic nuclide (10Be) dating of erratic boulders near the Laurentide glacial limit in the Aklavik Range suggest that the region was last glaciated prior to ~20.3 ka, 1.8 ka earlier than previously thought. Postglacial fan- and catchment-derived erosion rates (~1-7 mm/year), calculated using mass balance, radiocarbon (14C) dating, and optically stimulated luminescence (OSL) dating, exceed background rates by an order of magnitude or more. These results underscore that contributions to observed erosion rates from modern warming must account for persistent postglacial landscape disequilibrium in Arctic ice-marginal settings
Floating Signifiers: AI, Semiotics, and the Crisis of Meaning in Music
Full text linkThis thesis examines how AI-generated music disrupts traditional meaning-making processes in musical expression. Through semiotic analysis (Saussure, Peirce) and cultural theory (Hall), I demonstrate how AI produces technically proficient but culturally hollow compositions, what I term floating signifiers. Case studies reveal AI\u27s inability to replicate the lived experiences that give music its depth, despite accurate stylistic reproductions. The work identifies three fundamental losses: contextual grounding, authentic hybridity, and historical consciousness. I propose ethical frameworks for human-AI collaboration that preserve music\u27s essential humanity while leveraging algorithmic capabilities. Ultimately, this research shifts the debate from technical possibility Can AI compose? to cultural significance Can AI create meaning?
Soft Modular Robots: From Modular Tensegrity Structures to Bioinspired Sea Robots
Full text linkThe rapid advancement of robotics necessitates systems capable of adapting to complex, unstructured environments. Soft robots, with their flexibility and compliance, excel in delicate interactions, making them ideal for medical applications and search-and-rescue missions. Modular robots, on the other hand, offer reconfigurability, enabling diverse task-specific adaptations in dynamic settings. Despite their individual advantages, the integration of soft and modular robotics remains underexplored. This proposal aims to develop soft modular robots that combine the adaptability of soft robotics with the versatility of modularity. These systems will be capable of autonomously transitioning between locomotion, manipulation, and infrastructure assembly across land, water, and air.
This research is motivated by the limitations of traditional industrial robots, which are confined to predefined, repetitive tasks in controlled settings. In contrast, disaster response, environmental monitoring, and infrastructure development demand robots capable of role transitions in unstructured environments. However, soft robots often lack the structural integrity for load-bearing tasks, while modular robots struggle with compliance for sensitive interactions. Integrating these paradigms introduces key challenges, including (i) balancing mechanical adaptability and load-bearing capacity through stiffness-tunable mechanisms, (ii) developing robust self-reconfigurable architectures, (iii) enabling autonomy via real-time sensing and planning, and (iv) optimizing configurations for task-specific adaptation using data-driven approaches.
This proposal will explore four key directions: (1) tensegrity-inspired soft modular robots for deployable infrastructure such as shelters and bridges, (2) aquatic soft modular robots for trash collection, amphibious locomotion, and drone landing, (3) bioinspired soft modular robots, including dolphin-like designs for efficient fluid movement and (4) STEM education kits to make biomimetic soft modular robotics accessible for education and research.
By addressing these challenges, this research aims to develop adaptive, multifunctional robotic systems capable of autonomous decision-making and real-time adaptation in complex environments
Mechanistic Insights into the FLASH Effect: The Role of Oxygen and Radiation Chemistry in Ultra-High Dose Rate Radiation Therapy
Full text linkThe development of new cancer therapies focuses on widening the therapeutic ratio between tumor control and normal tissue toxicity. Over the last decade, ultra-high dose rate (UHDR) radiation therapy, commonly known as FLASH radiotherapy (FLASH-RT), has shown promising potential to reduce normal tissue toxicity while maintaining tumor control. However, the underlying mechanisms of the FLASH effect remain poorly understood. This thesis explores the radiation-chemical basis of FLASH-RT, focusing on the role of oxygen and reactive oxygen species in modulating biological outcomes.
A comprehensive set of in vitro studies demonstrated that UHDR delivery significantly alters radiation chemistry compared to conventional dose rates. Specifically, both hydrogen peroxide production and oxygen consumption per unit dose were reduced in protein-rich environments, with mean dose rate emerging as a more predictive parameter than instantaneous dose rate. Additionally, comparison between proton and electron UHDR beams revealed beam-specific differences in reactive oxygen species yields, suggesting that UHDR radiation chemistry is not uniform across modalities.
These chemical insights were translated to in vivo murine skin models together with real-time phosphorescence oximetry. Oxygen consumption during irradiation was found to be highly dependent on baseline tissue oxygenation, plateauing above 20 mmHg. The importance of this dependency was demonstrated in subsequent biological studies, where mice with higher pre-irradiation pO2 and greater radiation-induced oxygen consumption were found to be more likely to develop skin ulceration. Notably, the FLASH effect, characterized by reduced skin damage at UHDR, was significant under normoxic conditions but diminished under hyperoxic conditions, indicating a saturable relationship between oxygen tension and tissue sparing.
Further investigations into UHDR temporal dose delivery structures revealed that the timing of dose delivery modulates both oxygen consumption and biological response. Short beam interruptions preserved the FLASH effect, while longer gaps led to reduced sparing, emphasizing the temporal dynamics of oxygen recovery as a key factor. Together, these findings establish oxygen as a central factor in both the chemistry and biology of FLASH-RT. By linking tissue oxygenation, radiation-induced oxygen consumption, and normal tissue toxicity, this work provides a mechanistic framework to guide optimization of UHDR delivery in preclinical and future clinical applications