Dartmouth Institute for Health Policy and Clinical Practice
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FLASH effect is diminished by daily fractionation of electron RT in mouse skin
No full textObjective. While FLASH radiotherapy is known to reduce skin damage in vivo from ultra-high dose rate (UHDR) irradiation relative to conventional dose rates (CDR), it is not clear whether this sparing is preserved when delivered as fractionated. This study was designed to directly assess whether three daily fractions would maintain the sparing effects in murine leg models and preserve the murine skin sparing with single fraction treatments. Approach. C57Bl/6j female mice were irradiated with 9 MeV UHDR and CDR beams from a FLASH-capable Mobetron system, in a dose escalation study with doses ranging from single dose 22–30 Gy in a single fraction to three daily fractions of 10–16 Gy. The biological responses were scored by a visual skin damage response rubric using up to 5 blinded observers, and a leg contracture assay as a secondary measure of damage. Main results. There was a monotonic dose response in all treatment groups with irradiation dose, with skin damage onset at 9–10 d. In the single dose group a significant FLASH sparing was seen with a FLASH modifying factor (FMF) of approximately 0.73. Similarly in the single dose groups there were significant leg contracture differences between UHDR and CDR groups after 12–15 d. In comparison, there was no significant skin damage sparing between UHDR and CDR in the three daily fraction dose groups, and reduced sparing in the leg contracture assay. Significance. The results of this murine study show a significant reduction of the FLASH effect when the dose is split into three fractions of 10–16 Gy each, whereas there were substantial FLASH sparing effects noted for the single fractions of 22–30 Gy, showing a FMF of ∼0.73. These observations provide the data needed to optimize FLASH sparing experiments in further translational studies
Epithelial Mitotic Spindle Orientation Regulation: What Role Does PRC1 Component Psc Play?
No full textPolycomb Repressive Complexes (PRCs) are well known for mediating transcriptional repression, but their potential additional roles in development are less understood. Here, we investigate the function of Posterior sex combs (Psc), a core PRC1 component, in regulating spindle orientation during Drosophila embryogenesis. Focusing on the sieve alleles of Psc, which exhibit maternal-effect phenotypes, we originally observed that mitotic spindles in a subset of mutant embryos became misoriented relative to the epithelial plane during gastrulation. To uncover the molecular basis of this phenotype, we examined the localization of Discs large 1 (Dlg1), an apical-basal polarity protein critical for spindle orientation. In sieve mutants, Dlg1 retained its typical lateral membrane localization with subapical enrichment, but its distribution appeared more heterogeneous across the tissue compared to controls. Our preliminary analysis also revealed abnormal apical enrichment of non-muscle myosin II, suggesting defects in epithelial polarity. Our ongoing work aims to further characterize these polarity defects to identify new mediators of Psc function in spindle orientation. This work extends the known roles of PRC1 beyond transcriptional regulation and, given that loss of epithelial integrity is a hallmark of epithelial cancers, may provide new insights into the mechanistic links between PRC dysfunction and tumorigenesis.https://digitalcommons.dartmouth.edu/wetterhahn_2025/1017/thumbnail.jp
Investigating the mechanisms of microbial interactions using a model cystic fibrosis polymicrobial community
No full textCystic fibrosis (CF) airway microbial communities are complex ecosystems where interspecies interactions influence pathogen survival and disease progression. We leverage a CF-relevant in vitro four-species model composed of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica, alongside a microbiome dataset with over 4,000 respiratory samples from publicly available sequencing data of CF patient samples, to explore the dynamics of microbial interactions in CF. On a broader scale, we performed microbial network analysis to examine how the latest modulator therapy, elexacaftor/tezacaftor/ivacaftor (ETI), might influence CF microbial communities. Our analysis revealed a reduction in node connections and positive correlations between the most abundant genera following ETI treatment, which predicts fragmentation of microbial communities across different regions of the respiratory tract. By focusing on the interactions between P. melaninogenica, P. aeruginosa, and S. sanguinis, we found that P. melaninogenica, which cannot survive alone in mucin-containing artificial sputum medium (ASM), relies on P. aeruginosa through a dynamic mechanism of metabolic cross-feeding. We posit that P. melaninogenica ferments mucin into malonate and propionate, which P. aeruginosa respectively metabolizes into acetate and succinate, and provides these metabolites back to P. melaninogenica to support its growth in ASM. A genetic screen identified P. aeruginosa mutants in pathways responsible for propionate and malonate metabolism, which lead to the significant reduction of P. melaninogenica recovery in co-culture. Supplementing these co-cultures with acetate and succinate, rescued the growth of P. melaninogenica in co-culture. In addition to metabolic support, we observed that P. aeruginosa also shields P. melaninogenica from antagonism by S. sanguinis, which consistently inhibits P. melaninogenica growth in co-cultures. We identified reactive nitrogen stress as one mechanism through which S. sanguinis exerts its antagonistic effects. Analyzing these specific interactions will help us generate strategies that can modulate microbial communities to the benefit of pwCF, especially given the observed changes in community structures following ETI therapy
Design and Comparison of Air-core Miniaturized Magnetics
No full textAs magnetics have always taken up a large portion of the total volume of power electronic devices, miniaturization of the magnetics is important. Past works have studied how magnetic components can be miniaturized. In this thesis, we will follow the path of using air-core magnetics at high-frequency and explore how to design good miniaturized magnetic components under certain constraints. We studied toroid, solenoid, staple and spiral air-core inductor geometries; and concentric, end-to-end, interleaved, side-by-side, and stacked transformer topologies. For inductors in a buck converter at 30 \si{\mega\hertz}, solenoid inductors outperform toroid and staple inductors for a wide range of design parameters including footprint area and height. Solenoid inductors can also outperform spiral inductors with enough height. For transformers in an isolated DC-DC converter, the concentric solenoid is the best topology under 1 \si{\milli\meter}^2 area when height is greater than 0.7 \si{\milli\meter}. For stacked spiral transformers with the same area constraint, a pair of ground planes with 1.5 \si{\milli\meter} distance can provide EMI shielding with little performance impact. An isolated DC-DC converter with concentric toroid transformer is designed to achieve high efficiency, good thermal performance, and low EMI. This work presents a method for designing good magnetic components under constraints
INVESTIGATING THE HUMAN FACE PROCESSING NETWORK: INSIGHTS FROM ACQUIRED PROSOPAGNOSIA AND HYPERFAMILIARITY FOR FACES
Full text linkHuman faces provide essential social cues that we interpret rapidly, allowing us to recognize identities, interpret emotions, and gauge familiarity. This thesis explores face processing disruptions in four case studies, each offering new insights into the brain’s face recognition mechanisms.
Chapter one presents Annie, a 28-year-old woman who acquired prosopagnosia (face blindness) following COVID-19. After recovering from the severe symptoms of the infection, Annie experienced significant difficulty in recognizing familiar faces and navigating familiar environments. Testing confirmed her impairment in face recognition but showed her preserved cognitive and basic visual processing abilities. Annie was still able to recognize objects and scenes, pointing to a selective impact on face processing. A survey of individuals with long COVID revealed deficits with visual processing, highlighting a need for further exploration of long COVID’s cognitive and perceptual effects.
Chapter two thoroughly explores face processing abilities in two participants, Alma-Jean and Rose, who acquired prosopagnosia due to extensive damage to their right temporal lobes. Both participants exhibited severe impairments in face identity recognition while retaining the ability to recognize facial expressions, suggesting a dissociation between identity and expression processing. Alma-Jean also displayed intact facial sex recognition. Our findings provide evidence for separate processing pathways for facial identity and expression, as well as facial identity and sex.
Chapter three describes Nell who developed hyperfamiliarity for faces after a severe migraine. Nell experiences false feelings of familiarity with unfamiliar faces, names, and some object categories while retaining accuracy in recognizing actually familiar faces, names, and objects. Her prolonged response times on face tests suggest disruptions in familiarity mechanisms that interfere with processing efficiency.
Together, these cases reveal how distinct disruptions in face processing can stem from varied etiologies and increase our understanding of mechanisms underlying the complex neural systems that support social cognition and recognition
DESIGN AND SYNTHESIS OF CONDUCTIVE METAL–ORGANIC FRAMEWORKS FOR THE DETECTION AND UPTAKE OF TOXIC POLLUTANTS
No full textLayered, conductive metal−organic frameworks (MOFs) are a class of materials with properties that make them ideal candidates for multifunctional applications, including sensing, adsorption, and catalysis. My thesis focuses on the development of triphenylene-based MOFs as multifunctional materials for environmental remediation, gas sensing, and proton conduction, while investigating their structural diversity and deposition on substrates.
Chapter 1 highlights the applications of triphenylene based MOFs.
Chapter 2 explores the use of layered conductive MOFs based on 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) and 2,3,6,7,10,11-hexaiminotriphenylene (HITP); M3(HITP)2 and M3(HHTP)2 (M = Nickel or Copper) for the adsorption and sensing of toxic oxoions, dichromate (Cr2O72−) and permanganate (MnO4−), in water. The study highlights the high adsorption capacities and fast kinetics of adsorption. The MOFs retain structural integrity post-adsorption and can be regenerated and reused. A layer-by-layer (LBL) deposition of Ni3(HITP)2 on textiles further enables the simultaneous detection and capture of oxoions, demonstrating the potential for scalable applications in environmental remediation.
Chapter 3 investigates the development of smart textiles by integrating triphenylene-based conductive MOFs onto cotton substrates using a layer-by-layer (LBL) deposition method. This approach allows precise control over MOF loading and electronic conductivity. Functionalized textiles incorporating Cobalt, Nickel, Copper, and Zinc-based MOFs exhibit significant sulfur dioxide (SO2) sensing and adsorption capabilities, highlighting their dual functionality for sensing and capture in healthcare and environmental protection.
Chapter 4 presents the discovery of two distinct structures of a Manganese-based layered conductive MOF incorporating HHTP. The first structure follows the traditional hexagonal pore geometry of triphenylene-based MOFs, while the second exhibits rectangular pores with water molecules incorporated through coordination and hydrogen bonding. This unique arrangement enables proton conduction within the framework, thereby expanding the scope of these materials for energy storage and transport applications.
Taken together, the chapters of my thesis provide understanding of the applications of layered conductive MOFs, including analyte-MOF interactions, robust methods for MOF growth on cotton textiles, and the exploration of novel MOF structures. These findings highlight the structural diversity and multifunctionality of triphenylene-based MOFs, laying the groundwork for advancing these materials for real-life applications
Restoring the Ahupuaʻa: Community-Based Resource Management and Resilience in Kauaʻi
Full text linkThis thesis analyzes Kauaʻi’s evolving resource management practices, examining the intersections of historical governance frameworks, modern legal systems, and indigenous knowledge. Utilizing the traditional ahupuaʻa system, Kauaʻi’s approach once promoted holistic stewardship across water, land, and energy resources. However, colonial policies, corporate influence, and economic pressures have gradually shifted this framework toward a market-driven model, often prioritizing tourism and development over ecological resilience. Key policy shifts as they fight to return to an ahupua\u27a based model – from the Great Mahele’s introduction of private land ownership to water diversions for plantation agriculture – help examine how these changes continue to shape resource access and environmental sustainability on the island today. Through qualitative fieldwork and interviews with Kauaʻi’s farmers, corporate workers, government officials, and community leaders, I aim to determine whether Kauaʻi is a model for resilient resource governance, offering valuable insights into integrating indigenous knowledge and adaptive management to build sustainable futures amidst ongoing environmental and socio-economic pressures
Human-Centered Engineering Design - Lesson 05 - Prototyping and Feedback-Driven Iteration
No full textPurpose and audience. This is the fifth lesson in a series, “Human-Centered Engineering Design.” These lessons are intended to be integrated into introductory courses on engineering design at the undergraduate level, across any engineering discipline. They are designed to function either as a sequence or as stand alone lessons to fill an existing gap in a course.
This fifth lesson, Prototyping and Feedback-Driven Iteration, introduces two methods for prototyping, looks-like prototypes and works-like prototypes. The lesson also introduces the goals of prototyping and makes a distinction between “ideas,” “prototypes,” and “pilots.” Prototypes are more built-out than a simple idea on a Post-It, but unlike “pilots” they are cheap, fast, and might just be used to communicate and test part of a concept. A key underlying mindset is feedback-driven iteration, the habit of evolving ideas based on feedback from users, experts, and other stakeholders. In more engineering challenges, feedback-driven iteration should be paired with testing in controlled experiments (feedback might come from the natural world or from other humans).
This lesson is designed to follow the previous one on Creativity and Lateral Thinking, but it can be used as a stand-alone lesson as the instructor chooses. Links to our materials for this lesson can be found at this link.
This lesson series was funded by a Dartmouth Library’s Open Education Initiative grant. All materials have a Creative Commons license–they are free to use and adapt for non-commercial purposes with attribution to the authors and Thayer School of Engineering at Dartmouth College.
Structure at a glance:
Slides orienting this lesson and on prototyping rationale- 5 minutes
Works-like prototyping, slides and activity - 25 minutes
Looks-like prototyping, video and activity - 25 minutes
Testing slides and recap - 5 minutes
Discussion / Q&A - As time allow
