Boston University Theses & Dissertations
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This is the master collection of contemporary BU theses and dissertations. We plan to consolidate school- and college-specific collections into this one, and add school- and college-specific metadata to enable users to browse appropriately.
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Item Fabrication strategies to enable rapid prototyping of haptic devices and experiences(2025) Sánchez Cruz, Ramón E.; Boley, J. WilliamThe skin, with its high density of specialized neurons, provides a rich platform for discrete communication through haptic feedback technologies. However, current manufacturing techniques for haptic devices are labor-intensive and require significant technical expertise, limiting accessibility and broader adoption. Existing processes involve specialized PCB software for circuit design, followed by multi-step integration into a soft polymer matrix, resulting in prolonged lead times and limited design flexibility. Furthermore, these devices typically rely on external computing units for controlling tactile patterns and intensity, often decoupling the two. This work proposes fabrication strategies ranging from benchtop 3D printing to hybrid techniques that integrate innovative materials with intuitive interfaces, enabling customizable and accessible haptic devices. We aim to create wearable haptic devices with direct, human-in-the-loop customization of haptic cues. To simplify the creation of haptic feedback devices, we developed a toolkit comprising five wireless, wearable haptic modules that deliver the three most common tactile sensations: vibrotactile, skin-stretch, and probing. These customizable modules can operate individually or together to create multimodal haptic experiences, serving as a platform for rapid prototyping tactile displays. However, despite their accessibility and ease of assembly, the modules remain bulky, rigid, and limited in customization, relying on an off-board computer and technical expertise to function. To create truly body-compliant stretchable haptic electronics, we developed a 3D printed liquid metal (LM) emulsion for wiring that sustains high strains while maintaining electrical connectivity. To fabricate stretchable electronics, the LM emulsion was integrated into a soft polymer matrix through multi-material 3D printing, with manually placed off-the-shelf electronics. The LM emulsion is not conductive upon printing but can be render highly conductive with a single axial strain at low stress (< 0.3 MPa), resulting in activation stresses that are an order of magnitude lower than previous work. The LM emulsion also exhibits a maximum conductivity that is more than 300% higher than that of similar previous work. Its high conductivity and durability under strain make it ideal for stretchable electronics. To integrate the LM emulsion into stretchable electronics, we developed a computer aided fabrication strategy that streamlined the design and production of haptic devices. First, we created an intuitive graphical user interface (GUI) for sketching haptic devices, compatible with direct ink writing. Next, we developed an algorithm to convert circuit schematics into 3D printing commands. This strategy combines direct ink writing with automated pick-and-place of electronics in a single fabrication step. Using this process, we fabricated a wireless, self-powered tactile display comprising a haptic input device and a haptic output device. Together, these devices enable immersive human-to-human interactions by mapping real-time pressure patterns through the input device and generating proportional vibrotactile feedback with the output device. This approach represents a significant step toward enabling rapid prototyping of both haptic devices and haptic experiences.Item Causal investigations of rhythmic electrophysiological mechanisms underlying healthy cognition and disease using transcranial alternating current stimulation(2024) Grover, Shrey; Reinhart, Robert M. G.Learning from favorable feedback is fundamental for adaptive behavior. This learning is hypothesized to be facilitated by high beta-low gamma frequency (20-35 Hz) rhythmic activity, potentially originating from the orbitofrontal cortex (OFC), but no causal evidence currently exists. In Study 1, I tested this hypothesis using electroencephalography (EEG)-guided high-definition transcranial alternating current stimulation (HD-tACS) of OFC beta-gamma rhythms. In a randomized, double-blind, sham-controlled, between-subjects experiment with 60 healthy young adults (mean age 25.8, standard deviation [SD] 5.8 years), I showed that modulation of OFC beta-gamma rhythms selectively modulates reward-guided behavior without affecting punishment-guided behavior, supporting the hypothesis. Obsessive-compulsive (OC) behaviors involve abnormalities in reward processing and OFC activity. If OFC beta-gamma rhythms facilitate reward processing, then their modulation may be a strategy for improving OC symptoms. In Study 2, I investigated this hypothesis in 64 young adults (mean age 23.9, SD 3.8 years) using a randomized, double-blind, sham-controlled experiment. These participants did not have any neuropsychiatric diagnoses but exhibited a wide range of subclinical OC tendencies, as measured using the Obsessive-Compulsive Inventory – Revised (OCI-R; baseline scores: mean 20, SD 10.3; ≥16 indicates moderate OC symptoms). I found that repetitive entrainment of OFC beta-gamma rhythms in 30-minute sessions over five consecutive days rapidly reduced OCI-R scores. Improvements sustained for three months and were stronger for individuals with more severe symptoms at baseline. These findings set the foundation for novel rhythmic neurophysiological theories and therapeutics for OC behaviors. As tACS is an emerging technology, its overall efficacy remains a matter of debate. In Study 3, I examined whether tACS reliably modulates cognitive function by performing a statistical meta-analysis of 102 peer-reviewed studies. I found evidence for improvements in several cognitive domains (such as attention, working memory and long-term memory), with improvements also evident in subgroups of older adults (age > 60 years) and clinical populations. Using meta-regression analyses, I showed the importance of using current flow models and parameters such as modulation intensity and the timing of assessment of cognitive function. These findings suggest the promise of this tool for both causal investigational and translational purposes, and identify avenues for future improvement.Item Three essays on the distributional politics of green energy transition in Europe(2024) Hecan, Mehmet; Perez, SofiaThis dissertation consists of three essays (papers) on the distributional politics of green energy transition in Europe. The first paper contributes to the existing literature on climate finance by arguing that governments may choose to use consumer-funded policies as a way to circumvent the state budget and budgetary scrutiny. The paper also explains why these policies turn into a contentious practice over time even though they were initially seen as a practical way to finance energy transition policies without draining the state budget. The second paper explores why governments handle the distributional politics of consumer-funded policies differently. It argues that when faced with rising costs and opposition, governments respond with different distributive strategies to ensure the political acceptance of energy policies transition by spreading the cost and benefits of green energy transition across different consumer and producer groups such as households, industrial consumers and renewable energy producers. These strategies include economization, redistribution, and compensation. This research explains differences in the mixed use of distributive strategies by governments in Germany and the UK by analyzing the two dimensions of public choice dynamics: i) the partisanship structures of ruling political parties, and ii) the relative strength of organized interests of renewable energy producers and consumer groups. The paper three offers an institutional complementary to the second paper by studying the path-dependent dynamics of green energy transition policies in the context of renewable subsidies. More specifically, it seeks to explain why degression of renewable subsidies is more difficult in some countries than others. Using large-n cross national data and case study analysis, it argues that in countries where political institutions diffuse power over a broader array of actors, both horizontally and hierarchically, it becomes more difficult to roll back renewable subsidies once they are given. The paper shows that in such countries the renewable sector for solar power was better able to defend its interests thanks to their interest representation at different institutional levels, making it more challenging for the government to take back subsidies. This paper also offers a discussion on the advantages of different political institutional arrangements in determining the reform capacity of states and the importance of informal rules in the strength of political institutions.Item The evolutionary history and adaptive significance of UCP1-mediated thermogenesis in primates(2024) Gagnon, Christian Michel; Schmitt, Christopher A.Mitochondrial uncoupling protein 1 (UCP1), a key molecular component of brown adipose tissue (BAT), is pivotal to the process of non-shivering thermogenesis (NST). This dissertation provides a comprehensive investigation of UCP1 gene evolution in primates, spanning three distinct levels of analysis. I first examine the phylogenetic history of UCP1 in 41 primate taxa, in which I observed functional divergence between strepsirrhines and haplorhines with significant structural variation including clade-specific intronic insertions and duplications. This underscores the shifting patterns of directional selection on UCP1 in response to ecological pressures across primate lineages, potentially reflecting thermoregulatory challenges posed by varying body sizes and climatic habitats. I then explore population-level genetic variation in the UCP1 gene of wild savanna monkeys (Chlorocebus spp.), which ~450 kya expanded from equatorial to cold southernmost Africa. I identified several SNPs showing positive selective sweeps, for which derived allele frequencies were primarily associated with the strength of solar irradiance and winter precipitation; this was strongest in a population in the southern coastal belt of South Africa (isolated by the Drakensberg Mountains and the Nama Karoo). I suggest that reliance on sunbathing for warmth coupled with reduced solar irradiance potentially increases thermal stress in this coastal corridor, leading to selection on UCP1 due to increased reliance on NST. These SNPs are predominantly non-coding, suggesting the importance of UCP1 expression as a target of selection. Finally, I developed a novel method for converting archived wild savanna monkey fibroblast cell lines into chemically-induced brown adipose (ciBA). UCP1 expression via immunofluorescence staining, oil-red O stain confirming lipid formation, and mitochondrial activity shown by MitoTracker all indicate successful conversion into ciBA. The success of this method represents a critical step towards the validation of the functional significance of SNPs identified as having undergone recent selective sweeps in wild savanna monkeys. Overall, this research highlights the importance of NST as an adaptive trait in primates, while also underscoring the importance of convergent evolution in UCP1 expression as a vital adaptive response to colder environments in our own genus.Item Speckle decorrelation-based techniques for measuring cerebral dynamics with ultrasound and optics(2025) Liu, Bingxue; Boas, David A.Cerebral hemodynamics and cellular dynamics are crucial for maintaining brain health and function. Dysregulation of these processes is implicated in various neurological conditions, such as stroke and neurodegenerative diseases. Non-invasive imaging techniques, including functional ultrasound (fUS) and laser speckle contrast imaging (LSCI), have shown great promise for monitoring cerebral blood flow (CBF) in preclinical animal studies, offering high spatiotemporal resolution over large field of view. However, both methods face limitations in their ability to accurately quantify physiological parameters. fUS, typically relying on power Doppler signals as an indicator of cerebral blood volume (CBV), is often affected by system noise and motion artifacts, while color Doppler-based fUS is limited to detecting axial blood flow, resulting in incomplete assessments of cerebral blood flow speed (CBFspeed). Similarly, conventional LSCI models assume that speckle dynamics arise solely from blood flow, neglecting the potential for measuring cellular dynamics in brain tissue. To address these limitations, this thesis focuses on applying speckle decorrelation-based methods in both fUS and LSCI to improve the quantitative measurement of brain dynamics. First, we introduce an ultrasound speckle decorrelation-based time-lagged functional ultrasound technique (tl-fUS) for the quantification of the relative changes in CBFspeed, CBV and CBF during functional stimulations. Numerical simulations, phantom validations, and in vivo mouse brain experiments were performed to test the capability of tl-fUS in accurately parsing and quantifying these hemodynamic parameters, demonstrating superior performance compared to conventional Doppler-based fUS techniques. Next, we developed a multi-dynamics laser speckle contrast model that incorporates both fast blood flow dynamics and slow tissue dynamics. To enhance the sensitivity to slow tissue dynamics, we built a short-separation speckle contrast optical spectroscopy (ss-SCOS) system with point illumination and point detection using linear fiber arrays. Finally, an epi-illumination-based wide-field LSCI system was developed to map both fast and slow speckle dynamics. The system was demonstrated in transient and permanent stroke models, indicating slow tissue dynamics as a novel and important biomarker for studying stroke evolution and recovery.Item Advanced quantum structures for infrared detectors(2025) Glennon, John; Bellotti, EnricoType-II superlattices (T2SLs) have emerged as promising alternatives to the more established bulk material systems for infrared (IR) photodetection. This is due to predicted fundamental advantages, such as the tunability of the band gap and theoretically reduced Auger recombination rates. However, the superiority of these materials has not been experimentally realized, prompting the need for further investigation. A bottleneck in the development of improved superlattice (SL) structures and devices is the cost in time and resources required to prototype and characterize these materials as well as incomplete knowledge of the material properties and physical phenomena that characterize these structures. Therefore, the field would greatly benefit from simulation methodologies that enable the development of advanced T2SL materials. In this work, the field of IR photodetection is reviewed highlighting the most common T2SLs structures currently being experimentally implemented. A quantum transport model that includes the necessary physical mechanisms to model carrier transport in these structures will be presented. The results of an investigation on the extraction of vertical carrier mobility, a property important for carrier collection, from quantum transport simulations is presented for an example T2SL. It is demonstrated thatcarrier transport in these structures can be highly coherent. In this case, the apparent mo-bility is suppressed due to ballistic resistance, requiring care when predicting the intrinsic mobility of these materials. The best method of mobility extraction is one that considers the dependence of the resistance on device length. This method was applied to predict the quantum efficiency (QE) in curved focal-plane arrays composed of n-type mid-wave InAs/InAsSb and InAs/GaSb structures subjected to the effects of superlattice disorder and external strain imposed by the curving procedure. It is demonstrated that the external strain has a minimal impact on the QE relative to disorder in both structures suggesting the device design could be viable. Additionally, it was found that large magnitudes of positive axisymmetric strain could result in enhanced hole transport. Finally, a comprehensive investigation is presented that probed for optimized n-type long-wave InAsSb/InAsSb SL structures, a material known to result in low QE devices, for various substrate lattice constants. Several structures were found demonstrating hole mobilities with greater resilience to SL disorder providing potential candidates for future prototyping.Item Impact of waves and storms on salt marsh erosion and sedimentation dynamics(2024) Houttuijn Bloemendaal, Lucila J.; FitzGerald, DuncanSalt marshes are dynamic coastal environments that continuously undergo lateral and vertical changes due to erosion and sedimentation dynamics that are mediated by physical and biological processes. This dissertation focuses on edge erosion and the drivers behind this form of marsh loss, as well as sedimentation of the marsh platform from storms and the potential sources of these sediment influxes. By studying these erosion and sedimentation dynamics in a variety of marshes, this dissertation contributes to our understanding of sediment movement in marsh systems and the drivers of marsh loss and resilience. The marsh edge is vulnerable to wave attack, which can dislodge sediment or induce mass failure through undercutting and destabilizing action of the edge. Vegetation and geotechnical properties affect the erodibility of the marsh edge, and all these factors interact to enhance or mitigate edge erosion and produce certain marsh edge morphologies. The first chapter of this dissertation investigates these different parameters and their relationship to the type and distribution of edge erosion occurring in the Great Marsh, Massachusetts. This work demonstrates that there is no clear relationship among wind fetch, geotechnical properties, and the type of edge erosion observed because of heterogeneity of the marsh. Marsh edges can erode in both exposed and sheltered areas, and the geotechnical characteristics of the marsh edge do not serve as indicators of edge erosion. Parameters and processes beyond those generally ascribed to be the drivers of edge erosion may therefore be responsible for marsh loss. The second chapter takes a closer look at the relationship between waves and marsh shoreline retreat, as the nature of this relationship can help predict marsh loss under varying wind and wave conditions, as well as have implications on the impact of storms on edge erosion and marsh loss. This study shows that there is no universal or generalizable linear relationship between wave power and retreat as previously suggested, but rather the relationships between these parameters are site-specific and are often not linear at all. As a result, in one marsh, storms may have an outsized impact on retreat, while in another marsh more moderate wind-wave conditions may contribute to most of the retreat. Thus, it is important to calibrate these relationships for each marsh to fully constrain marsh loss due to wave attack and predict future marsh erosion. This work further highlights the importance of utilizing statistically robust analyses and regressions to investigate these relationships. Whereas storms contribute to marsh loss via edge erosion, they can also enhance vertical accretion and resilience of marshes to sea level rise (SLR) through storm-driven sediment transport and deposition. Major storms such as hurricanes can provide most of the inorganic sediment delivered to the marsh platform, though the source of these sediments is less understood for southeastern USA. Chapter 3 of this dissertation characterizes foraminifera communities in Hurricane Irma deposits in Sapelo Island, Georgia and compares them with the communities of surrounding sediment reservoirs to investigate the provenance of these storm-derived deposits. The foraminifera in the hurricane deposits resembled the foraminifera found in the surrounding marsh, rather than nearby sediment reservoirs such as tidal flats, channels, and offshore sediments. These similarities between the storm and marsh foraminifera assemblages are attributed to a mix of two processes: resilience of marsh foraminifera and rapid recolonization of these communities in the storm deposits following the passage of Hurricane Irma, and some reworking of marsh sediments into the storm deposits during the hurricane’s storm surge. The study also assesses the utility of foraminifera in identifying storm deposits, which has implications for the sensitivity of foraminifera paleostorm studies.Item The broken book: reading and materializing Middle English literary compilations(2024) Hertz, John J.; Appleford, AmyThis dissertation explores the multifaceted relationship between medieval books, their materiality, and the networks of human and non-human actors that shape their existence. Drawing from New Materialist studies and Bill Brown's "Thing Theory," it examines how medieval readers interacted with texts and material books, acknowledging the intricate web of people and objects involved in their production and reception. By focusing on the materiality of medieval books, this dissertation seeks to unveil the often-overlooked connections between various human and non-human actors involved in book production and reading. Each chapter delves into a specific case study, starting with the Auchinleck Manuscript, an early compilation of Middle English texts and romances. This chapter argues that the manuscript's composite nature reflects and encourages a similar mode of self-fashioning in its readers, linking English identity formation to the compilation of texts. The second chapter explores the Oxford Group Manuscripts and Chaucer's dream vision poems. It investigates how these manuscripts, produced in fascicles, parallel the imaginative process and recombination of sensory data in Chaucer's dream narratives. Chapter three examines the "compilation narratives" framing Thomas Hoccleve's poems, emphasizing their depictions of scribal labor and textual communion. Comparing these narratives to Hoccleve's holographs reveals the intersections between authorial self-fashioning and fifteenth-century bookmaking. The final chapter analyzes Sir Thomas Malory's Le Morte Darthur in its earliest forms, the Winchester Manuscript and William Caxton's printed edition. It argues that Malory's work is fundamentally a compilation, and that Caxton's edition represents a broader shift towards author-centric and commodified books. The chapter also explores the paratextual features of Le Morte Darthur in its manuscript and printed forms to discern the impact they would have had on the reception and interpretation of the text. This dissertation challenges traditional notions of authorship and intentionality in book production, highlighting the agency of material objects and their role in shaping the meaning and reception of medieval texts. It offers new understandings of the dynamic interplay between human and non-human actors within the networks that shape late medieval English book culture.Item The causal impact of user-centered counseling on women's reproductive health outcomes: evidence from Malawi(2024) Kurt, Yunus E.; Fernandez-Val, IvanNearly half of all pregnancies in the U.S. —and comparable numbers worldwide—are unintended, leading to adverse health outcomes for mothers and children, financial constraints and family instability, diminished educational and developmental outcomes for children, and worse labor market outcomes for women. Effective family planning counseling can mitigate these consequences by correcting misinformation and misconceptions around contraceptive methods, and improve overall contraceptive decision-making for women. User-centered counseling (UCC) refines the standard counseling approach by first eliciting women’s contraceptive preferences, then tailoring the session to discuss a subset of methods aligned with those preferences. We conduct a randomized controlled trial in Malawi involving over 700 women, where we evaluate the effects of UCC alongside partner invitation (PI), where women are encouraged to involve their partners in the counseling process. In the first chapter, we study the impacts of both interventions on several outcomes around contraceptive method use dynamics and fertility. We find that women encouraged to involve their partners tended to move from injectables to implants, suggesting a partner-driven preference. However, UCC appears to neutralize this effect. Contraceptive consistency, proxied by the maximum number of consecutive months women use same method or number of months women use any method, was significantly influenced by UCC, fostering more regular use of contraceptives, although it was somewhat mitigated when combined with PI. In terms of fertility outcomes, we observe that UCC seems to reduce pregnancies and births, but when combined with PI, the effect is the opposite. Finally, neither UCC nor PI significantly alter the likelihood of discontinuation. In the second chapter, we explore how women’s preferences over contraceptive methods evolve and whether method uses are concordant with these preferences or not. We first document that preferences vary significantly in both the short and long term. We then observe that both user-centered counseling and partner invitation interventions have minimal impact on aligning women’s contraceptive preferences with their actual usage, both in the short and long term. In the third chapter, we apply two methods to examine the heterogeneous impacts of UCC on a range of family planning outcomes. Firstly, we utilize the Sorted Effects method, which involves estimating and ordering partial effects based on covariates, graphically representing this variation, and also comparing the mean characteristics of the most with the least affected women. Secondly, we adopt the Generic Machine Learning method, suitable for our data’s high-dimensional nature, which helps estimate features (Best Linear Predictor (BLP) and Group Average Treatment Effects (GATES)) of the conditional average treatment effects without relying on predetermined covariates. Nonetheless, our experiment’s power to uncover meaningful heterogeneities in the impact of UCC is limited.Item Population genetics, environmental tolerances, and natural variation in infection frequency of the parasitic anemone, Edwardsiella lineata(2024) Lee, Joanna Claire; Finnerty, John R.Mnemiopsis leidyi, the sea walnut, is one of the most destructive invasive species in the world. The ctenophore has broad environmental tolerances, a high rate of zooplankton consumption, extensive regeneration capabilities, and extraordinary fecundity. While there is a substantial body of research on M. leidyi’s role as a predator of zooplankton and as prey to the ctenophore Beroe ovata, only a few studies have examined M. leidyi’s relationship with its parasite, the lined sea anemone, Edwardsiella lineata. Previous research has shown that E. lineata may be exerting top-down control on the ctenophore in areas where present along the Northwestern Atlantic; the parasite has not established a population in M. leidyi’s invasive range. While a handful of studies have examined the ecological relationship between host and parasite, all studies have taken place at the same site, Woods Hole, and some failed to report key parameters such as host size and parasite number. More detailed examinations of this relationship are necessary to understand the parasite’s potential for controlling host populations in both native and European waters and how this control may be affected under various abiotic conditions. In my dissertation I performed three studies exploring the ecological relationship between M. leidyi and E. lineata. First, I profiled the variation in infection frequency in populations in Massachusetts and Rhode Island and examined the relationship between host size, parasite load, and seasonality. My results show that in natural populations, infected ctenophores are larger than non-infected conspecifics. The pattern of infection was also highly variable across sites and time. Second, I tested the temperature and salinity tolerances of E. lineata larvae to determine if certain conditions, such as those found in the invasive range of M. leidyi are refuges for the host from parasitism. My data indicate that temperature and salinity conditions alone will not prevent E. lineata from establishing a population in Europe. However, developmental outcomes and survival are both reduced at lower salinities and higher temperatures. Finally, using a RAD-seq approach I profiled population connectivity between juvenile parasite and adult polyp populations of E. lineata in Massachusetts and Rhode Island. E. lineata populations were found to be panmictic like host M. leidyi, though some structuring appeared between parasite and polyp populations. While asexual reproduction was seen in polyp mats, none was found within hosts.These data help contribute to the wider body of research on the M. leidyi-E. lineata system and also provide data on sea anemone genetic structure, which is currently understudied. I suggest that future studies examine cues for asexual reproduction in both the parasite and host and profile infection frequency and genetic structure in populations further south.Item Caregiver-led exposure therapy: evaluating a novel storybook intervention for young children with anxiety(2024) Darling, Laura Nelson; Pincus, DonnaRecent research has highlighted the importance of developing accessible, low-intensity interventions for child anxiety. Bibliotherapy, which utilizes books and written materials as a form of therapeutic intervention, can increase access to evidence-based treatment approaches at an extremely low cost. The present study employs a brief storybook intervention (The Bravery Book) to guide caregivers and children (ages 4-7) to complete personally-relevant anxiety exposures from home, without therapist support. Participants included forty children (15 males, Mage = 6.1, SD = .97) identified by caregivers as exhibiting elevated symptoms of fear and/or anxiety.Study 1 examined the feasibility and acceptability of the storybook intervention. Results showed that all caregiver-child dyads in the experimental group (n = 20) read the storybook at least once, and a majority continued to utilize it during the 6-week study timeframe. On average, caregivers provided moderate to high ratings on indices of satisfaction with the storybook intervention. Results suggest that caregivers of children with less severe anxiety were more satisfied with the storybook than those with more severe anxiety. Overall, findings support the feasibility and acceptability of the storybook intervention for caregivers and young children with anxiety concerns. Study 2 evaluated whether the storybook improved children’s and caregivers’ knowledge about anxiety and exposure practices, and increased their preference for exposure-based approaches. Caregivers in the experimental group reported significantly more knowledge about anxiety and exposures by the end of the study relative to the waitlist control group. Overall, caregivers in both groups held favorable views of exposure at the start of the study. Contrary to our hypotheses, caregivers’ attitudes toward exposure and children’s approach- and avoidance-based responses to anxiety case vignettes did not significantly differ by condition. Study 3 examined whether the storybook intervention resulted in exposure engagement and decreased anxiety-accommodating caregiver behaviors. The storybook intervention resulted in the development of personalized exposure hierarchies and exposure engagement among a majority of dyads in the experimental group. Caregivers’ anxiety-accommodating behaviors significantly decreased as a function of time across both the experimental and waitlist control groups, but contrary to our hypotheses, the effect of condition was not significant. Though this study was limited by a small sample size, findings suggest that the storybook is an acceptable intervention that holds promise for improving caregivers’ and children’s knowledge about exposures and facilitating exposure engagement.Item Structural plasticity of NF-kappaB essential modulator demonstrates the active regulatory roles of scaffold proteins(2024) DiRusso, Christopher; Gilmore, Thomas D.Within the chaos of intracellular signaling pathways, scaffold proteins serve as the control boards to organize the comings and goings of a variety of signals and proteins. There are over 300 known scaffold proteins, which act as switchboards that lessen this chaos of the cellular “soup” and enable proper cellular responses. While the terms scaffold, adaptor, docking, and anchoring protein have sometimes been used interchangeably, this dissertation focuses on scaffolds as a distinct class of proteins that are central to enhancing signaling cascades, have multiple interaction domains to facilitate higher order complex formation, and are highly conserved. In addition, scaffold proteins are not simply inert or passive platforms. Rather, there are multiple examples of scaffolds that, while catalytically inactive, are dynamic in their mechanism of action. Studying these dynamic roles is critical to our understanding of signaling cascades and how signaling-related disease states occur. NF-κB Essential Modulator (aka NEMO or IKK gamma) is a scaffold protein that has a pivotal role in the NF-κB signaling pathway. In this dissertation, NEMO is examined both for its changes in activity upon mutation and the mechanical/structural effects of mutations within a highly conserved central region termed the intervening domain (IVD). The IVD of NEMO is essential for proper function of the protein and for the coordination of phosphorylation of the inhibitor IκBα in the activation of canonical NF-κB pathway. The proper structural organization of NEMO is required for cytokine-induced activation of IκB kinase (IKK), and the impact that the IVD has on this structural organization is demonstrated. Mutations within the conserved IVD core are detrimental to the activation of the canonical NF-κB pathway and reduce the ability of NEMO to form ubiquitin-induced liquid-liquid phase separated droplets in vitro. The effects of the IVD mutations also correlate with a reduced ability of NEMO to form signal-induced puncta in vivo. Thermal and chemical denaturation studies of truncated NEMO variants indicate that the IVD affects the stability of the full-length NEMO molecule, due to conflicting structural demands of this region on upstream and downstream domains. This conformational strain in the IVD mediates allosteric communication between N- and C-terminal regions of NEMO. Overall, these findings support the hypothesis that the IVD of NEMO participates in signal-induced activation of the IKK/NF-κB pathway by acting as a mediator of conformational change in NEMO. These findings demonstrate the importance of conformational change for scaffold protein function and provide new information about how clinical mutations in scaffolds can affect function and can serve as targets for therapeutic intervention.Item Synthesis, characterization, and reactivity of niobium perfluoropinacolate complexes(2024) Del Rosario, Cathlene Nicole Balacanao; Doerrer, Linda HSix new niobium complexes supported by bidentate dianionic perfluoropinacolate, ({OC(CF3)2}2)2-, denoted as pinF, have been synthesized and fully characterized: [Nb(NMe2)(NHMe2)(pinF)2] (1), (Me2NH2)[Nb(pinF)3] (2), {K(THF)3}[Nb(pinF)3] (3), {K(THF)3}2[Nb2(μ2-O)2(pinF)4] (4), {K(18C6)(THF)2}2[Nb2(μ2-O)2(pinF)4] (5), and {K(MeCN)7/3}3[Nb2(μ2-O)2(pinF)4] (6). Complex 1 exhibits fluxionality of monodentate and bidentate ligands; various methods of recrystallization repeatedly provided solid-state evidence of a cis isomer (1-cis), while VT 1H and 19F and 2D 19F NMR provided solution-state evidence of a trans isomer (1-trans). The twist angles of 2 and 3 range from 28.87° to 32.17°, classifying the complexes as an intermediate between trigonal prismatic and octahedral geometry. The 18-crown-6 encapsulation of K+ countercations of 5 elongate the Nb–O bond distances compared to those of 4; the K+ countercations of 4 exhibit multiple K⋯F and K⋯O interactions with the four chelating pinF ligands. Each of the soluble, {Nb5+(pinF)} complexes exhibit solution-state 93Nb NMR resonance features that support previous 93Nb NMR measurements made with static/MAS methods. The heteroleptic complex 1 was found to selectively dehydrate 2° and 3° alcohols to alkenes, historically observed by analogous insoluble niobium pentoxide (Nb2O5) and niobic acid (Nb2O5⋅nH2O). The dehydration of 1-phenylethanol to styrene under mild conditions exhibited no evidence for polymerization to styrene. Both 2° and 3° alcohol dehydration studies gave no evidence of condensation products. The transformation of 1 during dehydration was proposed from 1H, 19F, and 93Nb NMR spectroscopy. Cyclic voltammetry was used to determine the electrochemical reduction and oxidation potential of Nb5+/4+ in the all-O-donor environments of 2, 3, 4, and 5. Despite observing E½ = -1.303 V of 2 and E½ = -1.263 V of 3 (both in MeCN), the Nb5+ center could not be reduced in the tris-pinF complex. One-electron reduction of the {Nb2(μ2-O)2(pinF)4} dimer formed the mixed-valent complex {K(MeCN)7/3}3[Nb2(μ2-O)2(pinF)4], which was the first crystal structure of Nb in all-O-donor environment: (1) in a formal oxidation state lower than 5+ and (2) in a coordination number lower than eight. The solid-state SCXRD and in silico DFT data point to 6 as a Robin-Day Class II dimer, and additional experiments with the dimer in solution for UV-Vis and Evans method suggest electronic communication between the two Nb centers.Item Wild science: radical politics and rejected knowledge in nineteenth-century fiction(2024) Chapnick, Max Laitman; Lee, Maurice; Craciun, AdrianaThis dissertation examines how writers of fiction in nineteenth-century America and Britain employed the discourse of pseudo-science, what I call rejected knowledge, to challenge the consolidating power of science and the state. During the mid- to late century, practitioners of mesmerism, spiritualism, and African American conjure not only captured the imaginations of millions, they also participated in radical social movements such as abolitionism, feminism, socialism, and late-century anti-racism and anti-imperialism. While historians of science have taken these knowledges more seriously, this dissertation considers formal, literary questions that historians do not address. I begin with Charles Dickens’s relationship with Michael Faraday and the mesmerist John Elliotson to show how his engagement in electromagnetic field theory led to a reform-minded but politically-restrained aesthetic. Next, I discuss the radical possibilities of Louisa May Alcott’s gothic stories—including work I have newly identified. Then I turn to conjure in the early Black novel, and the contradictory politics, science, and fiction of Martin R. Delany. I conclude with Pauline Hopkins’s genre-bending thrillers as arguments against racist disciplinization. Together, these chapters tell the story of a hardening scientific establishment and the roaring radicals who harnessed the literary potential of rejected knowledge against it.Item Memorization and privacy in learning: fundamental limits and new algorithms(2024) Brown, Gavin R.; Smith, Adam D.Data analysts often work with records pertaining to specific individuals; the results of their analysis, by design, depends on the details of the individuals' data. This dependence may occur in surprising ways and have negative consequences. In this dissertation, we investigate the dependence of learning algorithms upon individual inputs through the lenses of memorization and privacy. We reveal fundamental limits on when memorization is inescapable, experimentally demonstrate the vulnerability of conventional learning methods, and design new algorithms with rigorous privacy guarantees. We present learning tasks, stylized variants of image classification and sequence prediction, and prove that any high-accuracy learner for these tasks must encode a huge amount of information about the training data. We show that much of this stored information is irrelevant to the learning task, taking the form of noise or useless features. For some tasks, we prove a further result: high-accuracy learners need to memorize almost the entirety of a large number of input examples. We identify similar phenomena in a streaming setting, where examples arrive one at a time. For natural sparse hypothesis classes, such as sparse linear classification over a polynomial kernel, we prove that nontrivial algorithms with few samples need large memories. This lower bound smoothly decreases as the sample size increases: with a longer stream, less memorization is required. Moving beyond theorems, we investigate whether this stored information can be extracted by an attacker. We show that standard classifiers may be vulnerable to data reconstruction attacks. In our experiments, the vulnerability is extreme, with an attacker able to recover high-fidelity copies of a large fraction of the training data. Finally, we approach data privacy from the other direction: how can we prevent individual data points from having a large effect on the output of an analysis? We design new differentially private algorithms for statistical estimation. Given samples from a subgaussian distribution, our algorithms accurately estimate the distribution's mean and covariance. These algorithms have low overhead relative to nonprivate estimators, requiring similar sample sizes and computational resources.Item Dissecting molecular consequences of opioid use disorder using single-cell RNA sequencing(2024) Cleary, John Patrick, Jr.; Cheng, Christine; Henderson, AndrewThe opioid epidemic is a global public health threat that affects countless individuals worldwide. These issues were precipitated by the significant, unchecked explosion of opioid prescriptions starting in the late 1990’s, leading to a drastic increase in opioid overdose deaths. While prescription rates have been curbed in recent years, the overdose consequences of over-prescription have continued to have consequences to this day. Opioid drugs exert their strongest effect in the central nervous system (CNS), which can be considered the “point of action” for these compounds, but research has also shown that these drugs have an impact on the behavior of cells in the peripheral immune system, which is referred to as the “point of entry”. Given the personal and social consequences of this classification of drugs, it is imperative to characterize the molecular consequences of said drugs; not only to describe the effects these drugs have on the body, but also to identify potential molecular targets for therapeutic intervention. With this goal in mind, the impact opioid drugs have on both the immune system and neurological reward system of opioid-dependent individuals was examined, using both humans and rodents. Peripheral blood mononuclear cells (PBMC) and tissue from the Nucleus Accumbens (NAc) of humans experiencing opioid use disorder (OUD) were examined, comparing them to individuals who were opioid-drug naïve. Rodent models of opioid addiction were also examined both to validate results from our human-participants, and to explore the temporal dynamics of these data. Our results indicate that opioid exposure leads to significant alterations to gene expression in both immune cells and the NAc, with significant consequences for the individuals with substance use disorder. In the peripheral immune system, disruptions to the ability of the body to defend itself from viruses were observed, likely driven by opioid crosstalk with the Toll-like receptor (TLR) pathway. By utilizing an in-vitro opioid exposure paradigm, it was further found that these alterations are fast-acting, with our previously identified perturbations occurring as quickly as 3 hours post-drug exposure, as assessed by both RT-qPCR and single cell RNA sequencing. In neurons of the NA of people with OUD differential alterations were found for synaptic activity, with interneurons gaining pro-synaptic gene expression and medium spiny neurons (MSN) losing expression of these genes, while increasing expression of genes associated with the primary cilium. In glia a consistent elevation to immunoreactive gene programs was observed, with a particular association with genes that have previously been shown to be connected to neurodegeneration. A cell-type-agnostic increase in expression of genes connected to energy metabolism was also found, presenting in parallel with an endothelial-cell-associated perturbation to gene expression programs controlling the integrity of the blood-brain barrier. These results were recapitulated using immunofluorescence (IF) in an in-vitro model of the neuronal microenvironment at the blood-brain barrier, indicating that our transcriptional results are borne out at the protein level. Examination of rodent samples subjected to an opioid addiction simulating protocol, with timepoints associated with drug intoxication, drug withdrawal, and long-term abstinence from drug, implicated both drug withdrawal and abstinence as being predominantly tied to the phenotypes identified in our experimentation with human tissue rather than active intoxication, suggesting removal of drug as the predominant driver of biologically relevant changes to gene expression. Given the overall societal consequences of opioid drug exposure, these experiments may lead to a greater understanding of the molecular underpinnings of OUD, while lending themselves to future therapeutic interventions to prevent the propagation of OUD-related morbidities.Item Developing high-speed surface-enhanced Raman bioimaging platforms(2024) Cheng, Ran; Yang, ChenSurface-enhanced Raman scattering (SERS) is an emerging technique with great sensitivities gained from plasmonic enhancement and many advantages inherited from Raman spectroscopy, including direct detection of the intrinsic molecular fingerprint spectroscopic information from diverse molecules, superior multiplexing capabilities due to narrow Raman bandwidths, high photostability of SERS signals, and low background from biological tissues and water. Therefore, SERS imaging has been extensively utilized as a powerful bioimaging platform to visualize biocomponents spanning from biomolecules to entire organisms, enabling broad biomedical applications such as observing subcellular or cellular structures, mapping intercellular connections, probing tissue complexities, and in vivo imaging of organs or detection of tumors, etc. Even though SERS has successfully demonstrated its capabilities as a versatile bioimaging platform through many exciting biomedical applications, SERS imaging suffers from a main drawback by presenting a relatively slow imaging speed of typically 1 to 10 seconds per spectrum, which largely limits its applications such as probing fast cellular dynamics or large-area mapping of biological tissues. To address the above challenges, we devoted our efforts in developing high-speed surface-enhanced Raman-based bioimaging platforms. Firstly, we developed gap-enhanced gold nanodumbbells that presented excellent SERS performances as ultrabright SERS nanoprobes to benefit high-speed SERS imaging. We successfully achieved single-particle detection of individual gold nanodumbbells with an imaging speed as fast as 0.1 seconds per spectrum. Secondly, by carefully evaluating the optical mechanism of SERS, which is a surface-enhanced spontaneous Raman process, we were inspired to develop surface-enhanced coherent anti-Stokes Raman scattering (SE-CARS) spectroscopy. The introduction of the coherent Raman process increased the imaging speed by at least 2 orders, enabling us to achieve single-particle SE-CARS detection within 1 millisecond per spectrum. Lastly, we developed the wide-filed surface-enhanced coherent anti-Stokes Raman scattering (WISE-CARS) microscopy that enabled parallel collection of over 1 million spectra within 1 second for cellular bioimaging and biomolecule detection. Through strategically improving Raman imaging speed step by step by a combination of sophisticated Raman nanotag design, the introduction of coherent Raman spectroscopy, and advanced instrumentation development, we successfully demonstrated that an overall imaging speed increase by nearly a million times over SERS could be achieved. The development of high-speed surface-enhanced Raman bioimaging platforms would open opportunities for more fascinating biomedical applications where rapid imaging speed is strongly required.Item Shaping ideal societies: Plato and Hobbes on family and education(2024) Erez, Omer; Sreedhar, Susanne; Gasser-Wingate, MarcThis thesis critically examines Plato's and Hobbes' perspectives on the ideal family structure and educational systems within the broader context of their societal frameworks. First, I deconstruct Plato's ideal family model. I then illustrate his ideal system of education in accordance with his societal goals. Second, I examine Hobbes' viewpoint on the same topics of family and education. Finally, I do a comparative analysis that juxtaposes the familial and educational institutions proposed by Plato and Hobbes. Through this examination, the thesis argues that Plato's holistic approach to family and education proposes a more compelling framework for achieving societal transformation, as opposed to Hobbes' more authoritarian stance, which prioritizes obedience and conformity over individuality and the overall enlightenment of the person.Item Choosing obligation: values and practice in a liberal observant Jewish community(2024) Ash, Ellie; Ammerman, NancyThis dissertation explores how American Jews who are both deeply engaged with rabbinic tradition and committed to liberal ideals relate to different forms of cultural and religious authority. It is based on participant observation, interviews, and an ethnographic survey that I conducted in a socially liberal, traditionally observant Jewish congregation called Minyan Kol Rinah. Members of this congregation took for granted many of the assumptions of contemporary cultural liberalism, expressed especially in progressive social values and a humanistic ethos. Against this background, they engaged self-consciously with the rabbinic discursive tradition. Most chose to obligate themselves to Jewish law (halakha), which they encountered not as fixed custom but as a dynamic, contested jurisprudential system. I argue that despite its traditionalism, Minyan Kol Rinah's religious culture is part of a broader phenomenon of religious liberalism in the United States. Minyan Kol Rinah was a partnership minyan, a 21st century innovation which allows more participation in public worship by women than conventional Orthodox synagogues. Minyan Kol Rinah bridged the Orthodox and non-Orthodox communities, and should be considered part of a “liberal observant” Jewish religious network that crosses denominational boundaries. This study uncovers the complex ways Jewish law functions in lived observant practice. It explores congregants’ pragmatic negotiations with a complex variety of sources of authority, including texts, public rabbinic conversations, rabbinic advisors, social models, and internalized moral commitments. I argue that liberal observant Jews typically experience Jewish law as a reified “external authority” which is partly independent of the rulings of contemporary rabbis. Kol Rinah participants were both social and theological liberals. Humanism, that is, the ethos that prioritizes worldly human welfare and autonomy, was a common thread of their social and theological liberalism. In religious cosmology, humanism appeared in the way participants insisted on respect for individual choices, conceived of ethics and social justice as the essence of religion, and approached Jewish scripture and symbols from a historicist, relatively disenchanted perspective. Congregants engaged deeply with rabbinic tradition through liberal frameworks, showing that “liberal” and “traditional” are not opposites. This study contributes an analysis of how different forms of authority, including religious law, work in practice in the lives of laypeople. It also shows the analytic importance of considering different modes of cultural authority, such as the difference between codified teachings and taken for granted “common sense.” Doing so helps us understand the complex ways people draw on and combine multiple sources of authority as they construct their religious lives.Item Ground- and satellite-based observations of column nitrogen dioxide: instrument performance, column-to-surface relationships, and the role of meteorology in coastal urban environments(2024) Adams, Taylor Jonathan; Geddes, Jeffrey A.Nitrogen dioxide (NO2) is a criteria air pollutant that is deleterious to human health and the environment, but characterizing its distribution is challenging. This challenge arises from its abundant and heterogeneous sources, short lifetime, and the limited spatial extent of surface monitoring networks. In lieu of comprehensive surface monitoring, space-based retrievals of NO2 abundance may address gaps in our understanding of its spatiotemporal variability. Space-based observations of NO2, however, have coarse-resolution sensors, requiring well-constrained inputs, and until recently have only collected one observation per day (at most), limiting their utility for characterizing diurnal variability or intra-urban heterogeneity. Throughout this dissertation, I constrain the precision of ground- and space-based remote sensing instruments dedicated to retrieving NO2 abundance, as well as explaining the spatiotemporal variability of NO2 to provide new insights relevant to urban air quality. Chapter 1 of this dissertation explains the motivation for this dissertation in more detail. In Chapter 2 of this dissertation, I quantify previously unexamined aspects of the diurnal precision of ground-based spectroscopic column NO2 observations using a high spatiotemporal resolution model of the 2013 DISCOVER-AQ campaign domain around the Houston, TX area. Pandora is a ground-based instrument commonly used to observe NO2 columns in the atmosphere. Networks of these instruments are distributed throughout the world, and their precision and accuracy make the instrument favorable for observing the spatiotemporal variability of NO2 and validating satellite instrument NO2 observations. Pandora-derived NO2 observations are often considered implicitly precise relative to satellite observations, thus motivating this evaluation. With this model I developed an instrument viewing “operator” to simulate the Pandora instrument’s operation. This operator creates synthetic direct-sun (DS) differential optical absorption spectroscopy (DOAS) columns which, when compared with modeled overhead columns, reveal that urban heterogeneity results in late-day (4-6 pm, LT) observations being less precise than previously estimated. In Chapter 3 of this dissertation (Adams et al., 2023) long-term collocated surface and column NO2 observations at Boston University were used to understand drivers of total column NO2 variability in a coastal urban setting. I found that variations in column and surface NO2 abundance were governed by different processes. The temporal variability of NO2 column density was highly dependent upon meteorology, while concentrations of NO2 at the surface were more dependent upon surface emissions patterns and boundary layer entrainment. I found that the apparent equal mixing height of NO2 plumes within the boundary layer were not sensitive to prevailing meteorology or boundary layer stability. Additionally, I found that the sea breeze fostered uniquely large temporal variations in column NO2. I demonstrated that sea breeze conditions challenge the ability of satellite-derived column NO2 observations to accurately characterize day-to-day variation. In Chapter 4 of this dissertation, I use long-term measurements of Pandora-derived total column NO2 at Boston University, Blue Hill Observatory (Milton, MA) and Harvard University. This long-term record confirmed that variation in temporal gradients in column NO2 observed in chapter 3 correspond to spatial gradients. Differences in column NO2 between sites as a function of time of day allowed us to infer the scale and formation of spatial column NO2 gradients. Finally, I evaluated to what extent satellite-derived column NO2 retrievals are capable of interpreting emissions differences across time and space. Generally, the TROPOMI satellite instrument overpasses struggled to characterize changes in column NO2 gradients across the Boston and Harvard University measurement locations between 2020 and 2021 relative to Pandora. However, TROPOMI resolved differences in the distributions of NO2 across urban-suburban scales that were not as obvious in the Pandora measurements. My results suggest that this difference in strengths at various scales is a result of the Pandora’s sensitivity to near-field emissions perturbations, in contrast with TROPOMI’s satellite footprint method which averages across larger-scales. Chapter 5 of this dissertation summarizes the conclusions from Chapters 2, 3, and 4 and provides suggestions for future investigators.