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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Sailors and slaves on the wood-cutting frontier: archaeology of the British Bay settlement, Belize
(Boston University, 1994) Finamore, Daniel R.
This research focuses upon the first 100 years of occupation of the British Bay Settlement (Belize), a period characterized by large-scale transformation from an egalitarian maritime society to a mainstream British colonial society. Toward the end of the seventeenth century, small groups of maritime laborers seeking alternatives to their arduous occupations began settling in Spanish territory along the southeastern coast of the Yucatan Peninsula and cutting logwood for the European dyeing industries. In the sparsely inhabited forest, the settlers created a highly collective society based on a system of rules and values that had evolved among shipboard communities of Atlantic working-class mariners in response to their dangerous work environment, low status in a hierarchical economic structure, and social isolation from mainstream European culture. By the late eighteenth century, a socially stratified settlement utilizing a large slave-labor force had evolved with a colonial economy oriented toward cutting and exporting mahogany. Although both the early and later communities were characterized by seasonal encampments in remote up-river locales occupied by socially marginalized and economically disenfranchised populations, data show that there were few actual similarities between the two divergent social and economic systems. A program of documentary research and archaeological survey undertaken in the New and Belize River valleys located and investigated an array of wood-cutter camps of the eighteenth and early nineteenth centuries. Seventeen historical-period sites were located and investigated through surface collection in the New River valley, many of which related to slave-based mahogany extraction. Excavations were undertaken at two Belize River valley locales: the barcadares was an early eighteenth-century community of independent logwood-cutting mariners, and is the earliest identified British settlement in Belize; Convention Town was a community of slave-owning wood cutters who evacuated the Mosquito Shore in 1787. Documentary analysis of maps, censuses, and accounts of travel is integrated with archaeological analysis of material culture from the wood-cutting camps in order to investigate, compare, and provide contextually-based explanations for the geographical patterning and social functioning of the settlement during the divergent eras of logwood and mahogany extraction.
Toward a transformational pedagogy for system-affected Muslims in America
(2025) Abdur-Rahman, Taymullah; McCarty, James
This thesis proposes a transformational pedagogy for system-affected Muslims in America. System-affected Muslims are Black people who have been adversely affected by one or more public systems in the United States. As a result, they are often excluded from participating in the larger Muslim cultural and intellectual narrative. Combining evidence from academic research, Islamic law, and teaching philosophies from modern educational theorists, I identify three fundamental problems that contribute to this exclusion: lack of access to Islamic culture, misrepresentation of Black identities in sacred scriptures, and the absence of practical Quran-inspired daily application. This thesis puts forward a way of learning and practicing Islam that makes the tradition more accessible, more representative, and more practical for system-affected Muslims in the United States.
Conservation impact assessment and SAR forest cover mapping in the Colombian Andes
(2024) French, Emily Dawson; Nolte, Christoph
This thesis addresses research questions from two distinct yet complementary fields—conservation science and remote sensing—through a case study in the Colombian Andes. In Chapter One, we explore the impact on forest cover of the largest and longest-running public land acquisition (PLA) program in the tropics between 2000 and 2021. Using matching and Difference-in-Differences with multiple time periods we find that as of 2021 there has been a 3.5% increase in forest cover on protected parcels and that impact increases for at least 10 to 12 years post-treatment. We also find that impact varies significantly by factors like slope, accessibility, and department. In Chapter Two, we attempt to improve the forest cover data used in Chapter One by integrating synthetic aperture radar (SAR) observations from Sentinel-1 for areas where persistent cloud cover precludes the use of optical data. We find encouraging evidence to suggest that SAR data can be used with the continuous change detection and classification algorithm to detect forest change in topographically-complex regions, but conclude that accuracy improvements and widespread workflow adoption are dependent on the accessibility of high resolution digital elevation models and improved radiometric terrain correction for Google Earth Engine.
Pretrial detention and the long mouth of incarceration
(2024) Rhoten, Kimberly; Miller, Sarah
The practice of pretrial detention, wherein individuals are incarcerated prior to their trial without conviction, represents a significant and growing phenomenon in the United States, raising profound legal, social, and ethical concerns. This paper explores the multi-faceted impacts of what this paper terms "unconvicted incarceration," a critical but underexamined aspect of the American penal system. Drawing from a wealth of sociological and legal theories, as well as empirical studies, the analysis reveals that pretrial detention is not merely a neutral, administrative measure but a form of punishment that perpetuates systemic inequalities and exacerbates the vulnerabilities of already marginalized populations. This paper examines the socio-legal dynamics of unconvicted incarceration through the lenses of total institutions, the pains of imprisonment, and management of the so-called "offensive rabble class," demonstrating how pretrial detention mirrors many of the punitive aspects of convicted incarceration despite the absence of a formal conviction. By integrating jurisprudential and sociological perspectives, this analysis highlights the constitutional dilemmas and public policy challenges posed by the practice, arguing for a critical reassessment of pretrial detention's role within the broader penal landscape. This research not only contributes to academic discourse but also engages with pressing public policy debates, aiming to inform future reforms that address the complexities of pretrial detention and its profound implications for justice in America.
Philosophy of biodiversity: conceptual and practical issues in measurement, data, and conservation
(2024) Bocchi, Federica; Bokulich, Alisa N.
This dissertation investigates the scientific practices involved in biodiversity conservation at the intersection of the philosophy of measurement, the philosophy of data, and the literature on values in science. With a focus on the epistemology, methods,and ontology of measuring biodiversity within the context of conservation science, it aims to develop a socially relevant and socially engaged philosophy of science. Chapter 1 challenges ”Biodiversity Skepticism,” which dismisses the usefulness of the concept of biodiversity due to the proliferation of heterogeneous, non covariant measurements. Instead, drawing from Norman M. Bradburn, Nancy L. Cartwright, and Jonathan Fuller’s model of the measurement process, I argue for understanding the pluralistic nature of conceptualizing complex measurands. In Chapter 2, I address the need for a proper justification of the claim that we are in a biodiversity crisis by analyzing the conceptual and data incommensurability between contemporary biodiversity and paleodiversity. Building on Carlos Santana’s ideas, I propose solutions for obtaining robust inferences about the status of environmental crises. Chapter 3 challenges the slogan implicitly endorsed in evidence-based conservation that ”the bigger the data, the bigger the evidence,” highlighting the complexity of turning data into evidence through an examination of the IUCN’s redlisting process. I contend that evidence relies on a complex infrastructure made of data communities and evidential standards, and undermine the facile equating of data with evidence. In Chapter 4, I counter the contention that performance metrics in conservation are value-neutral, using the philosophical framework of ”critical metrology.” This section exposes the fallacy of measurements’ inherent value neutrality and addresses the contribution of conservation science to ”scientific colonialism.” I also propose potential solutions for fostering an ethical and epistemically stronger conservation agenda. Chapter 5 concludes by going back to the measurement theory used to account for biodiversity measurement, and shows how this context reveals the ways in which Bradburn, Cartwright, and Fuller’s theory of measurement needs to be amended. It also sketches an adequacy-for-purpose view to evaluate measurements and elaborates on some implications of this view in relation to measurement validation and the irremediable value-ladeness of measurements. This dissertation offers novel philosophical insights into the theoretical and practical complexities of measuring biodiversity that is valuable to biodiversity scientists, offering a space for building actionable knowledge at the intersection of philosophy and conservation science.
Domain invariance for semantically consistent image manipulation
(2024) Bashkirova, Dina; Saenko, Kate
Image manipulation is a fundamental task in computer vision, spanning its range of applications from domain adaptation and data augmentation to visual content creation. At the root of the task lies two equally important goals -- generating highly realistic and diverse images and preserving the aspects of the input image not related to the desired edit. In this thesis, we explore the latter goal, answering the questions: what can be considered a semantically correct image manipulation, and how to evaluate it? given unpaired examples before and after the edit, can a generative model infer what aspects of the input we aim to preserve, and which we want to manipulate? what are the necessary conditions that allow us to guarantee that manipulation preserves the semantics? and many more. This thesis ties semantic consistency to the problem of disentanglement, formulating it as disentangling the domain invariant factors of variation -- aspects shared across the examples before and after manipulation, which allows a more rigorous and systematic approach to solving the task. We illustrate the advantages of disentangling the domain-invariant features for semantically consistent mappings on various image editing tasks, including general unpaired image-to-image translation, sketch-to-photo translation and object relighting.
Investigation of the pyruvate: ferredoxin oxidoreductase and its redox partner, ferredoxin
(2024) Bonitatibus, Sheila C.; Elliott, Sean
On a global scale, Fe–S clusters (among other essential redox cofactors, such as hemes, flavins, or amino acid residues) drive the core metabolic reactions of life by transporting electrons through a suite of redox-active enzymes—the oxidoreductase superfamily (Fuchs, 2011). On a per-active-site basis, these enzymes are the most efficient catalysts for several chemical reactions crucial for renewable energy (storage and usage); thus, understanding their inner workings is paramount for developing alternative, green technologies (Reda et al., 2008; Wang et al., 2014). Therefore, this dissertation examines the mechanistic principles of one class of enzyme catalyst bearing Fe–S clusters, the 2-oxoacid:ferredoxin oxidoreductase (OFOR) enzyme superfamily. Although OFORs are considered reversible enzymes, they appear to have an inherent bias toward either the reductive or oxidative chemistry, often believed to reflect the native function of the enzyme (Li et al., 2016). However, revealing the factors that influence an enzyme’s directionality has been difficult. Therefore, by examining a series of unique OFOR enzymes and mutants, this dissertation addresses the following questions: Given the diversity of OFOR enzymes (i.e., cofactor content, number of subunits, and domain modularity), what factors control catalytic bias of CO2 fixation or evolution? What role does the OFOR’s partner protein, ferredoxin, play in biasing reaction directionality? The electrochemical study of the structurally unique PFOR enzymes from C. tepidum, M. marinus, and M. acetivorans will provide critical information regarding the significance of the domain and structure composition of an OFOR enzyme. It will further reveal whether the native function of the enzyme influences the resting-state reduction potentials of the [4Fe–4S] clusters in the ET chain. Detailed site-directed mutagenesis studies of the Ct PFOR will provide a foundation for understanding the relationship between cluster potentials and ET/catalytic rates of the OFOR family and give insight into the role the protein matrix plays in tuning cluster potentials. Furthermore, electrocatalytic studies of the Ct PFOR/Fd system will provide an example of how the identity of a partner protein could direct or support enzyme catalysis and elucidate factors that contribute to successful intermolecular-ET. Understanding how Fd characteristics influence catalysis applies to many other biological systems, including the chemistry of hydrogenases or nitrogenases. Finally, the study of the Fe proteins from the nitrogenase provides insight into the thermodynamic driving force that initiates nitrogen fixation in the catalytic component of the nitrogenase, further improving our understanding of how the nitrogenase accomplishes its chemistry.
Novel reaction discovery with rapid high-throughput experimentation via infrared spectroscopy and enzymatic electrochemical oxidation of alcohols
(2024) Zhen, Jessie Jingxin; Schaus, Scott
Scientists in academia as well as pharmaceutical companies have been devoting numerous research efforts towards green chemistry since the establishment of the Pollution Prevention Act of 1990. The overarching goal of green chemistry is to incorporate environmentally benign reaction design into routine and novel synthesis in order to minimize the use of toxic substances and waste while maximizing the overall efficiency of reaction processes. Both projects reported here encompass the idea of sustainability and productivity. High-throughput screening (HTS) and high-throughput experimentation (HTE) has been widely used in the field of biochemistry to rapidly identify pharmacological targets. However, this method has been underused in organic chemistry due to the complexity of reaction design, strain in reagent handling, as well as the difficulty of data analysis and structure determination. Utilization of HTE in organic chemistry can increase the output of chemists and decrease wastes. A well-designed chemical HTE platform has the potential to generate enormous volumes of empirical standardized data that not only could be used for reaction optimization, but also readily integrated into a near-AI computational system in the future for reaction model prediction and discovery. A functional screening and analysis platform was developed to investigate the Petasis Borono-mannich reaction space and to explore possible novel reactivities. Using this system, more than 3000 distinctive microscale reactions were processed in under 6 months with 74% accuracy. By triaging the IR results, we prioritized time and efforts on analyzing and reproducing reactions with moderate to excellent yields. This helped to identify previously unknown reactivities, allowing for reproduction of novel reactions at bench scales, as well as furthering mechanistic studies of uncommon reaction partners such as thiophenol and pyrone. This preliminary success suggests that this platform could be transferable to other multicomponent reactions such as the Suzuki cross-couplings and Buchwald-Hartwig aminations. With deepened understanding of reagent selection and stereoselectivity of the catalyzed Petasis reactions from the HTS platform, we examined the possibility of electrochemical enzymatic catalysis. Galactose oxidase is known to selectively eliminate the pro-S hydrogen during oxidation of alcohol reagents due to the steric constraints of the active site. Electrochemistry tend to feature mild reaction conditions and fast turn over, while enzymatic catalysis is economical and nontoxic. By combining these two methods, a mild, diastereoselective oxidation could be achieved to provide the aldehyde component in the highly enantioselective, transition-metal-free Petasis reaction.
Quantifying four decades of disturbance dynamics in North American Arctic and Boreal ecosystems using Landsat time series
(2024) Zhang, Yingtong; Woodcock, Curtis E.
Climate change in the Arctic and Boreal Regions (ABR) is unfolding at twice the rate of the global average over recent decades. In the past 40 years, satellite observations have revealed extensive changes in land cover within this area, attributed to various disturbances coupled with a warming climate. However, with relatively sparse satellite data density in high latitudes, it has been challenging to quantify the extent of disturbances at moderate resolution and assess how climate change influences the nature and frequency of these disturbance events. The first step of mapping disturbances in the Arctic and Boreal Region is to determine the spatial and temporal frequency of usable satellite observations. Remote sensing satellites effectively characterize ecosystem changes and monitor disturbances, but finer details like logging patches and pest damage can be challenging to detect with sensors like AVHRR and MODIS. Our analysis indicates that the current acquisition status and strategies of the Landsat Program enable sufficient observations for time series analysis in high latitudes, expect for Alaska before 2000 (Zhang et al., 2022a). A new method using pre- and post-disturbance Tasseled Cap (TC) values at peak summer derived from the Landsat time series can distinguish multiple causal agents of disturbance over the core domain of NASA’s Arctic-Boreal Vulnerability Experiment, and was used to map disturbances caused by fire, insect, and logging activities on an annual basis from 1987 to 2012. In addition, an iterative post-processing procedure improved the accuracy of our map (Zhang et al., 2022b). Application of this new methodology and several significant improvements enabled the extension of the spatial and temporal scope for the quantification of disturbance agents of fire, insects and logging of Arctic and Boreal Canada and Alaska from 1987 to 2021. The findings indicate: 1) insect damage has increased significantly over the past two decades; 2) the area burned is highly variable from year to year but does not exhibit temporal trends; 3) interannual variability in logging is low, with macro trends in logging activities closely bound to economic factors and market dynamics; and 4) post-disturbance boreal forest recovery is too complex to be characterized exclusively by the widely used Normalized Difference Vegetation Index (NDVI). The Landsat-derived Tasseled Cap Wetness (TCW) index better characterizes the vegetation recovery, particularly in conifer forests. Results for field sites reveal that conifer forests often require 35 years for natural recovery, and insect-induced forest mortality even longer.
Chemically coalescing liquid metal emulsions for 3D printed soft conductors
(2025) Zopf, Stephanie Flores; Boley, J. William
Gallium-based liquid metal alloys (GaLMAs) have widespread applications ranging from soft electronics, energy devices, and catalysis. GaLMAs can be transformed into liquid metal emulsions (LMEs), a composite form with modified rheology, for simpler patterning, processing, and material integration in GaLMA-based device fabrication. One major drawback of using LMEs is reduced electrical conductivity, owing to the oxides that form on the surface of dispersed liquid metal droplets. LMEs thus need to be activated by coalescing liquid metal droplets into an electrically conductive network, which usually involve techniques that subject the LME to harsh conditions. In this thesis, we present a way to coalesce these droplets through a chemical reaction at mild temperatures (T ~ 80°C). This chemical activation is enabled by inclusion of halide compounds that chemically etch the oxide on dispersed microdroplets of eutectic gallium indium (eGaIn). We investigate the use of a covalent halide compound as an activator and elucidate its activation mechanism. Through nuclear magnetic resonance spectroscopy, we discover the ability of eGaIn to catalyze the dehalogenation of our covalent halide activator and confirm through X-ray photoelectron spectroscopy that chemical oxide etching is occurring. Consequently, we establish the mechanism for self-catalyzing chemically coalescing LMEs. We then optimize this emulsion as a functional ink for 3D printing by exploring activator concentrations that maximize post-heat electrical conductivity, compatibility with direct ink writing, and post-activation shape retention. As a result, we select a 3D printable formulation with an electrical conductivity of 1.5 × 10^3 S/cm for further characterization and 3D print parameter optimization. We also explore LME formulations containing halide salt activators, and find that chemically coalescing LMEs can reach a high electrical conductivity (2.4 × 10^4 S/cm) close to that of bulk eGaIn, but at the expense of shorter shelf-life and poorer shape retention. Rheology of the selected covalent halide-based emulsion reveals that the LME is shear thinning and shear yielding. Additionally, it exhibits a high plateau modulus (1.0 × 10^5 Pa) and high yield stress (~2 kPa), thus requiring high pressure and high print velocities, which is desirable for rapid fabrication of GaLMA-based devices. To provide a parameter processing guide for our ink, we construct a print phase diagram describing extrusion pattern types across a normalized print velocity range from 0.45 to 1.35. We also show that our ink can span distances up to 3 mm in length, following a mathematical model for viscoelastic catenaries that predicts an elastic modulus in agreement with experiment. Finally, to demonstrate the utility of our shelf-stable chemically coalescing LME, we incorporate it as a conductive ink in the hybrid 3D printing of custom-designed battery-integrated light emitting diode arrays, demonstrating simpler fabrication of GaLMA-based applications. This technology pioneers a new class of LMEs, providing the material basis for designing future chemically coalescing LMEs and patterning soft metal catalyzed multifunctional materials.
Targeted delivery of relaxin-2 as a novel protein therapeutic for the treatment of fibrotic diseases
(2024) Williamson, Amanda Kelly; Grinstaff, Mark W.
Fibrotic diseases affect thousands of individuals across various organs, yet there is no standard of care or curative option available when it comes to treatment. Fibrosis displays significant heterogeneity in its cause, onset timeline and severity across patients and tissues. Despite these differences, the foundation of fibrosis development remains consistent. It is caused by a dysregulated wound healing response to inflammation due to tissue injury. This inflammatory stimulus can result from infection, toxins, physical damage, autoimmunity or arise idiopathically. The normal healing processes become overactive, resulting in deposition of stiff extracellular matrix (ECM) proteins that causes the tissue to become impaired and lose functionality. In all forms of fibrosis, patient quality of life is impacted, whether from uncomfortable and unattractive scars on the skin, or loss of internal organ function resulting in death. Through various complex and interconnected positive feedback mechanisms, fibrotic signaling cascades and ECM build-up are constantly stimulated, making prevention and early treatment critical to success. In this work, we address some of the challenges of treating fibrotic diseases using the endogenous peptide hormone, human relaxin-2 (RLX-2), combined with mechanisms to enhance its therapeutic potential and antifibrotic efficacy. RLX-2 is a natural antifibrotic and antifibrogenic with the ability to both inhibit pathways responsible for fibrosis development and upregulate enzymes to degrade the stiffened matrix, making it poised as both a prophylactic and a treatment for established disease. However, RLX-2 has failed in previous clinical trials due to lack of efficacy. We hypothesize that these failures were due to inadequate concentration at the target tissue due to systemic delivery, as well as fibrosis-specific alterations to the RLX-2 receptor, RXFP1. We explore the antifibrotic effects of RLX-2 and methods to improve its efficacy in three different fibrotic diseases. First, we encapsulate RLX-2 into a polymeric microparticle formulation for the treatment of shoulder arthrofibrosis. Second, we are developing a sustained-release hydrogel for RLX-2 application to deep dermal wounds for the prevention and potential reversal of hypertrophic and keloid scars. Last, we explore RXFP1 gene expression in scleroderma patient dermal fibroblasts and demonstrate use of a corticosteroid to upregulate RXFP1 and potentiate the antifibrotic effects of RLX-2. Through targeted delivery strategies and understanding the pathology of the disease and target, these studies demonstrate methods to improve RLX-2’s therapeutic potential to treat fibroses.
Methods to evaluate overall and mediated treatment effects in the presence of death
(2024) Xiang, Qingyan; Lok, Judith J.; Sebastiani, Paola
In clinical practice, treatment decisions are often based on both the probability of survival and other clinical outcomes, such as Quality of Life (QoL) scores or neurocognitive test scores. When interest in a research study lies in both survival and other clinical outcomes, death before the follow-up assessment results in undefined clinical outcomes. Many authors refer to this setting as “truncation by death” to distinguish it from settings where the outcome is simply missing. It is well known that analyses without careful consideration of undefined outcomes due to death can lead to flawed treatment decisions. In this thesis, we focus on methods to evaluate overall and mediated treatment effects in the presence of death in three different projects. First, we advocate not always treating death as a mechanism through which clinical outcomes are missing or censored, but rather as part of the outcome measure. We propose summarizing the clinical benefit of a treatment by combining death and the clinical outcome into a composite outcome. We introduce the survival-incorporated median, the median of the composite outcome, as a simple and useful summary measure to inform clinical practice. We illustrate the application of the survival-incorporated median by analyzing a study that compares the clinical benefit of two treatment regimens in prostate cancer patients. Second, we develop an estimation method for the survival-incorporated median using observational data for a causal interpretation. Combining Inverse Probability of Treatment Weighting and a quantile estimation procedure, we propose an estimator in settings with point treatment and time-varying treatment. We prove consistency for the proposed estimator. Simulations demonstrate the usefulness of this estimation procedure in various settings. We apply the method to invetigate the effect of statins on cognitive changes in elderly individuals. Last, we investigate the relationship between Apolipoprotein E (APOE), lipids, and cognitive function using data from the Long Life Family Study (LLFS) and the New England Centenarian Study (NECS). We use a linear mixed model to estimate the rate of change in the Telephone Interview for Cognitive Status (TICS) score for each participant. We perform mediation analysis to examine both the direct effect of APOE and its indirect effect through lipids on the rate of change in TICS score. We discover no significant evidence of an indirect effect of APOE through lipids, but a significant direct protective effect of APOE e2 on the rate of change in TICS score.
Local gauge symmetry and emergence of topological order in quantum spin systems
(2024) Wu, Kai-Hsin; Chamon, Claudio; Sandvik, Anders
Topological quantum states of matter are a central focus in modern condensed matter physics and quantum information science. The study of topological order in quantum spin systems is closely linked to the concept of gauge symmetries. In this dissertation, we conduct detailed studies of two quantum spin systems with local gauge symmetries. Specifically, we numerically investigate a recently proposed theoretical model that realizes local Z2 gauge symmetry with only two-body interactions.We confirm the existence of topological order and explore other physical properties within the model in depth. In the study of the U(1) toric code, we enhance the conventional Kitaev’s toric code by introducing global U(1) symmetry. The study emphasizes the interplay between local Z2 gauge symmetry and constraints arising from global U(1) symmetry. This examination uncovers the presence of topological degeneracy and reveals an unconventional UV/IR mixing phenomenon within the system. We explore possible implementations of the U (1) toric code in superconducting wires and discuss potential future research directions based on the insights gained from our investigations of these two models.
Like mother, like daughter: three generations of socialist women in the German Democratic Republic, 1949-1989
(2024) Weiser, Rachel K.; Zatlin, Jonathan R.
Like Mother, Like Daughter: Three Generations of Socialist Women in the German Democratic Republic, 1949-1989 examines the writings of ordinary East German women from 1949 to 1989 to argue that many working mothers articulated support for certain aspects of the socialist project, even as they identified and grappled with its contradictions and shortcomings. By highlighting women’s voices, my research moves away from previous studies that portray East German women as passive victims of an authoritarian regime or as the grateful beneficiaries of a welfare state. Rather, I analyze written sources as varied as citizen petitions, brigade books, job applications, and letters to the editor to show how women—working mothers in particular—engaged in various methods and rhetorical strategies to make demands of the East German state while upholding some of its core principles. Women embedded and marshaled their own personal understandings of socialism, sometimes in alignment with state policies, and sometimes in opposition to them, in their characterizations of the GDR. I unpack the complexities of their narratives to demonstrate how working mothers negotiated with, challenged, and even schooled the regime on what a socialist society should look like. In doing so, women leveraged their various identities—as workers, mothers, teachers, gardeners, activists, volunteers—as sources of authority to make claims about their vision of socialism and its commitment to gender equality. One of the chief claims of this dissertation is that working mothers’ expressed demands, expectations, and strategies regarding socialism evolved over time and varied by generation. While each woman wrote in a unique voice and style, my project traces distinct generational rhetorical patterns and shifts in how women conceptualized the meaning of socialism on the page, based on their past experiences, present circumstances, and future goals, as well as on their relationships with the state, their mothers, their children, and their colleagues. Through their narratives, I argue, generations of women cast themselves as cocreators of a socialist society.
Novel statistical methods to improve precision medicine
(2024) Zhang, Xiaoyu; Liu, Ching-Ti
Precision medicine, also known as personalized medicine, refers to the tailoring of therapeutic or preventive interventions to specific subpopulations of patients based on the patients’ characteristics. Accurate disease subtyping could be essential for precision medicine, which aims to provide individualized treatments to patients. The development of precision medicine thus relies on a sufficient understanding of the underlying mechanisms of diseases. Recent technological advances, especially in genomics and molecular biology, have provided unprecedented opportunities to gain greater insight into disease subtypes and underlying mechanisms. However, translating this deep wealth of knowledge into clinical practice for precision medicine remains a challenging task.This dissertation intends to improve precision medicine from two statistical perspectives. The first is to identify disease subtypes and related biomarkers through clustering using multi-omics data, which could be the first step toward precision medicine. The second is to accurately stratify patients into subtypes through companion diagnostic devices (CDx) in clinical trials, which is directly related to developing targeted precision medicine therapy. We propose two novel convex clustering methods that allow the incorporation of prior information or knowledge and generate stable cluster results. One is information-incorporated Sparse Convex Clustering (iSCC), utilizing a text mining approach to retrieve existing information from previously published studies on available sources, such as PubMed, to identify disease-related biomarkers and improve disease subtyping. The other one is Prior Knowledge-assisted Integrative Convex Clustering (PK-ICC), incorporating prior biological knowledge on grouping information between features, such as biological pathways and the gene regulatory mechanism, through a group lasso penalty to improve disease subtyping and select relevant groups of features simultaneously. Both simulations and real data analysis have demonstrated that our proposed methods can identify more accurate disease subtypes and biologically meaningful biomarkers. We also propose a finite mixture model framework to quantify the impact of CDx measurement performance on clinical trials with binary or time-to-event outcomes, which helps future design of trials when using CDx. Overall, this dissertation has proposed statistical methods that may improve the identification of disease subtypes and the design of CDx incorporated trials, which may lead to better clinical outcomes through precision medicine.
The biochemical and biophysical characterization of a new bacterial cytochrome c peroxidase from Roseovarius lutimaris
(2024) Zhang, Li; Elliott, Sean J.; Liu, Pinghua
The di-heme bacterial cytochrome c peroxidase (BCcP) superfamily can be divided into two groups based on biological functions. Canonical BCcPs reduce hydrogen peroxide to water by taking electrons from their redox partner - cytochrome c. In contrast, MauG and its orthologs are involved in protein post-translational modifications using the bis-Fe (IV) species. One of the key factors that is highly corelated with the diversity of biological functions of BCcPs is the distal heme ligand on the electron transfer heme (E heme), demonstrating the significant structure-function relationships of BCcPs. Using the sequence similarity network coupled with genome neighborhood analysis, a new group of BCcPs has been discovered from marine bacteria. The sequence analysis indicates the lack of distal ligand on E heme. In addition, the conserved genome context consisted of PhnDCE phosphonate transporter and manganese dependent transcriptional repressor MntR suggests potential functions in phosphorus metabolism under metal dependent regulation, which is beyond the current understanding of the functions of BCcP enzymes. The biochemical and biophysical characterization of RolA, the newly discovered BCcP from Roseovarius lutimaris, reveals that it possesses no peroxidase activity but reacts with O2 when fully reduced, setting it apart from all known BCcPs. In order to investigate the biological function of RolA, genetic manipulation tools have been developed in R. lutimaris. Three deletion mutants including R. lutimaris ∆rolA, ∆mntR and ∆rolA-∆mntR have been generated. The qPCR analysis of R. lutimaris WT vs ∆mntR has shown up-regulation of rolA upon mntR deletion, confirming the transcription repression of RolA by MntR. Native RolA has been tagged and over-expressed in R. lutimaris. The UV-vis and EPR spectra have demonstrated that the heme environment of native RolA is different from known BCcPs. Like recombinant RolA, native RolA has no peroxidase activity and reacts with O2 under fully reduced state. Preliminary studies using R. lutimaris ∆rolA and ∆rolA-∆mntR have shown utilization of phosphonates as sole phosphorus source. Bioinformatics analysis of PhnD from R. lutimaris suggests RolA might be related with hypophosphite transformation. The investigation of biological function of RolA using growth assay and in vitro enzymatic activity assay is ongoing. The identification of RolA expands the knowledge and diversity of the BCcP superfamily.
Miracle of backwardness: a lay Daoism for young people in contemporary China
(2024) Xu, Rongrong; Weller, Robert P.
This dissertation examines young people’s engagement with the newly established lay Daoism in contemporary Shanghai. It begins with an ethnographic question: Why do well-educated urban young people commit to Daoism, a traditional Chinese religion that has been described as backward and feudalistic in mainstream discourse for more than a century, and under a social environment that worships modernization and economic development? Based on twenty-one months of fieldwork, this dissertation portrays the interactive dynamics between institutional Daoism, young lay Daoists, and the state, as the social matrix that has facilitated the emergence of an innovative lay Daoism. By doing so, the dissertation moves away from previous approaches that describe young people’s engagement with religion primarily as a solution for or alternative to the unsettled lives they live under conditions of rapid economic development and social change. It explores the ironic process that an anti-religious society coincidently facilitates a youth culture affined with religion, showing that the newly established lay Daoism is profoundly intertwined with contemporary youth culture, as well as with the life experiences and social relations of a particular generation of Chinese youth in urban China. Using this optic, this dissertation investigates how Daoism’s cosmology and practice correspond to young people’s lives, thoughts, and aspirations. It introduces the metaphor of “convergence” to describe this dynamic process. This dissertation suggests five aspects to explain how “convergence” between young people’s modern urban life and their commitment to Daoism takes place. Firstly, as social background, the current state’s political agenda -- which promotes national identity, the rapid expansion of markets for traditional Chinese fashion, and young people’s widespread nostalgia for an imagined past national glory -- encourages young people to embrace the cultural tradition that Daoism represents. Secondly, in the context of frantic urban life, young people embrace a Daoist temporality to reorganize their everyday lives. The dissertation documents multiple patterns in which Daoist and modern temporalities co-exist dynamically: overlapping, resettling, decoding, and converging. Thirdly, young women, who are identified as the “empowered daughters” of contemporary China, and who pursue equal gender relations with their partners, find a source of affirmation for their identity in Daoism’s theology of yin-yang equality, even though men dominate many Daoist institutions. Fourthly, Daoism’s philosophy that insists on “assisting the state and the people” fits comfortably with young people’s patriotic tendencies and asserts Daoism’s position as a valuable asset in a modern state. Lastly, young people discover their potential through exploring life’s complexity in the Daoist dialectical cosmology. Through this view, they explore several strategies to achieve the co-existence of multiple ontologies in daily life. In tracing these developments in a new Chinese lay Daoism, this dissertation contributes to anthropological discussions about traditionalism, temporality, gender, state-religion relationships, and multiple ontologies. In addition, it explores a new approach to understanding young people’s religious inspiration and practice under China’s secularist, even anti-religious, policy. In so doing, it contributes to a broader and important discussion on religion in modern secular societies worldwide.
Single molecule conductance spectroscopy: probing the gold-bio interface at the atomic scale
(2024) Pan, Xiaoyun; Kamenetska, Maria
This thesis uses single molecule conductance spectroscopy to probe the binding mechanisms and conductance characteristics of various biologically relevant molecules with gold at the atomic level. Firstly, we identify imidazole as a pH-activated linker for forming stable single gold molecule junctions, which present several distinct configurations and reproducible electrical characteristics. We then examine the resulting conductance signatures and identify corresponding binding geometries, which involve up to four imidazole molecules binding in the junction in parallel. In addition, we discover the distinct conductance signatures that indicate the in-situ formation of molecule-metal-molecule chains within the molecular junction. Building on this foundation, the investigation continues into the origin of the conductance enhancement observed in benzimidazole dimers compared to imidazole dimers. Density Functional Theory (DFT) calculations reveal that the parallel stacking of two benzimidazoles, due to the large π system between electrodes, represents the most energetically favorable configuration, leading to dimer conductance enhancement. The smaller size and greater conformational freedom of imidazole enable it to access a variety of stacking angles. Having understood the underlying mechanism, we use substituents to promote the cooperative in situ assembly of imidazole derivatives into a parallel binding configuration, subsequently enhancing conductance. Next, we shift our focus to adenine, one of the most important biological building blocks of deoxyribonucleic acid (DNA). By using structurally similar molecules, we can assign different conductance signals to various binding configurations of adenine. This approach also enables the differentiation between adenine and its biological derivatives, 2’deoxyadenosine and 6-methyladenine. Using single molecule conductance signals, we demonstrate the potential of single molecule conductance spectroscopy as a biosensing platform. Finally, we present a detailed study of the pH-activated intramolecular conductance features of histamine. By employing histamine and its derivatives, we associate different conductance features with specific binding sites. DFT calculation is used to simulate the different ethylamine configurations of histamine in molecular junctions, and flicker noise analysis is applied to identify and assign one of the conductance features to a hydrogen bond-assisted binding configuration. These results and insights collectively establish single molecule conductance spectroscopy as a robust platform for studying complex gold-biomolecule interactions.
The runaway horse: essays on the anxiety and representation of historical trauma
(2024) Prikhodko, Evgeniya; Kleiman, Irit Ruth
This dissertation investigates how the essay engages with historical and theoretical impasses related to the representation of traumatic memories in the wake of socio-political violence. Spanning several centuries, it encompasses the non-fiction texts exemplified by the sixteenth century works of Michel de Montaigne and Jean de Léry and essay films since the postwar era. Using close textual and visual analysis, I examine how the form of the essay, drawing from personal perspectives, moves between the exploration of individual trauma and the collective experience rooted in past traumatic events. The essay, I argue, presents formal innovations—from the use of subjective voice in literary form, transformed in the voiceover in essay films, to representation of animals—in the face of constraints on conveying historical trauma. With its tendency to emerge in times of crisis, the essay manifests itself as a critical response to historical violence. Michel de Montaigne’s Essais and the memoirs of Jean de Léry react to extreme events witnessed during the French Wars of Religion (1562–1598). The early essay film Le Sang des bêtes (1949) by Georges Franju, as well as later essayistic films by Chantal Akerman such as Dis-moi (1980) and No Home Movie (2015) grapple with traumatic memories of the Holocaust. My Friend Ivan Lapshin by Aleksei German (1985), a Soviet drama with essayistic elements, is haunted by the Great Terror under Joseph Stalin’s leadership. In attempt to re-write past individual trauma, the essay film Maison du bonheur (2017) by Sofia Bohdanowitz confronts oppressive patriarchal structures of societies. These divergent works share an urge to tell stories of traumatic experience from the margins of literature and cinema. In the studied texts, disturbance and cruelty as external forces relate uncannily to themes of consumption, where food becomes a locus of violence. Chapter one traces the origin of the genre of the essay film through analysis of Georges Franju’s short documentary film Le Sang des bêtes (1949) about animal slaughterhouses in the outskirts of Paris. Grappling with traumatic memories of the Second World War, Franju appeals to the origin of representation—the animal—to reinvent the form of documentary filmmaking and depict the trauma of witnessing French collaboration in deporting Jews during the Holocaust, alongside the dehumanization of war. The killing of horses for meat production brings to the fore the ambivalence of food tethered to ethical judgments of the self and others. Chapters two and three, based on close readings of Montaigne’s Essais and Jean de Léry’s memoirs, reconcile individual and collective trauma during a time of heightened violence of the Wars of Religion (1562—1598) and the colonization of the New World. In his Essais, Montaigne notably uses the shifting symbol of the horse and an errant figure of the author moving between personal experience and historical events to demonstrate the illusory line between “civilized” and “barbaric.” In Léry’s memoirs Histoire d’un voyage faict en la terre du Brésil (1578) and Histoire mémorable du siège et de la famine de Sancerre (1573), written in the wake of St. Bartholomew’s Day massacre, witnessing cannibalism and consumption of written records during extreme famine reflects his haunting fear of being unable to bear witness. Chapter four expands the notion of witnessing by accounting for an anxiety of transmission across generations. Introducing the question of gender in their works, filmmakers Chantal Akerman and Sofia Bohdanowitz explore individual and collective memory in post-Holocaust society through recourse to substitute grandmotherly figures. Scenes of cooking and non(eating) in their essay films become at once embodied representation of trauma and markers of new generation of filmmakers ignited by the second-wave feminism.
Functional and molecular properties of learning-related neuroplasticity in perirhinal cortex
(2024) McLachlan, Caroline A.; Chen, Jerry L.
Learning is actuated by plasticity, the remarkable ability of the brain to change and adapt in response to experience. A robust neural circuit level correlate of plasticity is a change in network activity, while on a molecular level, plasticity is mediated by immediate early gene (IEG) programs and finely tuned, highly specific downstream structural adaptations. Although plasticity occurs in all areas of the brain, the perirhinal cortex (Prh) in the medial temporal lobe (MTL) is a zone of convergence for higher order sensory association areas and a number of subcortical structures related to learning, memory consolidation and valence, and is therefore a particularly relevant structure for understanding the plasticity responses related to sensory- and goal-directed learning. However, it is currently unknown how Prh processes information from diverse regions of the brain to generate a flexible internal model related learning. Additionally, there is a gap in knowledge regarding the direct relationship between changes in gene expression and adaptations in network activity patterns that accompany complex, goal-directed learning in this region of the brain. To address these gaps in knowledge, we performed chronic two-photon calcium imaging of Prh layer 2/3 neurons while animals learned a whisker-based, go-no go delayed non-match to sample task. At the conclusion of behavior experiments, spatial transcriptomics was performed on functionally imaged neurons to identify molecularly defined, Prh-specific cell types and quantify expression of cell type marker genes and immediate early genes (IEGs) associated with neuronal plasticity. Using population analysis and generalized linear models, we analyzed the relationship between task-related responses, cell type identity, and IEG expression. We found that Prh encodes stimulus features as sensory prediction errors, and forms stable, stimulus-outcome associations that expand retrospectively from outcome back to the time of stimulus delivery and generalize as animals learn new contingencies. Additionally, we found that task-related responses were best explained by IEG expression patterns that spanned cell types. To confirm this role of IEGs, we perturbed the expression of brain-derived neurotrophic factor (Bdnf), a known regulator of task-related IEGs. We found that reward representations in Prh showed increased stability on a session-to-session basis in Bdnf conditional knockout (cKO) mice compared to control animals. Whereas, stimulus-reward associations emerged over sessions in control animals, those associations failed to form in Bdnf cKO animals. Taken together, this work demonstrates that Prh combines error-driven and map-like properties to generate a predictive map of learned task behavior and delineates the specificity in which gene expression participates in Prh-dependent task learning.

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