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Localized Impacts of International Interventions
No full textHow can the international community support governance at the local level in fragile states? Across three papers, this project seeks to deepen our understanding of the localized effects of foreign aid interventions in states affected by conflict or high levels of political instability through in-depth studies of the United Nations Development Programme (UNDP). In the first chapter, I conduct a large-n, cross-national study, theorizing that more projects and more funding in a small geographic area should help mitigate violence in fragile states in Sub-Saharan Africa. UNDP, as one of the largest peacebuilding organizations in the world, has the largest peacebuilding-specific budget, works in the most number of countries, and has worked with host countries for decades to help establish a stable peace. I argue that this level of commitment means that UNDP is the most likely organization to succeed in peacebuilding despite difficult circumstances. I collected a novel time-series dataset on the location and expenditures of UNDP peacebuilding projects to test whether higher expenditures and/or more projects can mitigate violence. My results suggest that an increased number of projects in an area is associated with decreased violence, and while increased project expenditures reduces violence perpetrated by non-state actors, this result is less robust. though this is not true for an increase in project expenditures. These findings emphasize that what international actors do to support fragile states can be just as or more important than how much money is spent. In the second chapter, I drill down on the importance of local presence introduced in my study on Sub-Saharan Africa. I examine a case study of a specific project by UNDP in a fragile state to ask how the international community might leverage the abilities of local governments for effective capacity building while avoiding rent-seeking in fragile states. Prior literature suggests rent-seekers can be induced to cooperate when they are closely monitored and would credibly be held accountable for poor behavior, but international actors are poorly positioned to do these tasks. I theorize that international actors can instead delegate those responsibilities to local citizens, who, under the right circumstances (including conservative budgets), can monitor elites and credibly hold them accountable. I test this theory using mixed methods by examining the Village Development Programme, a UNDP-led peacebuilding project during and after the civil war in Nepal. I quantitatively assess my theoretical expectations with a novel dataset I compiled from internal UNDP documents. Using standard statistical regressions and a Bayesian machine learning-based difference-in-differences model, I show participation increased village governments\u27 abilities to provide goods and services. Semi-structured interviews not only confirmed that the projects were successful but provided support for my proposed mechanism and reported little rent-seeking behavior. My third chapter is a methods paper, where I propose a method for improved event coding. Event coding -- the process of extracting information into an event dataset -- is integral to many political science studies, yet most political scientists rely on off-the-shelf event data. If political scientists need event data not covered by these datasets, they must decide whether they will manually extract information themselves or, if possible, use an automatic extraction model, both of which have advantages and disadvantages. But why not use both? I present a human in the loop procedure where political scientists use a large language model for initial information extraction without the need for a dictionary, and human expert coders review the cases where the large language model\u27s output is uncertain. Using an application of event coding from newspaper articles on Nepal, I show my procedure approaches gold standards with gains in time and financial efficiency. Together, this project highlights the importance of understanding local dynamics when analyzing international statebuilding interventions in fragile states. It also demonstrates the methodological difficulties of studying these local dynamics, both in terms of data availability, data quality, and the validity of assumptions required for existing methods. More methods work is needed to continue this important work. Based on my empirical findings, local actors choose violence or corrupt behavior after weighing the costs and benefits of their options, and international actors can sometimes influence those calculations. This is not necessarily through spending large sums, but instead being present and engaging with citizens to instigate a self-strengthening cycle of governance through local institutions
An Anthology of Interference in Law School Clinics
No full textAn Anthology of Interference in Law School Clinics explores interference in law school clinics in the United States, addressing its long history and the legal ethics, academic freedom, and First Amendment responses to that interference. Law clinics have faced interference in their representation of clients from elected officials, business groups, alumni and, at times, even their own school administrators. This interference has targeted clinics for providing individuals and nongovernmental organizations with legal representation on important matters, including racial and gender discrimination, environmental issues, prisoner rights litigation, death penalty cases, and immigration and human rights matters. In each instance, the interference has sought to subvert the legal process by preventing clinics from representing their clients rather than addressing the legal merits of their clinic clients’ claims. Interference with law clinic client representation also appears to be part of the broader attacks on public interest lawyers and other lawyers representing clients in disputes with governmental entities, business interest, or other more powerful adversaries. This book is designed to serve as a reference and resource to address future interference.https://openscholarship.wustl.edu/books/1069/thumbnail.jp
The Constellation of American Voters: Understanding Americans Who Live In and Out of American Municipalities
Full text linkMore than 130 million Americans live in unincorporated areas, or the spaces outside the boundaries of cities, towns, and villages. Despite this, relatively little attention has been paid to whether, how, and why residents of unincorporated areas differ from their municipality-dwelling counterparts. In this dissertation, I explore the answers to these questions by establishing a new theoretical framework that rigorously defines, bounds, and partitions unincorporated space. Drawing on the near-universe of American voters, I illustrate, with unparalleled precision, where and how Americans have sorted into and out of municipalities, and show that different mechanisms drive these phenomena. Furthermore, I explore the downstream consequences of sorting phenomena for important features of political attitudes and behavior. Finally, I consider this difference temporally as well as spatially by studying municipal disincorporation, or the ability of voters to democratically erase municipalities from existence
Leveraging Biomolecules to Illuminate the Landscape of RNA in Cells and Tissues
No full textAdenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional modification with established roles in transcript stability, protein recoding, and immune regulation. Despite its biological importance, our ability to interrogate A-to-I editing in situ has been severely limited by existing technologies that lack spatial resolution or require RNA extraction, thereby erasing the very context in which these editing events occur. This dissertation aims to address these limitations by developing and applying new tools to visualize, quantify, and explore the biological significance of A-to-I editing and RNA localization in fixed and live cells. In Chapter 2, we introduce Endonuclease V Immunostaining Assay (EndoVIA), which enables spatial mapping of inosine-containing RNAs with nanoscale resolution. This platform uncovers cell type-specific differences in editing localization and establishes the foundation for linking A-to-I editing with RNA trafficking and subcellular function. In Chapter 3, we present EndoVIA 2.0, an optimized workflow compatible with formalin-fixed paraffin-embedded (FFPE) tissues, allowing in situ detection of A-to-I editing in archival clinical samples. This method reveals editing heterogeneity across tissues and enables single-cell analysis of editing landscapes in disease contexts such as cancer. Building on the need to track RNA dynamics over time, Chapter 4 describes a photoaffinity-based strategy for covalently labeling fluorescent RNA aptamers in live cells. This approach provides temporal control and improved RNA tracking, enabling time-resolved imaging of RNA localization. Covalent labeling also opens new avenues for enriching and identifying RNA:protein interactions of spatially localized RNAs. Finally, in Chapter 5, we reflect on the broader implications of these technologies for advancing RNA imaging, investigating the spatial biology of RNA editing, and repurposing other naturally occurring proteins and enzymes for mapping the epitranscriptome. Collectively, this work establishes a versatile toolkit for studying A-to-I editing in its biological context and paves the way for new insights into how RNA modifications regulate cellular function, tissue heterogeneity, and disease progression
Ecological Momentary Assessment of Mechanisms Linking Racial Discrimination and Substance Use in Black College Students
No full textBlack college students experience elevated rates of racial discrimination, which has been linked to higher rates of substance use. However, most existing studies focus exclusively on alcohol and rely on retrospective, cross-sectional designs, which limits our ability to gauge the magnitude of racial discrimination and obscures its influence on other substances prevalent on U.S. college campuses. To address these gaps, this study employs ecological momentary assessment (EMA), a repeated collection of real-time data, to pursue two primary aims among a sample of Black college students (N=97) attending Predominantly White Institutions in Missouri. Aim 1 characterizes both same-day (concurrent) and next-day (lagged) effects of racial discrimination on alcohol, nicotine/tobacco, marijuana, and other drug use while examining between-person and within-person differences. Grounded in the Psychological Mediation Framework, Aim 2 investigates whether affective, cognitive, and social processes mediate the same-day relationship between racial discrimination and substance use, and explores differential mediation to test whether specific psychosocial responses serve as unique pathways. Over 14 days, a mobile app, Expiwell, randomly prompted participants 5x/day to report on all variables. In addition, waking surveys were delivered once every morning to capture overnight racial discrimination and substance use. Accounting for the complex EMA survey design, multilevel models were used for analysis. For both aims, a generalized linear model with a Poisson distribution was implemented for alcohol quantity (count), while a generalized linear model with a binomial distribution was applied to all other substances (dichotomous). Causal mediation analysis was conducted for Aim 2. All models controlled for age, gender, financial stress, and sexual orientation. Significant associations emerged for alcohol and marijuana use in Aim 1 and for alcohol as a count variable in Aim 2. Qualitative insights from a follow-up survey further illuminate Black college students’ lived experiences with racial discrimination, daily coping strategies, and the feasibility and acceptability of phone-based digital assessment tools in this research. Leveraging EMA and multilevel modeling, this study provides temporally sensitive evidence that daily racial discrimination significantly influences alcohol and marijuana use among Black college students, with same-day and next-day effects observed at between-person and within-person levels. The results indicate that substance use serves as both an immediate and delayed coping mechanism, with negative affect and rumination playing pivotal mediating roles. Extrapolating these two-week trends suggests that these students may experience substantial cumulative exposure to racial discrimination and associated substance use over a year, likely contributing to disproportionate substance use and mental health disparities. This dissertation serves as a methodological blueprint for more nuanced research on racial discrimination and substance use. In the context of a 2025 national climate marked by rolling back racial equity and neglecting systemic health disparities, these findings underscore the urgent need for targeted, real-time interventions to mitigate the adverse effects of racial discrimination and promote health equity on college campuses
Examing the Role of Complement Signaling in Viral Neuroinflammatory Responses
Full text linkThe complement system is an ancient pathway that serves dual roles as a key regulator of neuroinflammation and a critical regulator of neural networks. Few studies have addressed how these two pathways may interact during infection of the central nervous system. While some components of complement are expressed in the healthy developing brain, complement component 3a receptor (C3aR) is a G protein coupled receptor that is expressed by astrocytes, microglia and infiltrating immune cells during inflammatory states. We previously found that C3aR is required for engulfment of synaptic material by activated microglia during neuroinvasive viral infection. Here, we used a mouse model of West Nile neuroinvasive disease (WNND) to further address the role of C3aR during WNND. We examined its expression and function in the setting of acute infection in both wild-type versus C3aR-deficient mice, and C3aR-microglia specific conditional KO mice. First, we demonstrate that C3aR levels peak during acute infection, and the receptor is expressed primarily on myeloid cells. C3aRKO infected mice exhibit decreased resident and infiltrating myeloid cell numbers during acute infection, and a corresponding decrease in synapse elimination in the retrosplenial cortex, a region implicated in spatial learning and memory. Conditional deletion of C3ar from microglia leads to specific decreases in the resident myeloid cell population during acute infection, and decreased synapse elimination in the retrosplenial cortex. We also show that the changes in myeloid cell populations are linked to increased caspase-3 activity in these cells. Additionally, we explore the role of complement component C1q. Upon direct binding to pathogen surfaces or antibody-antigen complexes, C1q initiates enzymatic activity that results in downstream cleavage of classical cascade components. We have previously identified virally infected neurons and activated microglia as sources of CNS C1q during WNND. Here, we provide preliminary evidence for a dual role for C1q in synapse elimination and virologic control. We also demonstrate that this ligand may be a useful biomarker for cognitive dysfunction post recovery from WNND. All together, these results provide further insight into the role(s) of complement signaling in mediating viral neuroinflammatory responses
Exploring DDR2’s role in CAF extracellular matrix production and tumor progression
Full text linkOvarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, Discoidin Domain Receptor 2 (DDR2), promotes collagen production in human and mouse omental CAFs through arginase activity. CAFs with high DDR2 or arginase promote tumor colonization in the omentum. In addition, DDR2-depleted CAFs had decreased ornithine levels leading to decreased collagen production and polyamine levels compared to WT control CAFs. Tumor cell invasion was decreased in the presence CAF conditioned media (CM) depleted of DDR2 or arginase-1, and this invasion defect was rescued in the presence of CM from DDR2-depleted CAFs that constitutively overexpressed arginase-1. Similarly, the addition of exogenous polyamines to CM from DDR2-depleted CAFs led to increased tumor cell invasion. We detected SNAI1 protein at the promoter region of the arginase-1 gene, and DDR2-depleted CAFs had decreased levels of SNAI1 protein at the arginase-1 promoter region. Furthermore, high stromal arginase-1 expression correlated with poor survival in ovarian cancer patients. These findings highlight how DDR2 regulates collagen production by CAFs in the tumor microenvironment by controlling the transcription of arginase 1, and CAFs are a major source of arginase activity and L-arginine metabolites in ovarian cancer models
Effects of Pharmacologic and Genetic Manipulation of GABA-A Receptors on Network Activity
Full text linkGABAA receptors (GABAARs) are the primary inhibitory neurotransmitter receptors in the central nervous system. A rich diversity of receptor subtypes are produced by the combination of various GABA receptor subunits into a heteropentameric chloride channel. Inhibitory signaling through GABAARs occurs on timescales ranging from fast synaptic events lasting milliseconds to tonically active receptors providing standing inhibitory tone. GABAARs are modulated by many clinically important drugs including anesthetic, hypnotic, anxiolytic, and antidepressant agents. Of note, GABAARs are modulated by neurosteroids, which have recently been developed as novel therapeutic agents for psychiatric disease. The synchronized activation of GABAARs through coordinated activity of GABAergic interneurons is important for organizing large populations of principal cells into synchronized network activity. Both the manipulation of GABA releasing interneuron activity and modulation of GABAARs can alter the network activity observed as oscillatory signals in the brain. This thesis investigated both of these means of network perturbation to characterize modulation of neural oscillations by the neurosteroid allopregnanolone (AlloP) a positive GABAAR modulator, and to probe the function of δ subunit containing GABAARs in parvalbumin positive (PV+) interneurons with respect to their role in supporting coordinated network activity. First I characterized the EEG response to AlloP in comparison to other GABAAR positive modulators and the rapid antidepressant ketamine in attempt to differentiate AlloP effects from other GABA modulators and identify potential common signatures of rapid antidepressants. I found that non-sedative doses of AlloP most closely resembled the actions of pentobarbital a non-selective GABAAR positive modulator, and failed to identify any significant overlap between actions of AlloP and ketamine among any analyzed EEG parameters. This suggests that rapid antidepressants with different molecular targets maintain separate actions when measured across larger scales of neural activity. Next we considered whether the unique α1/δ GABAAR subunit partnerships found on PV+ interneurons could serve as a disinhbitory substrate for neurosteroids. We found that hippocampal PV+ interneurons exhibited very little sensitivity to modulation by AlloP, and that mice lacking Gabrd in PV+ interneurons (PV-δcKO) retained EEG responses to non-sedative AlloP doses similar to wild type animals. Finally, we sought to determine how inhibition through δ-subunit containing receptors in PV+ interneurons shape their role to support coordinated network activity. We found that PV-δcKO mice had altered EEG spectra, notably increased power of lower frequency activities during sleep. Additionally, we identified the emergence of high amplitude phasic bursts of activity prominently detected in frontal cortical areas that were mitigated upon viral reintroduction of Gabrd to PV+ interneurons. These studies expand our knowledge of neurosteroid modulation of mesoscale activities and highlight an importance of GABA signaling through δ subunit containing receptors on PV+ interneurons for maintaining integrity of oscillatory activity in the brain
Witch Aesthetics in Film Music & Sound, 1927-2024: A Queer Feminist Analysis
Full text linkThe witch persists across long spans of time and location. She is an unruly archetype, existing to trouble boundaries and power. However, the witch also emerges as a character with whom people identify, emphasizing her incredible flexibility as a signifier. I establish my intervention in the study of the witch as a cultural figure from the standpoint of sound and music studies. Based on my study of more than 140 films between 1927-2024, I argue that the witch is a profoundly musical and sonic creature, particularly as markers of her presence and power. I build on Carol Clover\u27s work on the possession film to argue that the witch\u27s voice particularly manifests her power, often in song. Fortified by the work of voice scholars such as Nina Sun Eidsheim, Mladen Dolar, Freya Jarman-Ivens, and Steven Connor, I offer two case studies that demonstrate two different deployments of witch vocality. Jennifer\u27s spell song in I Married A Witch (René Clair, 1942) exemplifies the relationship between the witch\u27s voice and the manifestation of her power. I also theorize the witch\u27s voice as an extreme example of the way that the voice is always already detached from the speaker\u27s body. The role of the non-diegetic diabolical chorus in Robert Eggers\u27 The Witch (2015) serves as a mediation on the unstable but powerful relationship between voice and body. An extended case study on The Autopsy of Jane Doe (André Øvredal, 2016) joins the two foci of my dissertation—the voice and pre-existing music. Here, pre-existing music stands in as the witch\u27s voice. Because the film\u27s central witch appears to be dead, her voice —Stuart Hamblen\u27s Open Up Your Heart (And Let the Sun Shine In) played through an onscreen radio—acts as the first and most direct indication that she is conscious and able to manipulate her surroundings without ever speaking or rising from her slab. The choice of this Christian children\u27s song invokes a host of vexed American histories, especially because Open Up Your Heart appears in structural opposition to a handful of masculine Southern rock songs. I argue for the utility of reading Autopsy in light of Christine (John Carpenter, 1983) because both Jane and Christine communicate with the men around them by playing popular music through their radios. I then demonstrate how pre-existing music continues to function in a magical register beyond the specific overlap of voice and popular music in The Autopsy of Jane Doe. Pre-existing music offers a variety of interpretive challenges because of the song\u27s accumulated meanings outside of the film. In Practical Magic (Griffin Dunne, 1998), the soundtrack\u27s pop songs operate as sung spells, especially in the two prominent montage complexes on which I focus my attention. In We Have Always Lived in the Castle (Stacie Passon, 2018), popular music marks the American mid-century time and place that threatens the Blackwood sisters\u27 queer domesticity, which is symbolized by an originally composed cue. I conclude by suggesting that witch aesthetics continue to spread outside of the witch film, a claim I demonstrate via brief case studies in television and popular music
Understanding host-pathogen interactions using the Caenorhabditis elegans – Orsay virus experimental model
Full text linkOver an evolutionary timeline, viruses have evolved ways to exploit biochemical pathways of the host for their propagation, whereas host organisms developed mechanisms to recognize virus infection and cope with them. Consequently, a better understanding of the different host factors involved in virus replication could provide insights into potential biological pathways or molecules for therapeutic targeting. Furthermore, detailed dissection of the mechanisms of virus sensing could reveal fundamentally important aspects of virus sensing that are evolutionarily conserved to mammals and offer insights into potentially underexplored areas of research. The C. elegans experimental model offers a useful platform for studying evolutionarily conserved host genes, as C. elegans and mammals share many important genes and biological mechanisms as exemplified by the discoveries made in RNA biology, developmental biology, neuroscience, and genetics. Combined with the Orsay virus, a natural pathogen to C. elegans, the C. elegans–Orsay virus experimental system offers a novel platform for interrogating host-pathogen interactions in unique ways compared to traditional tissue culture or animal models. For example, the small size of nematodes permits culturing in large numbers. Unlike mammalian animal models such as mice, C. elegans allows for forward mutagenesis screens at a whole-organism level. In my thesis, I established a forward chemical mutagenesis screen aimed at isolating host factors involved in the replication phase of the Orsay virus life cycle. This was achieved by leveraging a transgenic C. elegans model in which the virus lifecycle can be initiated from a stably integrated transgene. By performing random chemical mutagenesis, I isolated three mutant lines that harbored independent missense mutations in a previously uncharacterized gene, Y55F3BL.4 (renamed viro-9), and validated this result by trans-complementing the wild type viro-9. viro-9 contains a Pfam-annotated SRR1 domain with a poorly defined function. Since the function of the viro-9 is not known in C. elegans, I performed physiological assays to define any gross morphological defects in the null allele mutants and found that ablation of the viro-9 locus moderately reduced the life span and brood size. To gain insights into the potential functional conservation of the gene, I asked whether CBG23913, the Caenorhabditis briggsae (C. briggsae) ortholog of viro-9, can rescue the virus infection defect in viro-9 mutant C. elegans animals. The C. briggsae CBG23913 was sufficient for restoring virus replication, suggesting that the function of the SRR1 domain is conserved across 80–110 million years. Additionally, I compared the SRR1 domain-containing sequences across different eukaryotic kingdoms and identified highly conserved residues that were altered in the C. elegans mutant lines isolated during the chemical mutagenesis. Although the alteration of the chemically mutagenized sites did not dramatically affect the predicted VIRO-9 structure, it could be speculated that these residues may play important roles for protein-protein interactions. Besides studying pro-viral C. elegans host factors, I addressed the fundamental question of how virus replication is sensed in C. elegans upon infection. Although many experimental caveats remain to be resolved, I found that the expression of the replication-defective Orsay virus RNA1 segment in the genomic and complementary orientations, mimicking the double-stranded RNA (dsRNA), was sufficient for activating an antiviral response in C. elegans. This highlights that the mechanism of virus sensing in C. elegans is potentially similar to dsRNA recognition in mammalian cells, which depends on RIG-I-like receptor (RLR) family of proteins. In summary, I was able to address the theme of host-virus interactions from different angles. I have expanded our knowledge of post-entry C. elegans host factors by identifying viro-9 as a pro-viral host gene with an evolutionarily conserved function. Additionally, I identified potential substrates that may be involved in virus recognition in C. elegans, which may share similarities with those previously described in other organisms. Overall, these findings could open research avenues on biochemical pathways that could potentially be targeted as part of a therapeutic intervention