The evolution of Oskar function in insects

The emergence of genetic novelty underlies major shifts in the evolution of development. In this thesis, I investigate evolution in primordial germ cell specification in insects, with a particular focus on the gene oskar. As a lineage-restricted, rapidly evolving gene with essential roles not only in the germ line, but also in the developing nervous system of some species, oskar presents a compelling case study of how genetic innovation drives phenotypic evolution. First, I synthesize observational and experimental data on the origin of primordial germ cells to describe how germ cell specification has evolved in insects, and more broadly across panarthropods. I also speculate on how evolution in germ line gene expression and function may drive shifts in the mechanisms of germ cell formation. Next, I specifically investigate evolution in oskar, which has undergone functionally significant sequence divergence over a short evolutionary timescale. I determine how protein-coding sequence differences between oskar orthologs from Drosophila melanogaster and D. virilis prevent the D. virilis ortholog from rescuing D. melanogaster oskar loss-of-function. I identify domains of the D. virilis Oskar protein that differentially impact localization of germ line and patterning determinants and dramatically influence downstream cell fate decisions. By leveraging this natural sequence variation as an evolution-guided mutagenesis strategy, I uncover new insights into the in vivo mechanisms of Oskar function. These experiments also reveal how oskar gene dosage affects germ plasm assembly and germ cell specification, shedding light on how embryos respond to changes not only in gene sequence but also quantity. Finally, I explore the potential co-option of oskar to different tissue contexts. I present preliminary data testing the hypothesis that oskar is expressed in the central nervous system of D. melanogaster, and I describe ongoing efforts to characterize oskar expression and function in other insect species. This broader comparative approach will eventually allow us to reconstruct the trajectory of oskar’s functional evolution across insects. I conclude by outlining promising directions for future research into the evolution of development, particularly through the lens of the genes that both influence and are influenced by these processes.Biology, Molecular and Cellula

“Still Nothing About Silesia”: Codifying Regional Family Memory in Polish Literature After 1989

This dissertation examines how Upper Silesia is represented in post-1989 Polish literature. A historical region currently divided between Poland and the Czech Republic, Upper Silesia was once a contested borderland and site of contact between Polish and German cultures, as well as a hub of heavy industry, especially coal mining. After Poland’s current borders were decided in 1945, numerous factors—including mass migration and deportation, the repression of regional differences by the communist regime, Polish-language education, and ongoing processes like deindustrialization—had begun to radically alter the region’s cultural identity, drawing it closer to the Polish mainstream. Starting in the period of Poland’s transition from communism to democracy and ending in the present-day, my work asks how Upper Silesia is constructed within the Polish-language literary imagination, as exemplified by several books about the region that have gained prominence among national audiences and critics. The works studied are stylistically divergent, ranging from from an autobiographical essay, to historical novels, to book-length nonfiction, to a realist novel. Close readings of these texts identify genre conventions, as well as the cues that serve to code works as Upper Silesian or not. I argue that across formal conceits and time, a certain set of conventions, i.e., occasional Silesian language use and dramatic references to specific events of twentieth-century history, have become a shorthand for Upper Silesian identity on the contemporary Polish book market. Crucially, when these conventions are absent from literary works—-even ones that are set in Upper Silesia and centered on local life—the texts in question are not necessarily read as “Upper Silesian” or “regional” by audiences and critics. Nonetheless, images of family life, inheritance, and memory come into sharp focus in all of the texts I study, implying that works about life in Upper Silesia that have attained some degree of national prominence share themes of family and memory, regardless of how “regional” they are considered to be. Chapter One begins with the seeming absence of Upper Silesia from the regional writing boom of the 1990s. First, I argue that certain regions were better represented than others in this period due to genre conventions and the critical discourse surrounding nostalgic writing. Then, I turn to Adam Zagajewski’s 1991 autobiographical essay, “Dwa miasta” (“Two Cities”), suggesting that Zagajewski’s choice not to include references to regionally-specific language and history led many critics not to label the work as Upper Silesian, despite its setting. Chapter Two identifies the 2010s as a moment of emergence for Upper Silesian themes on the Polish book market, due in no small part to the historical novels of Szczepan Twardoch. I analyze his 2014 novel, Drach (Dragon or Paper Dragon in Silesian), one of the first texts centered exclusively on Upper Silesian history to achieve national success. I contend that Twardoch engages with and ultimately defies both the left- and right-coded tropes of the Polish media discourse as he constructs a compelling narrative about Upper Silesian anti-heroes and other flawed regional characters. Twardoch’s work is contrasted with Anna Dziewit-Meller’s 2016 novel, Góra Tajget (Mount Taygetus), which educates national audiences about the wartime and postwar suffering of Upper Silesians, at times referencing the Holocaust. Despite their differences, both novels seem to situate Upper Silesian cultural distinction in the dramatic events of the twentieth-century, just as they deploy the Silesian language. Chapter Three studies Zbigniew Rokita’s 2020 reportage, Kajś (Somewhere in Silesian), book-length nonfiction centered on the author’s decision to learn more about his Upper Silesian heritage in the hope of claiming a regional identity for himself. While this work offered national audiences an accessible guide to Upper Silesian history and an introduction to debates on the Silesian language, its very premise implies that regional belonging is in some way tied to familiarity with twentieth-century history and a basic knowledge of Silesian, rather than simply living in the region. Finally, Chapter Four reads Anna Cieplak’s 2021 novel, Rozpływaj się (Melt Away), which lays bare the inner voices of four struggling residents of Upper Silesia spanning from the 1990s to contemporary period. The novel’s protagonists do not display an interest in or knowledge of regional history and only speak Silesian when forced to by their elders. I conclude that Cieplak’s novel points to the contemporary ambivalence of Upper Silesian identity when it is not fixed on the events of the early to mid twentieth-century that are writ large in regional history. The dissertation ends with a brief epilogue about other art forms that express regional culture, emphasizing that Upper Silesian cultural expression should not be seen as exclusive to the particular conventions and audiences of Polish-language literature as they have developed in the past thirty years. Keywords: Poland, Upper Silesia, Literature, Prose, RegionalismSlavic Languages and Literature

Correlated interlayer excitons in van der Waals semiconductor heterostructures

Interlayer excitons (IXs) are bound pairs of spatially-separated electrons and holes that occur in in type-II van der Waals heterostructures. They exhibit long lifetimes and mutual dipolar repulsion, in addition to strong interactions with unpaired electrons and holes that lead to the formation of charged IXs. To study the effect of correlations and manipulate the IXs, we design highly tunable nanodevices based on atomically thin semiconductors. Our efforts enable the study of a wealth of correlated excitonic states. In two-dimensional light-emitting diodes, we reveal the effects of defect-mediated electron localization on IXs and diode operation. We unveil the novel phenomenon of steady state cooperative electroluminescence from incoherently injected, electrically generated IXs. Lastly, we employ gate-mediated electrostatic confinement to controllably trap IXs and study their behavior at high densities, discovering novel features about the IX ionization phase diagram. These results expand our understanding of non-equilibrium phases of matter, and hold promise for creating optoelectronic devices for both future classical and quantum technologies.Engineering and Applied Sciences - Applied Physic

Disruptive Innovation or Competitive Advantage? Generative AI and the Future of the Hollywood Studio System

Generative AI has been a global hot-button issue, but no more so than in the Hollywood film industry. Hollywood was blindsided when in 2022, AI technology such as DALL-E and later Sora, debuted, demonstrating how original images could easily be created solely from text prompts, or how traditional movie sets and locations for filming could be generated by AI, for a fraction of the cost to travel. The industry has since oscillated between states of panic, disbelief, and insurgency over the topic and its possible use to displace creative workers. This innovative technology even triggered a new crop of AI-native and hybrid studios to appear in the entertainment industry. Many of these new entrants are promising, highly efficient workflow models utilizing AI that could reduce filmmaking costs and circumvent the traditional workflow processes and tools employed by the traditional studio incumbents. Other new AI studio entrants specifically target AI to disrupt the traditional studios and democratize the film industry. But is GenAI really “disruptive technology”? Or could the incumbent studios use GenAI to gain a competitive advantage over their incumbent rivals, as well as fend off these new AI native challengers, while also better serving their consumers? If incumbent studios continue to resist this technology, is it possible for new AI studio entrants to disrupt and supplant their dominance over the entertainment industry? This thesis explores the current entertainment industry landscape in the shadow of rapidly emerging AI technology and dissects the historical complexity of the Hollywood studio system to identify historic themes and patterns, macroeconomic trends, and business model design elements. These are analyzed through the lens of grounded business theories, including Clay Christensen’s Theory of Disruptive Innovation. My aim is to gain insight into the industry’s behaviors and the studios’ institutional beliefs in order to better understand the scope of how AI could be a benefit or detriment to their strategic positioning and business offering.Extension Studie

STEM Characterization of Atomic and Ferroelectric Microstructure in Barium Titanate Thin Films

Thin film barium titanate is a promising material platform for photonic devices that allow for on-chip laser physics. These devices take advantage of the electro-optic effect, where the speed of light through a material varies with an applied electric field, and thus these devices must be fabricated on a material that has a high electro-optic coefficient. Barium titanate is one such strongly electro-optic material; however high-quality thin film barium titanate is challenging to fabricate due to its low Curie temperature that makes it prone to cracking. Thin film barium titanate can be grown from the bottom up with molecular beam epitaxy (MBE) and detailed characterization of MBE-grown thin films is needed to optimize growth. Additionally, the high degree of control that MBE affords means that films can be grown intentionally off-composition in order to inform the kinds of defects that may arise in films grown by other methods with less precise stoichiometry control. In this dissertation, I present scanning transmission electron microscopy (STEM) characterization of MBE-grown thin film barium titanate. STEM is used because it is an atomic-scale imaging technique that enables picometer-scale polar domain mapping as well as highly localized defect characterization. Using STEM, I demonstrate the high quality of films achievable with metal-organic hybrid MBE. I also investigate the effect of stoichiometry on atomic and ferroelectric structures in conventional-MBE grown thin film barium titanate. I identify an asymmetry in how the barium titanate lattice accommodates off-stoichiometry composition; excess titanium leads to disordered polar structures whereas excess barium forms a water-soluble surface layer on an otherwise well-ordered film.Engineering and Applied Sciences - Applied Physic

Target identification by chemical proteomics and bioinformatic investigations with small molecule ligands

Understanding the protein targets and mechanisms of action of bioactive small molecules remains a central goal in chemical biology and drug discovery. Unbiased approaches, particularly chemical proteomics and systems-level bioinformatics, have emerged as powerful strategies to uncover the molecular interactions and biological consequences of small molecule engagement in cells. In this thesis, I apply these complementary methodologies—activity-based protein profiling (ABPP), photo-affinity labeling (PAL), and bioinformatic analyses—to investigate two distinct but mechanistically rich chemical spaces: opioid analgesics such as heroin and morphine, and cereblon (CRBN)-binding immunomodulatory drugs (IMiDs) that induce targeted protein degradation. Chapter 1 introduces the conceptual and methodological foundation for this work, beginning with a background on ABPP and PAL, highlighting their ability to turn small molecules into molecular probes that illuminate their target landscapes through quantitative mass spectrometry. The chapter also introduces gene ontology (GO) annotations and the database for annotation, visualization, and integrated discovery (DAVID) bioinformatics suite, which are essential for contextualizing proteomic hit lists. Further, I provide an overview of machine learning principles and illustrate how these computational tools can accelerate target identification and therapeutic discovery. The chapter concludes with two thematic deep dives: a historical and pharmacological overview of opioids and their receptors and the development of chemical probes to study them, and a survey of CRBN biology, including the evolution of IMiD-based molecular glues and the discovery of the endogenous CRBN degron—the cyclic imide degron—formed either spontaneously from protein damage or enzymatically via Protein-L-isoaspartate O-methyltransferase (PCMT1). Chapter 2 describes the design, synthesis, and characterization of novel chemical probes for morphine and heroin, including photo-click morphine (PCM-1, PCM-2) and the acyl-donating probe Di-Alkynyl-Acyl-Morphine (DAAM). These tools were validated for their ability to engage opioid receptors and induce G-protein signaling. Confocal imaging revealed receptor-independent localization of these probes to lysosomes across diverse cell lines. Chemoproteomic analysis uncovered voltage-dependent anion channel 1 (VDAC1) as a shared target across all probes and identified lysine 234 of solute carrier family 25 member 3 (SLC25A3) as a selective site of acylation by DAAM. This residue was later confirmed to be directly acetylated by heroin itself, representing one of the first demonstrations of small-molecule-mediated post-translational modification by heroin. These findings suggest potential mechanisms for the mitochondrial and metabolic dysfunctions associated with chronic heroin use. Chapter 3 focuses on the proteomic and computational reanalysis of the Broad Institute’s PRISM screen using the CRBN-dependent degrader DEG-35. By separating wild-type from mutant populations and refining statistical comparisons, I report biologically meaningful indicators of sensitivity, including intact p53 signaling, protein Mdm4 (MDM4) dependency, and alterations in the switch/sucrose non-fermentable (SWI/SNF) complex. I report the development of a multilayer perceptron (MLP) model trained on the Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) viability data to predict DEG-35 sensitivity across the extended DepMap cell line repository. The model achieved strong performance (Area under the Receiver Operative Characteristic Curve (AUROC) = 0.98) and accurately identified sensitive cell lines, including SCCOHT-1, which is actively being experimentally validated. This work highlights the potential of integrating chemogenomics data with machine learning to stratify responders and uncover mechanistic biomarkers. Chapter 4 presents a novel inversion of traditional GO analysis using the DAVID tool: instead of applying GO terms post hoc to hit lists, I used it as a filtering method for hypothesis generation. Starting with all human proteins ending in C-terminal asparagine or glutamine—potential substrates for PCMT1-mediated cyclic imide formation—I performed annotation clustering and literature-driven prioritization. From this list, Hairy and Enhancer of Split 1 (HES1) emerged as a top candidate. In vitro assays confirmed that PCMT1 catalyzes the formation of the cyclic imide degron on the HES1 C-terminus, enabling CRBN binding. Full-length HES1 showed PCMT1-dependent CRBN engagement, and follow-up experiments in SH-SY5Y cells demonstrated that knockout of either PCMT1 or CRBN led to impaired neuronal differentiation, suggesting a role for this degradation pathway in developmental timing. These findings advance our understanding of CRBN’s endogenous substrates and open new directions for exploring its role in neurodevelopment. Together, this thesis demonstrates how integrative chemical biology—uniting chemical proteomics, computational modeling, and bioinformatics—can illuminate the complex interactions between small molecules and the proteome, uncover new biological mechanisms, and inspire new directions for therapeutic or biological discovery.Chemistry and Chemical Biolog

The Production of Democracy

Our economic cooperation is marked by hierarchical relationships. Most people work under the authority of unaccountable managers, while a minority of wealthy investors shape the future of productive enterprises. Yet, economic hierarchy is rarely considered as problematic as political hierarchy such as oligarchy or restrictions on voting rights. Democracy is thought to impose demanding requirements on state political institutions, but at best overridable recommendations on economic institutions. Behind this view lies the idea that the democratic state controls and regulates the economy from a higher standpoint of equality. However powerful economic superiors may be, they are ultimately subject to a political system that treats everyone as equals. Thus, democratizing the economy is unnecessary; political democracy can justify economic hierarchy. I call this line of thought the State-above-the-Economy Argument. My dissertation argues against it, in favor of what I call a dual-core theory of democracy. My argument proceeds in three steps. First, I clarify the political nature of the modern economy and the kind of justification it demands. Our economic cooperation is structured through asymmetrical subjection to power and authority, effected through society’s overarching institutional framework. These institutionalized relations of subjection constitute an informal political system, which must therefore be evaluated according to the principles of democracy, not just efficiency. Second, while economic institutions are often thought to be exempt from the requirements of democracy by virtue of being governed by a democratic state, I argue that this view is mistaken. The democratic state is itself constrained in its power, legitimacy, and knowledge by the very economic structure it is supposed to govern. Democracy’s demands on the economy cannot be outsourced to the state; economic institutions themselves must be brought within the scope of democratic justification. Finally, how are we to recover the democratic ideal in light of the economy’s profound constraint on politics? A common response demands moral discipline: economic actors must subordinate themselves to the sovereign democratic state’s will. I reject this view. Contestation in and through the economy, when properly structured, can be a force for democracy. Thus, the question is not whether but how economic rights constrain political decision-making. Rather than seeking to insulate politics from economic power, we must theorize democracy as a justifiable form of interdependence between the state and the economy.Philosoph

Reconnection-Driven Flares in Magnetized Astrophysical Plasmas: From the Solar Atmosphere to Sagittarius A*

Energetic flares are observed across magnetized astrophysical systems, from stellar coronae to the inner regions of black hole accretion flows. Interpreting their emission remains a challenge, as the underlying physics spans a vast range of spatial and temporal scales—from kinetic-scale particle acceleration to large-scale magnetic structures that govern global energy release. On the observational side, I present the development and first flight of a high-cadence soft X-ray imaging system flown in the 2024 NASA Solar Flare Sounding Rocket Campaign. The instrument leverages delta-doped, back-illuminated CMOS sensors to achieve sub-second imaging in the 0.5–10 keV band, enabling improved temporal resolution of flare dynamics in the solar corona. On the theoretical side, I present fully three-dimensional general relativistic particle-in-cell (GRPIC) simulations of magnetic reconnection in relativistic, high–guide field plasmas, motivated by flares from the supermassive black hole at the center of our galaxy. Through analysis of particle acceleration and synchrotron emission, we offer a physical explanation for the observed diversity in infrared and X-ray flares from Sagittarius A*. Taken together, these efforts demonstrate how new observational tools and high-fidelity simulations can jointly advance our understanding of reconnection-driven energy release across astrophysical environments.Astronom

GeopoliticalStrength in Religious Ties: How Diplomatic Relations Between the Vatican and Post-Revolutionary Iran have Bolstered Iranian Resilience

Numerous players influence those at the helm of the global political stage. Yet dominant state powers, especially democratic ones, remain at the forefront. They set the tone, reshape borders, dictate trade, and attempt to instill peace in times of instability and turmoil. In the today’s world, where information is immediate and no global event is “unsearchable,” traditional rules are no longer uniplanar as to what international relations and diplomatic means may drive intrastate dialogue and change. Unlikely players can hold immense power. This thesis outlines one salient example of significant impact relating to relations between two unique, noncentral players: the Islamic Republic of Iran, and the Holy See (herein referred to as “the Vatican”). At face value, most would not think that these two bodies share much in common. Beliefs, social norms, and political disposition vis-à-vis the rest of the world, are vastly different. Yet, upon deeper inspection we find many similarities, shared beliefs, common causes, and appreciation for what each represents. Importantly, both entities hold significant political and spiritual power over their citizens and adherents. Contrast this with the most powerful political authority on Earth, the United States. Hailed for democracy and freedom fighting, feared for its mighty military, and envied for its development and wealth, the U.S. sits at the top of all global powers. But this position comes with immense responsibility and expectations. Not only is the U.S. expected to assist in maintaining global stability, but the democratic values of the country’s leadership and its citizens empower it to export democracy to all who will listen and even to those who will not. While sentiments had been building for decades, the terror attacks of September 11 exacerbated intolerance for dissimilar players. If you are not democratic, it is difficult to be viewed positively by the U.S., however it is the right of individual nations to determine what political structure will bind them and that democracy is not always the choice. Some nondemocratic entities are benign, such as the Vatican, while others present an adversarial threat to democracy, for example, postrevolutionary Iran. Ironically, these two are similar politically in that they both follow theocratic principles. But one heads a list of top five foreign policy priorities and threats to the U.S., and the other heads a list of friends, eager to be engaged in times of needed counsel. Through this thesis, I will show how the U.S. and the Western world find relations with the Vatican useful when convenient. On the other hand, I will outline how a deeper, religious bond between the Vatican and Iran has come to supersede the mere diplomatic relationship between the U.S. and the Vatican. I will explain how Vatican– Iranian relations have yielded unexpected gains for Iran and have bolstered their political body when most of the world has stood against them.Extension Studie

Dissecting spatial tumor-immune microenvironment in response and resistance to immune checkpoint blockade in metastatic melanoma

Immune checkpoint blockade (ICB) therapies have markedly improved the prognosis for patients with stage III & IV metastatic melanoma by prolonging progression-free and overall survival rates. However, the variability in mechanisms of immune evasion and resistance present significant challenges in the clinical efficacy of ICBs. This project aims to define drivers of immunotherapy response and resistance by employing advanced genomic, single cell mRNA analyses, and spatial profiling techniques on tissue biopsies from metastatic melanoma patients. In this study, we developed a framework to analyze response and resistance, both intrinsic and acquired, via immune features in the tumor microenvironment in a standardized, uniformly processed, and deeply clinically annotated cohort of metastatic melanoma patients (n=61) treated with ICB as part of the human tumor atlas network (HTAN) initiative1,2. From the tumor samples, we conducted single-nucleus RNA sequencing, and for a subset of the samples, high-resolution spatial imaging (including protein mIHC, CODEX, and MERFISH transcriptomics). Standardized processing and data pipelines allowed for the integration of genomic, transcriptomic, and spatial features to elucidate characteristics and mechanisms in the tumor microenvironment and their relationships with resistance. For this thesis, I focused on MERFISH spatial transcriptomics analysis. Single-nucleus RNA sequencing analysis revealed CXCL13+CD4+ T cells and ISG+CD8+ T cells as the strongest predictors of durable clinical benefit (DCB) among all immune populations, independent of clinical confounders. We also identified five recurrent cellular neighborhood modules: extreme responders are enriched in B cell–enriched RCNs with close T–B cell distance, non-responders in tumor–myeloid and tumor–myeloid–stromal interface RCNs, and non-extreme responders in tumor-dominant and stromal–immune interface RCNs. This project integrates transcriptomic and spatial features to elucidate shared tumor and microenvironmental states and their relationships with resistance, guiding more personalized and effective treatment strategies for metastatic melanoma.Graduate Educatio