Washington University Medical Center

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    Barriers and Breakthroughs in the Evolution of Aggregative Multicellularity

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    The evolution of multicellular organization represents a key innovation in the history of life, yet fundamental questions remain about the evolutionary mechanisms that allowed some lineages to achieve remarkable complexity, while constrained others in their elaboration. The widely accepted single-cell bottleneck model provides a compelling explanation for the success of clonal multicellularity by reducing internal conflict and facilitating developmental integration. However, this perspective does not fully account for the stability and repeated evolution of aggregative multicellularity, where cooperation emerges among previously independent cells that may not be genetic relatives. Aggregative multicellularity demonstrates that the evolution of multicellularity is not a singular process and challenges our understanding of how multicellular complexity evolves and persists. These systems provide unique opportunities to examine how evolutionary and developmental processes intersect to enable major transitions in biological organization. My research focuses on an integrative analysis of aggregative multicellularity combining social evolution theory, experimental manipulation, comparative phylogenomics and transcriptomics. Using the social amoeba Dictyostelium discoideum as a model system, I examine three key aspects of aggregative multicellularity: mechanisms maintaining group integrity, developmental coordination between cells, and evolutionary constraints on developmental innovation. I demonstrate how collective behavior can emerge and persist despite potential genetic conflicts in the evolution of aggregative systems. First, through a comprehensive synthesis of empirical evidence from D. discoideum and the bacterium Myxococcus xanthus, I demonstrate how aggregative organisms employ multiple complementary mechanisms to maintain cooperation, including population structure, kin discrimination, and pleiotropic constraints on cheating. This analysis reveals that while aggregative multicellularity faces unique challenges compared to clonal development, robust solutions have evolved to maintain group cohesion. Second, I experimentally tested whether mixing genetically distinct cells impairs developmental coordination independent of social conflicts. Using experimentally evolved lines of D. discoideum that were not selected for social traits, I found that while basic coordination of slug migration remained intact in chimeric mixtures, there was a significant failure in coordinating migration with spore production. This provides the first direct evidence that developmental incompatibilities, separate from social conflicts, can emerge between divergent cell lines. Third, through phylogenomic and transcriptomic analyses spanning the developmental and evolutionary history of all protein coding genes in D. discoideum, I showed that early developmental stages are dominated by ancient genes while novel genes are predominantly expressed later in development. This pattern supports von Baer\u27s law of early developmental conservation and reveals how evolutionary innovations become integrated into aggregative development. Together, these findings demonstrate that aggregative multicellularity represents a distinct but viable evolutionary strategy that has solved fundamental challenges of collective organization through multiple mechanisms operating at different scales. This work advances our understanding of major evolutionary transitions and highlights how different routes to multicellularity navigate universal constraints while finding unique solutions

    Nanoengineered Constructs for Immunomodulatory Therapeutic Delivery

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    Immune processes are central to aspects of human health ranging from wound healing to pathogen recognition, yet even within the field of drug delivery, immunomodulatory therapeutics remain relatively niche. In this work we apply nanoscale peptide, lipid and polymer engineering principles to address present challenges in immunomodulatory therapeutics delivery, particularly in the treatment of non-healing wounds and vaccination against flaviviruses and other pathogens that exhibit antibody dependent enhancement. In both cases, nanoengineered delivery systems allowed us to overcome challenges associated with immune hyperactivation using targeted immune stimuli rather than nonspecific signals. A frequent driver of non-healing wounds is failure of local macrophages to “turn over” from a pro-inflammatory to a pro-proliferative phenotype. Although alginate based wound dressings have many favorable properties for wound healing, they are canonically crosslinked by Ca2+ ions, which can be potently pro-inflammatory if they leach into the extracellular wound environment. By developing two alginate sols, each composed of alginate polymer conjugated to several peptides of one member of a heterodimeric coiled coil pair, we were able to synthesize a self-supporting, self-healing hydrogel by mixing those sols. This coiled coil crosslinked gelinduced significantly lower macrophage driven inflammation than Ca2+ crosslinked alginate gels both in ex vivo culture of mouse peritoneal macrophages and after in vivo intraperitoneal implantation. Flaviviruses and other diseases that exhibit antibody-dependent enhancement are difficult to vaccinate against because immunization with the whole inactivated or attenuated pathogen can generate cross reactive and non-neutralizing antibodies to other pathogens which can make infections with those other pathogens far more lethal. To avoid this outcome, vaccines for such pathogens must contain only specific, highly-immunodominant, poorly-conserved epitopes so as to avoid antibody cross-reactivity. This presents difficulties with adjuvation as isolated peptides or epitopes have generally poor intrinsic immunogenicity. To address this concern, we developed nanocarriers that can localize specifically to plasmacytoid dendritic cells (pDCs), a cell population specialized in production of type-I interferons. To do this we capitalized on the homogenously high expression of CD71, a ubiquitous endocytosing iron transporter, by pDCs. By synthesizing nanoscale liposomes surface coated with poly(ethyleneglycol) and either gambogic acid or T7 as small molecule or peptide noncompetitive CD71 ligands respectively we were able to selectively deliver liposomes to pDCs over other leukocytes both ex vivo and in vivo. Further, we demonstrated that these liposomes effectively home to secondary lymphoid organs after subcutaneous administration and elicit type-I interferon stimulation through and IRF-7 dependent pathway when used to deliver ODN 2216 as a TLR9 agonist. Collectively, these developments contribute to a growing corpus of nanoengineered constructs for immunomodulation and may pave the way for enhanced wound healing technology, treatments for autoimmune disorders, vaccine and drug delivery and treatments for cancer

    The Other Delaware Effect

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    This paper examines the effects of Delaware’s 2015 ban on fee-shifting provisions in corporate charters and bylaws, a significant legislative intervention in corporate law aimed at curbing managerial powers. The Delaware Supreme Court had approved these provisions just one year earlier as part of a series of measures aimed at curbing shareholder litigation. Because of their perceived substantial potential to reduce wasteful litigation, the Delaware legislature’s ban led many to predict an exodus of corporations from Delaware and the continued spread of fee-shifting provisions in other states.Contrary to these predictions, this study finds that the ban did not trigger a significant departure of corporations from Delaware. More importantly, it also documents a sudden decline in the adoption of fee-shifting provisions outside Delaware, where most states did not enact similar prohibitions. The paper argues that this decline is most likely due to a spillover effect: Adoptions declined not because Delaware’s ban on fee-shifting provisions coincided with a shift in market sentiment against these provisions, but because this ban stymied their adoption nationwide. The paper explores the mechanisms through which Delaware’s corporate law can influence governance practices elsewhere, including shareholder empowerment and law firms’ reluctance to recommend provisions that have been outlawed in Delaware. It concludes that Delaware’s legal leadership might be able to set informal norms that influence the behavior of important gatekeepers and other actors in the corporate governance ecosystem, effectively constraining the actions space of managers of corporations incorporated elsewhere.By exploring these mechanisms, the paper contributes to a deeper understanding of the forces that shape corporate governance practices in the United States. It offers insights into the ways Delaware’s rules affect corporate governance practices that subsequently reverberate throughout the U.S. corporate landscape. Besides exploring important and previously overlooked aspects about Delaware’s role as a standard setter in today’s corporate law world, it also adds to our understanding of the diffusion of corporate governance innovations and regulatory competition. Additionally, the paper demonstrates the potential of artificial intelligence tools, such as large language models, to revolutionize empirical legal research by automating the extraction of legally significant provisions from corporate documents, allowing researchers to investigate previously underexplored questions at scale

    Matching Student-Debt Payments with Retirement Contributions Has High Appeal for Low-Wage Workers: Implications for SECURE 2.0

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    Whether to prioritize paying down student debt now or saving for future retirement is a difficult choice, especially for low-wage workers. The SECURE 2.0 Act of 2022 allows employers to match employees’ qualified student-debt payments with contributions into their retirement plans, essentially allowing the employee to save and invest while paying down debt. This research brief draws upon data from the Workforce Economic Inclusion and Mobility (WEIM) survey of a nationally representative sample of vulnerable workers in the United States to examine how such student-loan matching programs affect the retirement savings behaviors of how low-wage workers and how offering these programs would affect employee perceptions of their employer. IMPLICATIONS for SECURE 2.0 This is the first research brief in a series examining the implications of the SECURE 2.0 Act for the retirement security of low-wage workers in the United States. All briefs in the Implications for SECURE 2.0 series can be found at https://csd.wustl.edu/tag/secure-2.0

    Strategic Reactor Allocation for Deadlock-Free Execution

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    As it becomes harder to increase the computation power of a single machine, we are turning towards parallel and distributed systems to extract additional performance by breaking down the problem into pieces and solving it simultaneously. While this provides a great opportunity for increased performance,e it comes with additional problems not present in the sequential approach. One such problem is deadlock. Deadlock is defined as the state in which program execution stalls because the system has run out of resources to manage and execute the program properly, or there exists some circular dependency in the data between parallel or distributed processes. As distributed and parallel systems become more complex, it becomes harder to detect and account for potential deadlock before the system becomes stuck. A proposed system for deadlock prevention is the Live-P protocol which takes information about all potential program executions apriori and annotates a representative DAG to only dispatch tasks when deadlock is impossible. While Live-P is effective at ensuring a deadlock free system it makes certain assumptions about the allocation of tasks to sites that has the potential to create false negatives in the system where Live-P says deadlock is unavoidable but this is due more to a sub-optimal allocation on the system rather than the system itself. We propose a strategy for allocating tasks to sites in these DAG representations of parallel or distributed execution to maximize feasibility while maintaining the Live-P guarantees on deadlock avoidance and liveness

    Held Together, Falling Apart: Classical Ehlers-Danlos Syndrome as Embodied Abstraction

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    Reconciling life within a body defined by fragility, I create worlds of connectivity to embody and refigure Classical Ehlers-Danlos Syndrome (cEDS)–a connective-tissue disorder causing hypermobile joints, fragile skin, easy bruising, and poor wound healing. Large-format oil paintings employ a multi-layer method, layering paint like skin to reform the body onto canvas. Drawing on Surrealist automatic processes and theories of unconscious production, my methodology combines intuitive, process-based mark-making with traditional oil painting techniques and experimental material practices to subvert and reassert artistic agency, weaving between control and surrender. Scientific imagery, particularly SHG imaging of cEDS collagen tissue, informs a visual language that melds art and science in incidental and intentional biological mimicry and mimesis. The grotesque in art provides a theoretical framework through which I reclaim power with material and process-based abstractions of mind-body dissonance. As biomorphic constructions defy personification and traditional figuration, I negotiate cycles of growth and decay and traverse liminal convexities between body, space, and ecology. Building a world through iterative creation, my thesis engages discourses from Petra Kuppers, Lennard Davis, and N. Ann Davis surrounding invisible disability representation. I expand beyond visual markers of disability to expose physical and psychological realities while encouraging my art to grow beyond itself into a self-reflexive ecosystem of abstraction. Process becomes power as my practice weaves biomorphic ecosystems wherein body and environment coalesce, transforming personal experience into a visual language that mirrors how those with invisible disabilities are shaped by—but grow beyond—our diagnoses

    Women, Azaadi, Shadhinota, Freedom

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    This thesis investigates the intersections of performance, memory, race, and erasure through the lens of feminist, decolonial, and diasporic practice. Centering the body as both archive and site of resistance, I explore how performance intervenes in dominant historical narratives by foregrounding voices and experiences that have been silenced, displaced, or deemed unarchivable. Drawing from personal experience as a South Asian Muslim woman navigating academia in the U.S., my work examines how structures suppress grief, dissent, and political witnessing—particularly when the lives in question are racialized, feminized, or marginalized. Through installations, photographs, and time-based performances such as Aam Pata Jora Jora, What Is the Cost of Life? The Brown Pilgrim, Who Cleans After a Genocide? and Present: 0, I challenge the permanence of archives and monuments, proposing performance as a radical, embodied alternative for remembering. Each work addresses systemic violence—from colonial gender scripts and racialized policing to global genocidal silence—inviting the audience to confront their own roles as bystanders, beneficiaries, or implicated subjects. By referencing theorists such as Sara Ahmed, Gayatri Spivak, Michael Rothberg, Rebecca Schneider, I frame my practice within a critical discourse that interrogates institutional complicity and the politics of visibility. Ultimately, this thesis proposes performance as a fugitive space where erased histories and buried voices are momentarily resurrected, where mourning itself becomes a radical act, and where survival is reframed as resistance

    Developing a Protective PCM Layer for an Aluminum Sheet

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    As electric vehicles (EVs) become increasingly prevalent, improving the thermal safety of battery systems is essential. This study investigates the development of a high-temperature-resistant coating for aluminum sheets, aimed at mitigating thermal runaway events by incorporating carbonate-based phase change materials (PCMs). Using a PTFE binder and calcium carbonate as the primary PCM, the coating was applied via airbrush to maintain a thin, even layer. Initial results showed the coating was thermally resilient but suffered from poor adhesion and mechanical strength, as demonstrated by failed hardness tests and inconsistent thermoconductivity data. Surface etching with sulfuric acid improved visual adhesion, suggesting potential benefits for coating durability. However, the binder’s low scratch resistance indicated the need for stronger alternatives. Future work will explore new binders, improved application methods like blade coating, and surface pretreatments to enhance coating performance. These refinements aim to produce a coating that enables aluminum casings to resist extreme heat during battery failure, contributing to safer and more robust EV battery systems

    Efficient Maryland State Elementary School Classroom MEMS 400, Spring 2025

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    Elementary school children spend most of their developmental years attending and sitting in classrooms. The purpose of this this study was to design an energy, cost, and psychologically efficient classroom. Extensive research on mechanical, electrical, and architectural design options was performed. Codes, standards, and an interview with an elementary school teacher guided the design selection process. In the end, the classroom was modeled in Revit and mirrored create the wing of a school. It was found that most classrooms have similar design choices due to their combined efficiency in energy, cost, and psychology. However, as the world advances, small changes are made over time which could morph into an entirely different classroom design

    Spray-cooling methods for thermal management applications

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    he purpose of this independent study was to investigate spray-cooling methods for thermal management applications, particularly for relatively high heat flux, low-temperature systems (e.g., electronics cooling and advanced energy systems). The goal was to conduct a detailed literature review on related research to define key scientific questions and identify gaps in current methods, thereby formulating a focused thesis topic. By systematically examining recent advancements and techniques in spray cooling, this independent study report lays the groundwork for comprehensive experimental investigations in the next stage of my M.S. in Mechanical Engineering degree

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