Digital Commons Network^™

Understanding And Quantifying Behavior For Unraveling Brain Function, Daiyao Yi

Yale Graduate School of Arts and Sciences Dissertations

Understanding the relationship between neural activity and behavior is fundamental to uncovering brain function. With recent advancements in hardware and computation, we can now collect and analyze high-resolution behavioral and neural data in complex, naturalistic settings. However, challenges remain in effectively modeling and disentangling high-dimensional behaviors, particularly in social and multi-subject contexts, where subtle variations may reflect individual differences or underlying neural states.

This thesis presents a series of structured, interpretable deep learning frameworks that address this challenge by modeling behavior and its neural correlates across multiple levels. First, I introduce the Constrained Subspace Variational Autoencoder (CS-VAE), which uses semi-supervised …

Aberrant Splicing Exonizes C9orf72 Repeat Expansion In Als/Ftd, Suzhou Yang

Yale Graduate School of Arts and Sciences Dissertations

A nucleotide repeat expansion (NRE) (GGGGCC)n in the first annotated intron of the C9ORF72 (C9) gene is a common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While previous studies have shown that C9 NRE produces several toxic dipeptide repeat (DPR) proteins, how an intronic RNA segment can access the cytoplasmic translation machinery remains unclear.

By capturing and sequencing NRE-containing RNAs from patient-derived fibroblasts and neurons, I found that C9 NRE became part of an alternatively spliced exon 1 through the usage of various downstream 5ʹ splice sites. These NRE-containing splice isoforms accumulate in C9 ALS/FTD brains, …

The Gnda Microprotein Supports Atp Homeostasis In Escherichia Coli During Heat Shock, Jessica Jayne Mohsen

Yale Graduate School of Arts and Sciences Dissertations

Same-strand overlapping, or nested, open reading frames (ORFs) can optimize the information content of size-constrained viral genomes by increasing the number of proteins expressed from a limited nucleotide sequence. However, nested small open reading frames (sORFs) were previously omitted from prokaryotic and eukaryotic genome annotations. It was therefore surprising when numerous nested sORFs were recently discovered in bacteria and eukaryotes. Our case study of the GndA microprotein in Escherichia coli provides evidence of an emerging model that overlapping genes can be expressed from bacterial genomes to contribute to cellular fitness. GndA interacts with the electron transport chain and ATP synthase …

Adaptation Of Learning Dynamics And Feature Representations Via The Neural Kernel, Lianghui Peng

Yale Graduate School of Arts and Sciences Dissertations

The ability to learn from experience is essential for both biological and artificial agents. To learn efficiently in complex, high-dimensional environments, agents must generalize strategically from limited data by focusing on features relevant for the task. The generalization strategy, known as inductive bias, shapes the dynamics of learning. Previous works have established the theory of neural tangent kernels that describes the learning dynamics of artificial neural networks. However, a comparable framework for understanding and quantifying inductive bias in biological systems performing behavioral tasks remains underdeveloped. Here, we introduce a neural kernel framework to characterize inductive biases of humans and artificial …

Bridging Behavior And Neural Activity: Neural Dynamics Leading To Self-Initiated And Task-Driven Movements, Yongxu Zhang

Yale Graduate School of Arts and Sciences Dissertations

Understanding how populations of neurons generate behavior remains a fundamental question in neuroscience. While single-neuron analyses have provided valuable insights, behavior emerges from the coordinated dynamics of large neural ensembles that evolve over time and across states. A major difficulty is that neural population activity is non-stationary: it exhibits temporal distributional shifts, transitions between distinct dynamical regimes, and modulation by external or inter-regional inputs. Advances in artificial intelligence offer new opportunities to address this challenge. Yet, conventional models, such as standard recurrent neural networks, often fail to capture such complexity, limiting both predictive performance and mechanistic interpretability. This motivates the …

Impressions Contain Multitudes: Evaluative Inertia, Updating, And Lingering Impressions After Learning About Others, Arin Korkmaz

Yale Graduate School of Arts and Sciences Dissertations

People routinely learn new information that challenges their impressions of others, yet these impressions are not always updated. This dissertation investigates the conditions under which people retain or update their self-reported explicit and spontaneously activated implicit impressions in response to novel counterattitudinal information. It consists of three bodies of work showcasing the cognitive and contextual factors that lead to evaluative inertia or updating. First, it shows that people can make context-based inferences to retain their implicit impression of others, highlighting the role of higher processes in implicit impression updating. Second, it investigates what happens to initial impressions once they are …

Outside The Workshop: Alternative Spaces Of U.S. Printmaking, 1935–1977, Michelle Donnelly

Yale Graduate School of Arts and Sciences Dissertations

The studio, the land, the camp, and the home are vital locations of print production. Yet scholars have overwhelmingly focused on prints made in the workshop, or an institutional facility stocked with specialized equipment and overseen by “master printers.” This dissertation investigates how women artists and artists of color expanded the parameters of printmaking outside the traditional site of the workshop from 1935 to 1977 in the United States. Each spatially organized chapter centers on one artist: David Hammons, Sari Dienes, Matsusaburo “George” Hibi, and Ruth Asawa. All four artists practiced what I call emplaced printmaking: an engagement with the …

The Organization Of Autophagic Membranes And Proteins At The Phagophore Assembly Site, Devin Michael Fuller

Yale Graduate School of Arts and Sciences Dissertations

Autophagosomes are transient organelles which grow from a seed vesicle to encapsulate a target cargo and subsequently fuse with the lysosome to degrade its contents. This process occurs rapidly and requires the concerted effort of a host of unique membranes and proteins in a complicated cascade, which I detail in chapter I. Deletion of the lipid transport proteins ATG2A and ATG2B results in the accumulation of most of the preceding autophagic membranes and proteins in a large compartment. The ATG2 DKO compartment is advantageous as a model for the phagophore assembly site (PAS) for the following reasons: it is not …

Real-Time Minimum-Weight Parity Factor Decoders For Quantum Error Correction, Yue Wu

Yale Graduate School of Arts and Sciences Dissertations

Quantum error correction (QEC) is essential for fault-tolerant quantum computing, but its practical deployment is limited by the complexity of decoding. Most-Likely-Error (MLE) decoding offers near-optimal accuracy but is computationally challenging, especially for general quantum Low-Density Parity-Check (qLDPC) codes. This dissertation develops a family of Minimum-Weight Parity Factor (MWPF) decoders that accelerate MLE decoding by exploiting the locality and parallelism inherent in the decoding problem. We first improve locality by designing decoders that operate on the sparse decoding hypergraph rather than the dense syndrome graph. This leads to an almost-linear average runtime and enables a generalization to hypergraphs with certifying …

Incorporating Environmental Information Into Genetic Studies Of Psychiatric Disorders, Yue Hu

Yale Graduate School of Arts and Sciences Dissertations

Psychiatric disorders are among the most common diseases of humans, affecting a large number of individuals worldwide and contributing to a considerable burden of disease and disability. With a lifetime prevalence ranging from 5% to 17%, depression – characterized by a persistent low mood or loss of interest in activities for extended periods – is prominent amongst psychiatric disorders. Despite the availability of new medications developed over the past decade to treat depression, long-term treatment response remains disappointing; the risk of death by suicide is over 8-times national averages. Depression is multifactorial with both genetic and environmental factors, including demographic …

Warm Life, Cold Stones: The Effigial Tomb In Late Medieval English Literature, Maia Ruth Béar

Yale Graduate School of Arts and Sciences Dissertations

The effigial tomb is one of the defining features of Gothic sacred art. Tombs topped with grand effigies populated the churches, cathedrals, and chapels of late medieval England and many survive to this day. This dissertation explores the encounter with these tombs as represented in the literature of the period, in particular hagiography, romance, and narrative poetry. Although it literally demarcates the boundary between dead and living, the tomb is a powerful site of boundary-breaking in these texts at which the distinctions between life and death, flesh, and natural and artistic bodies are tested and often complicated. I consider various …

Advancing Neuroimaging Brain-Behavior Machine Learning Biomarkers, Brendan Adkinson

Yale Graduate School of Arts and Sciences Dissertations

Machine learning models trained on human neuroimaging data are increasingly used as tools for predicting individual behavioral phenotypes and enhancing precision medicine. However, multiple limitations hinder their current scientific and future clinical utility. In this dissertation, I address key challenges surrounding "brain-behavior" predictive model interpretability, generalization, and bias. In Chapters 2 and 3, I show that prevalent feature selection practices overlook features that are meaningful for both prediction and neurobiological interpretation. This suggests that prevailing approaches lead to feature overinterpretation and a misrepresentation of the neurobiological bases of brain-behavior associations. In Chapters 4 and 5, I demonstrate that brain-behavior predictions …

Distrust Of Psychotherapy For Biologically Explained Mental Disorders: A Validation Of Beliefs Underlying This Distrust And Interventions To Mitigate This Distrust, Annalise Perricone

Yale Graduate School of Arts and Sciences Dissertations

Lay and scientific communities alike increasingly attribute mental disorders to biological causes (e.g., genetic risk or neurobiological abnormalities). Biological explanations of mental disorders have some beneficial consequences, including reduced personal blame of individuals affected by such disorders. One adverse consequence, however, is that upon learning that a mental disorder has a biological etiology, people tend to show reduced trust in the effectiveness of psychotherapy. Given that the combination of psychotherapy and pharmacotherapy is often optimal for many mental disorders, reduced trust of psychotherapy could result in poorer clinical outcomes, if people elect not to receive such treatment. Although this distrust …

Investigating The Sequence Requirements For Translation Initiation By Viral Internal Ribosome Entry Sites, Sabrina Gulli Grunseich

Yale Graduate School of Arts and Sciences Dissertations

Protein synthesis is both essential and highly regulated. This process is complex and requires the concerted effort of many protein factors. Some viruses have evolved ways to co-opt host translation during initiation by using internal ribosome entry sites (IRESs). These structured RNAs allow the virus to bind to the host's ribosome in the absence of canonical requirements. This dissertation focuses on relating the sequence of viral IRES elements to their role in initiating translation. The Cricket Paralysis Virus (CrPV) IRES is short, uses a simple mechanism, and can function in diverse cell-free systems making it a useful tool to study …

Description’S Displacements: Writing Experience In Musil, Benjamin, And Bachmann, Aida Feng

Yale Graduate School of Arts and Sciences Dissertations

This dissertation unfolds the ways in which description emerged as an active site for reconfiguring human experience in the writing experiments of the 20th century. Description, as a procedure for presenting and arranging the phenomena of reality, typically constructs an epistemological realm of experience that progresses toward comprehension and internal consistency. Understood in this way, description mediates one kind of experiential reality while foreclosing others. This project enlarges description’s operative capabilities toward a presentational mode that does not merely re-describe the phenomenal objects in this reality. To do so, it foregrounds writers and thinkers who conversed directly with philosophical traditions …

Manufactured Enchantments: Technologizing The Self In The Twentieth-Century Americas, Isabel Ortiz

Yale Graduate School of Arts and Sciences Dissertations

Manufactured Enchantments examines the way in which forms of enchantment worked at various sites—from culture industries, to self-help doxa, to esoteric and occult practices, to intellectual life—to construct an ideal self tailored to geopolitical violence in the U.S. and Latin America during the twentieth century. The dissertation studies five technologies—psychoanalysis, film, the rotoscope, the enneagram, and the tarot—that each suggested a self that could be stretched, modified, or altered to meet conditions of violence, uncertainty and precarity stemming from pre- and peri-Cold War U.S. imperial expansion efforts in the Americas. In each case study, I examine how the featured technology …

Molecular Investigation Of Signaling Molecules Involved In Cerebrovascular Disorders, Kimberly Jean Vish

Yale Graduate School of Arts and Sciences Dissertations

The most common forms of cerebrovascular malformations are brain arteriovenous malformations (AVM), often caused by genetic mutations in the EphB4-p120RasGAP signaling pathway, and cerebral cavernous malformations (CCM), often caused by genetic mutations in the CCM signaling pathway. These pathways are well studied, but there are clear deficiencies in the molecular level understanding of how signals are transduced. Relevant to AVM, the GTPase activating protein (GAP) for Ras, p120RasGAP, is necessary for downregulating Ras signaling during vascular development, and loss of its activity is associated with impaired cerebrovascular development. In my thesis, I investigate how p120RasGAP uses its Src-homology 2 (SH2) …

Cell State Dependent Strategies For Resolving Fundamental Properties Of Ligands Via Receptor Processes, Andrew Goetz

Yale Graduate School of Arts and Sciences Dissertations

Ligands may carry information through features such as their concentration, identity, and spatial distribution. Cells that can resolve these properties gain access to additional dimensions of information which may be beneficial as certain ligand properties possess unique features (e.g., ligand identity does not disperse with distance the way concentration does). Cells can accomplish this, at least in part, through the use of signaling cascades initiated by membrane receptors which bind to the ligand and activate downstream processes. The properties of these signaling cascades depend on the "state" of the cell (a property encompassing important cell features like protein levels and …

Livy's Historiography Of Roman Colonization, Talia Boylan

Yale Graduate School of Arts and Sciences Dissertations

Many early modern and enlightenment readers of Livy’s Ab urbe condita approached that work as a trove of local, colonial histories rather than an account of Rome’s rise to power— the interpretation favored by modern scholars of Livy as well as, on occasion, by Livy himself (e.g., in Praef. 1). This dissertation recuperates the localized mode of reading employed by pre-modern readers of Livy by treating his notices concerning colonies as self-contained nuggets of Italian history embedded within the imperial edifice of the Ab urbe condita. It explores how Livy worked to accommodate the colonial history they contain to the …

Application Of Peptide-Based Organocatalysts In Asymmetric Catalysis, Tyler Myers

Yale Graduate School of Arts and Sciences Dissertations

This dissertation outlines our efforts in advancing small-molecule, peptide-based organocatalysts for applications in asymmetric catalysis. The catalytic systems developed span a wide range of reactivities, including transition-metal-catalyzed, Brønsted basic, Brønsted acidic, and Lewis basic transformations. Chapter 1 details the development of an enantioselective copper-catalyzed aromatic Finkelstein reaction, mediated by a guanidinylated peptide ligand for the remote desymmetrization of diarylmethanes (up to 95:5 er). Furthermore, by leveraging the reactivity differences of aryl iodides and aryl bromides in transition-metal catalysis, the resulting enriched aryl iodide products could be chemoselectively modified, allowing access to a diverse library of diarylmethane analogs from a common …

Streamlining Drug Discovery With The Aid Of Artificial Intelligence And Physics-Based Modeling, Anastasia Saar

Yale Graduate School of Arts and Sciences Dissertations

The drug discovery pipeline is both expensive and prone to high attrition rates with many compounds failing in late-stage clinical trials. Computer-aided drug design (CADD) has emerged as a pivotal part of the pipeline to mitigate these challenges by enabling earlier and more cost-effective assessment of compound viability. This work focuses on two major aspects of CADD: absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions and free energy calculations. First, neural network models are developed for the prediction of aqueous solubility and cytotoxicity, two key contributors to late-stage drug attrition. Ensemble models of graph convolutional networks (GCNs) and graph attention …

Development Of The Human Brain Networks During Infancy, Huili Sun

Yale Graduate School of Arts and Sciences Dissertations

In early infancy, the human brain undergoes rapid network construction and remodeling. Advances in neuroimaging have made non-invasive, in-vivo observation of these brain changes possible during the perinatal period. However, how the brain develops to support dynamic activity and cognitive function remains unclear. In this thesis, I leverage the network control theory to model brain controllability - the capacity to drive activity changes - and examine its role in neurodevelopment. I first outline the developmental trajectories of controllability during the perinatal period and link them to synaptogenesis with cross-species models. Next, I introduce a machine-learning framework to explore how white …

Causal Inference For Environmental And Text-Based Interventions, Megan Ayers

Yale Graduate School of Arts and Sciences Dissertations

Causal inference provides statistical tools for generating empirical evidence about causal relationships. In conventional settings, randomized experiments can enable estimation of causal effects with simple methods and under weak assumptions, but many pressing causal questions concern complex systems where standard approaches break down. This dissertation presents advances and insights for such cases, first in the context of carbon markets and conservation programs, and then in settings where text serves as treatment. In the first chapter, we develop a generalized causal inference framework for analyzing forest carbon protocols. Recent work has questioned the credibility of forest carbon offsets as an environmental …

Serving Subjects - Oratorical Self-Representation In Deliberative Settings In Aristotle, Quintilian, Christian Weise, And Adam Müller, Marc Petersdorff

Yale Graduate School of Arts and Sciences Dissertations

In this dissertation, I address the following question: how does the tradition of rhetoric answer the question of how a subject constitutes itself that can only act by constituting another subject that will act in its stead? For this purpose, I focus on the subject of oratorical self-representation in four theories of rhetoric to each of which one more or less self-contained chapter is dedicated. The first two are prominent examples from antiquity: Aristotle's Rhetoric and Quintilian's Institution Oratories. The other two come from German-speaking traditions: Christian Weise's Politischer Redner and Adam Müller's Zwölf Reden über die Beredsamkeit und deren …

Satellite Galaxy Kinematics: A Competitive And Complementary Probe Of The Galaxy-Halo Connection And Cosmology, Kaustav Mitra

Yale Graduate School of Arts and Sciences Dissertations

Most cosmological analyses of galaxy surveys under-utilize the data from the smallest scales. Firstly, analytical calculations become challenging in the fully non-linear regime. Moreover, the small scales are inherently plagued by several systematic uncertainties, such as the effects of baryons. Interestingly, analyses that have delved into the non-linear regimes of structure formation, mostly using galaxy clustering or weak gravitational lensing, often show an ongoing tension with the probes of early Universe physics, such as the cosmic microwave background, about the exact values of some of the cosmological parameters. This begs the following questions: (a) Can we think of a new …

The Roles Of Terrestrial Weathering And Marine Bioturbation In Shaping Earth’S Surface Habitability Across Time, Brian Beaty

Yale Graduate School of Arts and Sciences Dissertations

The existence of life on Earth for over 3.8 billion years implies continuously habitable conditions despite major changes to the planet’s climate and surface geochemistry. In this thesis, I explore two Earth surface processes – terrestrial weathering and marine bioturbation – and their roles in shaping environmental habitability across various timescales. Weathering has long been recognized as a fundamental component of the Earth system. On multi-million-year timescales, it is the primary source for limiting nutrients to the biosphere and primary sink for atmospheric CO2. This concept underlies recent interest in artificially accelerating global weathering rates to mitigate near-future warming. However, …

Two Systems For User Control On The Modern Web, Caleb Malchik

Yale Graduate School of Arts and Sciences Dissertations

Providers of web services and content are compelled to offer value in order to attract users, but they are also increasingly incentivized to abuse their users in order to maximize revenue. Interfaces that monitor, distract, manipulate, and addict users are commonplace, and means of resistance are largely individualized and dependent on technical proficiency. This dissertation advocates a collective approach to empowering users in their relationship to the web services that they use, centered on an organizational form known as the data co-op. We describe two software systems that pair naturally with data co-ops and are designed to improve users’ control …

Vaccine-Induced Immunity: Insights Into Sars-Cov-2 And Orthopoxvirus, Valter Monteiro

Yale Graduate School of Arts and Sciences Dissertations

Emerging infectious diseases like SARS-CoV-2 and re-emergent pathogens such asmpox (formally known as monkeypox) have posed substantial challenges to global health, often due to immune escape and antigenic variability. My research addresses these challenges by evaluating and designing vaccine strategies to enhance immune responses and cross-protection, focusing on SARS-CoV-2 variants and members of the Orthopoxvirus family. The central aim of my research is to understand and overcome limitations in immune responses to antigenically variable pathogens. My studies focus on humoral responses to SARS-CoV-2 variants through targeted booster regimens, exploring cross-protective immunity in Orthopoxvirus vaccines, and testing new mRNA vaccines to …

Epicurus’S Ethics: Pleasure, Deliberation, And The Goal, Max Duboff

Yale Graduate School of Arts and Sciences Dissertations

Although Epicurus was a highly systematic thinker, most discussion of his ethics has had too narrow a focus. To address this problem, I propose a unified account of pleasure, the absence of pain, and deliberation in Epicurus's ethics. I explain three puzzles which have plagued Epicureanism since Cicero and even before: why the absence of pain is called pleasure; why the absence of pain is the greatest good; and how the absence of pain governs deliberation, including about death. I develop a new view of Epicurean pleasure, and I argue against the standard framing of Epicurus's ethics as a "hedonistic …

Building Certified Systems With Compositional Semantics, Yu Zhang

Yale Graduate School of Arts and Sciences Dissertations

Formal verification has emerged as the most rigorous approach for building reliable computer systems. Certified systems, in particular, are accompanied by a formal specification and a machine-checkable proof of correctness, enabling independent verification by third parties. However, verifying large-scale, heterogeneous systems presents significant challenges that current techniques cannot adequately address. Such systems require compositional methods that can flexibly integrate diverse verification approaches, including program logic, certified compilation, and data abstraction. While compositional semantics offers a promising foundation, existing frameworks are typically built on specialized operational models that resist integration with one another. This dissertation presents a three-dimensional algebraic compositional structure …