VictorJuiz/thesis huggingface dataset:
How does oligodendrocyte calcium signaling regulate central nervous system myelination?

In this dissertation, I examine the role of oligodendrocyte calcium signaling in regulating myelination and oligodendrocyte cell biology, both in the context of development and during learning and plasticity. Myelin is essential for rapid nerve signaling is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length and thickness are regulated by neuronal activity and are likely critical for fine-tuning conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation and remodeling is unknown. In this dissertation, I have developed a suite of pharmacological and genetically-encoded tools to attenuate calcium during active myelination in the developing mouse CNS. I found that genetic calcium attenuation did not grossly abrogate myelin formation. Instead, calcium attenuation caused myelin defects: shorter myelin sheaths with abnormal morphology. Mechanistically, I found that dysregulation of myelin morphology was accompanied by reductions in actin filaments, and that an intact actin cytoskeleton was necessary and sufficient to achieve accurate myelin morphology. To follow up on this, I have begun to investigate the role of oligodendrocyte calcium signaling in regulating SNARE-mediated exocytosis. Second, I have found, excitingly, that oligodendrocyte calcium signaling is required for the acquisition of a dexterous forelimb reach task, suggesting that calcium signaling in oligodendrocytes may act as a cell biological bridge between neuronal activity and experience-dependent myelination. Together, my work reveals novel cellular mechanisms required for accurate CNS myelin formation and provides mechanistic insight into how oligodendrocytes may respond to neuronal activity to precisely sculpt myelin sheaths throughout the nervous system.

Keywords: Medicine.
Advisor: Zuchero J.
Cyert Martha
Monje-Deisseroth Michelle
Shatz Carla
Human-AI interaction under societal disagreement

Whose voices - whose labels - should a machine learning algorithm learn to emulate? For AI tasks ranging from online comment toxicity detection to poster design to medical treatment, different groups in society may have irreconcilable disagreements about what constitutes ground truth. Today's supervised machine learning pipeline typically resolves these disagreements implicitly by majority vote over annotators' opinions. This majoritarian procedure abstracts individual people out of the pipeline and collapses their labels into an aggregate pseudo-human, ignoring minority groups' labels. In this dissertation, I will present Jury Learning: an interactive AI architecture that enables developers to explicitly reason over whose voice a model ought to emulate through the metaphor of a jury. Through my exploratory interface, practitioners can declaratively define which people or groups, in what proportion, determine the classifier's prediction. To evaluate models under societal disagreement, I will also present The Disagreement Deconvolution: a metric transformation showing how, in abstracting away the individual people that models impact, current metrics dramatically overstate the performance of many user-facing tasks. These components become building blocks of a new pipeline for encoding our goals and values in human-AI systems, which strives to bridge principles of HCI with the realities of machine learning.

Keywords: Engineering.
Advisor: Bernstein Michael
Landay James
Hashimoto Tatsunori
Hybrid methods for wind farm simulation and control

Wind farm simulation and control involve a trade-off between accuracy and computational speed. I explore how hybrid methods combine the best attributes of each constituent method to achieve both accuracy and speed. First, I consider high-fidelity simulation of a wind farm. These simulations inform design and verification of farm layout optimization and control strategies and models. Typically simulations represent only a subset of the relevant physics, which includes the atmospheric boundary layer (ABL), blade near-wall turbulence, and turbine-turbine interactions. This hinders optimization and control development. I modify a hybrid between two fluid models, one Reynolds- Averaged Navier Stokes (RANS) and one large eddy simulation (LES), that is well suited to capture all three effects. I focus on modifying first the RANS closure, SST k-omega, and then the hybrid approach, Active Model Split (AMS), to accurately simulate the ABL, including the Coriolis effect and buoyancy. I show that the modified SST k-omega provides comparable accuracy to the RANS model more commonly used for this problem, k-epsilon. AMS improves upon SST k-omega, achieving accuracy comparable to that of LES. I then extend these results to a diurnal cycle with buoyancy. The second part of the work focuses on wind farm control, specifically wake steering. Wake steering yaws upstream wind turbines to deflect their wakes from downstream turbines, increasing the total power produced by the wind farm. Typically wake steering doesn't adapt to turbine status, which leads to lost power when turbines are inactive. I develop a hybrid between model- and learning- based control, differentiable control (DC), for adaptive wake steering. This includes implementing a control-oriented wind farm model in a learning package so that it is automatically differentiable and compatible with learning tools. It also requires identifying a neural network architecture which can learn the discontinuous functions that arise in wake steering. I show that DC accomplishes adaptive wake steering with comparable accuracy to the most common wake steering method, which is purely model-based, while reducing the offline run-time by over 90%. Furthermore, DC handles not only varying wind speed but also varying wind direction, an extension which is challenging for purely learning-based methods.

Keywords: Engineering.
Advisor: Iaccarino Gianluca
Gorle Catherine
Lele Sanjiva
Identification and characterization of human neural stem and progenitor cells

The prenatal human brain undergoes rapid development during the second trimester from a pool of neural stem cells (NSCs) known as radial glia (RG), which give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. We describe a method for the prospective isolation of multiple neural stem and progenitor cell (NSPC) populations from the developing human brain using various cell--surface markers that constitute their immunophenotype. The distinct NSPC populations include ventricular and outer radial glia (vRG, oRG), cells of excitatory and inhibitory neuronal lineages, oligodendrocyte precursor cells (OPCs), and astrocyte lineage cells. The purity of isolated NSPCs was assessed by correlating the expressed transcriptomes of individual index--sorted cells with their immunophenotype. We then confirmed the functional purity of isolated NSPCs regarding their lineage output potential through various in vitro differentiation assays, and through in vivo transplantation into the lateral ventricles of neonatal immunodeficient mouse brains. Histological analysis using human specific antibodies showed robust site--specific migration and engraftment of human NSPC subsets, which, after differentiation in vivo, gave rise to all three mature neural lineages in adult murine brains 6 months post--engraftment

Keywords: Medicine.
Advisor: Weissman Irving L.
Andreasson Katrin
Palmer Theo
Wyss-Coray Anton
Zuchero J.
Identifying and understanding microtubule associated proteins

Microtubules are intracellular polymers that are necessary for various essential processes ranging from cell division to maintaining cell structure. However, microtubules must adopt specific patterns in many of these processes even though the polymers are built using the same subunit. To achieve this range of patterns, microtubule associated proteins (MAPs) modulate microtubules by performing functions like nucleation and crosslinking. While the localization and function of many MAPs are known, we still do not understand how most microtubule patterns are achieved nor the role of MAPs in this patterning. In this study we used C. elegans as a model to find that the understudied MAP9 has a conserved and specific localization to microtubule doublets

Keywords: Humanities and Sciences.
Biology.
Advisor: Feldman Jessica L.
Shen Kang
Stearns Tim
Identifying Endocrine Bases of Parental Neglect and Infanticide in the Mimic Poison Frog

Parental care is often critical for infant-well being and species survival, yet the biological basis of such infant-directed behaviors remains unclear. There is increasing evidence that patterns in system-wide physiology, such as the signaling of circulating steroid hormones, may drive parental care decisions in a manner that is immediately responsive to environmental challenges. However, from an evolutionary perspective, there is remarkable variation in how hormones tune parental behaviors, especially when considering non-affiliative decisions such as infanticide. This study aims to characterize the environmental changes and endocrine activities that predict parental care, neglect, and aggression using a biparental, monogamous amphibian model known as the Mimic poison frog (Ranitomeya imitator). First, I performed a series of offspring manipulations, including cross-fostering and changing tadpoles’ locations in their parents’ tanks, which revealed that spatial familiarity is an indirect kin recognition mechanism in this species. Then, I designed a behavioral assay in which individual adults were displaced to a novel environment with conspecific eggs. I recorded and analyzed videos for infant-directed behaviors indicative of care, aggression, and neglect, wherein infant cannibalism was captured for the first time in this Genus. Steroid hormone titers (testosterone and corticosterone) were correlated with behavior. My analysis revealed that paired females, but not paired males, exhibit lower titers of testosterone when they perform infanticide rather than neglect, challenging the adage that testosterone is universally associated with increased aggression. This concerted analysis of hormonal changes and behavior lays a foundation for key endocrine mechanisms driving the plasticity of parental behavior in a tractable model, with downstream applications for comparative investigations in mammals.

Keywords:  Department of Biology
Goolsby, Billie
Parental behavior in animals
Infanticide
Cannibalism
Testosterone
Corticosterone
Kin recognition
Dendrobatidae
Steroid hormones
Biology
Text
Thesis
Advisor: Rodríguez Camilo
Ihara's lemma and multiplicity one

In this thesis, we formulate and prove a mod l multiplicity one result for spaces of automorphic forms on definite quaternion algebras over totally real fields, under some technical hypotheses so that Taylor's "Ihara avoidance" trick applies. We also explain how this can be used to deduce a special case of Ihara's lemma. To establish this multiplicity one result, we introduce a variant of the usual local deformation ring and calculate its Weil divisor class group using a strategy of Manning. A computation of its dualizing module then shows that this ring is Gorenstein. Finally, we construct a patched module from spaces of automorphic forms at different levels using the Taylor--Wiles--Kisin patching method and prove that it is free of rank one over a formal power series ring with coefficients in the local deformation ring.

Keywords: Humanities and Sciences.
Mathematics.
Advisor: Taylor Richard
Conrad Brian
Vakil Ravi
Il Francesco di Dante : una nuova prospettiva

My dissertation focuses on the figure of Saint Francis in the Divine Comedy. Particularly, the work wants to analyze Francis as a political role for Dante due to the value of Franciscan poverty. Moreover, it draws parallelism and discrepancies between the two medieval figures from an eco-theological perspective.

Keywords: Humanities and Sciences.
French & Italian.
Advisor: Harrison Robert Pogue
Prodan Sarah Rolfe
Wittman Laura
Illuminating cellular processes : developing new optic techniques to investigate cellular communication and translational control

The human body comprises trillions of cells. Within single cells, complex cellular activities are precisely executed by millions of diverse proteins translated by the ubiquitous translational factory ribosome. How ribosomes control translation of each individual protein within subcellular space therefore dictates the cellular protein landscape at the nanometer resolution. Meanwhile, at the intercellular level, intricate cellular communication is required to coordinate individual cells to perform complex physiological activities. How trillions of cells achieve precise communication through the intertwined signaling network therefore dictates the physiological outcomes at the organismal level. However, direct visualization of these cellular processes has been technically challenging due to the lack of tools with the required spatial resolution. Here, I present novel optical innovations to spatially investigate cellular communication and translational control, respectively. In the first project, I develop an optogenetic toolbox to manipulate cellular communications using artificial myosin motors. Utilizing this toolbox, I am capable of directly probing the molecules transported within long cellular extensions and controlling the dynamics of both filopodia and neurites. I further demonstrate the presence and importance of specialized filopodia in the re-establishment of a Sonic Hedgehog signaling gradient during axolotl limb regeneration. In the second project, I investigate translation control within subcellular space with two orthogonal approaches. Specifically, I develop an optimized expansion microscopy technique to visualize individual ribosomes and an optogenetic proximity-labeling technique to characterize their composition. Utilizing both techniques, I unveil enrichment of the 60S large subunit on the endoplasmic reticulum that is critical for the selective translation of transmembrane proteins. I further discover ribosomal heterogeneity on the mitochondria that is linked to the translation of metabolism-related transcripts. Taken together, these advancements in optic techniques empower us to shed light on cellular processes at different scales with unprecedented resolution.

Keywords: Medicine.
Chemical and Systems Biology.
Advisor: Barna Maria
Boettiger Alistair
Ferrell James
Jarosz Daniel
“I’M NOT A MATH PERSON” AND OTHER MYTHS: WHAT YOUNG ADULT FICTION TELLS US ABOUT MATH MINDSETS

How we can raise creative, creative thinkers who can succeed in our society and economy has been one of the most important tasks of education for many years. Mathematics is a discipline full of potential for inspiring and training young minds, but it is also a discipline fraught with performance anxiety, rigid stereotypes, and pronounced gender and racial inequities. The way that mathematics is learned and taught is influenced by many powerful and hidden factors, and while the classroom and curriculum are well-studied sites of research for improving attitudes around mathematics, this thesis instead considers young adult literature as a crucial, overlooked factor in how messages about math are transmitted to students. Through digital humanities methods including word embeddings, topic modeling, and close reading, this research investigates how math and math mindsets are portrayed in young adult literature by analyzing a corpus of over 5,000 young adult novels as well as 30 years of Hornbook guide reviews of young adult fiction. This thesis confirms earlier research, that math is portrayed in overwhelmingly negative and stereotyped ways, and contributes a deeper analysis of the ways that mindset influences these portrayals. In particular, this thesis finds that while both young boys and young girls are portrayed as both performing well and badly in mathematics, portrayals of growth mindset are more highly recommended and more prevalent for young boys than for young girls. In addition, the sentiments and social status surrounding mathematics varies widely throughout the corpus, and math often presents a source of stress and social isolation. Possible explanations for these trends are given, as well as a more detailed investigation of ways that math and mindset are associated with certain words and literary devices. This thesis concludes with a call to action for all educators, librarians, and other guiding forces in young people’s access to literature and development as learners: let’s challenge, complicate, and enliven the math narrative.

Keywords: Mathematics > Study and teaching
Young adult literature
Digital humanities
Identity (Psychology) in youth
Identity (Psychology) in literature
Mindset (Dweck, Carol S.)
Text
Thesis
Advisor: Kelman Ari
Levine Sarah
The image between appearance and being : iconic vision in Ukrainian and Russian worlds

This dissertation is a study of iconicity across three sites within the Slavic world. Taking the iconographic tradition of Eastern Christianity as its jumping off point, the project conceptualizes the image through a particular set of ethical and ontological grammars in which the image participates in an economy of formation rather than representation, and in which it is effective rather than descriptive. As such, the problem of iconic vision is not reducible to the phenomenology of optics. Rather, following these grammars, the dissertation reprises the question of the image as delineated by the viewing subject's relationship to it as an object of veneration. The project traces these questions across the following topoi: the first chapter studies a particular moment of reformation and modernization at the Kyiv Mohyla Collegium during the 17th-18th centuries. It argues that the resulting shifts in Ukrainian iconography demonstrate a significant remapping of the visual field, a change which is obscured when it is narrativized through projects of political, national, or religious identity which are premised upon a progressivist temporal break. The second chapter takes up the writings of Nikolai Leskov (1831-1895), first tracing the author's addresses to what I term a 'counterfeit' tradition of iconography together with his program for its rehabilitation, which pivots upon considerations of style and medium. It then shows how Leskov's desire to purify the iconographic tradition in some ways mirrors the "near-deification" of the wood and paint of the icon which he ascribes to the Old Believers in "The Sealed Angel", a tale narrated in the geographic and social hinterlands (Kyiv, Old Belief) of the Russian Empire. The third and final chapter looks to the filmography and writings of Andrei Tarkovsky (1932-1986), arguing that the filmmaker stages the impasse of the Kantian subject—whose transcendental ego ties the split domains of the aesthetic and the rational—in his filmography. In doing so, Tarkovsky reprises the question posed by this dissertation: that of the image, its beholder, and the real to which it stands in relation

Keywords: Humanities and Sciences.
Slavic Languages and Literatures.
Advisor: Safran Gabriella
Ilchuk Yuliya
Pentcheva Bissera V.
Imaging photoexcited states at the 1 nanometer scale using electron microscopy

Photons are the primary carriers of energy that drive life on earth. Photo-absorption of visible light involving an electronic transition forms the first step in ubiquitous processes such as photosynthesis, atmospheric chemistry processes, and is harnessed by us in photovoltaic devices. Imaging photoexcited states at the nanometer (nm) scale therefore offers fundamental insights about photo-excitation and recombination pathways, with numerous applications in photocatalysis, semiconductor physics, quantum emitters and so on. However, imaging photo-excited states at the 1 nm scale is nontrivial. As was discovered in the 19th century, traditional optical imaging techniques are limited by the Abbe diffraction limit to around 0.5 μm for visible light. Therefore, while optical microscopes have uncovered the microbial world, their resolution limit does not permit the observation of photoexcited states in systems like viruses (100 nm), proteins (10 nm), quantum dots (few nm) and atomic chemical bonds (1 Angstrom). Various optical super-resolution techniques have therefore been developed to address this problem. Some techniques employ clever work-arounds in Abbe diffraction limited systems such as centroid localization of stochastic emission to get a higher resolution reconstruction, an example of which is PhotoActivated Localization Microscopy (PALM) which won the 2014 Chemistry Nobel Prize. A second set of approaches use a near field evanescent optical source, such as a sharp metallic tip that scatters confined light near the sample. However, tip convolution artefacts make image contrast difficult to interpret. Because of all of these limitations, 1 nm scale photoexcited state imaging is not yet routine. Here we developed a new nanometer scale imaging technique called 'Photo Absorption Microscopy using Electron Analysis', or PAMELA, which uses high energy electrons to probe optically excited states of matter with nanometer resolution. We developed a conceptual basis for PAMELA in a Scanning Electron Microscope (SEM) and a Transmission Electron Microscope (TEM). We then implemented PAMELA in our in-house SEM showing, achieving about 10-20 nm resolution and deducing that surface photovoltage was the dominant contrast mechanism. We then attempted to improve the spatial resolution to 1 nm using TEM and STEM, but were limited by various instrumental limitations. Finally, we using aberration corrected SEM in collaboration with the Nion company (Kirkland, WA), we improved upon our previous result by 10x and achieved 1 nm resolution photo-absorption imaging. We then explored the resolution limits of secondary electron imaging using a sub-Angstrom probe and showed experimentally that the contrast mechanism behind atomic scale SE was core electron excitation events. We believe that these results are the beginning for PAMELA, and we envision a long and productive road ahead.

Keywords: Engineering.
Mechanical Engineering.
Advisor: Majumdar Arunava
Dionne Jennifer Anne
Sinclair Robert (Materials scientist)