VictorJuiz/thesis huggingface dataset:
Regulation and Biological Consequence of Retrotransposon Activation in Human Pluripotency

Mammalian genomes contain millions of transposable element sequences, but the overall impact they have on host biological processes remains poorly characterized. Retrotransposon insertions are known to actively shape embryonic development of model organisms, mainly by influencing transcription of host genes or by contributing functional protein or RNA products. Retrotransposons are also transcribed in human preimplantation embryos, and characterization of exapted retrotransposon families will help explain how human embryogenesis differs from other organisms. The second chapter of this dissertation presents studies on Human Endogenous Retrovirus-H (HERVH), which is a primate specific retrotransposon family functional in human embryonic stem cells (hESCs). The human genome contains over 2000 HERVH insertions and is associated with four distinct promoters, complicating efforts to understand host transcriptional regulation. Also, while HERVH RNA is clearly essential to maintain stemness, the mechanism of its action is unknown. To investigate the regulation of HERVH, we utilize bioinformatic prediction and reporter assays to identify transcription factor binding sites unique to the LTR7Y subfamily. A major finding of this dissertation is that HERVH regulation is recapitulated in naive and primed hESC culture, and the LTR7Y can be used to mark the naive state. We also find evidence that the primary mechanism of the HERVH RNA is in trans. We use genome engineering to delete an individual HERVH insertion and find it does not phenocopy family-wide HERVH knockdown or effect adjacent genes. Furthermore, ectopic overexpression of HERVH RNA effects the dynamics of BMP4/LY294002 induced mesendoderm differentiation, establishing a trans role for HERVH RNA in the postimplantation primitive streak. HERVH is the most active endogenous retrovirus (ERV) in preimplantation embryos, but we find other retrotransposons classes are more likely to modify adjacent cellular genes. In the third chapter of this dissertation, we identify a short interspersed element (SINE) insertion within ZBTB16, a developmentally important zinc-finger transcription factor. This SINE element serves as an alternative promoter, generating a transcript isoform found in the human oocyte that is capable of producing a truncated protein product. Using in vitro cell culture assays, we find the truncated ZBTB16 protein retains its function as a cell cycle regulator but shows altered subcellular localization and is resistant to post translational degradation, implying it may act to slow the cell cycle of early human embryos. The studies in this dissertation serve to clarify the complex regulation and mechanisms of function for retrotransposon families that are essential for human development. These findings advance the field of hESC biology by establishing clear markers of different pluripotent cell types, and ultimately add substantially to our understanding of how retrotransposons have shaped human pluripotency.

Advisor: He, Lin
A Dynamic-Stiffness Hydrogel Platform Utilizing Phytochrome B and Phytochrome Interacting Factor 6 as a Light-Inducible Crosslinker

Traditional cell culturing methods are generally static with respect to mechanical properties unlike in vivo conditions, suggesting that the results from in vitro experiments form an incomplete picture for downstream studies. My cell culturing platform utilizes phytochrome B (PhyB) and phytochrome interacting factor 6 (PIF6), plant proteins derived from A. thaliana which associate or dissociate based on two distinct wavelengths of light, as a controllable, reversible crosslinker within a hydrogel platform./nBoth PhyB and PIF6 were created in bulk within E. coli and purified via Ni-NTA, ion exchange, and size exclusion columns. The ex vivo activity of my synthesized proteins was tested via total internal reflection fluorescence (TIRF) microscopy. A hyaluronic acid (HyA) polymer gel was chosen as the base of the cell culturing platform for both its biological compatibility and its ability to be modified for protein conjugation. A semi-interpenetrating polymer network (semi-IPN) matrix was made by creating a base HyA hydrogel through thiol-ene click chemistry and incorporating a free HyA polymer stand which was modified to have methacrylate groups for protein conjugation. The modification of the HyA polymers was confirmed via proton nuclear magnetic resonance (1H NMR) spectroscopy. Confocal microscopy confirmed the covalent conjugation of fluorescently-labeled PhyB and PIF6 to the cell culturing platform. To confirm compatibility of the platform for cell culture, human mesenchymal stem cells were cultured for six days on the platform./nAtomic force microscopy (AFM) was used to measure the stiffness changes in the hydrogel platform when exposed to different wavelength light and preliminary data shows promising stiffness changes based on light cues. Future work on the platform will include establishing and characterizing the material properties of the hydrogel platform after variations are made on polymer lengths, protein density, and light intensity or duration. Upon optimization, this dynamic hydrogel platform could be utilized to mimic a variety of mechanical conditions found in vivo and provide insight to mechanobiological phenomena.

Advisor: Sohn, Lydia
Schaffer, David V
The Tree of Life: The Politics of Kinship in Meiji Japan (1870-1915)

This dissertation examines writings by transnational Japanese literary writers around the turn of the 20th century, showing how they drew upon the languages of the Victorian sciences in order to imagine broader forms of literary kinship outside the framework of a single national canon. I define “transnational Japanese writers” as writers who were registered by the state as Japanese citizens, but whose peripatetic careers and multilingual streams of influence make a compelling case for positioning their work outside of the frame of a single national literary canon.The primary argument of this dissertation is that Japan’s transition from nation to empire during the late 19th and early 20th centuries depended heavily upon the conflation of nationalist and familial rhetoric; yet, simultaneously, Japanese writers and thinkers were bound up in a transnational circuit of Victorian scientific discourse that posed serious challenges to the naturalness of the nuclear family form. From anthropological accounts of alternative kinship systems in the colonies, to Marxist critiques of the nuclear family as an upholder of private property, to Galtonian technologies of eugenics, Japan’s encounter with the British empire deeply challenged traditional notions of family, as well as the equation of family and state. The four chapters of this dissertation follow the writings of Natsume Sōseki (1867-1916) and Koizumi Yakumo, né Lafcadio Hearn (1850-1904), whose ambiguous position as Japanese subjects caught between the borders of nations afforded them a unique vantage point from which to criticize the language of kinship invoked by the state. By showing how these writers employed literary language to forge bonds of belonging between distant subjects not necessarily related by blood, my dissertation reveals how literary writing itself was imagined by these writers to constitute its own form of reproduction that ensured the continuity of one’s identity across space and time.

Advisor: Tansman, Alan
Role of Necroptosis in T Cell Activation

Abstract/nRole of Necroptosis in T Cell Activation/nby/nZhanran Zhao/nDoctor of Philosophy in Molecular and Cell Biology/nUniversity of California, Berkeley/nProfessor Astar Winoto, Chair/nNecroptosis is a programmed cell death pathway characterized by a necrosis-like/nmorphology and mediated in part by the kinase activity of receptor-interacting protein kinase 3/n(RIPK3) and, in most cases, its partner RIP1 as well. Necroptosis is a hidden cell death pathway,/nas it was initially only described in cells deficient in FADD or caspase-8. Necroptosis has been/nshown to play important roles in injury, disease models, and, more recently, in certain viral/ninfections. However, its role in a normal physiological setting is still not completely clear. Using/nNec-1, an inhibitor of RIP1 kinase activity, we have previously shown that a proportion of CD8/nT cells can be rescued from cell death induced by TCR activation in vitro. This observation led/nus to characterize the phenotype of T cells from mice deficient in RIP3 to examine the role/nnecroptosis plays in T cell activation. We found that inhibiting necroptosis can lead to increased/ncell number and activity of cytotoxic T lymphocytes (CTLs). Furthermore, Rip3-/- mice showed/nimproved tumor responses compared to littermate controls, with decreased expression of/ninhibitory markers on CTLs and reduced suppressive Treg populations in the tumor infiltrating/nlymphocytes. Using adoptive transfer, we showed that this effect is primarily driven by Rip3-/- T/ncells and that these T cells exhibit elevated activation activities and improved anti-tumor/nfunction. Necroptosis thus helps to regulate T cell activation to maintain the delicate balance of/nimmune homeostasis.

Advisor: Winoto, Astar
Through-going Muons in the LUX Dark Matter Search

Dark matter makes up most of the mass of the universe, and yet the true nature of this mysterious substance remains unknown. The LUX experiment uses a detector consisting of target xenon nuclei to search for Weakly Interacting Massive Particles, a promising dark matter candidate. The LUX detector is a 370 kg dual-phase xenon time projection chamber. Incident radiation interacts with xenon atoms, resulting in a recoil nucleus or electron that causes both ionization and excitation of Xe along the recoil track. De-excitation of Xe results in the emission of 175 nm scintillation light, and the properties of this scintillation can be used to determine the nature of the incident radiation - possibly identifying WIMP dark matter./nLUX has placed world-leading limits on the WIMP-nucleon interaction cross section. The rarity of such interactions requires a thorough understanding of backgrounds in order to implement appropriate background-reducing measures and an effective event-rejection methodology. The LUX water tank surrounds the xenon detector and serves as an active shield, reducing background radiation but also identifying high energy cosmic ray muons that can lead to the production of a highly undesirable neutron background. Since signals created by neutrons may appear very similar to those of WIMPs, care must be taken to not only reduce neutron backgrounds as much as possible, but to also understand any neutron backgrounds that may be present./nThe goal of this dissertation was to develop a method to identify cosmic ray muons that traverse both the LUX Xe detector and water tank, and to measure a muon flux at the LUX detector depth. The xenon gas-liquid interface served as a fiducial surface through which muon flux was measured. Simultaneous signals between Xe and water detectors were analyzed, and xenon pulse shapes were used to determine the energy and track geometry of the interaction. Muons passing the Xe liquid surface exhibited a particular signature in their pulse shape; this signature was used to identify through-going muons and calculate muon flux./nIn a previous work, muon flux measurements were taken at sites above the LUX detector, and muon transport models were used to predict vertical muon flux as 4.40 x 10^-9 muons s^-1 cm^-2 at the LUX detector depth. In this work, a flux of 4.60 +/- 0.33_(stat) x 10^-9 muons s^-1 cm^-2 is measured through the LUX water tank and xenon detector liquid surface. The resulting neutrons expected to be seen during the full LUX exposure is ~1 x 10^-1. While expected the background contribution from muon-induced neutrons poses little problem for the LUX WIMP search, an understanding of this background becomes increasingly important as target volumes grow for future generation experiments.

Advisor: Jacobsen, Robert G
The Labyrinth of Subjectivity: Constructions of the Self from Mullā Ṣadrā to Muḥammad Iqbāl

Referred to by some philosophers as “the knot of the universe,” investigations concerning human selfhood and subjectivity can help unravel questions of central contemporary relevance, such as what it is to be human in a globalized, secular world. As one scholar has pointed out, understanding our “selves”—our natures, capabilities, and possibilities—is the most captivating of all questions because, in the final analysis, it cannot be attained through empirical research alone. That is, there are no facts which can help us decisively determine whether our selves constitute parts of our bodies, or are incorporeal substances which somehow inhere in our bodies, or are epiphenomena of our minds./nAgainst the general backdrop of these kinds of concerns, my dissertation investigates the creative ways in which concepts of selves and selfhood have been constructed in early modern and late modern Islamic philosophy (spanning from the sixteenth to the twentieth centuries). I draw on the work of the three major thinkers during these time periods who made unique and lasting contributions in this regard: Mullā Ṣadrā (d. 1640), Shāh Walī Allāh (d. 1762), and Muḥammad Iqbāl (d. 1938). Alongside detailed analyses of each of these thinkers’ views on the self and selfhood, my study also situates their insights within the wider constellation of related discussions in late modern and contemporary philosophy, engaging the seminal theoretical insights on the self by thinkers such as William James, Jean-Paul Sartre, Michel Foucault, Richard Sorabji, and Daniel Dennett. This allows me to theoretically frame my textual inquiry within what can be called a tri-partite model of selfhood, taking in bio-physiological, socio-cultural, and ethico-metaphysical modes of discourse and meaning-construction./nOne key insight which emerges from my comparative inquiry is that the Muslim philosophers whom I study reveal themselves to be fundamentally concerned in their own unique ways with the problem of the human condition in general. Their manner of addressing this central issue from their differing perspectives devolves on the cultivation of what can be called an anthropocentric notion of the self that emphasizes self-knowledge, self-perfection and self-transformation./nBy putting the first-person perspective at the center of their conception of the self, these philosophers invite us to take a fresh look at our understanding of the self. This is because if the self is reduced to a set of cognitive functions or identified exclusively with various brain-states, as in neuroscience, one would downplay how the self appears from the first-person vantage point, thereby attenuating the concrete connection between human ethical agency and moral responsibility.

Advisor: Ahmed, Asad Q
Still Not Equal: Heuristics and Gender Stereotyping in American Elections

Research on gender in politics has long emphasized the gender gap—the number or proportion of women in office—as its chosen measure of women’s attainment. When women win elections at rates equal to men, as they do in the U.S., many scholars thus conclude that candidate sex must play little or no role in voters’ decisions. Yet the question of which women win should interest scholars of gender as much as how many women win—and tells us a great deal more about how politics is gendered./nHow then does candidate gender enter into voters’ decisions? Modern theories of voting behavior, observing that acquiring information about candidates is costly, often conclude that supplying voters with more information about the candidates would obviate reliance on cognitive shortcuts with known biases. This dissertation stakes a different claim: while heuristics and stereotypes do enable voters to “fill in” incomplete information, they also allow voters to simplify overwhelming information. Gender, as one of the simplest and most ubiquitous organizing principles of human behavior, helps us address the difficult task of voting in a candidate-centered electoral system by reducing a multidimensional task to a simple set of guidelines. This ensures biases in how we vote not only in low-information settings, but in high-information settings as well./nIn this dissertation, I use experiments and election data to test whether our decision-making process affects the descriptive representation of women in the U.S. I present evidence that voter reliance on gender as a cue affects the type of women elected at every level of office. In Chapter 1, I examine state legislative elections in Oregon and find that voters winnow the field by selecting women with attractive, stereotype-congruent appearances, even though voters have a great deal of information and partisan cues in such races. In Chapter 2, I show that in local elections in California, where voters often know little about candidates, women fare better when they run for offices that fit feminine stereotypes (city council and school board) and worse in stereotype-incongruent offices (mayor). In Chapter 3, I show that even in high-information and high-salience national elections, partisan voters feel more favorable towards women who exhibit gendered leadership styles congruent with their party’s preferences: feminine for Democrats, masculine for Republicans./nThe familiarity and simplicity of gender as an organizing principle suggests the use of gendered heuristics and stereotypes is inherent to any political system in which voters evaluate individual candidates. This holds whether voters have a great deal of information about candidates or only a little, in elections of high- and low-salience, and across both partisan and non-partisan races. Even when women win elections at rates equal to men, women who run counter to stereotype—in appearance, in office type, in party—are at a disadvantage compared to women who fit stereotypes.

Advisor: Lenz, Gabriel
Stoker, Laura
VALUE SHIFTS: The rise of multifunctional infrastructure

This dissertation examines the influence of urban sustainability on urban infrastructure. Thinking and practice around urban sustainability advocate the integration of urban services, such as water supply and sanitation, with goals such as natural resource conservation, climate mitigation and adaptation. I reflect on these multifunctional ideas about infrastructure in terms of the contexts taking charge of urban sustainability as a concept as well as a practical design experiment./nReflecting critically on the theory of urban sustainability, this dissertation shows how urban water infrastructure practices are critical in evolving conceptions about infrastructure. A history of urban water infrastructure specifically highlights the role of design experiments and evolving methods of practice revealed in urban sustainability ideas. The dissertation develops an ethnomethodology to examine the infrastructural methods behind urban infrastructure practice in Johannesburg, South Africa./nAs in many other African contexts, in Johannesburg, the single biggest investment to sustain future development will be in urban water systems, given that future water services depend on increasingly fragile natural resources and a changing climate. Apartheid era legacies of inequality remain, manifesting in disparate access to essential services such as fresh water and sanitation. The familiar "service delivery" agenda of many African governments, intersects with rapid urbanization that overrides much of the infrastructure already in place, requiring even greater investments to meet new urban needs./nAn ethnomethodology of infrastructure practice in Johannesburg informs my empirical assessment of responses to urban sustainability. I reveal the contexts that lie behind the scenes of the proverbial "end of the pipe" and that are essential in terms of the methods in use for activating urban sustainability. In light of the conceptual and practical trajectory of urban sustainability, this dissertation is part of a wider enquiry into how urban sustainability emerges in Johannesburg, compared to the global North, and into the practices that are available in each area.

Advisor: Hill, Kristina
Mozingo, Louse
Observing the Epoch of Reionization: Power Spectrum Limits and Commissioning Next Generation 21 cm Experiments

As one of the last unobserved frontiers in the Universe, the Epoch of/nReionization (EoR) marks the period when the Universe transitioned from a neutral state to an/nionized state, marking the last global phase change. Understanding how the EoR/nevolved over time and when it occurred will provide evidence for the nature of/nthe first luminous sources of the Universe. Specifically, we'll be able to/nanswer questions such as what were the first galaxies like in terms of their/nluminosities, masses, and spectral energy distributions? Were they similar to/ntodays galaxies? How did they form? How were they spatially distributed? These/nquestions and many others begin to probe the early times of galaxy formation, a/nfield in need of observations of the earliest galaxies./nIn the first chapter, I provide an introduction to 21 cm cosmology, which uses/nthe 21 cm line transition from neutral hydrogen to study the evolution of the/nUniverse. I briefly review 21 cm physics and the evolution of the/ncosmological 21 cm signal. The challenges of experiments measuring highly/nredshifted neutral hydrogen are discussed before describing the instruments/nused to make the measurements of the cosmological 21 cm signal./nThe second chapter in this thesis begins by presenting results from Donald C./nBacker Precision Array for Probing the Epoch of Reionization (PAPER) 64 antenna/nconfiguration. I start by describing the dataset used in the chapter, followed by the novel/nredundant calibration technique used to calibrate the grid layout of the PAPER array./nI then discuss the application of delay and fringe-rate filtering to suppress foregrounds and/noptimally combine time samples, respectively. Before presenting results, I/nlayout a quadratic estimator formalism for measuring the 21 cm power spectrum./nI finally present the results from the PAPER-64 dataset./nThe third chapter of this thesis shifts focus to the new Hydrogen Epoch of/nReionization Array (HERA), a close packed, redundant, low frequency array/ndedicated to detecting and characterizing the EoR and Dark Ages. As a new/nexperiment with terabytes of data being collected per day, the need for a real/ntime processing system is necessary to avoid a backlog of data and to avoid/ndata storage issues. I present the real time system (RTS) developed for/nanalyzing HERA data, which automatically detects and flags bad antennas,/nredundantly calibrates the array, and excises radio frequency interference/n(RFI) in real time. This work builds off the lessons learned from PAPER and/nthe Murchison Wide-Field Array (MWA) based in western Australia. I then present/nsome initial results from the RTS system./nIn the final chapter, I conclude the thesis by summarizing the work presented and discuss/nfuture directions for 21 cm cosmology.

Advisor: Parsons, Aaron R
Applications of the Intersection Theory of Singular Varieties

We develop tools for computing invariants of singular varieties and apply them to the classical theory of nodal curves and the complexity analysis of non-convex optimization problems./nThe first result provides a method for computing the Segre class of a closed embedding X → Y in terms of the Segre classes of X and Y in an ambient space Z. This method is used to extend the classical Riemann-Kempf formula to the case of nodal curves./nNext we focus on techniques for computing the ED degree of a complex projective variety associated to an optimization problem. As a first application we consider the problem of scene reconstruction and find a degree 3 polynomial that computes the ED degree of the multiview variety as a function of the number of cameras. Our second application concerns the problem of weighted low rank approximation. We provide a characterization of the weight matrices for which the weighted 1-rank approximation problem has maximal ED degree.

Advisor: Shende, Vivek