VictorJuiz/thesis huggingface dataset:
Exploring the human intestine in a dish: From physiology to disease

The differentiation potential of pluripotent stem cells allows the possibility of/nmaking nearly any cell type given the right set of cues. As developmental/nbiology continues to reveal how a cell is instructed to proceed to its fate, it/nis now possible to recreate in vitro methods to guide a cell to a specified/nfate. In addition to signaling cues in the form of growth factors or their/nanalogs, some cells owe their identity to a specialized supportive/nenvironment that integrates a variety of cues. In the human intestine, the/nintestinal stem cell niche provides a physically supportive matrix with/nmultiple overlapping gradients of growth factor signals. This niche can be/nreconstructed in vitro to maintain the progenitors that would maintain the/nepithelium for the life of a human. We call these in vitro tissues organoids./nThese cultures comprise progenitor stem cells that make the different cells/nof the intestine in a self-organizing tissue that has some of the functions of/nthe intestine. While more complex than traditional cell cultures, an organoid/nis a reduced model of a tissue that allows for the observation of more/nstereotypical physiology and can be manipulated to model disease. This/nnew mode of cell biology intersects with a time where genetic engineering/ntechnologies have expanded, become refined and now are easily/naccessible experimental systems./nUsing gene editing in pluripotent stem cells we made a system that/ngenetically identified a human intestinal stem cell that was derived from the/nspontaneous differentiation of embryonic stem cells into a benign tumor/ngrown in a mouse. By creating a culture system to maintain these cells in a/nnormal state long term in vitro, this has provided a model to biological/nquestions that have not been experimentally achievable in human thus far.

Advisor: Hockemeyer, Dirk
A Chemoproteomics Approach Towards the Discovery of Novel Anti-Cancer Covalent Ligands and Targets

While many disease-modifying protein targets have been discovered, most of these targets have remained untranslated as they are considered to be difficult to target with small-molecule drugs. In fact, most of the proteome is devoid of pharmacological tools, greatly hindering both basic and translational research efforts. Studies have demonstrated that the development of high-quality chemical tools for proteins of interest catalyze research into the function and therapeutic exploitation of those proteins, thus correlating the development of chemical tools for specific proteins with their associated research activity.1 In fact, only 2% of all predicted human gene products are currently targeted with small-molecule drugs and only 10-15% of all human genes are thought to be ‘druggable,’ with only a 25% overlap between druggable protein targets and known disease-modifying targets.2 Therefore, it is crucial to develop novel approaches and pharmacological tools that garter the entire proteome if we hope to accelerate drug discovery efforts towards curing complex diseases./nThe use of reactivity-based chemoproteomic probes and isoTOP-ABPP platforms has afforded the discovery of numerous sites within proteins that may represent a variety of functions such catalytic activity, protein- protein interactions, and allosteric regulation.3–6 In this dissertation, I present evidence of how chemical genetics and chemoproteomics approaches can be coupled to not only identify novel anti-cancer protein targets, but also covalent small molecule compounds that can inhibit or impair said targets. I also demonstrate how chemoproteomics as a whole allows for the target identification of almost any small molecule of interest, therefore accelerating drug discovery platforms by identify lead targets and the general promiscuity of a lead ligand. Overall, I provide work that details how we have identified novel sites within protein targets that can be drugged, as well as novel protein targets themselves. This work demonstrates how chemoproteomic platforms, when applied to multiple drug discovery platforms, allows for the rapid identification of novel anti-cancer covalent compounds, and their targets, ultimately providing an approach that can have a large impact on the fight to cure cancer.

Advisor: Nomura, Daniel K
Making and Breaking C‒F Bonds via Palladium-Catalysis

Making and Breaking C‒F Bonds via Palladium-Catalysis/nBy/nRichard Thornbury/nDoctor of Philosophy in Chemistry/nUniversity of California, Berkeley/nProfessor F. Dean Toste, Chair/nChapter 1 – A ligand controlled, palladium-catalyzed, enantioselective 1,3-arylfluorination of [2H]-chromenes was developed. The products were obtained in high enantioselectivity and with a syn- relationship of the introduced substituents. The pyranyl fluoride products were further derivatized to demonstrate the utility of the products. A ligand dependent divergent formation of 1,3- and 2,1- alkene difunctionalization products was also observed. This bifurcation in reactivity was investigated with a combination of experimental, computational, and statistical analysis tools. Ultimately, the site selectivity was found to be dependent on the ligand denticity and metal electrophilicity, the electronics of the boronic acid, and the donor ability of the directing group in the substrate./nChapter 2 – A palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes with boronic acids was developed. Broad functional tolerance arises from a redox-neutral process in which a palladium(II) active species which is proposed to undergo a β-fluoride elimination to afford the products. The monofluorostilbene products were formed with excellent diastereoselectivity (≥50:1) in all cases. As a demonstration of this method’s unique combination of reactivity and functional group tolerance, a Gleevec analogue, using a monofluorostilbene as an amide isostere, was synthesized in 4 steps from commercially available materials.

Advisor: Toste, Dean
On and Off-Policy Deep Imitation Learning for Robotics

As an alternative to explicit programming for robots, Deep Imitation learning has two drawbacks: sample complexity and covariate shift. One approach to Imitation Learning is Behavior Cloning, in which a/nrobot observes a supervisor and then infers a control policy. A known problem with this approach is that even slight departures from the supervisor’s demonstrations can compound over the policy’s roll-out resulting in errors; this concept of drift and resulting error is commonly referred to as covariate shift On-policy techniques reduce covariate shift by iteratively collecting corrective actions for the current robot policy. To reduce sample complexity of these approaches, we propose a novel active learning algorithm, SHIV (Svm-based reduction in Human InterVention). While evaluating SHIV, we reconsider the trade-off between Off- and On-Policy methods and find that: 1) On-Policy methods are challenging for humans supervisors and 2) performance varies with the expressiveness of the policy class. To make Off-Policy methods more robust for expressive policies we propose a second algorithm, DART (Disturbances Augmenting Robot Trajectories), which injects optimized noise into the supervisor’s control stream to simulate error during data collection. This dissertation contributes two aforementioned algorithms, experimental evaluation with three robots evaluating their performance on tasks ranging from grasping in clutter to singulation to bed-making, and the design of a novel first-order urban driving simulator (FLUIDS) that can fill gaps in existing benchmarks for Imitation Learning to rapidly test algorithm performance in terms of generalization.

Advisor: Goldberg, Ken
Constraints on Short Lived Signals at 150 GHz

Fast radio bursts (FRBs) are bright, millisecond flashes of radio radiation detected at frequencies between 800 MHz and 8 GHz. We present the first rate constraints on millisecond duration celestial transients like FRBs at 150 GHz. Using a year of data from the South Pole Telescope we searched for signals with a similar phenomenology at 150 GHz and found no evidence for a celestial population. The 0.9 upper confidence limit is $1.1 \times 10^{5} \text{sky}^{-1}\text{ day}^{-1}$ for 1 ms signals with fluence above 10 Jy ms. The search sensitivity is expected to increase dramatically with future microwave telescopes due to increases in spectral information and a reduced background rate./nThe first four chapters are dedicated to detailing how we convert a measured optical signal into a measurement of the power spectrum of the CMB. Particular emphasis is placed on the transition edge sensor bolometer readout, the map making and the power spectrum estimation from these maps. Chapter five focuses on how we can analyze the data to look for fast radio bursts.

Advisor: Holzapfel, William
Learning from and Getting Lost in Graphic Novels: Their Role in Promoting Vocabulary Learning, Comprehension, Motivation, and Engagement

This study examined the use of sequenced visual images (graphic novels and comic books) to scaffold incidental vocabulary learning and text comprehension while processing visual and textual information. Due to the recent growth of graphic novels as a popular text format, empirical investigation is needed to ascertain its value and to possibly incorporate this format into existing curriculua. This format was hypothesized to be particularly effective for English Language Learners (ELLs) due to the visual, non-linguistically loaded images that accompany text that may scaffold learning. Thus, both primarily English speakers and English Language Learners (ELLs) were examined. In this experimental study, 10th grade students’ ability to incidentally learn the meaning of targeted academic words from reading sequenced visual images versus text-only format was compared. Additionally, the interaction between format (text only versus text with images) and ELL status (English speakers in comparison to ELL) was examined. Further, the role of intrinsic motivation for reading and transportation was investigated, of students reading in each format were evaluated both as an outcome as well as a mediator of vocabulary growth and reading comprehension./nThis study showed that 10th grade students learned statistically significant amounts of academic vocabulary from both the script and graphic novel format of The Tempest and A Midsummer Night’s Dream. Further, these students showed the equal level of comprehension of the Shakespeare plays across the two formats, with some benefits in the graphic format observed in raw score. In addition, there were significant differences in the Intrinsic Motivation for Reading and Transportation scales depending on the format in which the play was read. The data suggests higher levels of intrinsic motivation for reading (Interest and Enjoyment of Reading scale and Perceived Competence scale) and feelings of Transportation (General and Composite scale) after exposure to the graphic novel format rather than the script version of a play. These significant effects of the graphic novel format were found to superseded the effects of the narrative’s transportative appeal in the Composite Transportation scale. However, only in the Intrinsic Motivation scale of Pressure/Tension felt when reading, students’ feelings were impacted more significantly by the narrative rather than the format. These findings do not show any specific benefit for ELL students in comparison to their predominantly English-speaking peers across all outcome measures. Lastly, moderating effects were unable to be found due to a lack of initial, meaningful relationship between the format and vocabulary learning. Overall, this study proposes an interesting starting point for the discussion of including the graphic novel format in academic environments to further learning and psycho-social benefits for students.

Advisor: Pearson, P. David
Low-Coordinate Silylarylamido Complexes of Early First-Row Transition Metals

Chapter 1. The amido ligand –N(SiiPr3)DIPP (DIPP = 2,6-diisopropylphenyl) was used to prepare two-coordinate complexes of CrI, CrII, and CrIII. The two-coordinate CrII complex was employed to prepare a three-coordinate CrIII iodide complex, which then afforded access to a stable CrIII methyl species./nChapter 2. Products resulting from the reduction of various CrIII complexes supported by the silylarylamido ligand –N(SiMe3)DIPP (DIPP = 2,6-diisopropylphenyl) were synthesized and characterized. The solid state structure of a dimeric chromium species, in which the ligands have undergone C–H bond activation, is also reported./nChapter 3. Products from reduction and attempted oxidations of low-coordinate manganese complexes supported by silylarylamido ligands –N(SiR3)DIPP2 (R = Me or iPr; DIPP = 2,6-diisopropylphenyl) were synthesized and characterized. Steric differences were found to have a noticeable effect on structure and even coordination number. In addition, the reduction of Mn[N(SiMe3)DIPP]2 under nitrogen afforded a dinitrogen-bound dimeric species./nChapter 4. Divalent complexes of vanadium were synthesized employing bulky silyl(aryl)amido ligands –N(SiiPr3)DIPP and –N(SitBu2Me)DIPP (DIPP = 2,6-diisopropylphenyl). Solid-state structural characterization revealed that although the ligand –N(SiiPr3)DIPP supports a rare two-coordinate complex of vanadium, its constitutional isomer –N(SitBu2Me)DIPP affords a homoleptic complex in which the vanadium center is sandwiched between the arene rings, an unusual binding mode for arylamido ligands. Magnetometry studies indicate that V[N(SiiPr3)DIPP]2 and V[(η5-DIPP)N(SitBu2Me)]2 have similar high-spin d3 electron configurations. However, spectroscopic methods, including electron paramagnetic resonance, nuclear magnetic resonance, infrared, and UV-visible spectroscopies, suggest that V[N(SiiPr3)DIPP]2 is stereochemically nonrigid in solution while V[(η5-DIPP)N(SitBu2Me)]2 is not. This nonrigidity explicitly impacts the reactivity of V[N(SiiPr3)DIPP]2, which can be used to access both amido-bound and arene-bound complexes. In addition, these divalent complexes exhibit rich reduction and oxidation chemistry. Both vanadium(II) complexes can be reduced to anionic vanadium(I) species, {V[(η5-DIPP)N(SiiPr3)]2}− and {V[(η5-DIPP)N(SitBu2Me)]2}−. Moreover, treatment of V[N(SiiPr3)DIPP]2 with single and multi-electron oxidants reveals a range of transformations including an intramolecular C–H bond activation.

Advisor: Tilley, T. Don
Ca Isotopes in Igneous and High-Temperature Metamorphic Systems and the Hydrothermal Chemistry of Paleoseawater

In the last two decades it has been increasingly recognized that Ca isotope fractionation at high-temperatures can greatly exceed fractionation at surface conditions. These effects have been used to trace recycling of crustal materials into the mantle, to estimate equilibration temperatures in mantle rocks, and to understand kinetic isotope fractionation during diffusion in experimental melts. However, little is known about the competition between kinetic and equilibrium Ca isotope effects in natural samples, which suggests that the use of stable Ca isotope variations as a proxy for carbonate recycling (or for mantle temperature) is significantly underdetermined./nThe Ca isotope evolution of continental crust, which is currently understudied, is intimately linked to the geochemical evolution of Earth’s mantle, oceans, and atmosphere. As such, this dissertation focuses dominantly on understanding radiogenic, kinetic, and equilibrium Ca isotope variations in igneous and metamorphic rocks from the continental crust, but also includes radiogenic Sr isotope models of hydrothermal circulation at mid-ocean ridges, which are critical to understanding continental weathering rates and the geochemical evolution of seawater over time./nChapter 2 explores the potential feed-back between the chemical and isotopic composition of paleoseawater and high-temperature hydrothermal fluids, which has been implied by Sr-isotope measurements in hydrothermal minerals over time (Antonelli et al., 2017). Chapter 3 presents results from radiogenic Ca isotope measurements in lower-crustal rocks and minerals, confirming that K is effectively lost from the lower crust during high-T metamorphism (Antonelli et al., 2018). Chapter 4 focuses on stable Ca isotope measurements in lower-crustal rocks and minerals, demonstrating that kinetic Ca effects are abundant in nature, both at the whole-rock and inter-mineral scales, and that they can be used to understand paragenesis and Ca diffusion in lower-crustal rocks (Antonelli et al., 2019b). Chapter 5 presents stable Ca isotope results from volcanic and sub-volcanic rocks and minerals, which imply that Ca isotopes can be used to estimate crystal growth-rates in igneous crystals (e.g. phenocrysts, comb-layers, and orbicules) and that associated volcanic eruption/recharge events are generally short-lived (Antonelli et al., 2019a).

Advisor: DePaolo, Donald J
Optodynamical Measurement and Coupling of Atomic Motion and Spin

The quantum nature of light makes it a basic component for models of quantum measurement and information exchange between disparate quantum modes, pioneered in the field of cavity quantum electrodynamics. The interaction of atomic ensembles with the mode of an optical cavity provides a flexible platform for exploring the coherent interaction of light with diverse macroscopic dynamics, such as collective motion and spin. This dissertation presents experimental results and theoretical models for continuous measurement and control of the center of mass motion and collective spin precession of an atomic ensemble, mediated by coupling to a high-finesse optical cavity. First, the theory of dispersive coupling between the cavity mode and the collective motion and spin of an atomic ensemble is derived, and then a general time-domain formalism is developed for theoretical analysis of multi-mode optodynamical systems. Single-mode optodynamical effects are introduced through experimental demonstrations of measurement and control of the collective atomic spin, providing a close analogy to cavity optomechanics./nNext, multiple collective atomic modes are considered within a single cavity, in order to assemble optically mediated interactions within multi-mode optodynamical systems. A demonstration of optodynamical interactions between the center of mass motion of two atomic ensembles is presented, coupled through an optical spring mediated by the cavity mode. Then simultaneous coupling of the center of mass motion and total spin precession of a single ensemble of atoms is described, yielding an experimental realization of a negative-mass instability, facilitated by the novel resource of the spin ensembles inverted state. A theoretical analysis of the negative-mass instability is presented, which indicates the possibility of generating two-mode squeezed states in the absence of excess incoherent noise. Finally, linear state retrodiction from the optodynamical signals is discussed, providing background and supplemental material for a forthcoming manuscript.

Advisor: Stamper-Kurn, Dan M
In Place/Of Solidarity: Acknowledgement and Reciprocity with/in Indigenous and Asian Canadian Writing

In Place/Of Solidarity argues the exigence of developing Asian Canadian critical praxes that align and move in solidarity with Indigenous sovereignties and radical resurgence movements. In the dissertation, I analyze a body of literary texts by contemporary Indigenous and Asian North American writers whose works contain instances of reciprocal representation. I argue that actions proceeding from and grounded in praxes of acknowledgement and reciprocity constitute openings to solidarity. By enacting Asian Canadian studies explicitly with decolonial solidarities in the foreground, I argue that Asian Canadian studies may not only work in ethical alignment with Indigenous knowledges and methodologies, but may also enliven and reconstitute the solidarities upon which Asian Canadian studies is premised./nBringing Asian Canadian studies into dialogue with scholarly work from Indigenous studies and recent research on Asian settler colonialism within a transnational Asian (North) American context, this dissertation considers reciprocal representations across a number of literary works by Indigenous and Asian Canadian women. Analyzing key texts by SKY Lee, Lee Maracle, Marie Clements, and others, and writing self-reflexively into the analysis through Trinh T. Minh-ha’s concept of “speaking nearby,” I theorize forms of relational critical praxis based on acknowledgement and reciprocity. The project takes up key urges read in the undercurrents of Asian Canadian studies to argue that even as the field grapples to enunciate its own coalitional position from which to initiate solidarity, it needs concurrently to deterritorialize and resituate Asian Canadian agency on new grounds./nThe goal of this project is to posit a praxical framework for enacting Asian Canadian creative solidarity that: first, moves in alignment with Indigenous resurgence and sovereignty movements grounded in place; second, is animated by a love-based ethic for research, writing, and activism that hails from legacies of intersectional, Women of Colour, and Indigenous feminisms; and finally, shifts from analyzing Asian Canadian settler-colonialism to illuminating practices of and directions for Asian Canadian unsettling and solidarity.

Advisor: Wong, Sau-ling C.