VictorJuiz/thesis huggingface dataset:
The design, synthesis and evaluation of guanidinium-rich molecular transporters for the delivery of antibiotics and oligonucleotides

The delivery of cell-impenetrable therapeutic agents across biological barriers represents a challenging problem in the field of life science research and medicine. Many bacterial pathogens are inherently resistant to glycopeptide antibiotics such as vancomycin due to the antibiotic's relatively large size and mode of action, which requires actively growing cells. Recently, genetically-resistant vancomycin strains have emerged, adding to vancomycin's inefficaciousness against certain bacterial populations. The emergence and understanding of phenotypically and genetically resistant bacteria coupled to a declining pipeline of antibiotic development necessitates new strategies to combat bacterial infections. As part of a collaboration between the Wender and Cegelski labs, we have designed, synthesized and evaluated a novel vancomycin cell-penetrating peptide conjugate. We have shown that this new conjugate exhibits a unique mode of action compared to vancomycin, allowing it to be extremely effective against vancomycin-insensitive bacterial populations.

Keywords: Chemistry.
Advisor: Wender Paul A. 
Burns Noah
Waymouth Robert M.
Destandardizing the standard (s) : ideological and implementational spaces in preservice teacher education

New teachers and teacher education programs in the US are expected to be culturally and linguistically responsive to the ever-diversifying demographic landscape of public schools. However, professional and content standards still rely on categories and language conceptions that are rigid, static or, at best, ambiguous, such as "English Language Learners" or "Standard English." This interpretive dissertation engages with this intellectual and practical tension from a dual perspective, Language Anthropology and Language Policy. First, a California policy document (the Teaching Performance Expectations, TPEs) is analyzed to identify language conceptions and their process of textual construction. Then, successive empirical chapters identify how student teachers and teacher preparation instructors endorse and counter linguistic ideologies in order to reappropriate and contextualize the target policy. Ultimately, it is argued that educators can use their agency to construct alternative ideological spaces that encompass dynamic and fluid notions of language. Such "heteroglossic ideological and implementational spaces" (Flores and Schissel, 2013) are emancipatory for both educators and students and sustain the language practices of minoritized populations.

Keywords: Education.
Advisor: Hakuta Kenji 
Valdés Guadalupe 
Gutiérrez Kris D. 
Rosa Jonathan
Detection and validation of genomic structural variation from DNA sequencing data

The comparison of individual genome sequences is a key task for modern studies of population genetics, genotype-phenotype associations, and genome evolution. The problem is difficult in part because commonly-used DNA sequencing hardware produces reads that are orders of magnitude smaller than the size of a single human chromosome. The detection of large genomic mutations known as structural variants (SVs) from these short sequencing reads has emerged has a particularly challenging problem. Numerous methods targeting this problem have been proposed, but it is difficult to assess their performance on real data since the ground truth is typically unknown. Moreover, complex SVs that escape detection by conventional algorithms are known to exist. We propose here a solution to both the complex SV detection problem and the issue of evaluating accuracy on real data.

Keywords: Statistics.
Advisor: Wong Wing Hung 
Palacios Roman Julia Adela 
Sabatti Chiara
Determinants of sensitivity to binocular disparity

Binocular disparity is an important cue for human to perceive relative distance. Setting aside normal developmental changes there is much reported variability in stereoscopic vision in adults who have excellent monocular visual acuity in each eye. Such naturally occurring variations can be used as a tool to reveal the association between behavioral task performances and the underlying neural responses. This thesis will first review the studies over the past several decades that have described individual differences of binocular depth perception as well as studies that have attempted to uncover the potential factors associated with such variability. It will then report two studies that used natural stereoscopic images to understand neural responses to disparity. Both of the studies used individual differences as a tool to uncover determinants to neural responses to disparity in natural images. The results suggest that the meaningful scene content embedded in the monocular image content may interact with disparity processing. Studying "pure disparity" such as those using random dot stereograms might not be enough to understand our stereoscopic ability in relation to everyday life.

Keywords: Psychology.
Advisor: Norcia Anthony Matthew
Gardner Justin
Wandell Brian A.
Determinants of tax avoidance and the real effects of tax risk disclosures

I model the determinants of corporate tax avoidance to estimate the real effect of tax risk disclosures. Prior research hypothesizes that firms forgo profitable tax-saving strategies due to non-tax costs, financial reporting incentives, and tax authority scrutiny. Because many of these frictions are not directly observable, I quantify their effects using a dynamic structural model in which the firm chooses a set of tax-saving projects in each period to maximize the discounted stream of future net income. Structural modeling also permits me to quantify the real effect of tax risk disclosures. I estimate the disclosure decreases tax avoidance by 7.6\% but overstates the expected repayment after including audit and inspections by 6.0 times. When I adjust the disclosure to reflect the expected repayment, I find tax avoidance increases by 5.7\%. Finally, I find that average non-tax costs decrease pre-tax earnings by 14.6\% but that the cross-sectional dispersion in effective tax rates primarily arises from differences in the ability to avoid taxes rather than differences in non-tax costs.

Keywords: Business.
Advisor: Larcker David F. 
De Simone Lisa
Hartmann Wesley R. (Wesley Robert)
Reiss Peter C. (Peter Clemens)
Determining the evolution and effects of hypervelocity plasma plumes [electronic resource]

Spacecraft are a major component of infrastructure and are essential to modern society. Though launch opportunities are expected to become less expensive and more frequent through commercial launch providers, spacecraft design, manufacturing, and deployment processes are far from routine. In addition, a spacecraft's operational environment is riddled with numerous hazards that may jeopardize its performance, and with a cost to orbit of

Keywords: Aeronautics and Astronautics.
Advisor: Close Sigrid
Cantwell Brian advisor. Thesis advisor
Senesky Debbie advisor. Thesis advisor
Developing Sense of Place in USA Zoos: Effect of Featuring Local Versus Exotic Species

Zoos are already important institutions for educating the public to be effective stewards of the environment and passionate nature conservation actors, yet their influence could be increased. For example, the type of species exhibited can impact visitors differently: featuring exotic animals can provide broad knowledge, while focusing on species from local ecosystems can offer more relational and specialized information. The effect of varying emphasis on local versus exotic species remains unknown despite many papers analyzing zoo education. Research has shown that a stronger ecological sense of place (an individual’s connection to a space based on experiences and memories related to people, nature, or other local features) encourages more pro-environmental behavior. Therefore, promoting sense of place is one way zoos could motivate behavior changes in visitors. In this study, it was hypothesized that visitors at zoos that emphasize local species would exhibit greater ecological sense of place. Ecological sense of place was measured through Likert scale statements, whereby the more visitors agreed with statements on an area’s characteristics, the higher their sense-of-place score. These questions were disseminated through a survey at nine zoos across the country, matched geographically to contrast local and exotic species emphases and providing a substantial sample size (N = 1008 respondents). Based on a linear mixed-effects model, zoos with a local species emphasis significantly correlated with higher sense-of-place scores. Focusing on individual zoo pairs, the local-focused zoos in Nebraska and Arizona correlated with higher sense-of-place scores (a significant increase, in both cases) but those in New York and California did not. In addition, across all zoos, visitors who were local to the zoo’s area or who were zoo members had significantly higher sense-of-place scores. These results demonstrate that local-focused zoos, local visitors, and zoo members should be further investigated as promising catalysts for conservation. These groups could be targeted through outreach and educational efforts in order to maximize the development of pro-environmental behavior and to cultivate the animal conservation advocates of the future – a critical societal need in light of the current anthropogenic impact on ecosystems and wildlife in particular.

Keywords:  Department of Biology
sense of place
zoo
conservation
pro-environmental behavior
local species
education
survey
Thesis
Advisor: Dirzo Rodolfo
Daily Gretchen
The development and analysis of new organic reactions in bulk solution and in microdroplets [electronic resource]

The first portion of this thesis concerns the methodological development and mechanistic analysis of new C--H functionalization reactions. Over the past twenty years, the invention of protocols for the site-selective functionalization of sp3 C--H bonds has irrevocably altered the state of organic synthesis. Two such reactions described here are the oxidative cyclization of carboxylic acids to lactone products using Cu(OAc)2/K2S2O8 and the C--H bromination of N-methyl sulfamate esters with Rh(oct)4/NaOBr. The latter reaction proceeds via an intramolecular C--H abstraction by a transiently formed N-centered radical, allowing for the predictable functionalization of a single C--H bond among the many present in a complex molecule. The substrate scope of each of these reactions is delineated, and mechanistic analyses with both conventional physical organic experiments as well as with emerging ones, including desorption electrospray ionization-mass spectrometry (DESI-MS) and online electrospray ionization mass spectrometry (online ESI-MS), are provided. A purely mechanistic investigation of a third C--H functionalization process, the Ritter-type C--H amination of menthol with CuBr2/Selectfluor®, is also described. In addition to these experimental results, a review of C--H functionalization reactions using peroxydisulfate is included. The second portion of this thesis describes the analysis of organic reactions in microdroplets generated by electrospray ionization. It has been previously demonstrated that reactions in microdroplets generated through electrospray ionization (ESI) are often orders of magnitude faster than their counterparts in bulk solution. Sharpless and co-workers previously studied the [2σ+2σ+2π] cycloaddition of diethyl azodicarboxylate (DEAD) and quadricyclane and reported that the addition of water to the neat reagents caused an acceleration in the reaction rate, giving birth to what has been called "on-water" chemistry. This same reaction is examined in aqueous microdroplets (ca. 5 μm diameter), where the cycloaddition reaction is accelerated even further (by a factor of 10^2) compared to that of the "on-water" reaction reported previously. Furthermore, using a variety of analytical techniques, the structures of several other species that are detected in these droplet reactions are elucidated and a mechanism suggesting their formation is described. Although it is well established that microdroplets provide unique environments for a variety of chemical reactions, the mechanisms underlying this phenomenon are not fully understood. Using the nucleophilic ring-opening of limonene oxide with morpholine as a model reaction, the effects of microdroplet size and speed, electrospray voltage, and solvent on reaction progress are delineated. These variables are all shown to profoundly affect the extent of reaction "in droplet", which is accelerated by a factor of ~10^5 relative to the process in bulk.

Keywords: Chemistry.
Advisor: Zare Richard N. primary advisor. Thesis advisor
Burns Noah
Kanan Matthew William
Development and application of new optical methods for the study of molecular motor regulation for multimotor transport in live cells [electronic resource]

Life is made possible by 1) making complex biological macromolecules which then have to 2) arrive at specific physical locations. This second transport step is critical and becomes increasingly difficult as cells become large as is the case with eukaryotic cells. The problem of transport is solved in nature by the development of active intracellular transport machinery. The base units of this transport are molecular motors which are subject to many layers of regulation to properly transport cargos to where they need to function in the cell. For long range transport the primary motors are dynein and kinesin, which can walk along microtubules for long distances. Both these motors have been studied in purified systems but our understanding of how they work in cells is still lacking. I present work developing and using new optical methods to study the dynamics of motor activity in live neurons. First, Nanoparticle assisted optical tethering of endosomes (NOTE) is developed to show that kinesin and dynein, when active, are mechanically similar in the context of axons. Second, multipolarization darkfield microscopy is developed to track the orientation of endosomes as they are transported. Combination of orientation and position tracking allows inferences into the dynamics of the motor team transporting the cargo.

Keywords: Biophysics.
Advisor: Cui Bianxiao primary advisor. Thesis advisor
Brünger Axel T. advisor. Thesis advisor
Shen Kang
Theriot Julie advisor. Thesis advisor
Development of catalytic metal-mediated C--H hydroxylation methods with improved functional group compatibility

Catalytic C--H hydroxylation methods constitute an enabling technology for the synthesis and structural diversification of organic molecules. Current methods are challenged by substrates that are densely functionalized and contain cross-reactive groups. In recent efforts to address such issues, we have developed two catalytic systems that advance the capability of chemists to functionalize highly complex molecules. Nitrogen-derived functional groups and N-heterocycles are ubiquitous in active pharmaceutical ingredients (APIs) and natural products, but are incompatible with most current chemical methods for oxidation. We describe the development of a new protocol for sp3-C--H hydroxylation. The reaction is performed in aqueous acid with catalytic cis-[Ru(dtbpy)2Cl2] (dtbpy = 4,4'-di-tert-butyl(2,2'-bipyridine)) and enables oxidation of structurally diverse amine- and heterocycle-containing molecules. Tertiary and benzylic C--H hydroxylation is strongly favored over N-oxidation in amine-derived and N-heterocyclic substrates. In efforts to further develop this technology, a multi-pronged mechanistic study was undertaken using techniques such as pressurized sample infusion high-resolution mass spectrometry (PSI-HRMS), 19F NMR spectroscopy, electrochemistry, and reaction kinetics analysis. This work has afforded insight into ligand structure-activity relationships and the identity of relevant active catalytic species. Turnover numbers (TONs) of a series of catalysts examined are strongly correlated to the rate and extent of ligand dissociation that occurs under the reaction conditions. Insights gained from these studies should give way to the design of next-generation catalysts for efficient C--H oxidation of complex molecules. In related studies, we describe the development of a Mn-catalyzed hydroxylation reaction that uses H2O2 or peracetic acid as the bulk oxidant. This method complements our Ru-based chemistry by enabling the functionalization of stronger, less reactive C--H bonds. The protocol features exceptionally low catalyst loadings, accommodates a variety of simple ligands (including 2,2'-bipyridine), and favors 2º alcohol products over the corresponding ketone derivatives. Preliminary studies aimed at understanding catalyst degradation/arrest mechanisms are also described.

Keywords: Chemistry.
Advisor: Du Bois Justin 
Burns Noah
Waymouth Robert M.
Development of CRISPR-based mouse models for scalable and quantitative in vivo functional cancer genomics

Large-scale genomic analyses of human cancers have catalogued somatic point mutations thought to initiate tumor development and sustain cancer growth. However, determining the functional significance of specific alterations remains a major bottleneck in our understanding of the genetic determinants of cancer. A diverse set of approaches—from genetic screens in cancer cell lines to the generation of defined alterations within organoids, allografts, and xenografts—have been used to study the function of genetic drivers of cancer. This thesis describes advances in cancer modeling that have stemmed from the implementation of genome-editing and next-generation sequencing in autochthonous mouse models of human cancer. Specifically, this dissertation focuses on the development and applications of higher-throughput mouse models that enable precise and quantitative analysis of the effects of multiplexed and/or combinatorial alterations on tumor growth in vivo. I discuss the potential impacts of these models on functional cancer genomics and outline the ways in which these models will improve our understanding of cancer. Finally, I speculate on additional innovations that will further increase the scope, precision, and value of in vivo models of human cancer.

Keywords: Genetics.
Advisor: Winslow Monte 
Fire Andrew Zachary 
Lipsick Joseph Steven
Sage Julien
Development of efficient transporter strategies for the delivery of chemotherapeutics and biomolecules

All living systems require biological barriers. For therapeutic molecules to reach their targets, a diverse set of barriers needs to be breached in vivo, including but not limited to the lipid bilayer cell membrane, retinal-blood barrier, blood-brain barrier and skin barrier. Therefore, the design, synthesis and application of efficient delivery vehicles for therapeutic and diagnostic compounds across biological membranes are critical due to the increasing demand for precision medicine. Consequently, a number of novel physical, chemical and biological approaches have been explored to overcome these protective barriers. In addition to delivering into human cells or tissues, other colonizing organisms inside or on our body are also among the targets for drug delivery. The ultimate goal of this thesis is to develop efficient drug delivery strategies for clinical applications. Different approaches of delivery were explored by taking advantages of the chemical modification of drug molecules and delivery vehicles, either covalently or non-covalently. This thesis included 5 different projects covering the delivery of the largest known ribonulceoprotein, vaults; the delivery of oligonuleotide messenger RNAs; the delivery of glycopeptide antibiotics for Gram-positive bacterial infections; the delivery of glycopeptide antibiotics for Gram-negative bacterial infections; and the delivery of latency reversal agents for HIV/AIDS eradications.

Keywords: Chemistry.
Advisor: Wender Paul A. 
Cimprich Karlene 
Cui Bianxiao
The development of human high-level visual cortex

Humans possess a remarkable ability to rapidly recognize a wide variety of ecologically important stimuli, stemming in large part from a constellation of specialized regions in the ventral temporal lobe referred to as high-level visual cortex. In adults, neurons causally involved in the perception of faces, words, and scenes cluster in anatomically-anchored locations of ventral temporal cortex, making both their structural and functional signatures readily detectible with in vivo magnetic resonance imaging. Given that the recognition of faces or words are practiced abilities that take time to develop, human ventral temporal cortex (VTC) is an ideal test bed to examine the role of visual experience in shaping the function and structure of cortex throughout development. Indeed, the collection of studies presented here is conducted within VTC, which demonstrate through innovative multi-modal single-subject techniques previously undocumented aspects of functional and anatomical brain development in human visual cortex. These results provide foundational insight into the origins of the human visual system and inform future research regarding what happens when this development goes awry.

Advisor: Grill-Spector Kalanit 
McNab Jennifer (Jennifer A.)
Newsome William T. 
Wandell Brian A.
Dimensionality reduction of linear open quantum systems with delayed coherent feedback

Broadly, this work explores dimensionality reduction methods for open quantum systems. As networks of quantum systems become more complex, there is a greater need for tools to simulate them efficiently. I will focus on open linear quantum systems with coherent time-delayed feedback. This work will show how the transfer function formalism can be used to construct physically realizable reduced systems which approximate the correct input-output relation for this class of systems, providing an appropriate basis for simulations. Towards this goal, I will show how the transfer function can be decomposed into a (possibly infinite) cascade of canonical terms, each corresponding to a single degree of freedom, or a single mode of the system. We will do this first for passive systems, and then for active systems, requiring a more general representation. I will present a theorem that specifies conditions for the convergence of the cascade. Truncating this cascade results in the desired approximate model. I will discuss some examples where this approach can be useful, such as networks with degenerate parametric amplifiers that exhibit enhanced squeezing properties once time-delayed feedback is introduced.

Keywords: Applied Physics.
Advisor: Mabuchi Hideo 
Hayden Patrick (Patrick M.)
Weissman Tsachy
Diplomatic Breakthrough: Politics, Reform, and Trust in the Restoration of US-Cuba Relations

What explains the re-establishment of US-Cuba relations under President Barack Obama and President Raúl Castro? Conventional wisdom points to public opinion shifts within the Cuban-American community and domestic reform within Cuba. These two factors, while important, are insufficient to account for the re-establishment of US-Cuba relations. This thesis argues that the development of a working trust between Obama and Castro was critical to diplomatic breakthrough. Decades of hostility fueled a deep mistrust between the United States and Cuba. As this thesis details, Obama and Castro communicated a series of cooperative and trust-building signals – aided by Pope Francis and the Catholic Church – that allowed diplomatic breakthrough to emerge.

Keywords:  Program in International Relations
Cuba
Obama
Castro
Pope Francis
Diplomatic Trust
Program in International Relations
Thesis
Advisor: Magaloni Beatriz