VictorJuiz/thesis huggingface dataset:
Single cell expression analysis of human cellular reprogramming [electronic resource]

The ability to reprogram adult human cells into induced pluripotent stem cells (iPSCs) has allowed us to study development like never before. By studying the reprogramming process, we are able to dissect molecular and developmental events that give rise to all cells of the human body. Despite intense interest and research into the molecular mechanisms of reprogramming, we still lack full understand the reprogramming process itself and downstream effects on the resulting cells. What we do know is that there is a significant amount of heterogeneity in the cells that result from reprogramming and in the way that individual, otherwise homogenous, cells respond to reprogramming factors. In order to better understand the reprogramming process, I used an mRNA reprogramming technique to modulate the types and numbers of mRNAs used in an attempt to identify novel reprogramming factors. I generated a large dataset of gene expression data from single iPSCs and parental fibroblasts to uncover some of the expression patterns that define different developmental time points. This dataset includes two cell lines (fetal and adult), four developmental time points (fibroblasts, passage 0, passage 3, and passage 20 iPSCs), as well as two growth conditions (5 or 20% oxygen). Using this dataset, I was able to address critical questions about the effects of reprogramming on female cells. Female cells have a unique biology linked to X chromosome inactivation, which is required to equalize the gene expression between males and females. As this X chromosome-based epigenetic regulation is set up in early development, there has been much interest in the state of the X chromosome during the reprogramming process. Here, I show that passage 0 iPSCs maintain XCI but that these cells lose XIST expression, which is the non-coding RNA that regulated the silencing, by passage 20. These results have significant implications for the clinical translation of stem cell therapies into clinics, especially for women.

Keywords: Genetics.
Advisor: Baker Julie (Professor of genetics) primary advisor. Thesis advisor
Fire Andrew Zachary advisor. Thesis advisor
Reijo Pera Renee
Sage Julien advisor. Thesis advisor
Soft correspondences for consistent collections of shape maps [electronic resource]

Finding an informative, structure-preserving map between two shapes has been a long-standing problem in geometry processing, involving a variety of solution approaches and applications. Such a map should capture ambiguity in relations, minimize distortion, be smooth, and be invertible or symmetric. The increase in availability of 3D models has also fueled an interest in finding maps among collections of shapes, not just individual pairs. Such maps should be consistent with one another in the sense that all the maps agree on the correspondences between a given pair of shapes, regardless of how we compose the maps through other shapes. This quality can often be at odds with the desired qualities for an individual map. Furthermore, the operations for manipulating maps may appear simple mathematically, but they can become unwieldy if not outright impossible depending on the choice of representation. I will reconcile these issues by proposing soft correspondences as a way to represent maps, as well as cycle consistency optimization as a way to induce agreement within a collection of maps. I will also present several means of producing soft correspondences incorporating various forms of information and desired qualities.

Advisor: Guibas Leonidas J. primary advisor. Thesis advisor
Sahami Mehran advisor. Thesis advisor
Ye Yinyu advisor. Thesis advisor
Solitude in postwar Italian and French cinema [electronic resource]

This dissertation examines solitude in Italian and French films of the 1950s, '60s, and '70s. Through close analyses of the canonical oeuvres of four preeminent directors -- Roberto Rossellini, Robert Bresson, Jean-Luc Godard, and Michelangelo Antonioni -- I provide a new theory for the development of film aesthetics in Italian and French cinema during the postwar era. I argue that the shift from the apparent cohesion and transparency of realism to the narrative ambiguity and audio-visual fragmentation of modernist film form in their work is principally determined by the representation of solitude.

Keywords: Art and Art History.
Advisor: Levi Pavle primary advisor. Thesis advisor
Bukatman Scott
Ma Jean
Steimatsky Noa advisor. Thesis advisor
Solution deposition of semiconductor thin films for photovoltaics [electronic resource]

Thin film photovoltaics are among the most promising clean, renewable energy technologies and have the potential to meet future world energy demand by covering only a small fraction of the earth's surface. To meet this challenge, annual production of photovoltaic modules, despite recent escalation, must still increase several orders of magnitude, and the development of inexpensive and scalable thin film deposition methods is of crucial importance to this effort. The cost and scalability limitations of the standard high-vacuum thin film deposition methods may be overcome by using solution-based methods. Furthermore, the transition from photovoltaic materials containing cadmium, indium, and tellurium to materials comprised of earth-abundant, non-toxic elements is expected to accelerate their large-scale deployment. Here, I present several strategies for the improvement of inorganic thin films synthesized by solution deposition. In this work, two low-cost, solution-based methods (chemical bath deposition and nanocrystal inks) were applied to the deposition of thin films of ZnS, SnS, and Cu2ZnSnS4 (CZTS), all potential earth-abundant non-toxic materials for photovoltaics. First, through the chemical bath deposition of SnS, I show how film quality is a function of deposition kinetics and can be manipulated through control of bath compositions and post-annealing parameters to improve film properties In the same SnS system, using nanocrystal inks, I show that control over nanocrystal morphology can be used as a strategy for improving thin film quality. A selective synthesis was developed for the production of high-aspect ratio sheet-like nanocrystals. Nanocrystal inks formulated from these crystals were capable of producing extremely highly-oriented thin films through the lamellar stacking of SnS sheets, which yielded favorable optical and electronic properties. The second major study in nanocrystal inks examined the efficacy of inorganic ligand exchanges and the resulting effect on film formation. Ammonium polysulfides were demonstrated as a novel species for ligand exchange on cubic ZnS nanocrystals, where they were shown to remove native ligands with high efficacy and improve film quality. Finally, this ligand exchange was applied to CZTS nanocrystal inks with promising implications for the deposition solar absorber layers. The use of these ligands has the potential to improve efficiency and lower costs in the production of CZTS photovoltaics and other chalcogenide thin films.

Keywords: Chemistry.
Advisor: Bent Stacey primary advisor. Thesis advisor
Chidsey Christopher E. D. (Christopher Elisha Dunn)
Kanan Matthew William
Sparse covariance estimation using Stein's unbiased risk estimator (SURE) [electronic resource]

The problem of estimating an unknown covariance matrix is among the most widely-studied problems in multivariate statistics. A popular estimator was proposed by Stein which regularizes the sample covariance matrix by shrinking its eigenvalues together. Although numerical studies have found that Stein's estimator performs well relative to other estimators, its somewhat complicated functional form makes it difficult to analyze theoretically, and therefore few theoretical properties of Stein's estimator have been established. We undertake a detailed investigation of Stein's covariance estimator in both the finite-sample and asymptotic regimes. We also suggest alternative estimators based on the same approach which can sometimes lead to significant risk reductions over Stein's proposed estimator, and which can also generalize Stein's methodology for other loss functions, including those for the inverse covariance (precision) matrix. Finally, we propose a novel framework for constructing sparse estimates of the covariance matrix by augmenting the objective function minimized by Stein's estimator with a sparsity-inducing penalty function; the resulting optimization problem is convex and can be solved efficiently via a simple block coordinate descent approach. We demonstrate that the resulting estimator performs well via numerical simulations and establish conditions under which it yields an asymptotically consistent estimate of the population covariance parameter.

Advisor: Taylor Jonathan
Johnstone Iain advisor. Thesis advisor
Tibshirani Robert advisor. Thesis advisor
Spatiotemporal resolution of T-box function in early mesoderm patterning [electronic resource] : an optochemical approach

Zebrafish mesoderm development is largely regulated by a network of T-box transcription factors comprised of the Brachyury ortholog no tail a (ntla), spadetail (spt), and tbx6-like (tbx6l). Conventional genetic mutant analyses have demonstrated the importance of these factors in mesoderm patterning; however, the non-conditionality of these perturbations have limited our understanding of how these genes function in space and time. Exploiting the optical transparency of early zebrafish embryos, our lab has developed photoactivatable caged morpholinos (cMO) that permit light-inducible gene silencing with spatiotemporal precision. The focus of this dissertation is on the application of these optochemical probes to resolve the function of the T-box gene spt in two distinct developmental contexts: 1) paraxial mesoderm patterning and 2) posterior medial floor plate (MFP) formation. In Chapter 1, I provide a brief survey of zebrafish mesoderm development, describe the dynamics of T-box gene expression during gastrulation, and detail the mesodermal phenotypes observed upon loss or gain of function of these factors. In Chapter 2, I apply a cMO targeting spt with photoactivatable lineage tracers, fluorescence-activated cell sorting, and RNA-sequencing to reveal 124 transcripts that are differentially expressed within a population of cells enriched for paraxial mesoderm progenitors upon loss of Spt function. Furthermore, I uncover a novel Spt-dependent regulation of collinear hox gene activation in these cells. In Chapter 3, I combine the spt cMO with a conventional ntla MO to characterize the temporal and spatial requirements of these genes in posterior MFP development. These studies indicate that ntla and spt act specifically within lateral margin derived progenitors during gastrulation to promote posterior morphogenetic movement of MFP progenitors in the midline without affecting Nodal-dependent MFP fate specification. This dissertation highlights the advantages of light-activated technologies to spatiotemporally characterize gene function during early vertebrate development.

Keywords: Chemical and Systems Biology.
Advisor: Chen James
Meyer Tobias advisor. Thesis advisor
Talbot William
Wysocka Joanna
Speech, variation, and meaning [electronic resource] : the effects of emotional prosody on word recognition

This dissertation investigates the effect of phonetically cued emotional information (i.e., emotional prosody) on spoken word recognition. Even words whose meanings are not emotionally laden (e.g., pineapple) can be uttered in a way that conveys anger, happiness, or sadness through phonetic modulation, and the current work investigates how this phonetic variation in the speech signal affects the way spoken words are perceived, recognized, and ultimately understood. Based on the results from five cross-modal priming experiments, I claim that social information from speech is available early and influences spoken word recognition, that all linguistic experience is not equal in that two atypical forms prompt different listener behavior, and that a full explanation of spoken language understanding must include an attentional mechanism. I argue for a new approach to spoken word understanding based on a recent proposal made by my colleagues and me (Sumner, Kim, King and McGowan, 2014). This approach is grounded in existing theories of exemplar dynamics, but expands on the notions of socioacoustic encoding and social weighting. The speech signal is simultaneously mapped to social representations (via socioacoustic encoding) and linguistic representations. The socioacoustic encoding activates social features and categories (e.g., information about the speaker's age, gender, and emotional state) from the speech signal early in lexical processing. Once activated, the social features and categories interact with other social or linguistic representations and they modulate the allocation of cognitive resources (i.e., attention) to the linguistic signal, effectively weighting the significance of each linguistic experience differently (social weighting). This dissertation significantly broadens the current understanding of spoken word recognition by demonstrating the crucial influence of phonetically cued emotional information, offering a new approach that embraces the rich informational contribution contained in phonetic variation.

Keywords: Linguistics.
Advisor: Sumner Meghan primary advisor. Thesis advisor
Eckert Penelope advisor. Thesis advisor
Jurafsky Dan
Podesva Robert advisor. Thesis advisor
Spiny armor reduction in sticklebacks due to a splicing change in MSX2A [electronic resource]

Threespine sticklebacks (Gasterosteus aculeatus) are named for their characteristic dorsal spines, but different populations show variation in spine size and number. Marine populations typically have long spines that form part of their defensive armor, whereas many freshwater populations exhibit reduction or loss of the spines. In a large F2 cross used previously for QTL mapping, dorsal spine length maps to chromosome 4, to a locus that contains MSX2A. An enhancer sequence near MSX2A drives expression in the spines, and the MSX2A transcript shows allele-specific expression bias in F1 hybrids. However, the expression bias appears to be primarily caused by a difference in mRNA splicing. A single-nucleotide change in freshwater fish creates a predicted hnRNP binding site that favors the formation of a much smaller transcript. In F1 hybrids, the full-length transcripts are produced mainly from the marine allele, and short transcripts are produced from the freshwater allele. Reintroduction of the marine version of the gene significantly restores spine length in transgenic freshwater fish. Thus, the reduced spines of freshwater sticklebacks appear to have evolved in part due to the appearance of a new functional element affecting splicing. Additionally, the lack of MSX2A in certain fish species that have lost their bony armor suggests that the gene may have played a role in other instances of armor reduction in teleosts. Additional QTL for spine length and other skeletal traits were identified in a new cross between sticklebacks from Boulton Lake, British Columbia, and Bodega Bay, California. The Boulton Lake population differs from other freshwater populations in the nature of its dorsal spine and pelvic reduction. The MSX2A locus was again the major QTL identified for dorsal spine length, but the set of minor QTL included a new locus at the end of chromosome 6 that affected spine 2 specifically. Pelvic spine length was linked to the MSX2A region of chromosome 4 in this cross, not to the major locus on chromosome 7 observed in several other populations, and there was evidence for additional QTL on chromosome 4 and on 9 other chromosomes. Among the F2s of the new cross were fish carrying an extra dorsal spine. The presence of this 4th spine was mapped as a binary trait, and QTL were found on chromosomes 1 and 6. Although the Boulton Lake and Bodega Bay cross parents had 2 spines and 3 spines, respectively, the 4-spine phenotype was associated with Boulton genotypes at both QTL. These results suggest that, in the context of marine genotypes at certain other loci, Boulton freshwater alleles can increase spine number beyond the range observed in either parental population.

Keywords: Chemical and Systems Biology.
Advisor: Chen James
Kingsley David M. (David Mark) primary advisor. Thesis advisor
Talbot William
Wysocka Joanna
Spools, Hats, and Handbags: Narrative Entropy in the Plays of Samuel Beckett

A thesis exploring the intersection between narratology and dramatic literature using three plays by Samuel Beckett: Krapp's Last Tape, Happy Days, and Waiting for Godot. Through the employment of narrative entropy, these three plays yield significant challenges to the picture of life-as-narrative, interrogating both the dramatic form and the narrative form using the literary-performative combination of both.

Keywords: Beckett
Stanford English Department
Stanford Department of English
Stanford University
narrative
narratology
drama
dramatic literature
narrative entropy
Happy Days
Krapp's Last Tape
Waiting for Godot
Thesis
Advisor: Moya Paula
Lupic Ivan
Wainstein Nathan
Stability and transparency of bilateral teleoperators and haptic displays [electronic resource]

Bilateral teleoperators and kinesthetic haptic displays use force feedback to render a realistic sense of touch to a human operator. In bilateral teleoperation, a human manipulates a master robot that controls a slave robot, and feels force feedback as the slave interacts with a remote environment. In haptic displays, a human manipulates a robot to interact with a computer-rendered virtual world. Teleoperators and haptic displays are used in a wide range of applications such as surgery, human motor control research, mining/exploration, and rehabilitation. Ideally, they should be capable of rendering a large range of dynamics to the operator accurately and precisely. However, designing force-feedback systems is challenging because they have limited control rates, finite sensor resolution, and time delay, and they are dynamically coupled to the complex time-changing dynamics of the human operator. This thesis focuses on the design and control of impedance-type bilateral teleoperators and kinesthetic haptic displays. We examine one-degree-of-freedom models that include the effects of robot and human dynamics, sampling, position quantization, filtering, and time delay, with the goal of creating high performance systems that are simultaneously stable, free of noisy force signals, and accurately render the desired dynamics to the human operator. Our analysis establishes stability limits for rendering large impedances using virtual stiffness and damping, and rendering small impedances using virtual mass. We present a general sufficient condition for quantization error passivity, and sufficient conditions for position quantization induced limit cycles. We analyze factors affecting the dynamics rendered to the human operator using a novel system decomposition called ``effective impedances, " to identify important parameters for closed-loop haptic display accuracy and bilateral teleoperator transparency. We also characterize how joint space quantization error propagates to operational space coordinates and their derivatives for an arbitrary-degree-of-freedom robot. The results of this thesis serve as design and control guidelines for haptic devices, teleoperators, and exoskeletons, and are particularly relevant for applications such as surgery and rehabilitation.

Keywords: Mechanical Engineering.
Advisor: Okamura Allison primary advisor. Thesis advisor
Cutkosky Mark R. advisor. Thesis advisor
Salisbury J. Kenneth advisor. Thesis advisor
Stable moduli of flat manifold bundles [electronic resource]

Flat manifold bundles (i.e. manifold bundles with foliations transverse to the fibers) are classified by homotopy classes of maps to the classifying space of diffeomorphisms made discrete. In my thesis, I studied the homology of the classifying spaces of discrete diffeomorphisms for certain type of manifolds including surfaces, higher dimensional analogue of surfaces and disks with punctures. I established homological stability of discrete surface diffeomorphisms and discrete symplectic diffeomorphisms which was conjectured by Morita. To study the stable homology of these family of groups, I described an infinite loop space related to the Haefliger space whose homology is the same as group homology of discrete surface diffeomorphisms in the stable range which is the analogous of the Madsen-Weiss theorem for discrete surface diffeomorphisms. Similar theorems were proved for punctured 2-dimensional disk and higher dimensional analogue of surfaces. I utilized these new techniques of studying discrete diffeomorphism groups to obtain interesting applications to the characteristic classes of flat surface bundles and foliated bordism groups of codimension 2 foliations.

Keywords: Mathematics.
Advisor: Galatius Søren
Cohen Ralph L.
Eliashberg Y.
Mirzakhani Maryam advisor. Thesis advisor
Stage-specific transcriptional repression directs selective gene activation in an adult stem cell lineage [electronic resource]

A single fertilized embryo gives rise to more than 200 distinct cell types in the human body. Regulation of cell type specific gene expression is one of the most critical molecular processes in specifying and maintaining these diverse cell fates. Here we show that cell type specific transcriptional repressors, along with activators, play key roles in selective gene expression in cell fate determination. In the Drosophila male germ line stem cell lineage, when progenitor cells cease mitotic proliferation and initiate terminal differentiation, they turn on one of the most dramatic cell type specific transcriptional programs in Drosophila. To investigate how this dramatic cell type specific gene expression is set up, I developed an in vivo synchronous differentiation system to identify the first transcripts turned up, with the idea that these early expressed genes may include "first regulators" that help initiate the terminal differentiation program. Progenitor mitotic spermatogonia that accumulated in bam-/- mutant testes were triggered to differentiate by a single heat shock pulse of expression of Bam. Global gene expression profiling by microarray and RNA-seq across time as spermatogonia synchronously differentiate into spermatocytes identified three distinct steps - 'downregulation', 'initiation', and 'terminal differentiation' -- in the gene expression cascade in the switch. Functional knock down of the first 39 upregulated genes identified 16 new genes required for proper differentiation, 6 of which exhibited particularly strong and early defects. One of the newly identified early genes, tZnF, encodes a multiple zinc finger spermatocyte-specific nuclear protein, required for repressing gene expression of somatic transcripts in male germ cells. Results from double mutant analysis suggest that tZnF is required in spermatocytes to prevent promiscuous activation of somatic transcripts by the testis-specific Meiotic Arrest Complex (tMAC) when it activates testis specific transcripts required for spermatocyte differentiation My results demonstrate how a cell can prevent collateral activation by a promiscuous activator to ensure correct differentiation of a specific cell type. In chapter 4, I characterize five additional genes identified from the early regulator screen. The products of the five genes --testis-specific ATP synthase [beta] chain (CG5389); B9 domain (CG14870); pipsqueak type homeodomain like domain (CG30401); smooth or hnRNP-L, RNA binding domain (CG9218); and tBRD-1, bromodomain (CG13597) -- have diverse molecular functions, ranging from signaling, transcription, and RNA-processing, suggesting that terminal differentiation into spermatocytes is a complicated process involving complex regulatory mechanisms.

Keywords: Chemical and Systems Biology.
Advisor: Fuller Margaret
Chen James
Ferrell James Ellsworth advisor. Thesis advisor
Khavari Paul A. advisor. Thesis advisor
Lipsick Joseph Steven