VictorJuiz/thesis huggingface dataset:
Developing high-performing business models
Keywords: Management Science and Engineering.

Strategy and innovation scholars point to the rising importance of business models for firm performance. While prior research offers some insight into high-performing business models, it largely focuses on established firms with stable business models. Yet, this overlooks how entrepreneurial ventures develop and scale novel business models. This dissertation addresses this gap with three closely linked studies. The first is a comprehensive review of prior literature linking business models to firm performance. The second uses a novel theory-building methodology — machine learning and multiple cases -- to fit revenue models (i.e., value capture) with underlying activities (i.e., value creation) in high-performing business model configurations. The third is a longitudinal multiple-case theory-building study that unpacks how entrepreneurs build scalable business models in nascent markets. Jointly, the studies in this dissertation offer rich theory regarding how entrepreneurs can effectively develop and scale novel business models. Overall, this research contributes to literature on strategy, innovation, and entrepreneurship, as well as to practice
Developing tools for pluripotent stem cell-based therapies using AAV6/Cas9-mediated genome editing
Keywords: Stem Cell Biology and Regenerative Medicine.

The application of AAV6/Cas9-mediated genome editing to human pluripotent stem cells (hPSCs) offers the opportunity for efficient in vitro disease modeling, correction of disease-causing mutations, and a platform for engineering novel properties for clinical applications. Here we describe how to edit the genome of hPSCs, ranging from modifying single base pairs to the integration of large transgene cassettes. We then show how with this protocol we can build safety systems to minimize the risk of hPSC-derived teratoma formation. We show how orthogonal safety switches can be used prevent and intervene in the case of an adverse event following the transplantation of hPSC-derived cells. We also demonstrated the utility of this technology by creating isogenic series of the Huntington CAG repeat to model the pathogenic phenotype in vitro. Finally, we show how we can engineer hPSCs to secrete neurotrophic factors such as BDNF and GDNF that have been shown to ameliorate the symptoms of the disease
Development of a fluorescent molecular probe for transglutaminase 2 activity in mammals
Keywords: Chemical Engineering.

Celiac disease is an autoimmune disorder in genetically predisposed individuals where ingestion of gluten drives an inflammatory response that presents as enteropathy of the small intestine. A necessary but not sufficient genetic predisposition in individuals involves harboring the HLA-DQ2 or HLA-DQ8 gene cluster, with HLA-DQ2 being far more common. The disease is estimated to affect approximately 1 in 100 individuals worldwide, with an estimated 6 million patients between the U.S. and Europe and an estimated 2.5 million undiagnosed and at-risk Americans. There have also been studies showing that late diagnosis of celiac disease increases the risk of further autoimmune disorders. Clinically, the primary symptoms include crypt hyperplasia, a massive increase in intraepithelial lymphocytes (IELs), and villous atrophy. The only diagnostic method for the disease involves a small intestinal biopsy through upper gastrointestinal (GI) endoscopy, although elevated levels of anti-TG2 antibodies aid in the diagnosis. Currently, the only treatment for celiac disease is a lifelong avoidance of gluten as efforts to develop pharmacological treatments for celiac disease have been hindered by fundamental gaps in our understanding of its molecular pathogenesis, particularly involving the role of transglutaminase 2 (TG2). The work in this thesis helps address these issues. First, we highlight the structure-based design of a new TG2 probe named RZ-5 using available crystal structure data and develop a novel synthesis route towards developing 6-diazo-5-oxo-L-norleucine (DON) based peptides and probes. We highlight the challenges involved with DON synthesis prior to this work and present a solution to efficiently produce RZ-5 and similar analogs such as DP3-3 to validate the versatility of this method. After producing a novel probe, we explored the in vitro characteristics of RZ-5 and DP3-3 to validate RZ-5 as a potent TG2 inhibitor and interaction partner through various kinetic assays. We also present a novel assay to survey strong irreversible binding partners to TG2 and present kinetic parameters for RZ-5. Additionally, we studied RZ-5 in tissue and cell-based assays to validate its efficacy as an inhibitor and sensor. Starting with studies on frozen thin sections, we then moved towards higher-order biological systems. We present data validating RZ-5's binding and probing efficacies towards TG2 in mouse embryonic fibroblasts (MEF) systems, and show promising preliminary data of its potential as a compound capable of labeling TG2 in live animal systems either through direct delivery or through enteric formulation as an orally available drug. Collectively, these works serve as a guideline to highlight our work towards a next-generation probe for TG2 that has the potential to label the active enzyme in live animals. Future usage of this probe can strongly advance our molecular understanding of the roles of TG2 activity in celiac disease pathogenesis and its flexibility can lead to understanding of TG2 in other systems
Development of accessible quantum chemistry through virtual reality and cloud computing
Keywords: Chemistry.

The key bottleneck in many ab initio computational chemistry calculations is the electronic structure, i.e. what are the electrons doing in response to the atomic nuclei and/or other external influences. This is particularly problematic when considering that many electronic structure calculations are needed in most workflows, such as geometry optimization or molecular dynamics trajectories. As a result, many large or accurate calculations rely on high-performance computing (HPC) systems, such as large distributed systems (e.g. supercomputers with many compute nodes) or specialized coprocessors [e.g. graphical processing units (GPUs)]. The current state of scientific software for quantum chemistry centers on monolithic packages designed to run on remote clusters with batch job submission; however, this strategy limits the speed of method development and creates a significant barrier for educating aspiring chemists and the general public. In line with recent trends of code abstraction and encapsulation in the community, I present my work on a new socket-based interface for our GPU-accelerated electronic structure package, and furthermore my development of a cloud-based framework for distributing electronic structure calculations (on either academic HPC systems or renting commercial cloud resources) utilizing this new interface. I will demonstrate how this platform was applied to several key quantum chemistry workflows that require high-throughput calculations, including dataset generation, excitation energy transfer in multichromophoric systems, and automated reaction network discovery. Additionally, I detail the advancements made in real-time ab initio interactive molecular dynamics (AI-IMD) simulations to use virtual reality (VR) headsets to provide a virtual playground for interacting with quantum chemistry for students and other non-expert users
Development of DARS II for the measurement of pressure dependent quality factor and compressibility of small rock samples
Keywords: Geophysics.

Sample quality factor remains largely ignored due to difficulties in quantifying and repeating results. This thesis describes a Differential Acoustic Resonance Spectroscopy system, (DARS II), an acoustic method developed to study sample quality factor as a function of confining pressure at a kilohertz frequency scale. The work is subdivided into five parts: A review of the proof-of-concept system, DARS I; DARS II design and construction; DARS II empty-system characterization; Non-porous sample compressibility and attenuation estimates as a function of pressure; and Shale sample quality factor and attenuation estimates as a function of pressure. The primary contribution of this study is the design and construction of a system which estimates the resonant frequency, amplitude, and linewidth of porous and non-porous media with variable confining pressure at about 1000 Hz. The DARS II resonant frequency and linewidth measurements are used to estimate sample compressibility and quality factor with change in pressure measured at low frequencies. The method may be applied to regular or irregular shaped non-porous and porous samples
Development of instaFLARE Technology for Immediate Cell Activation Reporter Signal
Keywords:  Department of Biology
fluorescent labeling
calcium labeling
split infrared fluorescent protein
biology
Thesis

Changes in intracellular calcium are a hallmark of many cellular processes, including spiking activity in neurons, activation of G-protein coupled receptor cascades, or metabolic regulation in the mitochondria. It would be beneficial to have a technology that can rapidly and stably label cells exhibiting an increase in intracellular calcium following some stimulus. These cells could then be processed and analyzed to reveal calcium-dependent changes in gene expression or protein localization. There are various biotechnological tools that label activated cells after elevated intracellular calcium with a stable read-out, such as photo- conversion of a calcium-sensitive fluorophore (CaMPARI) or a calcium-dependent transcriptional reporter (FLARE); however, these tools either have limited sensitivity or require approximately 9 hours to provide the transcriptional read-out of activity. An efficient cell labeling tool that generates a stable signal within minutes would benefit researchers interested in investigating dynamic processes in cells that take place quickly after periods of high intracellular calcium. Here, we present instaFLARE, a novel technology that addresses the need for rapid and stable reporter expression; by using a reconstitutable, split infrared fluorescent protein (Split-IFP) instead of a transcription-initiated reporter gene, it is possible to engineer a tool that has much faster kinetics of reading out cells undergoing high intracellular calcium. instaFLARE’s faster time scales of activation and cell labeling has been tested by introducing the engineered proteins into HEK293 cells, exposing the cells to blue light and calcium at the same time, followed by subsequent imaging of the reconstituted IFP reporter at different time stamps after light and calcium introduction. In the future with further engineering, instaFLARE will allow for quick labeling of activated cells, which will enable researchers to investigate dynamic changes in the cell after rises in calcium that would otherwise be undetectable.
Development of Subject Matter Knowledge and Pedagogical Content Knowledge Through High-Level Cognitive Mathematics Tasks: The Case of a Teacher Education Program in Chile
Keywords: Chile
teacher education
pedagogical content knowledge
subject matter knowledge
curricular standards
Stanford Graduate School of Education International Education Policy Analysis
Thesis

This study seeks to understand whether the use of high-level cognitive mathematics tasks supports the development of subject matter knowledge (SMK) and pedagogical content knowledge (PCK) in pre-service teachers. It analyzes curriculum materials implemented in the content-focused mathematics methods courses in a teacher education program in Chile. In comparing the curriculum materials across the five courses, inconsistencies are found among the PCK components covered. Another result is that the Chilean curricular and teacher education standards are present in all the analyzed syllabi; however, they are not equally operationalized in the in-class tasks or the graded assignments of those same courses. This study also shows that there is little connection between the level of cognitive demand and the type of mathematics in-class tasks in the courses analyzed. Finally, the data reveal that the easier the mathematics content of the course, the larger the percentage of components related to PCK. In order to improve the effectiveness of teacher education programs for future mathematics teachers, Chilean education policies should more explicitly specify how to connect SMK and PCK in those programs and courses.
Dialectic Redemption: Lang Jingshan, Literati Landscape in Photomontage, 1920s-1940s
Keywords:  Center for East Asian Studies
Stanford Global Studies
East Asian Studies
Photomontage
the Aesthetic of Redemption
Allegorical Impulses
Intercultural Politics.
Thesis

Whereas most existing studies on Lang Jingshan’s landscape photomontage center around a nationalistic and pictorialist perspective, this article explores the political implications of Lang’s montage as a way to revisit the problematic relations of the past, identity, and political aspirations in the Republican Era. The first part of the article delineates the cultural landscape of the era within which the artist’s symbolic “return” to past imagery, aesthetics and sensibilities could be adequately understood. For those who were not yet convinced that the present course of events could not be resisted – whether the encroachment of urbanization and its unsettling fragmentary spectacles, a long-established Western Orientalist gaze, or modern technology’s suspension of genuine human expressions – the author argues, the decision to redeem the hopes of the past might well have seemed the antidote for the current pathosis. Furthermore, through situating Lang’s globally acclaimed landscape iconography in intercultural politics, I seek to portray a historical conjunction between Chinese neotraditionalism and anti-Enlightenment Western philosophy, with respect to their allegation of the tyrannical discourse of modernity. By using photography in bringing past landscapes and aesthetics to the unsettling present, the author argues, Lang resorted to a device of immanent critique, extended the scope of what was confined in the May-Fourth-mythicized modernity, and anticipated a dialectical image of the future, a reality that was yet to be.
Dimensional reduction of halide double perovskites
Keywords: Chemistry.

Dimensional reduction, or conversion of a three-dimensional (3D) structure to a lower dimensional derivative, can afford dramatic changes in a material's optoelectronic properties. While the effects of dimensional reduction on the family of lead-halide perovskites have long been studied, dimensional reduction of the more compositionally diverse family of halide double perovskites has remained largely unexplored. I investigate the effects of dimensional reduction on two electronically distinct 3D double perovskites, Cs2AgBiBr6 and Cs2AgTlBr6, through the synthesis and characterization of lower-dimensional analogues of mono- and bilayer thickness. These studies reveal that quantum confinement has a much larger effect on the optical properties of the Ag--Tl materials than on their Ag--Bi analogues due to the more delocalized electronic character of the Ag--Tl lattice. Interestingly, electronic structure calculations reveal a substantial change in bandgap symmetry upon dimensional reduction. At the monolayer limit, the indirect bandgap of Cs2AgBiBr6 becomes direct, while the direct bandgap of Cs2AgTlBr6 becomes indirect. To understand these changes, I develop a model to describe and predict the band structures of 2D halide double perovskites based on the atomic orbitals of their constituent elements which reveals the underlying factors that drive the bandgap transitions. Finally, I describe how the increased structural flexibility of the 2D perovskite framework can be used to expand the compositional and functional diversity of the perovskite family through the synthesis of a mixed-valence Cu+--Cu2+--In3+ 2D perovskite. The unusual composition of this material affords optoelectronic properties which are not commonly found in 2D perovskites of monolayer thickness
Discovering and validating methylated cell-free DNA biomarkers for cancer
Keywords: Bioengineering.

Methylated cell-free DNA (cfDNA) biomarkers have shown promise for blood-based cancer detection, in part because of their biological properties. Methylation of CpG dinucleotides in the promoter regions of tumor suppressor genes plays an early role in cancer development, and methylated DNA wraps around nucleosome proteins, protecting it from degradation by nucleases in the blood. Recent studies have mined high-dimensional epigenetic datasets to discover methylated cfDNA cancer biomarkers, employing statistical selection methods that may risk-rank correlative biomarkers with undefined biological relationships in a cancer type above biomarkers with known epigenetic roles. Accordingly, causative biomarkers with reproducible predictive power between patient cohorts could be filtered out during the discovery process. We hypothesized that utilizing a knowledge-based biomarker enrichment method to first decrease the dimensionality of these datasets followed by individual screening of the remaining biomarkers in the data would identify causative biomarkers that collectively embody a tumor-specific methylation signal in cfDNA. Our method, Layered Analysis for Methylated Biomarkers (LAMB), leverages meta-analysis to select an enriched set of CpG biomarker candidates in high-dimensional microarray data and then filters the biomarkers against public tissue methylation data from hundreds of cancer patients and lysed whole blood methylation data from over a thousand healthy patients. In this thesis, I will introduce LAMB and demonstrate that it can discover targeted methylated cfDNA biomarker panels that: (i) detected hepatocellular carcinoma (HCC) tumors in at-risk cirrhosis patients and (ii) differentiated prostate adenocarcinoma (PRAD) patients by their tumor's response to abiraterone acetate and docetaxel. I will also describe a targeted bisulfite sequencing assay that I created to analyze LAMB biomarkers (termed LAMB-Seq). I will demonstrate that LAMB-HCC biomarkers exhibited excellent read coverage and high-resolution methylation quantification through LAMB-Seq. Through this thesis, I will show that LAMB can be used to find cancer biomarkers that have potential for improving at-risk screening and therapy monitoring. I will also lay the groundwork for its application to other cancers and provide evidence for the benefits of using the LAMB-Seq platform to validate LAMB biomarkers
Divine transactions : the transformation of Buddhist communal liturgies at Dunhuang (8th--10th centuries)
Keywords: Religious Studies.

The current dissertation centers on a host of communal liturgies at Dūnhuáng from the eighth through the tenth centuries. In this period, Buddhist ritual flourished by localizing the existing Chinese ritual elements and absorbing ritual techniques from Tibetan sources. The Dūnhuáng corpus discovered around 1900 CE contains a wealth of ritual documents written in Chinese, Tibetan, and occasionally in a combination of the two. These texts provide a rare window into the practice of premodern Chinese Buddhism and Buddhism on the ground. The dissertation can be divided into two parts. The first three chapters discuss how to classify Indian, Chinese, and Tibetan communal liturgies from a structural perspective; the next six chapters study six distinct genres of liturgies by analyzing relevant liturgical scripts in the Dūnhuáng corpus. Chapter 1 focuses on the so-called "lay ritual events" in Indian Mainstream Buddhism, which constitute Mainstream communal liturgies. Based on how they are discussed in the vinayas, these liturgies can be classified into eight distinct categories. Chapter 2 examines a host of communal liturgies termed zhāi in the Tang and at Dūnhuáng. Chapter 3 evaluates the structural issues in Tibetan Buddhist ritual and how it changed over time. Chapters 4 to 8, relying on relevant liturgical texts, explore four different categories of zhāi-liturgies: prayer feasts, sūtra-rotation liturgies, the afterlife-related liturgies, the dedicatory rites, and holiday liturgies. Chapter 9 analyzes the early Tibetan adaptation of the Indic tantric feast and how tantric concepts and ritual technology transformed the communal feast. The Conclusion focuses on seven themes: a comparison between the thanksgiving prayer and the zhāi-script, the dissolution of the zhāi-liturgical system, Sino-Tibetan zhāi-liturgies, the classification of Buddhist rituals, the kammatic and nibbanic dimensions of communal liturgies, the existence of two different kinds of merit, and cultural embeddedness
Do we look like our spouses and our names? Re-examining the convergence in physical appearance hypothesis with modern computational methods
Keywords: Electrical Engineering.

Faces change over our lifetimes. The causes for these changes can be physical, such as age and diet, or mental, such as emotions and personality. The interplay between these physical and mental factors over time influences how our faces change in specific directions. This can lead to surprising, but not unreasonable, phenomenons. However, traditional studies in these subjects have been limited by challenges in data collection and subjective measurement methods. Recent advances in crowdsourcing and artificial intelligence have allowed us to address these challenges and conduct empirical studies with larger samples and in more objective ways. This dissertation presents two works that applied these modern computational methods to re-examine convergence in physical appearance with two factors: spouses and names. The first work asks the question of why we look like our spouses. The widely disseminated convergence in physical appearance hypothesis posits that long-term partners' facial appearances converges with time due to their shared environment, emotional mimicry, and synchronized activities. Although plausible, this hypothesis is incompatible with empirical findings pertaining to a wide range of other traits—such as personality, intelligence, attitudes, values, and well-being—in which partners show initial similarity but do not converge over time. Using two independent methods of estimating their facial similarity, human judgment and a facial recognition algorithm, we show that while spouses' faces tend to be similar at the beginning of marriage, they do not converge over time, bringing facial appearance in line with other personal characteristics. The second work asks whether we look like our names. The correlation between facial appearance and one's name is not controversial. First, both innate facial features and naming conventions vary across socio-demographic groups, defined by factors such as gender, ethnicity, profession, generation, etc. Second, people actively change their facial appearance to conform to social conventions of their socio-demographic group. However, it has been hypothesized that the link between facial appearance and one's name goes beyond socioeconomic and demographic factors, and that a name alone can affect an individual's facial appearance, as individuals conform to social expectations of how a person with a given name should look. Similarly, we used human judgment and a facial recognition algorithm to show that the face-name matching effect exists, but there is no proof that people alter their facial appearance to match pre-conceived notions of what they should look like