VictorJuiz/thesis huggingface dataset:
From G1 to S : understanding cell-cycle entry through single-cell microscopy techniques

Tight regulation of the cell cycle is critical for development and tissue homeostasis, and misregulation can lead to development defect, cancer, and degenerative diseases. While most of the individual components have been mapped out, our knowledge of the cell cycle remains incomplete. This is in part due to the popularity of bulk-cell assays in classical studies, where timing and kinetic measurements can be obscured by heterogeneity on a population level. In this thesis, we present two studies that take advantage of live, single-cell microscopy techniques. In the first study, we reveal how cells can proliferate without the kinase cyclin D-CDK4/6, a common target for cancer therapy. We found that in the start of this "alternate" pathway, the ordering of two critical events is inverted. We further demonstrate that in mice small intestinal crypt cells, this inverted sequence of events can be found alongside the canonical pathway that relies on cyclin D-CDK4/6. Our data thus suggests that wild-type, non-cancer cells can use two different paths to start the cell cycle. In the second study, we demonstrate how unperturbed cells use the kinase ATR, which detects DNA replication stress, to control CDK2 activity to rapidly modulate DNA synthesis rate. Besides fundamental characterizations, the two studies contribute to our understanding on how cells safeguard DNA replication. Cells need to achieve irreversibility prior to starting S phase to prevent reversion back to G1 (reversion results in over-replicated DNA). Once started, cells also must faithfully complete DNA replication. In the first study, we demonstrate that without CDK4/6 activity, cells have a different point of no return due to the inversion of signaling events. In the second study, we demonstrate that inevitable replication stress slows down DNA synthesis rate via an ATR-mediated negative feedback loop, thus preventing further accumulation of stress. Both studies enhance our knowledge on how cells maintain genome integrity. The studies also have potential clinical implications. An alternate pathway can at least partially explain how patients tolerate CDK4/6 inhibitors, and also explain how cancer cells bypass CDK4/6 inhibition. Finally, since many cancers have increased replication stress, understanding how cells resolve this stress may reveal synthetic lethal vulnerabilities in the future.

Keywords: Chemical and Systems Biology.
Advisor: Meyer Tobias 
Cimprich Karlene 
Ferrell James Ellsworth
From Malinaltenango to Waukegan: A Case Study on Non-migrant Identity

This research explores complex identities rooted in displacement, poverty, and migration. It provides a historical overview of the relationship between two distinct places that are tied together by its people. Malinaltenango, Mexico is a small town tucked away in the valley of the State of Mexico. It is also my parent’s hometown, and a place I have only recently started to consider part of my own identity. In this essay, I provide a historical overview of the town and its relationship with a place I have always known to be home: Waukegan, Illinois. I began to ask myself, why is it that identity is rooted in the birthplace? Who has a stake in this identity, and how does this identity change through migration? In addition to understanding places like Waukegan as an extension of Malinaltenango, I argue that we should understand Malinaltenango identity as a byproduct of migrant lives in Waukegan. I provided an analysis of interviews conducted in the summer of 2018. Ultimately, I hope that my work shines light on non-traditional migrant groups typically explored by U.S. scholars, and births new understandings of identity and transborder relationships between the U.S. and Mexico.

Keywords: identity
transborder
transborder migrants
migration
migrants
State of Mexico
Estado de Mexico
Malinaltenango
Waukegan
Mexico
Tonatico
undocumented
poverty
NAFTA
bracero program
Illinois
Stanford University
Center for Latin American Studies
Thesis
From metagenomes to genomes : new tools for complex bacterial communities

Characterizing the individual genomes of organisms within the human gut microbiome is a critical first step toward understanding this complex community as a whole and its impact on many aspects of human health. Thus far, efforts to characterize the genome sequences of gut microbiome bacteria have been largely based on short read sequencing and reference-based tools. Although these have benefited from advances in short read assembly and binning approaches as well as large-scale sequencing efforts, they face fundamental limitations that necessitate improved methods for metagenomic sequencing and assembly. This dissertation details some of the molecular and informatic challenges facing the field of metagenomic research within the gut microbiome, explores the limits of the existing methodologies, offers novel technological solutions, and applies those solutions to uncover novel biological insights into the gut microbiome. Chapter 2 describes the application of existing short read-based approaches to the gut microbiomes of cancer patients receiving fecal microbial transplant. Chapter 3 describes a new approach using read cloud sequencing to improve metagenomic assembly. Chapter 4 applies this read cloud approach to study insertion sequence mobilization within bacterial strains over the course of a patient's treatment for a hematological malignancy. Finally, chapter 5 describes a second new approach using nanopore long read sequencing to assemble full-length genomes directly from human gut metagenomes. Together, these chapters provide a deeper understanding of the challenges facing metagenomic assembly of the human gut microbiome, two new approaches to solve them, and new biological insights they have revealed.

Keywords: Genetics.
Advisor: Bhatt Ami (Ami Siddharth) 
Fordyce Polly 
Sherlock Gavin 
Snyder Michael
From sad salad tweets to twisted carrots and dynamite beets : leveraging tasty and enjoyable attributes of healthy foods to promote a culture of healthy eating

Rising rates of obesity, diabetes, and cardiovascular disease call for interventions that promote healthier dietary intake. Many approaches have aimed to improve dietary intake by emphasizing the long-term importance of eating healthily and highlighting the nutritional benefits of healthier food choices, but these health-focused approaches have had limited success. In this dissertation, I draw on theory of cultural cycles of mutual constitution ("culture cycles"), mindsets and implicit theories, and insights from wise interventions to propose an integrated theoretical framework for analyzing this problem. I use this integrated theoretical framework to understand why Americans make unhealthy food choices, despite knowing what constitutes a healthy diet and wanting to live a healthy life. Studies 1-7 present evidence that the descriptive language used in popular American culture perpetuates and reinforces negative mindsets about healthy foods, both at the institutional and interactions levels of the culture cycle. In Studies 8-11, I use this framework to design and test a new solution, a taste-focused promotional approach for healthy foods that counteracts prevalent negative mindsets. I show that taste-focused labeling increases healthy food choices across a range of healthy foods and settings, concluding with a multi-site replication. Studies 12-15 further explore the psychological mechanisms by which these changes occur. Together, this research shows that a culturally informed theoretical framework of how particular mindsets are formed and reinforced can aid design of wiser intervention approaches. This research represents one small step towards changing a culture of negative mindsets surrounding healthy eating.

Keywords: Crum, Alia degree supervisor.
Psychology.
Advisor: Dweck Carol S.
Markus Hazel Rose
From Scribbles to Shapes: Measuring Developmental Changes of Visuomotor Abilities in Drawings

How do infants who can barely control their limbs grow into children who can produce richly meaningful drawings that express what they are learning about the world? One plausible contributor to this developmental change might be enhanced visuomotor control with age. In order to evaluate the developmental change of children’s visuomotor ability, we designed a set of tablet-based tasks to trace and copy primitive geometric shapes and recruited 4880 children, whose age ranges from two to ten, to complete these tasks. To evaluate the 9967 tracing and copying images from children, we then developed an automatic procedure to quantify children’s performance and collected adult ratings on a subset of the data to train and validate the model’s evaluation. The model is able to reproduce similar evaluations as human raters. Using the model on the full dataset, we found an age-related increase in children’s visuomotor ability in drawing.

Keywords: Visuomotor Ability
Drawing Development
Symbolic Systems Program Thesis
Thesis
Advisor: Frank Michael C.
Fan Judith E.
Long Bria
From time-resolved to frequency-resolved x-ray scattering

Gas-phase time-resolved x-ray scattering (TRXS) measures internuclear separations in a molecule following laser-induced photoexcitation. TRXS constitutes an indirect measurement of the molecular motion because it captures information in reciprocal-space and real-time, which then must be inverted to recover the charge density as it changes in time. The spatial resolution of the recovered charge density is fundamentally restricted by the x-ray wavelength used in the experiment. There is no corresponding technical restriction on the ability to scan the delay between the pump-laser pulse and the x-ray-probe pulses, and thus no lower limit on the ability to resolve beat frequencies from TRXS measurements. This observation motivates transforming the measured TRXS in reciprocal-space and real-time into its reciprocal-space and reciprocal-time representation through a temporal Fourier transform. This representation is called frequency-resolved x-ray scattering (FRXS). The novel aspect of this approach is that an interpretable and compact representation of the experimental measurement may be obtained in reciprocal-space and reciprocal-time without the difficulty of inverting the measurement to the traditional real-space and time representation, and thus FRXS presents an alternative to traditional analyses of TRXS. The traditional approach based on pair correlation functions is limited by the range of momentum transfer, Q, that is accessible at x-ray free electron lasers (FELs). FRXS does not suffer this limitation, and in fact, FRXS leverages the strengths of FELs, namely fine time resolution and (relatively) fast data accumulation. This enables a long range of pump-probe delays to be measured in an experiment, thus improving the frequency resolution of an experiment, while maintaining sufficient temporal resolution to measure high beat frequencies. These advantages have been used to obtain compact representations of bound states and dissociations along lines in reciprocal-space and reciprocal-time, demonstrating an alternative to traditional analyses of time-resolved x-ray scattering for gas-phase photochemistry.

Keywords: Physics.
Advisor: Bucksbaum Philip H. 
Martinez Todd J. (Todd Joseph)
Reis David A.
Functional Divergence of Plexin B Structural Motifs in Distinct Steps of Drosophila Olfactory Circuit Assembly

Plexins are evolutionarily conserved receptors for Semaphorin signaling that carry out diverse and multitudinous neurodevelopmental processes. However, the molecular mechanisms behind how such proteins employ their structural architecture in vivo to perform distinct roles in neural circuit wiring remain unknown. Here, we systematically mutagenized structural motifs of Plexin B (PlexB), generating nine transgenic fly lines carrying mutant PlexB constructs expressed from the same genomic locus. We then assayed the efficacy of these variants at executing known PlexB-mediated neurodevelopmental processes in olfactory circuit assembly, namely axon fasciculation, trajectory choice, and synaptic partner selection. We found that certain structural motifs were involved in some processes but not in others. Furthermore, we report the first in vivo functional study of PlexB cleavage, revealing its regulatory role in multiple processes. Thus, PlexB differentially engages its signaling architecture in distinct wiring steps, allowing it to play varied roles in neural circuit assembly.

Keywords:  Department of Biology
Biology
Plexin
Neurodevelopment
Structure-to-Function
Drosophila
Thesis
Advisor: Luo Liqun
Shen Kang
Fundamental Fractures: Children and Gendered Difference in Hisaye Yamamoto’s Seventeen Syllables

For all its thematic complexity and literary prowess, Asian-American literature continues to be categorized and dismissed as cultural artifact. Unfortunately, the application of critical literary theory within the context of Asian-American works remains largely incomplete. In this thesis, I approach three stories from Hisaye Yamamoto's anthology "Seventeen Syllables" through the lens of critical feminist and historicist theory.

Keywords:  Department of English
Department of English
Asian-American Literature
Japanese-American
Short Story
Hisaye Yamamoto
Feminist Critical Theory
Thesis
Advisor: Fisher Fishkin Shelley
Jones Gavin
GaAs based long wavelength vertical cavity surface emitting lasers

Long wavelength GaAs-based vertical-cavity surfaceemitting lasers that operate in continuous wave mode at and above room temperature are demonstrated.The VCSELs employ a dilute-nitride GaInNAsSb/GaNAs multiple quantum well active region, two n-doped Al- GaAs/GaAs distributed Bragg reflectors and a tunnel junction. Typical devices have threshold current densities of 2 kA/cm2. Single mode operation was achieved from a 7 mm aperture device. The devices have 3 dB frequencies above 4 GHz.

Keywords: Materials Science and Engineering.
Advisor: Cui Yi
Harris J. S. (James Stewart)
Brongersma Mark L.
Gelatin microribbon-based macroporous hydrogels for enhancing stem cell-based bone regeneration

Bone loss due to trauma, disease, or cancer resection remains a large clinical concern and causes significant pain and discomfort to patients of all ages. To this day, bone grafting remains the gold standard in treating such defects, making bone the second most transplanted tissue after blood. Bone grafting, however, suffers from insufficient donor supply as well as significant donor site morbidity. Bone tissue engineering approaches offer a promising alternative to bone grafting by using stem cells, biomaterials, and biochemical cues to regenerate bone. Mesenchymal stem cells (MSCs) are a particularly attractive cell source as they are well characterized, can differentiate into all skeletal tissues including bone and cartilage, and are known to be immunoprivileged, making them a promising allogenic cell source. The load-bearing environment of bone requires the use of biomaterials to provide cells mechanical and structural support. To this end, our lab recently developed gelatin-based microribbons (µRBs) using a two-step crosslinking mechanism that remain injectable upon mixing in cells homogenously. After filling any irregular shaped defect, the µRBs can then be crosslinked into any desirable 3D shape or form with interconnected macroporosity. Encouraged by the highly desirable properties, this thesis aims to investigate the potential of gelatin-based µRBs as a universal scaffold for bone tissue engineering. As bone develops through two distinct pathways (endochondral ossification and intramembranous ossification), the ability of µRBs to recapitulate both pathways using MSCs was examined. First, gelatin µRBs were compared to a gelatin hydrogel in forming the required cartilage template before the full endochondral ossification pathway was studied in vivo. In order to examine the ability of µRBs to support intramembranous ossification, the role of substrate stiffness and the incorporation of osteoinductive hydroxyapatite into the scaffold was analyzed. The gelatin-based µRB platform described in this thesis may offer a universal scaffold material for bone tissue engineering and provide a clinical alternative to bone grafts for treating bone defects. The strategies to form bone in this thesis were intentionally designed to use only the minimum required materials and signals to reduce costs and support clinical translational potential. However, gelatin-based µRBs could support additional complexity, such as drug-releasing strategies to further enhance tissue formation. Furthermore, this work exclusively focused on MSCs, however, gelatin-based µRBs also supports other stem cell populations (i.e. pluripotent stem cells), adding additional versatility to the platform. While this thesis investigated bone regeneration, gelatin-based µRBs have many desirable properties that suggest it could also be used for engineering other tissue types such as cartilage, fat, and even ligaments and tendons.

Advisor: Yang Fan (Bioengineering researcher and teacher) 
Heilshorn Sarah 
Smith R. Lane (Robert Lane)
Gender Disparities and District-Level Distribution Shifts in Lung Cancer Rates in Beijing, China from 2000-2013

Background – Cancer has become the leading cause of death in China since 2010; with lung cancer, specifically, the most common incident cancer and leading cause of cancer death in the country. While prior research has focused on lung cancer rates and trends for men and women on a national and provincial scale within China, there has been little attention focused at the city- and district-level lung cancer rates, particularly in suburban areas.
Objective – This research examines whether trends in lung cancer incidence rates from 2000-2013 in Beijing indicate gender and district-level disparities.
Methods – Lung cancer incidence rates were determined and analyzed using data from the Beijing Cancer Registry. The data were analyzed for differences in rate changes over time after linear regressions for age-standardized incidence rates were determined.
Results – A total of 86,822 incident cases of lung cancer were identified. Substantial gender differences were observed: men had significantly higher age standardized lung cancer incidence rates than women in all 16 districts at every time point. Age-standardized lung cancer incidence rates increased over time in most districts, with evidence of a widening gender disparity, and the effects were more pronounced in suburban districts compared to urban districts.
Conclusion – The findings replicate a strong gender effect in lung cancer incidence in Chinese adults and reveal a particularly pronounced and growing effect in suburban districts. With attention to the very high smoking prevalence among Chinese men and concerns with air pollution as leading risk factors for lung cancer, these findings can inform preventive guidelines and public health policies for lung cancer prevention and treatment in Beijing to address this growing epidemic.

Keywords:  Department of Medicine
Community Health and Prevention Research
Department of Medicine
Stanford University
lung cancer
China
Beijing
gender
suburban
urban
district
disparity
Thesis
Advisor: Prochaska Judith
Gendered Agentic Language Patterns in Evaluative Text

Differences in the way men and women are described in textual evaluations have been documented in letters of recommendation, professor evaluations, and performance evaluations. To this point, most studies have been done qualitatively. Several studies show that there are differences in the way men and women are described with agentic language, or language describing individual accomplishment with terms like execute, drive, or ambitious. These gendered differences can be consequential in terms of overall performance assessment. A recent study showed that agentic language increases with performance for men but only does so to a point for women before decreasing at the highest levels. Here, we apply computational techniques to show gendered differences in agentic language patterns hold at the scale of an entire technology company for the first time. We construct a lexicon based on relevant literature to obtain frequencies of agentic language terms in the corpus. We find that our analysis of agentic language patterns conceptually replicates a similar study’s findings using entirely new data and methods. We model the findings and find robust significance regarding a positive increase in agentic language for men rising to the top of the organization, but a decrease in agentic language in the reviews of top-performing women. We discuss the implications of a simple computational technique’s ability to capture this phenomenon. We consider potential future applications of this technique to other companies and discuss future research directions.

Keywords: gender
language
symbolic systems
agentic
computational
performance
evaluation
Thesis
Gendering generations : redefining masculine life stages in modern China

This dissertation, drawing on archives and collections in China, Hong Kong, and Taiwan, is a cultural history of how Chinese masculine life stages changed and coexisted over the course of the tumultuous twentieth century. In four case study-based chapters, it shows how new ideas of age- and gender-appropriate behavior for Chinese men at differing life stages in disparate historical moments emerged in tandem. New life stages were created in dialogue with longstanding traditions, international debates, and emerging problems of modernity. Each chapter centers on a life stage that proved key to the formation of a new understanding of masculinity, beginning with boyhood in the early twentieth century and closing with old manhood at the turn of the twenty-first century. This life-cycle structure overlays the historical timeline on the biological timeline and reveals how gender norms interacted with ideas about age-appropriate behavior. It also illustrates how generationally-divided understandings of gender and life stages existed simultaneously. Rather than provide a comprehensive taxonomy of age-specific masculinities, Gendering Generations emphasizes the life stage as a category of analysis and identity in China's gender history.

Keywords: History.
Advisor: Mullaney Thomas S. (Thomas Shawn) 
Freedman Estelle B.
Sommer Matthew Harvey