VictorJuiz/thesis huggingface dataset:
Gait modifications for knee osteoarthritis : design, evaluation, and clinical translation

In individuals with knee osteoarthritis, the large forces transmitted through the tibiofemoral joint during walking are related to pain and disease progression. Gait retraining is a promising non-surgical treatment for knee osteoarthritis that aims to reduce knee loading by modifying an individual's walking pattern. This dissertation describes two gait modifications that reduce knee loading during walking: one by altering kinematics and another by altering muscle coordination. First, we demonstrated that training individuals with knee osteoarthritis to walk with a personalized foot progression angle modification improves pain and reduces knee loading more than a sham gait retraining control. However, the efficacy of this intervention hinges on our ability to prescribe personalized modifications that reduce each individual's knee loading. This process requires an expensive gait analysis laboratory that is not available in a clinical setting. To solve this problem, we developed an algorithm that, together with human pose estimation tools, will facilitate the measurement of knee loading using a smartphone camera. Finally, we used musculoskeletal simulations to design a biofeedback tool that teaches individuals to change their muscle coordination pattern in a way that reduces knee loading. These results suggest that muscle coordination retraining may be a promising new treatment for knee osteoarthritis. More generally, using simulations to design biofeedback devices that teach individuals to adopt more favorable movement patterns has applications in rehabilitation, injury prevention, and sports performance

Keywords: Mechanical Engineering.
Advisor: Delp Scott
Beaupré Gary Scott
Gold Garry E.
GameStop: How Technology and Social Media Form Modern Market Dynamics

How does digitization affect the social and technical components of financial markets? This research shows that automation reconfigures the social nature of financial markets, but it does not eliminate the prevalent political and hierarchical structure that exists. Through analysis of previous technologies and their incorporation into the trading process, this thesis displays how the interaction of social and technical attributes has formed the identity of American financial markets since their inception, and it continues to do so today. It argues that the modern technologies of high-frequency trading algorithms and mobile trading platforms provide an opportunity for equal access, but the way that they are currently being used is reinforcing a social hierarchy in the markets. This argument is formed based on the results of a case study on a market event involving GameStop and Robinhood, as well as a historical analysis of the phases of digitization in American financial markets. This research indicates that technology and electronification of the trading process is not enough to dissolve the inequities present in the markets today. This discovery leads to the conclusion that it is necessary for the government to take regulatory action to improve price transparency and protect the interests of retail investors.

Keywords: GameStop
Science Technology and Society
Stanford University
finance
financial markets
markets
Robinhood
mobile trading platforms
high frequency trading
algorithmic trading
retail traders
Thesis
Advisor: Granovetter Mark
GENDER STEREOTYPES AND VOICE AI: AN APPLICATION TO PERCEPTIONS OF DIGITAL VOICE ASSISTANTS

This thesis seeks to provide clarity around how gender impacts human perceptions of
VAs. The thesis consists of two parts: a scholarly literature review and an in-lab empirical study.
In the literature review, I review relevant work to show the importance of anthropomorphism in
HCI research and the specific importance of gender as a determinant for how humans interact
with and perceive digital technologies. In the second part, I present the results of an in-lab
empirical study that I conducted to understand whether interacting with gendered VAs has an
effect on attitudes towards VAs, focusing on warmth and competence, perceptions of
anthropomorphism, and mood.

Keywords: gender stereotypes
voice AI
anthropomorphism
Thesis
Gendered racial boundary maintenance : social penalties for White women in interracial relationships

Throughout American history, formal laws and social norms have discouraged interracial romantic relationships. Interracial relationships blur the boundaries between racial groups, challenging the essentialized racial categories that define Whiteness as an exclusive, high-status identity. Despite the importance of racial homogamy to White identity and status, we argue that gender roles make violating norms against intimate intergroup contact more costly for women than men, leading to Whites' greater resistance to interracial relationships involving White women. In a representative American sample using a natural quasi-experiment, as well as three follow-up lab experiments, we find that White women face differential social penalties for intimate intergroup contact-- being perceived as gender deviant and low status within the group. This research demonstrates the existence of a gendered double standard for intimate intergroup contact among Whites, revealing that gender norms play a critical role in the maintenance of American racial boundaries

Keywords: Business.
Advisor: Lowery Brian
Gruenfeld Deborah H. 
Martin Ashley
Gendering digital infrastructure and peripheral urban formation in Tunis, Tunisia

A few years after Tunisia's revolutionary uprising of 2010-2011, the internet materialized as a household necessity in low-income areas of Tunis, the capital. This dissertation documents the proliferation of digital infrastructure in the most populous, low-income area of Tunis by foregrounding its social character and role in the growth of peripheral urban landscapes. The dissertation thus departs from ethnographic studies of experts who build the web and software architectures that structure computing and internet functionality. The approach to "digital infrastructure" advanced here stems from two guiding motifs operating as methodological principles: firstly, that it has to be discovered what "digital infrastructure" comprises in a given place; secondly, that researchers should investigate the techne (artful technique) of how people use the internet in order to undermine the internet's cerebral association with air and clouds as opposed to the making and doing that personal computers were designed for and for which they are actually used. Through a comparison of the inner and outer periphery of this area in terms of internet use and urban experience, the study demonstrates that relationships are central to the status of emplaced digital infrastructure, where online chatting represents the bulk of how residents used the internet. Relationships were also central to lending and borrowing that underpins the slow growth of neighborhoods over time. A focus on the relationships of a group of women participants serves to counter the area's overdetermined association with law-breaking young men. At the same time, the study highlights that gender relations change as women move through urban landscapes, where their experiences of crime and masculinity serve as indices of urban growth and development. Based on 15 months of ethnographic research and a quantitative survey in Hay Ettadhamon (Solidarity District), the study further shows how women employ techne online and in their relationships in ways that serve the place-making of neighborhoods

Keywords: Anthropology.
Advisor: Ebron Paulla A.
Ghannam Farha
Inoue Miyako
Tambar Kabir
Gene regulation and the physical genome

Interpreting genetic or genomic data requires an understanding of DNA as a tangible, dynamic object with particular physical properties. In most eukaryotes, DNA is packaged in the nucleus as chromatin, with proteins called nucleosomes that determine the accessibility of the genome to biochemical activity. In this work, I chart chromatin accessibility and gene expression in a three-dimensional induced stem cell-derived organoid model of human cortical development, nominating specific molecular factors that may drive differentiation and maturation of glial, excitatory neuronal, and inhibitory cell lineages. I identify putative enhancers that may regulate corticogenesis and developmental states that harbor increased vulnerability to genetic perturbations associated with neurodevelopmental disease. Separately, I studied the three-dimensional organization of a unique eukaryotic organism that does not package DNA with nucleosomes, the dinoflagellate Symbiodinium minutum. I found that the domain-scale architecture of its chromosomes was completely dependent on ongoing active transcription, highlighting a fundamental connection between gene expression and genome organization

Keywords: Bioengineering.
Advisor: Greenleaf William James
Bintu Lacramioara 
Bryant Zev David 
Chang Howard Y. (Howard Yuan-Hao)
Genetic and functional investigations of the pathogenesis of African salmonella typhimurium isolates that cause systemic disease

Salmonella enterica serovars can cause a range of disease in human hosts. The human-adapted Salmonella enterica serovar Typhi causes enteric (typhoid) fever by entering through the gastrointestinal tract to invade systemic sites such as the blood, liver, spleen, and bone marrow. In contrast, non-typhoidal serovars of Salmonella enterica are primarily confined to gut tissues in otherwise healthy humans. Across Africa, outbreaks of systemic bloodstream infections with Salmonella have caused increased morbidity and mortality. These cases of disease are notably caused by isolates belonging to non-typhoidal Salmonella serovars Enteritidis, Choleraesuis, and Typhimurium. Such invasive non-typhoidal Salmonella (iNTS) infections appear to be associated with age (the very young and elderly) and co-morbidities like malaria, HIV, or malnutrition. Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major contributor to iNTS disease burden in sub-Saharan Africa. The outbreaks of iNTS disease due to S. Typhimurium serovars are clonally-related and many of these isolates classify as sequence-type 313 (ST313). To understand this evolution in pathogenesis of S. Typhimurium iNTS, we compared the genomes of African S. Typhimurium ST313 isolates with other S. Typhimurium from sequence-types that have mainly caused outbreaks of gastrointestinal disease. This comparative genomic analysis revealed several macA and macB gene variants unique to African isolates of iNTS. MacAB forms a tripartite efflux pump with TolC and has been shown in mouse infection models to be important for S. Typhimurium pathogenesis. We show that macAB transcription is upregulated during macrophage infection and after antimicrobial peptide exposure, with macAB transcription being supported by the PhoP/Q two-component system. Constitutive expression of macAB improves survival of Salmonella in the presence of the antimicrobial peptide C18G. Furthermore, African S. Typhimurium ST313 macAB variants affect replication in macrophages and influence fitness during colonization of the murine gastrointestinal tract. Importantly, the infection outcome resulting from these S. Typhimurium ST313 macAB variants depends upon both the S. Typhimurium genetic background and the host gene Nramp1, an important determinant of innate resistance to intracellular bacterial infection. Our studies provide additional mechanistic insights into the functional role of the MacAB-TolC efflux pump for Salmonella pathogenesis. Furthermore, the variations we have identified in the MacAB-TolC efflux pump in African S. Typhimurium ST313 may be an example of convergent evolution toward loss of MacAB function that reflects adaptation to particular human host populations with compromised ability to control intracellular bacterial infections. This dissertation furthers our knowledge about this important group of Salmonella that remain a substantial disease burden in Africa

Advisor: Monack Denise M. 
Bhatt Ami (Ami Siddharth) 
Chien Yueh-Hsiu
Sonnenburg Justin
Genetic and molecular features of placental abnormalities : preeclampsia, placenta accreta and mouse models

Pregnancy is a complicated process were the maternal body dramatically adjusts to accommodate e developing embryo. The mediator of maternal-fetal interactions during pregnancy is the placenta, a transient organ that develops from extraembryonic cells in the blastocyst. Placental cells called trophoblasts promote remodeling of the uterine vasculature to ensure proper exchange of nutrients, gases and waste between the two organisms. In humans, these trophoblast cells in the maternal-fetal interface are highly invasive, and any misstep in regulating trophoblast invasion can bring about pregnancy complications that can be fatal to both mother and child. One of such complications is preeclampsia, where shallow placental invasion leads to limited perfusion to the placenta in the third trimester, causing organ damage and hypertension in the mom. If the placenta is not delivered, preeclampsia can develop into eclampsia, which leads to seizures and death. The rate of preeclampsia is about 5% worldwide, but incidence and death rates are much higher in non-European populations, where it has primarily been studied. In Chapter 2 of this thesis, I study indigenous families in the Andean highlands in Peru, where preeclampsia incidence is 16 20%, and find genomic regions associated to preeclampsia and its phenotypic features in the three organisms—mom, dad and child—involved in the disease. These regions include genes with both known and unknown roles in pregnancy that can be subject of functional studies to further understand healthy placentation and the root causes of preeclampsia. In Chapter 3, I and others perform the largest GWAS metanalysis on mothers of European descent and uncover four new regions of small effects in preeclampsia risk on the maternal side. Another placental disease is placenta accreta, in some ways opposite to preeclampsia, where trophoblast cells invade the uterus beyond the maternal-fetal interface because a proper barrier does not form. In Chapter 4, I describe some of the proteins that are overexpressed in these invasive trophoblasts, and then investigate the maternal plasma proteome to develop a biomarker-based diagnostic assay that can aid in early detection and intervention of accreta. Finally, in Chapter 5, I move into the mouse as a model organism to understand invasive trophoblast biology and describe the transcriptomic differences in two knockouts with altered trophoblast function related to the polyploid nature of these cells

Keywords: Genetics.
Advisor: Baker Julie (Professor of genetics) 
Bassik Michael 
Bhatt Ami (Ami Siddharth) 
Red-Horse Kristy
The genetic basis of parallel and divergent evolution in threespine stickleback

A central goal of evolutionary biology is to understand the nature and extent of genetic patterns underlying adaptive phenotypes. For example, when faced with similar environmental challenges, does evolution use similar molecular solutions, and if so, how are they similar? And do diverse changes in common traits arise from modifying different genes, or particular genes in different ways? The threespine stickleback provides an excellent model system to study these questions due to its unique natural history and diverse ecological niches. In my thesis work, I utilize experimental and computational approaches to both the parallel and divergent aspects of stickleback evolution to address these key evolutionary issues from multiple perspectives. To examine recurrent patterns in parallel evolution, I identify a large set of genomic loci that change repeatedly during colonization of new freshwater habitats by marine stickleback. The same loci used in these extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors. Both the speed and location of changes can be predicted using empirical observations of recurrence in natural populations or fundamental genomic features like allelic age, recombination rates, density of divergent loci, and overlap with mapped traits. A composite model trained on these stickleback features can also predict the location of key evolutionary loci in Darwin's finches and cichlids, suggesting similar features are important for evolution across diverse taxa. To study patterns in divergent evolution, I analyze different wild populations of freshwater stickleback that have either increased or decreased the lengths of their prominent dorsal and pelvic spines and identify a new regulatory locus with a major morphological effect on spine length. Natural alleles at this locus are differentiated between marine and freshwater sticklebacks; however, alleles found among freshwater populations are also differentiated, with distinct alleles found in short- and long-spined freshwater populations with reciprocal regulatory effects on the bone growth inhibitor gene Stanniocalcin2a. Many other stickleback loci similarly show three or more major alleles, suggesting that diverse alleles at key loci may represent a common mechanism for producing diverse phenotypes from a smaller toolkit of genes

Keywords: Developmental Biology.
Advisor: Kingsley David M. (David Mark)
Jarosz Daniel
Talbot William S.
Villeneuve Anne
Genetic screens to understand the C9ORF72 repeat expansion in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative movement disorder. The most common known genetic cause of ALS to date is a GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene. There are currently three hypotheses as to how this mutation can cause neurodegeneration in ALS. First, the repeat expansion leads to reduced gene expression and therefore, C9ORF72 haploinsufficiency could contribute to the disease. The remaining two hypotheses focus on gain-of-function consequences arising from the bidirectional transcription and translation of the repeat. Both the sense and anti-sense repeat RNA form foci that may sequester RNA binding proteins, preventing them from performing their normal functions. Finally, the non-canonical translation of both the GGGGCC and GGCCCC transcripts produces six distinct species of dipeptide repeat proteins (DPRs): glycine-arginine, glycine-alanine, glycine-proline, proline-arginine, proline-alanine, and proline-glycine. The arginine-rich DPRs cause overt toxicity in various model systems, suggesting an obvious link to neurodegeneration, but many questions remain about all three hypotheses and their relative roles in driving ALS pathogenesis. This dissertation is an attempt at addressing some of these questions. Chapter 2 examines the glycine-arginine and proline-arginine DPRs to see whether the two species have a shared mechanism of toxicity. Yeast genetic screens identified numerous genes that block glycine-arginine toxicity when deleted. After comparing our findings to previously identified modifiers of proline-arginine toxicity, we discovered that only half the proline-arginine hits were identified in the glycine-arginine screens. This incomplete overlap suggests that glycine-arginine and proline-arginine may act on distinct pathways within the cell. Chapter 3 shifts to address the question of endogenous C9ORF72 function. In hopes of gaining additional insight into C9ORF72 function, we performed a genome-wide synthetic lethal CRISPR screen in human myeloid cells to identify genetic interactors of C9ORF72. We discovered that loss of FIS1, a gene encoding a mitochondrial membrane protein, is synthetic lethal with loss of C9ORF72. FIS1's role in mitophagy suggested an obvious parallel to C9ORF72's role in autophagy, but surprisingly, follow-up experiments moved the genetic interaction away from mitochondria and pointed instead to a role for FIS1 and C9ORF72 in immune regulation

Advisor: Gitler Aaron D.
Bassik Michael
Reimer Richard J. 
Wyss-Coray Anton
Genetically mapping adipogenesis by using a genome-wide CRISPR-based screen

Obesity, as characterized by the expansion of white adipose tissue (WAT), has become a global health crisis. The inappropriate storage of excess nutrients in the form of hypertrophic adipocytes is correlated with many metabolic diseases, and their sequelae. Herein, we performed a genome-wide sgRNA CRISPR KO screen in the mouse 3T3-L1 cell line to identify the key genetic regulators with the in vitro proxy for two key features of stem cell biology, the ability to self-renew and differentiate. By using a pooled screen approach followed by FACS to isolate population based on their uptake of a lipophilic dye BODIPY 493/503 we were able to enrich for genes that played key roles during the two phases of 3T3-L1 differentiation: mitotic clonal expansion (MCE) and lipogenesis. These analyses were supplemented by proteomic work, which revealed that changes in protein abundance during differentiation were being largely driven by selective protein translation and degradation, and not transcription. Together, these protein-based and genomic approaches yielded new insights into the specialized translational program driven by the hypusination of Eif5a, and the role of the neddylation/ubiquitin pathway in insulin sensitization within the adipocyte precursor cell. By identifying the genes involved in MCE and lipogenesis, we defined two paths for future therapeutic intervention. We anticipate genes involved in MCE can be used to manipulate the tissue resident preadipocyte to self-renew while genes involved in lipogenesis can be leveraged to control the inappropriate size of the disease correlated hypertrophic adipocytes

Advisor: Jackson Peter K. (Peter Kent)
Majeti Ravindra
Weissman Irving L.
Wernig Marius
Genomic and physiological features of slow-growing chloroflexi

Fast growing organisms adapted to high substrate concentrations have almost exclusively been the focus of microbiology research and led us to discover what we know about microbial metabolism. However, growth in Nature is usually not as fast and substrate conditions not as ideal. This work is an attempt to study how microorganisms adapt to slow growth and starvation conditions. Dehalococcoides mccartyi, a member of the Chloroflexi phylum and obligate strictly anaerobic organohalide respirer, was grown in chemostats adjusting doubling times between 5 and 50 days. The influence of growth rate on the microorganism's cell cycle was investigated using flow cytometry in combination with mathematical modeling showing that all phases of the cell cycle increased quasi-proportionally with doubling time. D. mccartyi chemostat cultures were also subjected to three months of substrate starvation and their protein and ribosome abundance was monitored during the onset of starvation revealing a 66% decrease in ribosomal content after 1.5 month of starvation but a remarkable stability of the overall proteome composition. Finally, the Chloroflexi phylum, to which D. mccartyi belongs, is a highly diverse phylum with few isolated representatives and which is enriched in the marine subseafloor. Metagenomic reconstruction of the genomes of 31 marine subsurface Chloroflexi revealed the quasi-ubiquitous presence of a functional catabolic Wood-Ljungdahl pathway and oxidation pathways for H2 and diverse organic compounds, making a strong case for a heterotrophic acetogenic lifestyle in these organisms

Advisor: Spormann Alfred M. 
Criddle Craig 
Dekas Anne