VictorJuiz/thesis huggingface dataset:
Dissecting genes and signals controlling pancreatic islet morphogenesis and differentiation [electronic resource]

The pancreas is a mixed endocrine and exocrine organ associated with the digestive tract. Pancreatic islets are spheroid endocrine micro-organs dispersed throughout the pancreas which secrete hormones into the bloodstream, whereas acinar and ductal cells form a branched epithelial network which transmits digestive enzymes into the intestine. During development, islets, ducts, and acinar cells originate from common progenitors. Islet cells begin to differentiate, exit the ductal epithelium, migrate outward, and cluster to form islets. Genes and signals controlling islet cell differentiation and islet morphogenesis in space, time, and lineage remain to be discovered. Additionally, whether the functions of genes and signals characterized in model organisms are conserved in human pancreas biology is frequently difficult to assess. This thesis presents findings and methods that advance knowledge of mechanisms of islet morphogenesis and differentiation at the cellular and tissue levels. In Chapter 2, we address discordance between mouse and human mutant phenotypes by assessing the functional consequences of human gene mutations associated with clinical disease. In Chapter 3, we define a radial axis in islet morphogenesis encoded by the Semaphorin signaling through Neuropilin receptors. In Chapter 4, we identify the transcriptional corepressor ETO as a regulator of islet progenitor development, and in Chapter 5, we develop tools for genetically labeling human α cells. Along with these findings, we describe methods for single-cell resolution live imaging of developing islet cells, somatic delivery of transgenes to intact developing pancreatic tissue cultured ex vivo, and whole-organ high resolution confocal imaging. Overall, the work here contributes to the study of pancreas organogenesis, defining genes and signals that act at regulatory points in development to enable the formation of pancreatic islets.

Keywords: Developmental Biology.
Advisor: Kim Seung K. primary advisor. Thesis advisor
Kingsley David M. (David Mark) advisor. Thesis advisor
Krasnow Mark
Talbot William
Dissecting proton delocalization and the electrostatic contribution to catalysis in ketosteroid isomerase with non-canonical amino acids [electronic resource]

The origin of enzymes' catalytic power is a long-standing and still largely unsolved problem in biochemistry. To compare and evaluate the role of various catalytic strategies, I have turned to a model protein ketosteroid isomerase (KSI). Low barrier hydrogen bonds (LBHB) and electrostatic stabilization are two popular theories proposed to explain KSI's catalytic proficiency. The primary difference between the two hypotheses lies in the nature of the interaction between the transition state (TS) of the reaction and the extended H-bond network in KSI's active site, which preferentially stabilizes the TS to contribute to catalysis − in a LBHB formulation, the TS would enjoy an additional energetic benefit from the presumed covalent (delocalized) nature of a strong H-bond. To enable a side-by-side comparison of the two hypotheses, I utilized amber suppression and prepared a set of 'conservative mutants' by incorporating noncanonical amino acid 3-chlorotyrosine to each of the three tyrosine residues (Y16, Y57, Y32, denoted as 'tyrosine triad') within the extended H-bond network of KSI. The site-specific incorporation enabled the incremental and simultaneous tuning of the proton affinities and the electrostatic properties of KSI's active site, as suggested by small but systematic changes in KSI's catalytic rate. Moreover, X-ray crystal structures of the mutants verified the preservation of the extended H-bond network with minimal structural perturbation. The series of conservative mutants allows me to (1) dissect the quantum delocalization of protons within the extended H-bond network of apo-KSI; (2) critically test the linear correlation between KSI's electric field and its catalytic proficiency, reinforcing the dominant contribution of electrostatics in KSI catalysis; (3) and elucidate the functional connection between the strength of the active site H-bond and the electric field it exerts, suggesting a potential unification of the two hypotheses on the origin of enzymes' catalytic power.

Keywords: Chemistry.
Advisor: Boxer Steven G. (Steven George)
Cegelski Lynette advisor. Thesis advisor
Markland Thomas E.
Distinct mechanisms of multisite phosphorylation of the transcriptional inhibitor Whi5 regulate the budding yeast cell cycle [electronic resource]

Budding yeast cells link their rate of division to growth via the transcriptional inhibitor Whi5. Cell growth dilutes, and thereby partially inactivates, Whi5, allowing the expression of two cyclins, Cln1 and Cln2. Cln1 and Cln2, in complex with cyclin-dependent kinase (Cdk1), further inactivate Whi5, completing a positive feedback loop that drives cells into S-phase by inducing expression of hundreds of genes. An additional cyclin-Cdk1 complex, Cln3-Cdk1, has been thought to contribute to the initial inactivation of Whi5 through phosphorylation. Using phos-tag SDS-PAGE to assay the phosphorylation state of Whi5 in vivo, we show that, although Cdk1 activity is required at S-phase entry, Whi5 phosphorylation during G1 does not require Cdk1. We identify the specific residues on Whi5 that are phosphorylated during G1 and show that their ablation has a moderate effect on cell cycle progression, as assayed by cell size. We also find that two of these phosphosites match the consensus motif for PKA, suggesting a possible additional Whi5 regulatory mechanism. We show that rapid Whi5 phosphorylation at S-phase entry depends on the phospho-threonine binding activity of the cyclin-Cdk1 subunit Cks1. Finally, we find that blocking Cks1 binding to Whi5 phospho-threonines yields a size phenotype equivalent to blocking all Whi5 phosphorylation by cyclin-Cdk1. This suggests that Cks1 binding to Whi5 phospho-threonines is essential to the function of Whi5 phosphorylation by cyclin-Cdk1.

Keywords: Biology.
Advisor: Skotheim Jan
Stearns Tim advisor. Thesis advisor
Straight Aaron
Distributed energy resource networks [electronic resource] : planning, control and market design

Distributed energy resources (DERs), such as energy storage and distributed generation, are rapidly replacing centralized power generation due to their environmental, economic and resiliency benefits. Integrating DERs into power network presents new challenges to power system planning, control and market design. In the first part of the thesis, we analyze a simple greedy strategy for the planning problem of placing energy storage in a power network. Using structural characterizations of the underlying power network control problem, we identify conditions under which the placement value function is submodular so that the greedy strategy has a performance guarantee. We then develop a computational procedure to certify these conditions for any given problem instance based on multi-parametric programming. In the second part of the thesis, we consider the stochastic control problem for operating energy storage devices connected in a power network. As the exact solution of the problem based on dynamic programming suffers from the curse of dimensionality, we propose a simple online algorithm for the problem utilizing a stabilized greedy (myopic) controller. For a rather general setting, we establish performance guarantees for the proposed method. Finally, we study fundamental requirements for power network reliability in designing novel power markets to integrate DERs. We demonstrate a transaction or trading based market, on top of a system operator implementing these reliability requirements, could achieve the same efficiency as centralized stochastic dispatch. We also obtain structural results for radial networks which indicate efficient market outcomes can be reached with bilateral trading for distribution networks.

Advisor: Rajagopal Ram primary advisor. Thesis advisor
El Gamal Abbas A. advisor. Thesis advisor
Johari Ramesh
DNA fragility in the parallel evolution of pelvic reduction in threespine stickleback fish (Gasterosteus aculeatus) [electronic resource]

Evolution generates a remarkable breadth of living forms, but many traits evolve repeatedly, by mechanisms that are still poorly understood. A classic example of repeated evolution is the loss of pelvic limbs in stickleback fish (Gasterosteus aculeatus). Repeated pelvic loss has been mapped to independent deletions of a pelvic enhancer upstream of Pitx1, an essential transcription factor. Here, we identify molecular features that contribute to this unusual spectrum of adaptive deletions. We find that Pitx1 enhancer sequences form non-canonical DNA structures in vitro and increase DNA double-strand breaks ~50-100 times in vivo. The fragility of the enhancer also depends on DNA replication direction and is caused by (TG)-dinucleotide repeats. Modeling shows that high mutation rates aid evolution under widespread demographic conditions, including those relevant for sticklebacks and humans. Our results suggest that DNA fragility is an important mechanism for generating adaptive alleles in natural populations.

Keywords: Biochemistry.
Advisor: Kingsley David M. (David Mark) primary advisor. Thesis advisor
Herschlag Daniel advisor. Thesis advisor
Krasnow Mark
Does Welfare Reduce Mortality? Evidence from the Supplemental Security Income Program

In this thesis, I analyze whether transfer payments from the Supplemental Security Income (SSI) program result in a reduction in infant mortality or homicide rates in U.S. counties. SSI is a government program that provides payments to low-income people who are either aged (65 or older), blind, or disabled. In 1990, in it’s Sullivan v. Zebley decision, the Supreme Court relaxed medical eligibility criteria for children on SSI.
This resulted in a dramatic rise in child enrollment rates and a large influx of income
into some of the poorest areas in the U.S. I use an instrumental variable strategy,
exploiting geographical variation in the expected treatment effect of this federal policy change, to determine whether this increase in child SSI enrollment had a causal impact on infant mortality or homicide rates. I find that a 1 percentage point increase in child SSI enrollment leads to a 1.45 percentage point reduction in infant mortality rates and an insignificant change in homicide rates.

Keywords:  Department of Economics
welfare
Supplemental Security Income
crime
health
Stanford Department of Economics
Thesis
Advisor: Duggan Mark
Dominant group members' experiences of entitative subordinate groups [electronic resource] : the role of valence and variance in subordinate group collectives

This dissertation examines how highly entitative subordinate group collectives may induce a threat of status loss among dominant group members. Extending past research on entitativity to the context of hierarchies with more than two groups, I explore two factors that may increase dominant group members' perceptions of subordinate group collectives' entitativity: 1) Positive attitudes between members of subordinate groups, and 2) The homogeneity of subordinate group collectives. The first chapter of this dissertation examines the possibility that White Americans experience a threat of losing their dominant group position when they learn about positive (as compared to negative) inter-minority group attitudes. I argue that inter-minority group harmony signals the existence of an entitative superordinate minority category, which can more effectively challenge the status quo hierarchy. In initial support of this, I found that Whites' perceptions of Black-Latino relations are positively associated with their perceptions of Blacks' social standing relative to Whites (Study 1). Across three experiments, I found causal evidence that Whites' perceptions of positive inter-minority group attitudes lead to perceptions of greater minority collective power (Study 2), and this relationship is partially mediated by Whites' perception that minorities share a common in-group identity (Studies 3a-c). Furthermore, consistent with the idea that positive inter-minority group attitudes induce a threat of status loss and motivate dominant group members to reinforce the hierarchy maintenance, Study 4 found that pro-dominance Whites oppose affirmative action in response to learning about positive, as compared to negative, inter-minority group attitudes. The second chapter explores how White Americans perceive and respond to collectives composed of members of multiple minority groups (e.g., an Asian-Black interracial couple) as compared with collectives composed of members of a single minority group (e.g., a Black couple). Given that heterogeneous collectives are likely to be perceived as less entitative and thus less hostile than homogenous collectives, I hypothesize that Whites will judge multi-minority collectives more positively than single-minority collectives. In support of this prediction, Study 5 found that high-dominance White college students judge multi-minority group student organizations more positively than single-minority group student organizations. Additionally, a large-scale field study of White wedding planners found that Whites respond to emails from Asian-Black interracial couples more quickly, using with more words, compared to emails from Asian and Black same-race couples (Study 6). Implications to literatures in intergroup relations, social hierarchies, and diversity are discussed.

Keywords: Business.
Advisor: Lowery Brian
Halevy Nir
Laurin Kristin
Don't hesitate! The length of inter-turn gaps influences observers' interactional attributions [electronic resource]

What can we learn from a pause? This dissertation examines whether a pause between speaking turns in a conversation (a gap) can change how we view that conversation and its participants (a gap effect). In particular, it asks whether the length of a gap can influence interactional attributions—that is, attributions of the participants' engagement with each other (e.g., attentiveness) and the overall quality of their interaction (e.g., its awkwardness). In four experiments, I manipulated the length of the gap between spontaneous, recorded questions and answers, and then asked observers to listen to each question-answer pair and rate a range of interactional attributes. These experiments addressed four primary research goals: extend the gap effect to new attributes, develop a broader account of gap effect moderation, clarify the role of gap length in the gap effect, and generalize the gap effect to new measures and stimuli. Indeed, lengthening the gap changed observers' interactional attributions (Experiments 1, 2 and 3). These attributions were moderated by observers' expectation that a long gap would occur, which was shaped by the presumed mental effort required to process or respond to the question (Experiment 3). These attributions were not due to conscious reasoning about the gap or changes in the observers' listening experience (Experiments 2 and 3). However, none of these effects replicated when the question-answer pairs were presented in their original conversational context (Experiment 4). There is still much to learn about what a pause can tell us in everyday conversations.

Keywords: Psychology.
Advisor: Clark Herbert H. primary advisor. Thesis advisor
Clark Eve V. advisor. Thesis advisor
Thomas Ewart A. C. advisor. Thesis advisor
Drawn together [electronic resource] : using visualization as a problem-solving strategy in project management

Spatial inscriptions of information--visualizations--can be a great asset to problem solving. Calendars and Cartesian graphs are two examples of visualizations that reorganize non-spatial information (temporal and quantitative) into a visual format. People readily rely on these visualizations to plan and see patterns, which intuitively attests to their value. Pre-made visualizations, however, are not always available. As we document here, people can produce their own as needed, even for novel tasks, yet they often do not. This is a problem of transfer, where people have the requisite knowledge and skills but they do not spontaneously apply them when it would be appropriate to do so. We provide four hypotheses that might explain a lack of transfer. Three studies examine whether and when people spontaneously visualize and how to encourage the transfer of visualization to a novel problem. In the first study, we demonstrate that people infrequently visualize spontaneously on a project scheduling task that is similar to what one might find in a project management textbook. We show that performance on the project scheduling task without a visualization is poor. We also find that just seeing visualizations that reveal information not obvious in a table format will not support spontaneous transfer to a spatially-based problem or a temporally-based problem. In the second study, we teach participants explicitly to make a visualization for a spatially-based network problem. We see that people can make sense of a matrix in answering questions about a spatially based problem. We also find that seeing a visualization of that problem helps people to correctly use that visualization to answer questions. Therefore, the lack of visualizations in Study 1 was not due to participants not understanding the problem or not being able to interpret a visualization. Finally, we find that even though people can read and make visualizations for a spatially-based problem, this does not transfer to a temporally based problem. In the third study, we teach participants explicitly to make a visualization for a spatially-based network problem again. We also introduce a task between the spatially-based problem and the temporally-based problem that has both spatial and temporal surface features. The participants who received this "bridge" task spontaneously transferred visualization on the temporally-based project scheduling task.

Keywords: Education.
Advisor: Schwartz Dan
Bailenson Jeremy advisor. Thesis advisor
Wieman C. E. (Carl Edwin) advisor. Thesis advisor
Dress & Power in the Legal Profession: Gender, Uniformity, & Commerce

This paper explores the historical, cultural, and economic factors that have influenced professional dress norms for women in the legal profession. A multi-method approach, using market data, retailer purchasing data, and qualitative ethnography, seeks to paint a holistic picture of the diverse forces that shape the clothing choices these women make. The male suit is the standard “uniform” for men in most formal professions, but no equivalent standard exists for women. Existing research articulates the tension between looking too “masculine” when emulating the male suit, and looking too “unprofessional” when wearing traditionally “feminine” garments. This phenomenon is well documented in the legal profession, where formal suits are generally expected of men and define the image of professionalim. However, little work has been done to explore how this dichotomy arose, and what roles apparel marketplaces have played in their formation. This paper seeks to add depth to this conversation, and begin analysis of the impacts of e-commerce marketplaces on shopping and selection behavior. Ultimately, this paper concludes that a professional female uniform remains elusive; given the lack of a coherent standard, these women seek to express power through constrained, carefully balanced displays of powerful individuality. While this is a compelling strategy, it ultimately does not address the issues generated by the absence of cohesion, yet the interests of the online apparel industry seem firmly poised to perpetuate this behavior.

Keywords:  Department of Science
Science Technology &amp; Society
law
gender
fashion
clothing
aesthetics
power
retail
Thesis
Advisor: Caroline Simard
Dual-stage crosslinking hydrogels for cell extrusion in bioprinting and transplantation applications [electronic resource]

Nature has provided the human body with complex systems of wound healing that enable us to overcome many of the assaults inflicted upon us. Typically, these systems are categorized as either regeneration, where the native tissue and its structure are replaced, or repair, where a different tissue structure forms in the wound site. While there are several strategies in the literature to achieve this goal, this thesis focuses on two: the delivery of regenerative aids in vivo to promote regeneration at the wound site and the development of tissue replacements ex vivo for future implantation. This thesis proposes two families of hydrogels that each employ two stages of crosslinking to specifically tune material properties for various biomedical applications. The use of protein engineered materials to create a shear-thinning, injectable hydrogel is central to both. For promotion of in vivo regenerative wound healing, cell transplantation within a biomaterial scaffold will be explored. This thesis explores the use of Shear-thinning Hydrogel for Injectable Encapsulation and Long-term Delivery, or SHIELD, for Schwann cell delivery in vivo for a spinal cord injury model. This material uses a thermal secondary crosslinking mechanism for altered material properties at body temperature. To be able to engineer tissue replacements ex vivo, bioprinting has emerged as a promising technique due to its ability to precisely pattern multiple cell types into structures found in native tissues. This work discusses the design and development of a dual-stage crosslinking bio-ink for use in 3D printing, named Recombinant-protein Alginate Platform for Injectable Dual-crosslinked ink or RAPID ink, to overcome some of these challenges. This ink uses an ionic secondary crosslinking mechanism to maintain the printed structure and allow for full cell hydration during printing.

Keywords: Materials Science and Engineering.
Advisor: Heilshorn Sarah primary advisor. Thesis advisor
Appel Eric (Eric Andrew) advisor. Thesis advisor
Plant Giles advisor. Thesis advisor
Dynamic control of processing systems for jobs with decaying value [electronic resource]

In myriad processing systems, delays can degrade the internal state of jobs in the system. Explicitly modeling the decay in internal job value allows us to generalize the concept of a "hard" deadline to that of a "soft" deadline: while hard deadlines are characterized by abrupt value decay, soft deadlines allow for gradual value decay. We leverage optimal control and stochastic simulation methodologies to study two models that incorporate job value decay as an essential modeling attribute. The first model, motivated by patient triage problems, features jobs that are characterized by stochastic service times and deterministically decaying internal value. Since the internal value of a job models the overall health of a patient, we aim to find a non-preemptive scheduling policy that maximizes the total expected value of the jobs after they have completed service. Finding an optimal scheduling policy is computationally intractable so we choose to focus on some heuristics. We provide an- alytic performance guarantees and use numerical experiments to compare the policies in a variety of scenarios, including patient triage scenarios. The second model, motivated by wireless streaming systems, is a service rate control model in which jobs decay in value only upon reaching the server. When a job has zero value, the job is ejected from the queue. In packet streaming, this value decay ensures that the stream does not get "stuck" on any single packet. We formulate an optimal control problem in which power is used to modulate the service rate. We characterize the monotonicity structure of the optimal control and use these analytic results to build power control schemes that adapt to the backlog and decaying value. Simulations show that our proposed schemes outperform benchmark algorithms.

Keywords: Electrical Engineering.
Advisor: Bambos Nicholas primary advisor. Thesis advisor
Wein Lawrence advisor. Thesis advisor
Weissman Tsachy advisor. Thesis advisor