VictorJuiz/thesis huggingface dataset:
Toward a whole-cell model of Escherichia coli [electronic resource]

Whole-cell computational models comprehensively simulate the growth and division of single cells, explicitly accounting for the functions of all known gene products and their interactions. Such models have the potential to revolutionize biology by serving as a platform to interpret complex behaviors, prioritize experiments, and enable design. In 2012, our lab completed the first whole-cell model of the simplest culturable organism, Mycoplasma genitalium. Since then we have focused our efforts on modeling Escherichia coli, one of the foundational model organisms in biology. In addition to having 10 times more genes and 50 times more molecules than M. genitalium, E. coli exhibits sophisticated regulation in response to environmental stimuli and perturbations. Currently, we have an E. coli model that incorporates the function of over 1200 genes and synthesizes tens of thousands of data points collected from both high- and low-throughput experiments performed over the last six decades. In building this model, we have incorporated many of E. coli's feedback control mechanisms, included hundreds of kinetic constraints in a model of metabolism, decreased simulation runtime more than ten-fold, and demonstrated the ability of our simulated cells to reliably reproduce over multiple generations. Furthermore, we have used the model to explore behaviors that arise from the interactions of multiple biological processes. In doing so, we have uncovered and quantified the prevalence of sub-generational gene expression. As the model continues to expand in size and scope, we hope that it will further our understanding of cell physiology and find practical applications in synthetic biology and medicine.

Keywords: Bioengineering.
Advisor: Covert Markus primary advisor. Thesis advisor
Altman Russ advisor. Thesis advisor
Bryant Zev David advisor. Thesis advisor
Toward sustainable sourcing in global supply chains [electronic resource]

This dissertation develops insights about the design of sourcing policies to achieve sustainable sourcing in global supply chains. I focus on two supply chains and their environmental sustainability issues: (1) the Merino wool supply chain and desertification in Argentine Patagonia and (2) the palm oil supply chain and illegal deforestation in Indonesia. These themes were inspired by and formulated around operational gridlocks faced by companies in the implementation of their sustainable sourcing goals. Chapter 2 illustrates that solving such operational gridlocks requires innovative approaches to mainstays of supply chain management, including contract design and inventory management. Chapter 3 analyzes one of these innovative approaches in depth and develops a general theory about conditions under which it may work. Combining this analysis with panel data on 1,252 transactions in the Merino wool supply chain reveals new insights about the design of procurement contracts to help address the challenge of severe land degradation in Argentine Patagonia through sustainable sourcing. Chapter 4 proposes a novel incentive mechanism to achieve no-deforestation commitments in palm oil supply chains that originate from the growing number of smallholder farmers in Indonesia. This incentive's proposal draws on 58 interviews along the palm oil supply chain and a survey of 420 smallholder palm oil farmers. It is designed for commodity supply chains that are characterized by bulk processing, commodity-based pricing, spot market trading and vast production by small farmers in developing countries. Finally, I conclude with future research directions, including the implementation of controlled supply chain experiments to test the paradigms proposed in this dissertation.

Advisor: Field Christopher B. primary advisor. Thesis advisor
Iancu Dan primary advisor. Thesis advisor
Lee Hau Leung advisor. Thesis advisor
Naylor Rosamond advisor. Thesis advisor
Towards a More Enlightened University: The Opening Up of Stanford University in the 1960s

This thesis traces Stanford’s transition from a conservative and apathetic student body in the 50s and early 60s, to a progressive, activist and liberal campus by the end of the 60s and onward. There were internal events, decisions, and people who contributed to not simply a shift towards greater activism and involvement in national policies (as can be said of other universities) but a shift towards a more progressive university. Through its change in admissions and efforts to become a premiere institution and not just a “country club,” Stanford shaped a student body that was more willing to speak their minds and more likely to do something about instances of injustice than any other generation of Stanford students. The rise in political involvement and activism among the student body occurred at the same time that university prestige and academic standing kept rising. Internal changes within the university, combined with the influence of external events, led to tensions not felt previously among students, faculty and administrators. This thesis provides a lens into student activism and the university’s political and social metamorphosis. It does so by filling in the historical memory of the times and determining the role of the administrators, faculty and students in changing Stanford and by researching what cultural (social, political, academic) changes Stanford underwent during the decade that contributed to its activist and academic ascension by the late 60s. Stanford’s dramatic changes during the 60s and its contributions to the movement culture and the university institution have been analyzed in this thesis to prove that Stanford deserves a place in the history books alongside schools such as UC Berkeley, Harvard, Columbia, or MIT.

Keywords:  Department of Communication and Journalism
Department of Communication
activism
1960s
the sixties
student protest
Stanford University
counterculture
progressive
movements
political activism
social activism
David Harris
Freedom Summer
academic freedom
Allard Lowenstein
Cold War University
Armin Rosencranz
Vietnam War
Free Speech Movement
Stanford Research Institute
Grove House
LSD
ASSU
Wallace Sterling
Mark Mancall
Board of Trustees
Stern Hall
in loco parentis
Thesis
Advisor: Turner Fred
Towards a whole-cell model of growth rate and cell size control in Escherichia coli [electronic resource]

A central challenge in biology is understanding how systems level behaviors arise from their underlying molecular mechanisms. While significant progress has been made characterizing the mechanisms of individual cellular processes, a complete understanding of cell physiology remains an open challenge. Computational models of cell physiology that are both predictive and comprehensive are needed to integrate the scientific community's diverse knowledge into a single computational theory. Using an integrative modeling methodology we have made made significant progress towards a whole-cell computational model of Escherichia coli (E. coli). The model simulates the life cycle of a single E. coli cell growing exponentially, and includes representations of cellular processes like metabolism, transcription, translation, chromosome replication, and transcriptional regulation. Furthermore, the model is implemented with feedback mechanisms that control its cellular composition, growth rate, cell size, chromosome state, transcriptional expression, and metabolic capacity in response to its medium environment. The result is a model that grows for an arbitrary number of cell divisions, adapts to three different medium conditions, and simultaneously enables the observation of the abundance, activity, and interactions of every molecular species in E. coli. We have used the E. coli model as a computational theory to validate diverse experimental datasets and to integrate them into a consistent modeling framework. In this way we were able to show that the varied knowledge of individual cellular processes largely integrate into a single consistent understanding of cell biology in E. coli. We have also demonstrated that the model can guide biological discovery including a new pattern of RNA expression in which the majority of genes in the E. coli model transcribed at a rate of less than once per cell cycle, which leads to proteins being expressed only once in many generations with a higher fold change. This thesis presents a model that represents significant progress towards a whole-cell model of E. coli. We hope that expansions of this model will enable a more complete understanding of cell physiology, enable the construction of whole-cell models of other prokaryotes and higher organisms, and serve as a predictive theory to guide synthetic biology, engineering, and medicine.

Keywords: Chemical Engineering.
Advisor: Covert Markus primary advisor. Thesis advisor
Dunn Alexander Robert primary advisor. Thesis advisor
Spormann Alfred M. advisor. Thesis advisor
Towards DIUx 2.1 or 3.0? Examining Defense Innovation Unit Experimental's Progress Towards Procurement Innovation

Defense contracting is responsible for procuring the tools used by the defense community. Defense procurement, however, has become emblematic of scheduling delays and cost overruns, fueled by the outsized influence of traditional Beltway military contractors in defense acquisition. As American adversaries utilize novel technologies across domains physical and cyber, the DoD faces pressure to match this pace of innovation in their defense strategies. In 2015, then-Secretary of Defense Ashton Carter announced the creation of Defense Innovation Unit Experimental (DIUx), an outfit within the DoD to expedite contracting with small technology outfits pioneering defensive technologies. DIUx has faced criticism for not addressing the federal acquisition regulations that render the DoD a difficult customer for small technology outfits, in addition to challenges in continued engagement with defense startups. This thesis examines the realities underlying these criticisms. Specifically, it argues that DIUx occupies a previously missing junction in the defense innovation ecosystem: namely, the process of connecting DoD-supported R&D to defense community customers and facilitating contracts between these two entities. It also finds that DIUx has made marked improvements in facilitating relationships with small technology firms by utilizing Other Transaction Authorities (OTAs) to expedite contracting. OTA contracts, however, may not be conducive to longer-term business relationships between the DoD and small technology vendors. The adoption of OTAs raises further questions about DIUx’s balance between serving as a federal acquisition regulation reformer versus serving as a relationship manager between the DoD and high-technology firms.

Keywords: Center for International Security and Cooperation
Defense Contracting
Defense Innovation
Thesis
Advisor: Lin Herb
Towards engineering the human adaptive immune system [electronic resource] : nucleic-acid-sequencing-based studies in health, disease and immunotherapy

The recent successes of cancer immunotherapy illustrate that long-intractable diseases can benefit from treatment approaches that focus on re-engineering aspects of the body's own defense system -- the immune system. The adaptive component of the immune system learns over time in response to external stimuli by a process of receptor evolution that can now be studied thanks to advances in high-throughput DNA sequencing. These advances also allow expression profiling of thousands of genes across thousands of individual cells at a time, facilitating the reconstruction of immune cell differentiation trajectories. The goal of my dissertation is to use these tools in order to gain a better understanding of systemic fallibilities of adaptive immunity -- which underlie the existence of deadly infections, autoimmune disease or cancer -- and to explore immunotherapies as a manner of engineering an improved immune system. First, I will elucidate age-related immune deterioration by analyzing the phylogeny of healthy elderly individuals' antibody repertoires, investigating the immunogenic challenges of influenza vaccination and chronic infection. Next, I will discuss the antibody repertoires of patients afflicted with a severe autoimmune disease, systemic-sclerosis-associated pulmonary arterial hypertension, a subset of whom received experimental suppressive immunotherapy with the B-cell depleting agent rituximab. I identified disease signatures at the molecular level and quantitatively modeled the process of reconstitution that follows B-cell depletion. Finally, I will expose the undesirable phenomenon of T-cell exhaustion in chimeric antigen receptor (CAR) T-cells designed for cancer immunotherapy. I characterized the basis of this phenomenon at the gene expression level so as to inform approaches of eliminating exhaustion by gene knock-out.

Keywords: Applied Physics.
Advisor: Quake Stephen Ronald primary advisor. Thesis advisor
Mackall Crystal advisor. Thesis advisor
Nicolls Mark
Towards high-efficiency electrically-driven nanobeam lasers [electronic resource]

Optics has been used for long-distance communications for decades thanks to its large capacity. Continuing growth of the network and computer usage cannot be supported by electrical interconnects in both energy consumption and bandwidth, and use of optics for shorter distance communications have drawn a great interest. The introduction of the photonic crystal cavities enables us to obtain ultra-small laser structures with low threshold current and energy operation for off-chip and on-chip optical interconnects, but an efficient current injection into such small structures has remained problematic. In this thesis, two photonic crystal nanobeam cavities are designed to realize lasers with low threshold currents and efficient electrical injection using wet etch and oxidation, then detailed work to realize those structures are described. Simulation results of the revised nanobeams with wet etch and oxidation show that high cavity quality (Q-) factors can be obtained with effective electrical injection by placing carrier guiding structures properly. We employ the designed nanobeam cavity with wet etched P and N regions and investigate oxidation process and analyze results to form a current blocking layer. We demonstrate laser threshold behaviors under room-temperature and continuous-wave optical pumping condition from the wet etched structure, and suppressed leakage current through the InGaAs sacrificial layer and InP substrate by defining a trench structure around N electrode.

Keywords: Electrical Engineering.
Advisor: Harris J. S. (James Stewart)
Fan Shanhui
Miller D. A. B. advisor. Thesis advisor
Towards robust dynamical models of biomolecules [electronic resource]

Biology is the ultimate emergent phenomenon, and we largely lack a full picture of its function at the smallest scales. Molecular dynamics purports to model biomolecules like proteins with all-atom resolution. Among other challenges, merely analyzing the large quantities of data that result from a simulation has become a bottleneck. In this dissertation, I present my work towards building reduced-complexity models that faithfully capture the relevant functional dynamics of biomolecular simulations. In chapter 1, I introduce a mathematical language for dealing with stochastic processes and show the connection to established modeling methods like Markov modeling and tICA. Chapter 2 develops and characterizes a method for including solvent degrees of freedom in Markov state models. In chapter 3, we apply state-of-the-art MSM modeling to understand multi-scale conformational dynamics of a potassium ion channel. Chapter 4 provides an overview of a curated selection of modeling building blocks accessible through our carefully designed software package. Chapter 5 introduces a new non-linear basis which unites the MSM and tICA approaches. Finally, in chapter 6, I introduce parameterized sets of basis functions and use the variational principle directly to optimize the basis set itself. It is my hope that these novel algorithms aided by well-engineered software implementations and validated by characterization on real biomolecular systems will lead the field closer towards truly robust dynamical models of biomolecules.

Keywords: Chemistry.
Advisor: Pande Vijay primary advisor. Thesis advisor
Markland Thomas E.
Martinez Todd J. (Todd Joseph)
Tracing electronic gesture [electronic resource] : a poetics of mediated movement

Focusing on the choreographic coupling of human embodiment and digital media in new media art of the 21st century, this study traces a poetics of what I call electronic gesture. With such mediated movements, a musician executes exquisite choreographies on digital controllers using performance gestures from classical piano, and a digital technology distills the creative gestures of the eye from the hand, enabling a paralyzed street artist to draw by looking. Analyzing these hybrid human-machine gestures, I map the potential of kinetic engagements of human bodies and new media to generate new forms of sensory experience and creative agency. Reframing longstanding theorizations of the fracturing effects of new media, I argue that it is precisely these qualities that allow digital art to assert presence. Drawing on media theory, performance theory, and histories of technology, I construct a taxonomy of electronic gesture across "classical" arts in different media: writing, drawing, dance, and music. Examining a wide range of works by artists working in different media including dancer Bill T. Jones, cartoonist Lynda Barry, poet Theresa Hak Kyung Cha, musician Onyx Ashanti, and many others, I demonstrate how such art retroactively theorizes and selectively appropriates dynamic elements of gesture from prior, "analog" forms. Rather than impeding human expression, the digital structure of the bit licenses this borrowing. Underwritten by a conception of the gesturing body as atomized dynamic data, these new media art works and practices bring something of the original choreographic body with them, even as they leave it behind. These gestural samplings of older media forms allow emerging digital art to produce new forms of presence and in so doing, highlight new embodied agencies. Encompassing different mediations of gesture, from practices of inscription, gesture as signmaking and markmaking, to movement in recorded and live performance, my analysis moves across the whole art system. It traces how digital media quicken, remediate, morph or otherwise alter these existing mediations. Examining experimental new media such as electronic poetry, virtual dances created with digital motion capture and musical "controllerism, " I analyze the dynamics of distributed creative agency across electronic gesture. I demonstrate how, across media, both human and digital actors collaborate in these creative gestures. Ultimately, I show how our gestures invent our machines as well as ourselves. Through these artists, this study thus makes visible the complex interplays of human and digital agency, software and hardware, material history and discourse that animate electronic gesture. Performing the poetic affordances of electronic gesture, these artists offer creative dispositions for acting, moving, inventing, and becoming with new media and emergent digital technologies.

Advisor: Bukatman Scott
Ngai Sianne primary advisor. Thesis advisor
Menon Jisha
Transitions of control in partially autonomous vehicles [electronic resource] : driver response and the design of vehicle interfaces

How should autonomous vehicles interact effectively and safely with human drivers? These are questions that vehicle designers and manufacturers need to investigate as partially autonomous vehicles continue expanding in scale and the capabilities of vehicle automation keep on improving significantly. To better understand how autonomous vehicles are expected to function and to discover critical issues that need further examination, we conducted 5 sets of empirical studies at the Driving Simulator at Stanford - Exploratory Wizard of Oz study, Driver Intervention Studies, Minimum Necessary Time Studies, Robotic Transforming Steering Wheel Studies and LED Transforming Steering Wheel Study. The objective of our research is to find out how drivers respond to different ways of transitioning control in partially autonomous vehicles. We examined the role of the control interface design, demographics, tasks before transitions, and alert modality on people's ability to successfully resume driving after a transition of control from vehicle automation. These research studies help us understand what factors influence drivers' preferences in interacting with partially autonomous vehicles and their takeover performance in transition of control scenarios. We then used these insights to design and evaluate multiple novel prototype driving interfaces to better assist drivers. From the findings of these studies, we form a set of design recommendations that can better inform vehicle manufacturers regarding the design of autonomous vehicles to improve the safety and comfort of drivers.

Keywords: Mechanical Engineering.
Advisor: Ju Wendy
Leifer Larry J. primary advisor. Thesis advisor
Cutkosky Mark R. advisor. Thesis advisor
Follmer Sean advisor. Thesis advisor
Transoceanic blackface, imperial whiteness [electronic resource] : performing "race" in the global nineteenth century

During the long nineteenth century, the capitalist world-system turned on the economic and affective investments of two Anglophone empires -- the British Empire and the United States of America. These far-flung empires were knitted together not merely through the circulation of commodities via transoceanic trade routes but also through the global itineraries of popular performers and performances and their circulations of affect. Transoceanic performance networks trafficked heavily in racial impersonation such as blackface minstrelsy and its cognate forms. Though much research has explored the racial politics of blackface minstrelsy in the United States, this study focuses on the broader circulations of racialized performance and its entanglements with global processes of colonization. Throughout the Anglophone empire -- and particularly in the Indian Ocean littoral -- blackface performance animated white, colonial affective publics, forging popular cultures around impressions of non-white subjects. Within this "theatrical public sphere, " white performers and audiences alike invested in "common sense" feelings and beliefs about "race, " tracing numerous color lines across the globe. These enactments were not strictly discursive representations; rather, they circulated within the repertoires of imperial whiteness to animate popular beliefs about the non-white peoples of the expanding Anglophone world. The transmission of these repertoires via transoceanic performance tours signal the interconnectedness of histories of performance, "race, " and politics, as well as the deep imbrications of colonization with global theater. Such transhistorical repertoires offer fertile ground for reconsiderations of globalization, world theater, and the cultures of imperialism.

Keywords: Theater and Performance Studies.
Advisor: Menon Jisha
Brody Jennifer DeVere advisor. Thesis advisor
Cole Catherine
Elam Harry Justin advisor. Thesis advisor