VictorJuiz/thesis huggingface dataset:
RegulomeDB: An Updated Resource for Annotating Regulatory Regions of Personal Genomes
Keywords:  Department of Biology
Stanford University Biology Department
personal genomics
computational biology
SNPs
Thesis

Genome-wide association studies have uncovered thousands of single nucleotide polymorphisms (SNPs) that are statistically associated with diseases or phenotypes of interest.  Most efforts to understand these results have focused on SNPs that disrupt coding regions of the genome, despite the fact that a majority of variants are found in noncoding areas. To address this imbalance, we previously developed the RegulomeDB database, which allows for the improved identification and characterization of regulatory SNPs.   RegulomeDB annotates SNPs provided by the user, indicating how likely each is to have a functional effect on gene regulation based on experimental evidence from the Encyclopedia of DNA Elements (ENCODE) Consortium, Gene Expression Omnibus (GEO), and other sources.  However, the scoring system is entirely heuristic, making it difficult to interpret and use the results.  To improve this system, we develop a machine learning based approach to determine whether a SNP without direct experimental evidence is likely to affect transcription factor binding. This work is the first in a series of steps to improve RegulomeDB as a tool for annotating potentially damaging regulatory SNPs in personal genomes.
Reliable functional composition of a recombinase device family [electronic resource]
Keywords: Bioengineering.

This dissertation describes design principles and demonstrates applications of a recombinase device family to provide examples for how to compose reliable synthetic gene systems. I begin by introducing the functional composition challenges in building a cell cycle counter, a theoretical example of complex synthetic gene systems requiring hundreds of genetic parts. I develop novel designs for combinatorial counters that could store exponentially more states than existing examples. Using numerical simulation, I demonstrate the feasibility and limits of each design; the lack of reliably rewritable binary state devices for use in genetic counting systems is also highlighted. I then focus on experimental proof-of-concepts, failure analyses and design principles for a Recombinase Addressable Data (RAD) device built from bacteriophage integrases and excisionases. RAD devices based on Bxb1 integrase-excisionase are capable of storing state over one hundred cell generations and can be switched repeatedly without performance degradation. The tedious process of engineering a first RAD device raises the question of whether it is practical to scale such devices beyond a single bit, to implement other logical operations beyond set-reset, and to couple such devices to application-specific control signals. To address these questions, I reconfigure RAD devices to operate entirely from genomic DNA, generalize rewritable RAD principles to three other integrase-excisionase pairs, and implement single-use two input logics, buffer gates and integrase-excisionase cascades. I also demonstrate the feasibility of using competitive binding to multiplex the control of different recombination sites via the same recombinase. Finally, I show that the outcomes of composing recombinase devices with novel transcription sources can be predicted, leading to an implementation of autonomous switches driven by growth-phase dependent promoters. Taken together, the work developed here comprises an initial framework for composing complex yet reliable genetic systems using recombinase enzymes.
Representation and realism in Descartes's meditations [electronic resource]
Keywords: Philosophy.

Recent scholarship regarding Descartes's theory of ideas as presented in his Meditations makes a case for regarding Descartes as a direct realist: someone who believes in the existence of extra-mental objects, and who believes our cognitive activity involves the direct apprehension of those objects. On this view, we have direct cognitive access to those objects through ideas, but such ideas are conceived simply as acts, or operations, of the mind, not as mental objects before the mind. This contrasts with a long-standing view of Descartes as a representational realist: someone who believes in the existence of extra-mental objects, and who believes our cognitive activity involves a mediated relationship with those objects. On this view, we have direct cognitive access only to mediating mental objects, called ideas. In this dissertation, I generally defend a representational realist interpretation of Descartes against several direct realist interpretations. I reject John Yolton's sign-signifier, direct realist interpretation, Deborah Brown's Thomistic direct realist view, and John Carriero's quasi-Aristotelian direct realist view. I also reject the view that we ought to interpret Descartes as a direct realist because the concepts involved in his theory of ideas are owed to direct realist, Scholastic predecessors.
Resonances [electronic resource] : for wind instruments
Keywords: Music.

This dissertation is comprised of a single work, Resonances, which was written and premiered by Elision Ensemble. The compositional motivation behind Resonances was driven by the following two questions pertaining to the acoustic peculiarities of wind instruments: (1) Is it possible to design an algorithmic system to formulate various degrees of polyphonic correlations, which would yield multiple formal relations as a function of acoustic distinctiveness?; (2) If so, how perceptible would the resulting polyphony be? Focusing on the deviation degrees of acoustic properties, Resonances views the instruments as complex acoustic mechanisms. I represent the complexity of each instrument in a matrix, the inputs of which are various acoustic measurements of a wind instrument. An algorithm operates on these matrices to generate new matrices. Then, the output matrices are plotted in a multidimensional space through which various geometric relations (in terms of deviational scaling) are devised to formulate formal structures.
Resource utilization and discovery for wireless media streaming [electronic resource]
Keywords: Management Science and Engineering.

We study the issues governing user experience for media streaming in next-generation wireless networks by investigating problems in access point utilization and discovery. When there are many potential points of attachment to the network, a mobile station must be able to retrieve content from the best access point via handoff control before user mobility or a fluctuating wireless environment causes service interruption. With the aim to develop efficient yet effective control algorithms, we formulate models to study the implications of optimal control policies and their tractable approximations in various relevant settings. By analyzing and characterizing the factors affecting their performance, we arrive at many insights about practical system design.
Response of regional climate to global forcing [electronic resource] : the dynamics of climate change in West Africa
Keywords: Environmental Earth System Science.

There is now unequivocal evidence that the Earth's climate is changing as a result of human activities. These changes pose a number of potential risks for human and natural systems. Within the Sahel, a semi-arid region of northern Africa that is home to over 50 million people, climate-related stresses on human systems are exacerbated by a limited capacity for climate adaptation and persistent uncertainty in projections of future climate. In this dissertation I utilize a suite of numerical modeling techniques in conjunction with observational data to study the multi-scale interactions that shape rainfall and atmospheric circulation in northern West Africa. This dissertation consists of three chapters. In the first chapter, I use an ensemble of general circulation model experiments to examine the relative roles of different global drivers in shaping projected changes in West African climate. Specifically, I assess the response of precipitation and atmospheric circulation in West Africa to the individual influences of direct atmospheric radiative forcing from projected increases in greenhouse gas concentrations and greenhouse gas-induced sea surface temperature forcing. In the second chapter, I evaluate the simulation of synoptic-scale weather disturbances, known as African easterly waves, in the latest generation of global climate models. African easterly waves serve as an important source of Sahel rainfall and play a critical role in Saharan dust transport and the initiation of the most intense Atlantic basin hurricanes. In this work I identify key reasons for biases in the simulation of African easterly waves, and offer several new insights for improved climate modeling efforts in West Africa. In the third chapter, I explore the response of atmospheric circulation in West Africa to projected increases in greenhouse gas concentrations. Models exhibit a robust increase in monsoon strength and African easterly wave activity in response to the pattern of future warming in West Africa. These results suggest the possibility of a number of future climate-related impacts on human and natural systems in West Africa and the greater Atlantic basin.
Rethinking sanitation [electronic resource] : quantifying and capturing resource flows in "waste" across geographic and economic contexts
Keywords: Civil and Environmental Engineering.

Sanitation, or the effective management of human excreta, is a basic societal function without which it is virtually impossible to preserve public health, human dignity, or the environment. Society today faces a variety of front-end and back-end sanitation challenges. In low- and middle-income countries, a large fraction of the population lacks access to proper front-end sanitation, toilet facilities that are clean and reliably isolate waste from people. An even larger fraction lacks back-end waste management systems that will minimize the potential for excreta to cause illness or environmental damage. In wealthier countries, we have largely delivered front-end and back-end sanitation, but the infrastructure that supports these services is old and needs replacement under new financial, regulatory, and environmental constraints. This dissertation examines the potential for container-based sanitation (CBS) and resource recovery from waste to reduce the costs of sanitation service delivery in various contexts. Case studies in Cap Haitien, Haiti; Bocas del Toro, Panama; and San Francisco, USA are used to quantify material and resource fluxes in human waste; evaluate the cost of capturing those fluxes; and determine the potential value of the resources. The dissertation also provides a discussion of conditions under which these approaches can provide viable and effective alternatives to conventional sanitation approaches.
The return of tragedy [electronic resource] : an ecology of form from Ancient Greece to 1904
Keywords: Theater and Performance Studies.

This dissertation examines the ways in which tragedy produces, and challenges, human subjectivity in three distinct periods of western theatrical production. It also tells a story of their ahistorical continuity based on tragic repetition. Readings of Aeschylus' Oresteia, Sophocles' Oedipus Tyrannos, and Euripides' Bacchae ground this argument in the Greek original. Specific constructions of fate, agency and justice provide sites for understanding the evolution of a tragic consciousness. Charting a meta-narrative of tragic inheritance through Greek tragedy, Renaissance tragic drama, and the modern drama, I establish an alternative view of western theatre's past—one that embodies its own consciously adopted tragic form. Renaissance artists repressed the knowledge structures contained in the artifacts of a past consciousness in service of Christian morality and bourgeois rationality. By creating a hybrid moral tragedy rooted in contemporary ways of knowing, they valorized the human perspective in contradiction to the world-centered one that Greek tragedy staged. As a result, the dramatic tradition increasingly excluded that which could not self-disclose from its catalogue of the real. It secured the illusion of autonomous human agency, creating the conditions for its own literary and historical tragic reversal. Marlowe's Doctor Faustus, Shakespeare's Macbeth, Hamlet and Winter's Tale model this contradiction. Finally, I retheorize Szondi's "crisis of the drama" reading Strindberg's Miss Julie, Ibsen's Hedda Gabler and Chekhov's The Cherry Orchard as a final cycle of tragedy that stages historical transformation as the suicide of dramatic realism.
A review of renewable energy infrastructure [electronic resource] : a technology and cost comparison
Keywords: Civil and Environmental Engineering.

With the global share of renewable energy generation increasing every year and renew- ables accounting for over 40% of new electricity generation in 2013, the construction of renewable energy infrastructure is and will be oﬀering a lot of opportunities in the construction industry. This thesis presents a review of the renewable energy infrastruc- ture from a construction management perspective. In a ﬁrst part, the energy conversion mechanism of solar photovoltaic, solar concentrated, wind, geothermal and biomass is oﬀered. We present the product breakdown structure for a power plant for each gener- ation and the main construction steps. In the second part of the thesis, we present a comparison of the diﬀerent renewable energy generations according to diﬀerent frame- works: installed and predicted capacity, environmental impact, and impact of natural disasters on infrastructure. We also compare the capital, operational and levelized cost for each generation. Finally we oﬀer a summary of the strength and weaknesses of each generation. The goal of this review is to oﬀer a condensed source of information for con- struction students and practitioners, interested in understanding the renewable energy infrastructure.
A rhetoric based approach to occupational identity and identity change [electronic resource] : a study of industrial designers
Keywords: Management Science and Engineering.

Existing identity and occupation theories assume a coherent occupational identity within a particular occupational group. Identity change has accordingly been assumed to happen only at critical transition points such as job changes and career transitions. Drawing on ethnographic data collected from the in-house design center of a major communication technology company, I challenge these assumptions by showing that, first, workers maintain and use alternative, mutually incoherent occupational rhetorics to build their occupational identities; and second, identity change happens not only during career or work-role transitions but also within the parameters of a particular work role, in the form of longitudinal variation in the composition and use of alternative occupational rhetorics. Such change results from people's constant maneuver, shift, and negotiation within and across the distinct rhetorical stances in situated social interactions. In developing a rhetoric based approach to occupational identity and identity change, this dissertation contributes to our understanding of the role of rhetoric in the social construction of self, the occupational basis of identity, and the ways in which identity evolves.
Rigidity and flexibility phenomena in general relativity [electronic resource]
Keywords: Mathematics.

This thesis is devoted to the investigation of certain aspects concerning the large scale structure of asymptotically flat initial data sets for the Einstein equation in General Relativity. In the first part of this work, we show that if an asymptotically Schwarzschildean 3-manifold (M, g) of nonnegative scalar curvature contains an unbounded, properly embedded stable minimal surface, then it is isometric to the Euclidean space with its flat metric. This implies, for instance, that in presence of positive ADM mass any sequence of solutions to the Plateau problem with diverging boundaries can never have uniform height bounds, even at a single point. The same result can be extended up to ambient dimension seven, under a strong stability assumption and provided the volume growth of the hypersurface in question is known a priori to be polynomial. Furthermore, we study the restrictions imposed by the dominant energy condition (DEC) on stable, marginally outer trapped surfaces. We first prove that an unbounded, stable MOTS in an initial data set (M, g, k) is conformally diffeomorphic to either the plane C or to the cylinder A (thus extending Hawking's theorem on the topology of black holes) and in the latter case infinitesimal rigidity holds. As a corollary, when the DEC holds strictly this rules out the existence of trapped regions with cylindrical boundary. If the data are asymptotically flat and have boosted harmonic asymptotics, the former case is also proven to be globally rigid in the sense that the presence of an unbounded, properly embedded stable MOTS forces an isometric embedding of (M, g, k) in the Minkowski spacetime as a space-like slice. In the second part of the thesis, which is based on joint work with Richard Schoen, we observe that the above assumptions on the data asymptotics are essentially sharp, by constructing initial data sets that have positive ADM mass but are exactly trivial outside a cone of arbitrarily small aperture.The gluing scheme that we adopt allows to produce a new class of N-body solutions for the Einstein equation, which patently exhibit the phenomenon of gravitational shielding:for any large $T$ we can engineer solutions where any two massive bodies do not interact at all for any time 0< t< T, in striking contrast with the Newtonian gravity scenario.
Robust design and fabrication of highly stretchable sensor networks for the creation of intelligent materials [electronic resource]
Keywords: Mechanical Engineering.

Taking advantage of the state-of-the-art CMOS/MEMS technology, a cost-effective fabrication method was developed to integrate large arrays of micro/nano scale sensors, switches, and electronics into materials as a step to create a new class of next generation materials that are capable of self-sensing and self-diagnosing the state of a structure in real time. The method was built upon a highly stretchable sensor network that could be stretched to span more than 10,000% of its original area, and embedded into polymer materials during cure at elevated temperatures such as advanced aerospace composite materials. The method included three major efforts: 1). Design a sensor network fabricated at the micro/nano scale but expandable to more than 10,000% its original size to cover a large, macro, areas of materials without experiencing failures. 2). Develop a robust micro/nano manufacturing method to incorporate sensors and switches into the network. A high-resolution fabrication process based on spin-coated-on polyimide was developed to integrate large arrays of micro/nano scale sensors, switches and electrodes into the network. This enables multiple layers to be integrated together with high precision alignment (sub-micron). Designs were developed to integrate organic thin film diodes into the network as switching devices. 3). Confirm the survivability of the network through an elevated cure process for aerospace composite material applications. A stretched sensor network was embedded into carbon fiber composite materials and put through a composite curing process with elevated temperature (350°F) and pressure (27 psi). Tests were made to ensure good insulation between the stretchable sensor network and the conductive carbon fiber composite materials. Network sensitivity was tested with a composite panel with a built-in sensor network that was able to sense the temperature change and impact loads through a simple electronic readout. Finally, an off-the-shelf robotic arm was integrated with a sensor network to exhibit the sensing, decision-making and control concept for intelligent material systems through the robot.
The role and maintenance of diversity in a multi-partner mutualism [electronic resource] : trees and ectomycorrhizal fungi
Keywords: Biology.

The tree of life is filled with examples of multi-partner mutualisms, in which one guild of organisms interacts with one or multiple other species for mutual benefit. How are these multi-species mutualisms maintained, and what is the functional role of species diversity within them? To address these questions, this dissertation uses the ancient mutualism between trees and ectomycorrhizal fungi. Partnerships between trees (primary producers) and fungi (decomposers) are of great ecological significance because they link two fundamental ecosystem processes. I use field surveys, experimental manipulation, and mathematical models to explore the maintenance and function of fungal diversity. My dissertation highlights the importance of spatial heterogeneity (e.g., in edaphic conditions or in host plants), temporal heterogeneity (e.g., seasonal patterns in resource availability), and species interactions (e.g., host investment and competition among fungi) to the maintenance of fungal diversity. In turn, the diversity of fungal taxa has functional implications, from the ability of host trees to meet nutritional needs in stressful environments, to the increased growth of seedlings partnered with competitively dominant fungi, to the ability to efficiently gather fluctuating resources. These results have implications for our understanding of the maintenance of species diversity, the evolutionary stability of mutualisms, and the individual and ecosystem significance of metabolite exchange.
The role of microbiota metabolites in post-antibiotic nutrient acquisition by Clostridium difficile [electronic resource]
Keywords: Microbiology and Immunology.

Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea, however the mechanisms underlying its ability to expand after antibiotics have not yet been described. Understanding how a dysbiotic gut microbiota is able to promote C. difficile, and conversely, how a healthy gut microbial community inhibits C. difficile are of great interest. The work in this thesis has led to an understanding of the instrumental roles that the microbiota plays in C. difficile gut colonization using gnotobiotic and conventional mouse models. Chapter 1 contains a review describing what is known about the important functions of the gut microbiota and its contribution to pathogenesis. In Chapter 2, we demonstrate that C. difficile and Salmonella typhimurium both utilize microbiota-liberated host sugars to expand upon antibiotic-treatment. In Chapter 3, we reveal other expansion strategies used by C. difficile and highlight the use of a microbiota-derived metabolite succinate by C. difficile to expand after perturbations. Chapter 4 contains three collaborative projects including two novel treatments for C. difficile-associated diseases, a prebiotic and a toxin inhibitor, as well as a new model used to study C. difficile-microbiota interactions. Finally Chapter 5 describes future considerations for this work and the field. These studies have revealed the basic mechanisms employed by C. difficile to expand upon antibiotic treatment and identified novel treatment strategies for C. difficile-associated diseases.