VictorJuiz/thesis huggingface dataset:
Detecting, Measuring and Manipulating Copper in Biological Systems

Copper is an essential micronutrient for eukaryotic systems and, thus, an essential mineral in the human diet. As a redox-active metal, copper plays a key role as a catalytic cofactor for a number of enzymes, including those responsible for cellular respiration, neurotransmitter synthesis, extracellular matrix crosslinking, and pigment synthesis. However, the one-electron chemistry that makes copper so valuable within enzymes also makes it potentially toxic to cells, as copper may also generate reactive oxygen species within biological systems. For copper to be loaded into enzymes without causing toxicity, it must be acquired by an organism from the environment and trafficked to the correct tissues, cells, organelles, and proteins. Understanding the complex system of proteins and small molecules that acquire and chaperone copper within vertebrate organisms is a fascinating and challenging puzzle, raising such questions as: Which tissues, cells, and organelles accumulate copper, and which exclude it? Which proteins handle copper during copper trafficking, and which receive copper at its final destination? Is there a role for copper in biological systems beyond enzyme catalysis? What are the functional consequences of copper overload and copper deficiency for an organism? And can copper or copper chelators be used as nutritional supplements to combat disease? Here, we address these questions in the following ways: Chapter 1 provides a review of techniques for mapping the distribution and localization of transition metals within biological systems. Chapter 2 outlines the application of laser ablation ICP-MS and nanoSIMS metal mapping to study the retinal tissue of the zebrafish model of Menkes disease. Chapter 3 explores proteomics methods to find proteins that bind copper transiently, outside enzyme active sites. Finally, Chapter 4 outlines efforts toward genetic tools to study the copper import protein, CTR1.

Advisor: Chang, Christopher J
A Highly Productive Implementation of an Out-of-Order Processor Generator

General-purpose serial-thread performance gains have become more difficult for industry to realize due to the slowing down of process improvements. In this new regime of poor process scaling, continued performance improvement relies on a number of small-scale micro- architectural enhancements. However, software simulator-based models, which computer architecture research has largely relied upon, may not be well-suited for evaluating ideas at the necessary fidelity./nTo facilitate architecture research during this fallow period of Moore’s Law, we propose using processor simulators built from synthesizable processor designs. This thesis describes the design of a synthesizable, industry-competitive processor built on recent advancements in open-source hardware: we leverage the new open-source RISC-V instruction set architecture, the new Chisel hardware construction language, and the Rocket-chip processor generator./nOur processor generator is called BOOM, and it designed for use in education, research, and industry. Like most contemporary high-performance cores, BOOM is superscalar (able to execute multiple instructions per cycle) and out-of-order (able to execute instructions as their dependencies are resolved and not restricted to their program order)./nThe BOOM generator was implemented using the Chisel hardware construction language, allowing for the rapid implementation of parameterized designs. The Chisel description generates synthesizable implementations of BOOM that can target both FPGAs and ASIC tool-flows. The BOOM effort culminated in a test chip that was fabricated in the TSMC 28 nm HPM process (high performance mobile) using the foundry-provided standard-cell library and memory compiler./nThis thesis highlights two aspects of the BOOM design: its industry-competitive branch prediction and its configurable execution datapath. The remainder of the thesis discusses the BOOM tape-out, which was performed by two graduate students and demonstrated the ability to quickly adapt the design to the physical design issues that arose.

Advisor: Patterson, David A
Asanovic, Krste
American Puritanism and the Cognitive Style of Grace

The present monograph initiates the lapsed possibility that Puritanism in the New World was an endpoint, rather than an origin, by contextualizing Puritan cognitive and literary styles within a history of the “craft of thought” that stretched from antiquity to the Renaissance. New England divines Thomas Hooker, Cotton Mather, and Jonathan Edwards, I argue, applied imagistic, linguistic, and mathematical models for thought in an effort to meet the vexed imperative of moving closer to God in a predestinarian theology that held one’s grace had already been determined. Why acts of thinking should serve to navigate this explicitly Puritan ordeal, I also contend, proceeds from the fact – largely unrecognized by either Puritan studies or cognitive literary studies – that many of the fields we today designate as cognitive sciences were first understood as cognitive arts. Plotting a correspondence between acts of creative thinking and a distinctly Puritan concept of grace, I show that the Puritans were radially more creative than we may have realized, precisely because they forged out of a long and diverse intellectual heritage an art – what I term a ‘cognitive style’ – that mediated between intellection, representation, and belief./nMemorial, copious, and infinitary ‘styles of thinking,’ I contend, discern American Puritanism at the juncture of British intellectual history, Anglo-American lived experience, and Calvinist doctrine. When first-generation New England divine Thomas Hooker uses both imagistic and dialectic models for the memory to explain the spiritual potency of recollection, he composes what was known as the doctrine of preparation as a memorial art. To read preparation as this cognitive style is to grasp how the program joined intellection and grace. When Cotton Mather collates ecclesiastical and personal confessions with the conclusions of a 1662 Massachusetts synod, he models copia to insist that the synod’s expansion of church membership was not dangerous innovation but a recombination of orthodox policy. Mather’s use of this style reconceives the Halfway Covenant as a literary rather than socio-political event. And Jonathan Edwards, trying to staunch social ills flowing from revivals in the Connecticut Valley that had become ungovernable, appealed to contradictory accounts of the infinitesimal to reconcile the Calvinist tenets of predestination and conversion. Grounding his responses to the revivals in this mathematical epistemology, Edwards evinces a knowledge of God that was both Enlightened and Awakened, because it took the form of a leap between mystery and sense. Tracing these intellectual movements and the corollary literary modes they imparted across Hooker’s sermon literature, Mather’s ecclesiastical history, and Edwards’ philosophical theology, I show that a Puritan theology of grace comes into view when we attend to the style Puritanism engendered, both of rhetoric, and through rhetoric, of thought.

Advisor: Donegan, Kathleen
Studio/World: Photography's Other Nature

Intervening in longstanding debates about the impact of the shift from analog to digital technology, this dissertation rethinks an aesthetics of photographic space in light of the information age. I argue that digital technology is transforming the very “nature” of the photographic medium as we know it. Since its invention in the early nineteenth century, the photograph has been widely thought of as a “mirror” or “window.” Critics and scholars have consequently tended to focus on the medium as a tool of realism: it either provides proof of the reality before the camera or serves as a visual record of the past. I demonstrate the photograph’s parallel evolution as a site for constructing novel spatial models for looking at and thinking about the world. I show how the photograph—alternately figured as a grid, a map, a table, or a studio—continually undermines the dominant metaphors of its own transparency./nMy central claim is that we are witnessing the definitive breakdown of a worldview built around the fixed mastery of perspective to one that privileges the dynamic proliferation of pattern. To illustrate this trajectory, I juxtapose the work of canonical figures alongside the innovations of current practitioners. The first two chapters outline and complicate the camera’s traditional tie to the conventions of one-point, linear perspective as a “truthful” framing of the world. Reading the photographic interiors of Eugène Atget and John Divola, as well as the “eye exercises” and “perspective games” of Lázló Moholy-Nagy and Elad Lassry, I establish the photograph as a tool for generating what I call “ambiguous space.” The next two chapters elaborate on this new paradigm for picture-making and looking. As the photograph enters the mutable terrain of the digital screen, space is rewritten as information. Tracing this other genealogy of photographic space, I redefine two key terms within photographic discourse: the “index” and the punctum. From the plant taxonomies of Karl Blossfeldt to the mimicry of the screen’s entropic logic and the “retouching” of physical and virtual space by artists Michele Abeles, Katja Novitskova, Sara Cwynar, and others—I reveal how crucial perspectival cues such as depth, scale, and a vanishing point infinity are being overturned. I address the effects of this loss of perspectival orientation for how we imagine ourselves as locatable subjects in the world. I discover this other “nature” of the photograph as a richly ambiguous and synthetic space—rather than one that is self-evident and realist—in order to illuminate the ways that photographic practices are reinventing the limits and conditions of how we perceive and organize space, both in the picture and in the world.

Advisor: Doane, Mary Ann
Advances in Density Functional Theory Calculations and Their Analysis

This thesis is primarily concerned with the development of tools aiming to improve the efficiency of electronic structure calculations using modern density functional theory (DFT), and to utilize the results of DFT-based energy decomposition analysis (EDA) for probing and modeling intermolecular interactions. It covers three distinct while also related topics: (i) development of a novel scheme to perform self-consistent field (SCF) calculations using a minimal adaptive basis (MAB) that is optimized on-the-fly; (ii) development and assessment of energy decomposition analysis (EDA) methods, including a new EDA scheme that is capable of probing the observable effects of intermolecular interactions, and a thorough discussion on the definition of the charge-transfer term in EDA methods; (iii) application of EDA to the development of potential energy surfaces for molecular simulations, including an assessment of the AMOEBA polarizable force field, and the formulation, implementation, and analysis of a mutually polarizable QM/MM scheme employing AMOEBA.

Advisor: Head-Gordon, Martin P
Learning to Synthesize and Manipulate Natural Images

Humans are avid consumers of visual content. Every day, people watch videos, play digital games and share photos on social media. However, there is an asymmetry -- while everybody is able to consume visual data, only a chosen few are talented enough to effectively express themselves visually. For the rest of us, most attempts at creating or manipulating realistic visual content end up quickly ``falling off'' the manifold of natural images. In this thesis, we investigate a number of data-driven approaches for preserving visual realism while creating and manipulating photographs. We use these methods as training wheels for visual content creation. We first propose to model visual realism directly from large-scale natural images. We then define a class of image synthesis and manipulation operations, constraining their outputs to look realistic according to the learned models. The presented methods not only help users easily synthesize more visually appealing photos but also enable new visual effects not possible before this work./nPart I describes discriminative methods for modeling visual realism and photograph aesthetics. Directly training these models requires expensive human judgments. To address this, we adopt active and unsupervised learning methods to reduce annotation costs. We then apply the learned model to various graphics tasks, such as automatically generating image composites and choosing the best-looking portraits from a photo album./nPart II presents approaches that directly model the natural image manifold via generative models and constrain the output of a photo editing tool to lie on this manifold. We build real-time data-driven exploration and editing interfaces based on both simpler image averaging models and more recent deep models./nPart III combines the discriminative learning and generative modeling into an end-to-end image-to-image translation framework, where a network is trained to map inputs (such as user sketches) directly to natural looking results. We present a new algorithm that can learn the translation in the absence of paired training data, as well as a method for producing diverse outputs given the same input image. These methods enable many new applications, such as turning user sketches into photos, season transfer, object transfiguration, photo style transfer, and generating real photographs from painting and computer graphics renderings.

Advisor: Efros, Alexei A
High Dimensional Reachability Analysis: Addressing the Curse of Dimensionality in Formal Verification

Automation is becoming pervasive in everyday life, and many automated systems, such as unmanned aerial systems, autonomous cars, and many types of robots, are complex and safety-critical. Formal verification tools are essential for providing performance and safety guarantees for these systems. In particular, reachability analysis has previously been successfully applied to small scale control systems with general nonlinear dynamics under the influence of disturbances. Its exponentially scaling computational complexity, however, makes analyzing more complex, large scale systems intractable. Alleviating computation burden is in general a primary challenge in formal verification./nThis thesis presents ways to tackle this "curse of dimensionality" from multiple fronts, bringing tractable verification of complex, practical systems such as unmanned aerial systems, autonomous cars and robots, and biological systems closer to reality. The theoretical contributions pertain to Hamilton-Jacobi (HJ) reachability analysis, with applications to unmanned aerial system. In addition, this thesis also explores two frontiers of HJ reachability by combining the formal guarantees of reachability with the computational advantages of optimization and machine learning, and with fast motion planning algorithms commonly used in robotics. The potential and benefits of the theoretical advances are demonstrated in numerous practical applications.

Advisor: Tomlin, Claire J
A novel method for combining phthalates in a cumulative framework: Implications for exposure disparities and intervention opportunities

We are exposed to multiple chemicals throughout our lives from the air we breathe, the water we drink, the food we eat, the products we use, and the social context in which we live. These factors are interconnected and each affects our vulnerability and resilience in the face of cumulative exposures and their potential health implications. Yet we have little guidance on how to capture and quantify multiple chemicals in a construct that is truly relevant for human health./nIn this dissertation, I address one piece of this complex picture by advancing a method that combines endocrine-disrupting chemicals into a cumulative framework for use in exposure science, risk assessment, and epidemiology research. The metric relies on benchmark doses and recommendations set forth by a 2008 National Academy of Sciences (NAS) report, Phthalates and Cumulative Risk Assessment: The Tasks Ahead./nIn Chapter 1, I describe the historical backdrop of cumulative methodologies in the United States, introduce the concept of endocrine-disrupting chemicals and anti-androgenic phthalates, and describe why they are suitable candidates for cumulative assessment. I develop a potency-weighted cumulative metric for phthalates exposure in Chapter 2, providing rationale, sample calculations, and an evaluation of the method’s limitations by comparing the metric across racial/ethnic groups of U.S. reproductive-aged women. Chapter 3 includes another use of the metric to characterize phthalates exposure in a small cohort of Vietnamese immigrant nail salon workers. In Chapter 4, I use the metric to investigate dietary sources of cumulative phthalates exposure in U.S. children, adolescents, and adults; namely, by comparing consumption of food prepared away from home (i.e. dining out) to eating food prepared at home (i.e. purchased at a store). Chapter 5 concludes the dissertation by reflecting on the strengths and challenges of the cumulative exposure metric, providing recommendations for how to resolve some of its limitations and apply the method in future work.

Advisor: Morello-Frosch, Rachel
Engineering microbial production of terpenoids

Terpenoids are a broad class of natural products that have applications in medicine as well as commodity chemicals and biofuels. However, many terpenoids are sourced from field grown plants, which suffer from inconsistent yield and composition. Additionally, many terpenoid biosynthetic pathways are poorly understood or completely uncharacterized due to limitations regarding genetic resources and heterologous expression. Recent improvements in synthetic biology such as DNA synthesis, targeted genome editing, and next generation sequencing have enabled accelerated research and development in this field. In this work I will describe my contributions to the characterization of two plant-derived medicinal terpenoid pathways: the prostratin and valerenic acid biosynthetic pathways./nChapter 1 begins with a discussion of the challenges and successes associated with engineering terpenoid production in yeast as well as other commonly engineered microbes. This chapter covers their applications in medicine, biofuels and other commodity chemicals./nChapter 2 presents my work in developing transcriptomic resources for identifying P450s and other candidate genes involved in the biosynthesis of prostratin. This work also functionally characterized the Jatropha curcas casbene synthase, as well as ~40 P450s from two Euphorbiaceae species, three of which showed activity on the casbene intermediate. Unfortunately, another group published on the activity of two of these P450s before we could. This study shows the utility of coexpression in the discovery of terpenoid biosynthetic genes./nChapter 3 develops a high-titer yeast chassis for the production of jolkinol C, an important intermediate in the biosynthesis of prostratin and related compounds. The P450s identified in Chapter 2 were optimized to produce >1 g/L total of triply-oxidized casbanes, and 800mg/L of the target product, jolkinol C. Additionally, this study clarified the role of a short chain alcohol dehydrogenase (ADH) in the pathway; while not necessary for jolkinol C formation, the ADH improved the product formation, suggesting it is important in planta, as this gene is found in the jolkinol C biosynthetic gene cluster of J. curcas./nChapter 4 elucidates the final unidentified step in the biosynthetic pathway of a sesquiterpenoid drug, valerenic acid. Specifically, the P450 VoCYP71DJ, identified from coexpression analysis with the preceding step valerena-4,7(11)-diene synthase, produces oxidized valerena-4,7(11)-diene. Interestingly, the expression of an alcohol dehydrogenase and aldehyde dehydrogenase with VoCYP71DJ1 were necessary to produce valerenic acid in yeast./nThe final chapter summarizes this work, as well as suggesting future efforts to further enable the engineering of terpenoid biosynthesis in microbes.

Advisor: Keasling, Jay D
Scheller, Henrik
Queering Frontier Identities: Archaeological Investigations at a Nineteenth-Century U.S. Army Laundresses' Quarters in Fort Davis, Texas

This dissertation examines the historical and archaeological traces of a group of Black, Mixed-Race, and Mexican U.S. Army laundresses’ and high ranking enlisted soldiers’ families who lived in a small neighborhood of laundresses’ quarters at the late nineteenth century Fort Davis, Texas. This far West Texas frontier post is distinguished by its association with Black enlisted troops and a ethno-racially diverse population situated on both a geographic frontier and a race relations frontier. In this complex environ, the families of laundresses and high ranked enlisted soldiers were positioned in such a way that their socio-economic and military status marked them as community leaders and care-takers; as such, the inhabitants at the quarters were situated on the edge, yet at the center of military and civilian life, working-class and middle-class status, and Black-White-Mexican race relations. Thus, their daily interactions occurred across various scales — with family members inside the home, between larger groups of fellow working women and soldiers, within the larger racialized military community, and as members of the larger town community./nI suggest that the laundresses’ quarters’ community’s location within a matrix of highly ambiguous social and geographic landscapes resulted in inhabitants constantly embodying and actively negotiating between multiple lived realities that were shaped by various coexisting and (sometimes) conflicting ideologies. I employ a queer theoretical framework combined with third-space theory to understand the fragmentation and fluidity of experiences that occurred throughout the resident’s daily lives and social interactions. (Re)orienting how identification processes in cultural meeting spaces shaped and altered structuring beliefs highlights contextually specific past practices and performances and how enmeshed their identities truly were. In particular, the material traces of past identity making behaviors can bring to light the dis/misorientations of social actors that do not fit the static and boxed categories so often used to describe and order stories of the past. Rather than trying to describe the complexly variable experiences of past peoples with categorizable identities, I show that it is more effective to engage the ambivalent, inconsistent, and diverse meanings in the material record. This allows for a more nuanced understanding of the past and illustrates how queer moments of unintelligibility regularly occur in lived reality, both past and present.

Advisor: Wilkie, Laurie A.