VictorJuiz/thesis huggingface dataset:
Under doctors' eyes [electronic resource] : private life in Russian literature in the first half of the nineteenth century

My dissertation deals with the figure of the doctor in early Russian nineteenth-century prose, which manifests a shift in the way literature depicts human physicality and the characters' everyday life. My major source is 1820s-1840s prose, mostly published in the literary and cultural journals Biblioteka dlia Chtenia, Syn Otechestva, and others. My sources reflect the impressive expansion in Russian literature and medicine in the first quarter of the nineteenth century. Using documentary and literary sources, I demonstrate that the artistic representation of physicians in Romantic and Realist prose contributes to the introduction of previously unknown themes into literature: medical perspectives on physical suffering, the private everyday lives of ordinary people, and even the mystical view of other worlds. The combination of medical and mystical discourses in the vocabulary of real doctors in the first half of the nineteenth century gave them the authority to judge human bodies, lives, and, they believed, souls: they seemed to observe from inside and outside at the same time. By including a doctor among their characters, fiction writers thus could use a powerful instrument that let them introduce new topics. As I show, through the mid nineteenth century, the fictional doctors situated at the margin of literary plots performed the role of an important textual device: they served as go-betweens among other characters, mediating, connecting or splitting them. They affected the relationship between characters, the plot's trajectory, and the readers' perception. The situation shifts in mid century; with the gradual separation of doctor from his instrumental function, this character moves to the center of the plot and loses his structural power.

Keywords: Slavic Languages and Literatures
Advisor: Safran Gabriella
Freidin Gregory advisor. Thesis advisor
Greenleaf Monika
Understanding and predicting RNA structure [electronic resource]

RNA is an important biological macromolecule that carries out a variety of roles in the cell. To function, RNA needs to fold into precise three-dimensional structures. Different physical forces like entropy, base-pairing and stacking interactions, tertiary contacts and electrostatics affect this folding process. In the first part of this thesis, we focus on nucleic acid electrostatics; RNA molecules have negatively charged backbones that require counterions to neutralize charge-repulsion and facilitate folding. We discuss the ion conditions necessary for a riboswitch (gene-regulating RNA found on 5' or 3' ends of messenger RNA) folding, studied how the flexibility of single stranded DNA is affected by the presence of different amounts of counterions and present a benchmark experimental dataset that can be used for direct comparison to electrostatic theories. The second part of the thesis deals with computational and analysis tools developed to model and understand nucleic acid systems with the ultimate goal of being able to predict RNA structure. Since RNA typically folds hierarchically, we devised a general hierarchical sampling protocol that naturally explores RNA three-dimensional conformational space efficiently and can be used in concert with any force field, such as an RNA knowledgebased potential that we also discuss in this thesis. Additionally, we examined a clustering method that can assist analysis of structural models. Lastly, we applied our modeling techniques to study simple two-way RNA junctions with all-atom representation, and probed the modeled effects of sterics, chain connectivity and sequence on dynamic RNA behavior.

Keywords: Applied Physics
Advisor: Doniach S. primary advisor. Thesis advisor
Levitt Michael
Herschlag Daniel advisor. Thesis advisor
Understanding Current Trends and Outcomes in Generic Drug Patent Litigation: An Empirical Investigation

This thesis examines the role of patent litigation in the generic drug approval process.
Generic drug companies wishing to enter a brand-name drug market early may challenge
a brand-name’s patents by filing for an Abbreviated New Drug Application (ANDA) with a
paragraph IV certification. While anecdotal evidence on the characteristics of paragraph IV
lawsuits abound, there has yet to be a comprehensive study on these unique cases. Leveraging
a new dataset of district court cases, this thesis presents an empirical investigation
into some of the current trends in generic drug litigation from January 1, 2006 to August 1,
2011. Using several basic econometric specifications, I study the determinants of settlement
and other outcomes in these cases, observing that factors such as declaratory judgment, the
size of a pioneer company, the level of patent protection, and remaining exclusivity may be
significant factors.

Keywords: ANDA
Pharmaceuticals
Hatch-Waxman
Paragraph IV Certifications
Text
Thesis
Advisor: Lemley Mark
Understanding methanotrophic polyhydroxybutyrate (PHB) production across scale [electronic resource] : life cycle assessment, pure culture experimentation, and pathway/genome database development

While the 140 million tons of plastics produced each year may contribute to quality of life, they also come at a significant cost. Their production requires large quantities of nonrenewable resources, contributing to climate change; they accumulate in landfills and natural environments; and they often contain harmful additives. One way to address the multiplicity of problems that arise from the widespread use of synthetic plastics--without compromising convenience and disposability—would be to replace them with functionally equivalent materials that are biobased, biodegradable, and biocompatible, such as polyhydroxyalkanoates—a class of bioplastics. Bacteria known as "methanotrophs" consume methane as feedstock, and some produce the PHA polymer poly-ß-hydroxybutyrate (PHB). PHB production from methane could take advantage of the abundant biogas methane that is currently flared or allowed to escape to the atmosphere by the waste sector (landfills and wastewater treatment plants) to produce a valuable product that biodegrades to methane at end-of-life, creating a closed-loop cycle. This research evaluates methanotrophic growth and PHB production across scale. (1) Life Cycle Assessment (LCA) is used to anticipate the environmental impacts of PHB production from waste biogas by extrapolation from laboratory scale studies. LCA is used as an early-stage design tool to identify opportunities for pollution prevention, reduce resource consumption, guide environmental performance improvements, and identify research needs. The LCA also enables comparison with published LCAs for PHB produced from other feedstocks. (2) Stoichiometry and kinetics are evaluated and modeled for PHB-producing methanotrophs to describe the effects of oxygen and nitrogen on growth and PHB production by two PHB-producing methanotrophs. Significant differences were observed, with major implications for the use of these species in biotechnology applications. Such analyses can better inform bioreactor design, scale-up models, and life cycle assessments (LCAs). (3) A pathway genome database is developed for Methylosinus trichosporium OB3b as a model organism using pathway reconstruction to predict the metabolic composition. The database provides a platform for the visualization of experimental data from omics experiments, facilitates comparative studies of pathways across species, and provides a resource for biotechnology applications of methanotrophs, such as through flux balance analysis.

Advisor: Criddle Craig primary advisor. Thesis advisor
Karp Peter D. advisor. Thesis advisor
Lepech Michael advisor. Thesis advisor
McCarty Perry L. advisor. Thesis advisor
Understanding spacecraft electrical anomalies [electronic resource] : theory and experiments characterizing hypervelocity impact plasma dynamics

Small meteoroids, with masses less than a microgram, are common within the solar system and routinely impact spacecraft. In Earth orbit, human-made debris also presents a risk of impact. This thesis provides the first characterization of the threat of electrical damage from these hypervelocity impacts. When an impactor encounters a spacecraft (typically at 60 km/s for meteoroids or 10 km/s for debris), its kinetic energy is converted over a very short timescale into energy of vaporization and ionization, resulting in a small, dense plasma. This plasma can produce radio frequency (RF) emission, causing electrical anomalies within the spacecraft. The behavior of hypervelocity impact plasmas was studied through ground-based experiments and a corresponding plasma expansion model to interpret the data. The experiments were conducted using a Van de Graaff dust accelerator at the Max Planck Institute for Nuclear Physics in Heidelberg, Germany. Impacts of iron projectiles ranging from 0.1 fg to 10 pg at speeds of up to 70 km/s were studied using a variety of target materials. Novel plasma sensors were designed and built to characterize the plasma expansion from impacts on these targets under a range of surface charging conditions representative of space environment effects. Impact plasmas associated with bare metal targets as well as spacecraft materials were studied. The expansion behavior of the impact plasma was found to depend strongly on the surface charge of the target. From a correlation of experimental measurements with theoretical models, the dependence of plasma composition and temperature on target material, impact speed, and surface charge was analyzed. This work includes three major results. First, the initial temperature of the impact plasma is at least an order of magnitude lower than previously reported, providing conditions more favorable for sustained RF emission. Second, the composition of impact plasmas from glass targets, unlike that of impact plasmas from tungsten, has low dependence on impact speed, indicating a charge production mechanism that is significant down to orbital debris speeds. Finally, negative ion formation has a strong dependence on target material. These new results can inform the design and operation of satellites in order to prevent impact-related electrical anomalies. Since spacecraft charging is strongly dependent on orientation and surface material, deleterious electrical effects of hypervelocity impacts can be mitigated through design and operational practices that account for the influence of spacecraft geometry and the space environment on the behavior of impact plasmas.

Keywords: Aeronautics and Astronautics
Advisor: Close Sigrid
Cantwell Brian advisor. Thesis advisor
Kalman Andrew
Rock Stephen M. advisor. Thesis advisor
Understanding the interaction of organic functional groups with single-walled carbon nanotubes (SWNTS) for solution processable electronics [electronic resource]

Single-walled carbon nanotubes (SWNTs) have shown impressive electrical properties but are synthesized in mixtures of metallic and semiconducting tubes that prove difficult to separate. However, we have recently discovered that different organic functional groups, when confined to surfaces, can efficiently separate SWNTs. Amine surfaces yield semiconducting (sc) nanotube networks, while aromatic surfaces yield metallic (met) networks. It is proposed that aromatics interact preferably with met-CNTs via [pi]-[pi] stacking, but the effect on the amine surface is more difficult to interpret. Explanations for this interaction include charge polarization, electrostatic forces, or the influence of defect sites. In my presentation, I present a series of experiments used to elucidate the exact nature of the amine / sc-SWNT interaction. The electrostatic influence on the amine-SWNT interaction was studied by altering the pH of the environment around the amine. Subsequently, by altering the density of the amine on the surface, the ideal structure of an amine surface to optimize the SWNT sorting was under analysis. Finally, alternate functional groups were considered to further optimize the sorting and remove the need of amine silanes, which were typically difficult to handle. Once the interaction is better understood, it can be controlled and used to optimize conditions for high quality nanotube network transistors and sensors.

Keywords: Chemical Engineering
Advisor: Bao Zhenan primary advisor. Thesis advisor
Bent Stacey advisor. Thesis advisor
Fuller Gerald G.
Understanding the mechanis of mammalian damage tolerance proteins in suppressing damage-specific mutagenesis [electronic resource]

Post-replication repair (PRR) pathways play important roles in restarting stalled replication forks and regulating mutagenesis. In yeast, Rad5-mediated damage avoidance and Rad18-mediated translesion synthesis (TLS) are two forms of PRR. Two Rad5-related proteins, SHPRH and HLTF, have been identified in mammalian cells, but their specific roles in PRR are unclear. Here, we show that HLTF and SHPRH suppress mutagenesis in a damage-specific manner, preventing mutations induced by UV and MMS, respectively. Following UV, HLTF enhances PCNA monoubiquitination and recruitment of TLS polymerase eta, while also inhibiting SHPRH function. In contrast, MMS promotes the degradation of HLTF and the interactions of SHPRH with Rad18 and polymerase kappa. Our data not only suggest that cells differentially utilize HLTF and SHPRH for different forms of DNA damage, but also, surprisingly, that HLTF and SHPRH may coordinate the two main branches of PRR to choose the proper bypass mechanism for minimizing mutagenesis. Though the degradation of HLTF is required for the SHPRH-Rad18 interaction in MMS-damaged cells, knockdown of HLTF is not sufficient to induce SHPRH-Rad18 binding in undamaged cells. Thus, an unidentified factor, in addition to HLTF degradation, is required to fully activate SHPRH and Rad18 upon MMS damage. We have noticed that Rad18 is deubiquitinated after MMS treatment, and that this de-ubiquitination is correlated with the degree of Rad18-SHPRH interaction. Moreover, we show that promoting the ubiquitination of Rad18 has an inverse effect on the interaction with SHPRH both in vitro and in cells. Surprisingly, though, the ubiquitinated Rad18 shows a stronger self-interaction than the wild-type Rad18, opposite from the SHPRH binding results. As the zinc-finger motif of Rad18 has been previously shown to bind ubiquitin, this may be a logical mechanism to control the switch between Rad18 dimerization and its interaction with other proteins. Interestingly, ubiquitinated Rad18 appears to be inactive, not only from loss of its ability to interact with SHPRH, but also through the inability to form damage foci and suppress MMS-induced mutagenesis. Altogether, our data reveal a unique regulation of Rad18 through self-ubiquitination and dimerization. In summary, our studies have revealed a number of new mechanistic insights into the post-replication repair pathways in human cells, including the interesting conclusion that protein degradation, deubiquitination, and other key cell processes may be controlled in a DNA damage-specific manner.

Keywords: Chemical and Systems Biology.
Advisor: Cimprich Karlene primary advisor. Thesis advisor
Kopito Ron Rieger
Meyer Tobias advisor. Thesis advisor
Wandless Thomas advisor. Thesis advisor
Unified tracking and recognition with rotation-invariant fast features [electronic resource]

Mobile Augmented Reality (MAR) systems overlay virtual content on a live video stream of real-world content. These systems rely on content recognition and tracking to generate this overlay. Typically, these two components use disjoint image processing pipelines, which complicates and slows the system. We propose a new keypoint detector and local feature descriptor that enables the unification of tracking and recognition. This Rotation-Invariant Fast Feature (RIFF) is fast enough to track in real-time on a mobile device, and accurate enough for large-scale image recognition. We propose a tracking algorithm that efficiently matches RIFF descriptors between consecutive frames. This tracker operates with state-of-the-art accuracy at 30 fps on a 1 GHz mobile phone. The same descriptors used for tracking can be matched against a database for image recognition without the need for a separate descriptor pipeline. We evaluate the retrieval performance of RIFF on a challenging, real-world database of 1 million images. By using the same features for largescale image retrieval and video tracking, we have shown that these two tasks can be unified, providing particular benefit to MAR applications.

Keywords: Electrical Engineering
Advisor: Girod Bernd primary advisor. Thesis advisor
Guibas Leonidas J. primary advisor. Thesis advisor
Grzeszczuk Radek
Using conflicting information and holistic judgments in diagnostic computer models [electronic resource]

Diagnostic computer models use observable variables, referred to as features, to generate predictions. Experts often identify feature observations as the input for diagnostic computer models. In addition to these feature observations, I propose obtaining those experts' holistic judgments about the diagnosis to improve the overall system diagnostic performance. I develop what I call the Holistic Feature Integration (HFI) framework, which allows a decision maker to integrate the holistic judgments of multiple experts along with their (possibly conflicting) feature observations into an overall diagnosis. To resolve expert disagreement I need to model the accuracy of each expert; because the HFI framework only requires one such assessment for each expert, it can be easily implemented in practice. In those situations where the experts can be calibrated on test cases, I develop a statistical procedure for estimating accuracy parameters. Through a case study of medical diagnosis with thyroid sonograms, I demonstrate that the HFI framework substantially improves prediction quality by incorporating experts' holistic judgments. Some of this benefit can be obtained by a simple mixture model of the diagnostic computer model with the expert judgments, especially when there is only one expert. In my case study, the holistic judgments alone in the HFI framework are more beneficial than the diagnostic computer model alone. However, using both holistic judgments and the diagnostic computer model yields even better performance in the HFI framework. I see increasing marginal benefit as additional experts were included. I also develop a new technique for eliciting experts' holistic judgments, which are valuable in the HFI framework. I introduce a new class of strictly proper scoring rules parameterized by a simple tradeoff significant to the decision maker and the risk attitude of the expert. I prove that my new scoring rule incentivizes experts to report their risk attitudes and assessments honestly.

Keywords: Management Science and Engineering
Advisor: Howard Ronald A. (Ronald Arthur)
Shachter Ross D. primary advisor. Thesis advisor
Rubin Daniel (Daniel L.) advisor. Thesis advisor
Using integrative genomic approaches to understand the biology of pancreatic cancer [electronic resource]

Pancreatic ductal adenocarcinoma, subsequently referred to as pancreatic cancer, is one of the most deadly cancers with a five-year survival of only 5%. Typical treatment regimens include surgery and chemotherapy while targeted therapies are lacking. A better understanding of the underlying cancer biology may yield novel therapeutic targets. The field of genomics has transformed our ability to study cancer. Over the past two decades, microarray and sequencing based innovations have enabled biology to be carried out at the --omic scale (discussed further in Chapter 1). This dissertation employs --omic level analysis to query the differences between the pancreatic cancer genome and the normal human genome. First, high throughput structural characterizations were performed in order to annotate the mutated, rearranged, deleted, and amplified genes across seventy pancreatic cancers. These assays identified hundreds of candidate cancer genes. Among these candidates, SMURF1 was validated to be an oncogene (Chapter 2). Furthermore, various subunits of the SWI/SNF chromatin remodeling complex were validated to be tumor suppressor genes (Chapter 3). While SMURF1 and SWI/SNF were validated individually, the other candidates from structural studies were evaluated in parallel shRNA competive growth screen. From this, we characterize nine genes further -- some previously known to play a role in cancer and some novel (Chapter 4). The sum total of all of this work is a much deeper understanding of the biology of pancreatic cancer, yielding many novel therapeutic targets and hopefully allowing scientists to gain a foothold in the fight against this disease.

Advisor: Pollack Jonathan D.
Chang Howard
Lipsick Joseph Steven
Lowe Anson W. advisor. Thesis advisor
Using virtual machines in modern computing environments with limited architectural support [electronic resource]

Virtualization has gone through a full ``popularity cycle''. Originally conceived in the mainframe era, virtual machines provided an efficient, isolated, and compatible duplicate of the hardware of the underlying machine. Systems designed in that era provided specific architectural support for virtualization. Virtual machines quickly lost popularity with the increased sophistication of operating systems, and subsequent processor architectures were designed without consideration for virtualization. This dissertation proposes to use virtual machines to address limitations of commodity operating systems on modern architectures, even in the absence of architectural support for virtualization in the hardware. The primary technical contributions of this dissertation were developed as part of two systems, each built for platforms with limited architectural support for virtualization. First, Disco ran commodity operating systems on scalable MIPS multiprocessors. Disco enabled virtual machines to form a virtual cluster that could transparently share the resources of the underlying multiprocessor. Second, VMware Workstation is a successful commercial product that allows multiple, unmodified operating systems to run concurrently on the same x86 system, allowing users to decouple their guest operating systems from the underlying hardware. VMware Workstation was the first 32-bit virtual machine monitor for the x86 architecture, and demonstrated that the x86 architecture was indeed virtualizable, despite a lack of architectural support. Today, and in part because of the impact of Disco and VMware, virtual machines once again play a foundational role in Information Technology, and current-generation hardware provides architectural support for virtualization, similar to what already existed decades ago on mainframes.

Advisor: Rosenblum Mendel primary advisor. Thesis advisor
Mazières David (David Folkman)
Ousterhout John K. advisor. Thesis advisor