VictorJuiz/thesis huggingface dataset:
An Examination of Subtype B HIV-1 Genetic Infection Tropism Prediction
Keywords:  Department of Biology
HIV
HIV coreceptor
viral tropism
tropism prediction
CCR5
CXCR4
antiretroviral therapy
Biology
Infectious Disease
Thesis

HIV usually makes use of either the CCR5 or CXCR4 co-receptors to gain entry into cells. Which coreceptor the virus uses (the tropism) determines the efficacy of different cell entry-inhibiting antiretroviral drugs, and is therefore important medical information. HIV tropism may be accurately assessed with sensitive recombinant virus phenotyping tests such as the Trofile assay, but these tests are often prohibitively expensive. Viral genome sequencing and interpretation of genotype using free online software programs such as Web PSSM and Geno2Pheno offer a low-cost alternative by predicting tropism from the V3 loop sequence in the HIV env gene. However, these programs' predictions are insensitive to minority viral variants and may be less accurate than the commercial recombinant virus phenotypic assays.
We sequenced proviral subtype B HIV-1 DNA from peripheral blood mononuclear cell (PBMC) samples obtained from patients under drug-induced viral suppression and viral RNA from plasma samples obtained from the same patients after viral re-emergence. Predictions of re-emergent viral tropism were made by Geno2Pheno and Web PSSM assessment of the proviral DNA V3 loop sequences. Trofile tests were performed on plasma samples to provide a gold-standard re-emergent virus phenotype. Through statistical and qualitative analysis of these paired prediction and tropism data, we tested the hypothesis that the tropism of virus re-emerging into the blood following drug interruption can be accurately predicted by Geno2Pheno and Web PSSM analysis of proviral DNA.
We show here that proviral DNA sequence analysis was able to predict re-emergent plasma virus tropism with 83.3% success, and exclusive R5 tropism with 87.0% success. Generalized linear modeling showed a highly significant relationship between prediction-tropism discordance and lower DNA-RNA sequence similarity. Qualitative analysis of clone env sequences demonstrated sequence interpretation accuracy by both Geno2Pheno and Web PSSM. Together, these results suggest that proviral PBMC DNA consensus sequences may fail to predict the re-emergent plasma virus tropism in more than 10% of cases. Differences between proviral DNA-based tropism predictions and re-emergent plasma virus phenotype may result from the selection of minority variants and the evolution of plasma virus.
Analysis and design of high density RRAM arrays [electronic resource]
Keywords: Electrical Engineering.

Among the emerging nonvolatile memory technologies that could potentially replace flash memory, RRAM (resistance change random access memory) is particularly appealing thanks to its small size, short switching time, low operation voltage, and good compatibility with the standard CMOS process. However, for RRAM to be a cost-competitive candidate for high-density and high-capacity commercial products, some architectural-level challenges must be tackled. In this dissertation, research results that advance the design of high-density RRAM arrays are presented. After a brief review of the RRAM device and array fundamentals, a complete analysis of cross-point arrays in read operations is presented. The analysis concludes with a proposal for a new bias scheme that increases the read margin of the cross-point RRAM array. A compact, one-transistor-four-RRAM (1T4R) array architecture, with corresponding read/write and decoding schemes, that achieves high RRAM density is then introduced. Circuit simulation results that validate this new architecture and a proof-of-concept test chip with fully integrated RRAM devices are described. For this test chip, a particular sequence to form the cross-point RRAM array is presented. Measurement results of successful array operations demonstrate the feasibility of high-capacity integration of the proposed architecture. The research then focuses on the scaling effects of on-chip interconnects on RRAM array performance. Due to the continuously shrinking process feature size, the voltage drop along the interconnect gradually reduces the voltage available to operate the RRAM device. To more efficiently analyze this effect for an arbitrary array size, a compact array model is developed. Simulations using this model are shown to quantitatively illustrate the maximum achievable array size in the future. Interconnect electromigration and parasitic capacitance effects are then considered at the end.
Anarchy or Regulation: Controlling the Global Trade in Zero-Day Vulnerabilities
Keywords: Center for International Security and Cooperation
zero-day vulnerabilities
zero day
cybersecurity
Thesis

The global trade in zero-day vulnerabilities – software flaws unknown to the maker and the public – constitutes a serious cybersecurity problem. Governments use zero days for military, intelligence, and law enforcement cyber operations, and criminal organizations use them to steal information and disrupt systems. The zero-day trade is global and lucrative, with the U.S. and other governments participating as buyers. Cybersecurity experts worry this trade enables governments, non-state actors, and criminals to gain damaging capabilities. The U.S. government’s participation raises concerns because keeping purchased zero days secret to preserve military, intelligence, or law enforcement utility undermines U.S. and global cybersecurity. These problems are generating a nascent, but growing, policy debate about the need to regulate the zero-day trade.
This thesis contributes to this debate by analyzing domestic and international options for controlling the zero-day trade. Domestically, it investigates criminalization, unilateral export controls, and increased oversight of U.S. executive branch actions. It concludes that increased executive branch oversight is the best national strategy to address the problems of existing U.S. policy. Internationally, this thesis analyzes international legal approaches, voluntary collective action through export controls, and cooperation through collective defense organizations. It concludes that voluntary collective action to harmonize export controls on zero days through the Wassenaar Arrangement is the most feasible international option.
This thesis demonstrates how difficult regulation of the global zero-day trade will be, signaling the pervasiveness of realpolitik in cyberspace. It argues that, without U.S. action and international action, the pull of anarchy over regulation will prevail.
Application of nanoapertures to fluorescence fluctuation correlation spectroscopy [electronic resource]
Keywords: Applied Physics.

Fluorescence Fluctuation Correlation Spectroscopy (FCS) is a single molecule spectroscopic technique that uses the correlations in photon arrival time to compute the diffusion coefficient and concentration of diffusing dye molecules. The technique is handicapped by the diffraction limit in traditional confocal optical microscopes because low concentrations of about pico-molar to nano-molar levels are required to maintain single molecule levels. Thus, biologically relevant concentrations at micro-molar and above are not accessible without some method of reducing the observation volume. A method using nano-apertures to confine the excitation and emission volume is proposed to solve the low concentration requirement in FCS. Near-field electromagnetic field enhancements in c-shaped apertures will be exploited to overcome the signal fall off as the size of the apertures is decreased as higher concentration levels are desired, while maintain single molecule levels inside the observation volume. Experiments using square and c-shaped apertures milled in metallic thin films show strong wavelength dependence and initial experiments in spin coated R6G shows about 10 fold enhancement in the overall signal in c-shaped apertures over square shaped apertures of the same equivalent cross-sectional area. Further, an FCS experiment was carried out using Atto655 dye to confirm the focal volume reduction and fluorescence enhancement. Photon counting histogram techniques were used to reveal the detailed mechanism of the aperture resonance and the fluorescence enhancement. Finally, an application to pulsed interleaved excitation Forster resonance energy transfer (PIE-FRET) in ssDNA (single stranded DNA) pairs was carried out at a high enough concentration to stabilize the hybridized dsDNA (double stranded DNA). The nano-aperture results show that the PIE-FRET technique can be applied to solutions containing FRET pairs at 1000x the concentration than previously possible using diffraction limited focal volumes.
An approach for integrated risk and opportunity quantification and assurance in design [electronic resource]
Keywords: Mechanical Engineering.

Increasing demand for better performance, a compressed schedule for design and development, and a competitive market drive for a more cost effective design elevates the risk of failure to meet product requirements in the presence of uncertainty. Such a failure is addressed by either accepting the consequence without a change or by requiring a change in the design, or in the design process, to meet the requirement. For projects with long scale development period and the associated high investment cost, these alternatives increasingly become unacceptable as a design evolves. The impact of design change becomes more costly to implement, and accepting the consequence is either not an option or violates the guaranteed features of the product. Risk is employed as a metric to indicate the level of assurance for compliance to a requirement, or an objective due to uncertainty or variations in design parameters or in design processes. The requirements may include technical requirements on safety and performance of the design, or process requirements on cost, schedule of a system, subsystems or components. A risk identification and classification method based on a system's compliant robustness in the presence of uncertainty in parameters is introduced. A methodology for risk assurance comprising of the Risk Assessment Process and the System Development Process is presented. This integrated process provides assurance to meet an acceptable risk level, and to minimize likelihood of a need for change in either the design or the design process due to uncertainty as the design maturity is progressed. Major advantages of the proposed methodology include its integration with the System Development Process and its compatibility with the existing recommended engineering practices.
Artifacts reduction techniques in X-ray cone-beam computed tomography reconstruction [electronic resource]
Keywords: Electrical Engineering.

CBCT is an important tool in image guided radiation therapy. With the existing reconstruction methods, however, various artifacts arise in the image, which are caused by under-sampled projection data, large-area detector, and/or presence of metal implants in patients. This dissertation addresses issues for improved CBCT image quality and clinical decision making. In practical CBCT systems, a circular trajectory is commonly used to acquire projections and reconstruct the volume. However, incomplete data might be collected in a short scan either because of mechanical constraint or dose reduction consideration. In such situation, FDK algorithm cannot provide an accurate image due to the theoretical limitation. In this dissertation, an iterative optimization using prior knowledge and rigid image registration is proposed to handle the limited angle reconstruction problem. The algorithm is derived based on the prior image constrained compressed sensing (PICCS) framework. The proposed algorithm is experimentally validated and compared with PICCS algorithm and demonstrates superior reconstruction accuracy. Large-area flat panel detector induces more scatter, which results in cupping and shading artifacts in the images. Various scatter correction methods have been proposed to reduce the artifacts from both hardware and software sides, but still suffer clinical applicability. In this dissertation, a single-scan scatter correction method using periphery scatter detection and compressed sensing technique is proposed and tested. The algorithm integrates the scatter measurement/reconstruction and projection acquisition into one scan with simple design of boundary lead blockers. It shows effective scatter artifacts reduction ability as well as promising practical usage for the existing CBCT systems. The presence of metals in patients may cause streaking artifacts in x-ray CT, which has long been recognized as a problem that not only limits the quality of CT images, but also makes dose calculation in radiation therapy planning problematic. In this dissertation, a method for binary reconstruction of metal objects is proposed to serve as the first step of metal artifacts reduction. The boundaries of metallic objects are obtained by using a penalized weighted least-squares algorithm with the adequate intensity gradient-controlled. A series of experimental studies are performed to evaluate the proposed approach, and show that when the projection data are sparse, a non-linear manipulation of projection data can greatly facilitate the binary reconstruction process to achieve accurate binary CT images.
Assessments of historical thinking [electronic resource] : three validity studies
Keywords: Education.

Learning standards across the United States have increasingly called for history students to engage in aspects of historical thinking, a term used to describe the complex disciplinary processes that historians use to make sense of the past. Although students are expected to learn these complex processes, little is known about how to assess achievement in these areas. Extant tests purport to assess historical thinking, but little validity research has been done to explore whether these tests are, in fact, sound measures of these processes. The present dissertation comprises three articles, each of which was designed to help meet the need for validity research about assessments of historical thinking. Each article featured studies that used think-aloud protocols to investigate aspects of cognitive validity, which is a consideration of whether assessments elicit the cognitive processes they are designed to measure. Article I explored whether selected multiple-choice items from the National Assessment of Education Progress (NAEP) Grade 12 US History exam elicit the aspects of "Historical Analysis and Interpretation" that they were designed to measure. Protocol analysis revealed that, instead of historical thinking, the items prompted students to engage in the construct irrelevant processes of factual recall/recognition, reading comprehension, and test-taking processes. The results undermine a validity argument about the use of these items to measure aspects of historical thinking. Article II investigated whether multiple-choice items from a new historical thinking measure, the Historical Thinking Test (HTT), tapped the intended historical thinking constructs of sourcing, corroboration, and contextualization. It also compared the processes elicited by HTT items with those elicited by multiple-choice items from two extant standardized tests. The think-aloud data suggested that items from the HTT elicited historical thinking at higher rates among high school history students than did items from extant tests. Yet, each of these new items also elicited construct-irrelevant reasoning that could limit their usefulness as measures of historical thinking. Article III examined whether new constructed-response items, called History Assessments of Thinking (HATs), elicited the intended aspects of historical thinking. Results suggested that HATs, for the most part, elicited the targeted constructs and that student answers reflected proficiency in aspects of historical thinking. The study also compared the processes elicited by HATs with those elicited by stem-equivalent multiple-choice items. The findings suggested that the stem-equivalent multiple-choice items elicited aspects of historical thinking, but that they also elicited irrelevant processes that could undermined an argument for their use as measures of historical thinking.
Atmospheric plasma deposition of transparent coatings on polymers [electronic resource]
Keywords: Applied Physics.

Atmospheric plasma enables plasma assisted coating deposition in ambient air at low temperature on large and/or complex geometry substrates. It has huge potential for coating synthesis and materials surface treatment at lower cost without the necessity of vacuum equipment, for applications of energy, display, aerospace, etc. In this dissertation, I present the results of atmospheric plasma deposition of transparent hard protective coatings on polymers. In order to deposit high quality coatings, we find that the interaction between atmospheric plasma, coating, and polymer substrate should all be optimized. Firstly, I studied the interaction between atmospheric plasma and polymer substrates. Atmospheric plasma was used to pretreat polycarbonate and stretched poly(methyl methacrylate) surfaces in order to enhance the adhesion of polymers to inorganic coatings. The treatment time and the chemical structure of the polymers were found to be important factors. For polycarbonate, a short treatment increased the adhesion energy by four times, while longer treatment resulted in low molecular-weight species formation and decreased adhesion. Next, I deposited dense silica coatings on polymers using atmospheric plasma. The coating deposition rate, molecular network structure, density, Young's modulus and adhesion to polymers exhibited a strong dependence on the precursor delivery temperature and rate, and the functionality and number of silicon atoms in the precursor molecules. The highest Young's modulus of the atmospheric plasma silica was four times higher than that of commercial sol-gel polysiloxane coatings. After that, I successfully deposited carbon-bridged hybrid organosilicate coating using atmospheric plasma, with the ethyl bridges incorporated in the silicate network under the ambient air environment. These coatings doubled the adhesion energy to polymers due to the molecular bridging effect, compared to commercial sol-gel polysiloxane coatings. Finally, I deposited a hard, adhesive, and highly transparent bilayer structure on polymers, with the bottom layer highly adhesive to polymer and the top layer hard to resist scratches. The method overcomes the challenge of fabricating coatings with high mechanical and interfacial properties in a one-step process. The bilayer structure exhibited ~ 100% transmittance in the visible wavelength range and no sacrifice of the hard or adhesive properties of the single sub-layers.
Atom interferometry in a 10 m fountain [electronic resource]
Keywords: Physics.

This thesis presents experimental results from the Stanford 10 m atom drop tower. We use atomic physics and laser spectroscopic techniques to test both general relativity and quantum mechanics. By dropping different types of atoms and observing their free-fall accelerations, it will be possible to test the equivalence principle and other general relativistic effects in the lab. By observing coherence after splitting an atom by up to 8.2 cm, we have probed the quantum-to-classical transition with increasingly macroscopic superposition states.
Atomic Postalgia: Antiquity, Modernity and the Origins of the Nuclear Program in India
Keywords: India
Homi Bhabha
Jawaharlal Nehru
nuclear
postalgia
nostalgia
constructive history
antiquity
modernity
Indian
Peaceful Nuclear Explosion
Indira Gandhi
Center for International Security and Cooperation
Thesis

This paper examines the origins and motivations for the nuclear program in India. It focuses particularly on the inception of the program in the early 1940s—a period of Indian nuclear history that is often overlooked in favor of analyses of the later nuclear missile tests of 1974 and 1998. These later analyses, although well-intentioned, are either too limited in their historical scope or too vague to be of much use in understanding the initial motivations for a nuclear program. As an alternative, this paper finds that an in-depth historical investigation of the program’s early formation, and especially that of its two main instigators, Jawaharlal Nehru and Homi Bhabha, is essential to understanding the deeper motivations and perceptions shaping the program as it developed in later years. By tracing the intellectual journey of these ‘two fathers’ of Indian atomic power across their writings and letters, this paper brings out a uniquely Indian sense of modernity, derived from the vision of a morally and socially advanced ancient India. This blend of modernity and antiquity is then used to coin the concept of postalgia—the nostalgia for a past that may never have existed—that, as a form of constructive history, can be used to explain the subsequent evolution of the nuclear program in India. The result is a model that not only helps to provide insight into the Indian case today, but also has the potential to be used in other similar cases that rely on the intersection of intellectual history with policy.
Atomic-scale engineering of nanomaterials for solar energy [electronic resource]
Keywords: Mechanical Engineering.

Energy consumption determines the economic, environmental and political viability of many nations. With limited resources in our planet, it is imperative to industrialize renewable energy technology. Solar energy is a promising alternative to fossil fuels but current solar technology is limited in energy conversion efficiencies and cost effectiveness. Advances made in nanoscale solar technology suggest that the necessary engineering breakthroughs will stem from our ability to develop devices with sophisticated and precise atomic structures. Thus, a major obstacle preventing the commercialization of solar technology is our inability to cost-effectively fabricate materials with atomic-level precision. In this work, the energy conversion and transport properties of solar-energy-harvesting nanomaterials are tuned by engineering their atomic structure with atomic layer deposition (ALD), a commercially available technique. Charge transport in zinc oxide thin films was engineered by introducing aluminum dopants that increased the population of weakly bound electrons. Energy conversion in lead sulfide (PbS) was engineered by making use of island growth mechanisms during the initial cycles of ALD, resulting in quantum dots (QDs) with tunable band gaps above 1 eV. Charge extraction between PbS QDs and metal oxide nanoparticles was enhanced by inserting atomically-thin barriers at their interfaces. Additionally, a combination of ALD with x-ray absorption enabled atomic-level insight at junctions between PbS QDs and metal oxide nanoparticles. This combination is novel in its ability to finely characterize and control the bonding environment between two structurally-distinct nanomaterials. Overall, this work provides examples of enhancing performance of solar energy nanomaterials and expands the necessary framework to engineer materials with atomic-level precision.