VictorJuiz/thesis huggingface dataset:
Single-molecule studies of nucleic acid folding [electronic resource]
Keywords: Biophysics.

Nucleic acids--DNA and RNA--are critical to life, involved in the storage and decoding of genetic information in the cell as well as the regulation and catalysis of specific biological processes. The function of a nucleic acid molecule is determined in large part by the structure it adopts, which in turn depends on its sequence. The mechanisms of sequence-directed nucleic acid folding remain incompletely understood, particularly for large RNA molecules. The work presented in this thesis uses single-molecule optical-trapping techniques to study nucleic acid folding, where reversible folding is induced and measured in individual molecules through the application of force. In Chapter 2 we demonstrate direct measurement of the full folding energy landscapes of DNA hairpins, which comprise a model system for studying nucleic acid secondary structure, and show how such landscapes are sensitive to sequence. In Chapter 3 we study the electrostatics of DNA hairpin folding by measuring trends in folding energies under different ionic conditions and comparing these trends with those predicted by Poisson-Boltzmann theory. Finally, in Chapter 4 we examine folding of the TPP riboswitch aptamer, an RNA molecule with complex secondary structure that also adopts tertiary structure upon binding a small-molecule ligand. We measured the folding energy landscape of the aptamer and perturbations of this landscape resulting from mutations and ligand binding, and propose a kinetic model to describe the coupling between aptamer folding and ligand binding. Taken together, the results presented here demonstrate the usefulness of the energy landscape framework for characterizing nucleic acid folding in conjunction with single-molecule measurements.
Single-walled carbon nanotubes (SWNTs) as near infrared fluorescent imaging agents in biological systems [electronic resource]
Keywords: Chemistry

The near infrared range has long been known to be advantageous for biological imaging and sensing applications. In particular, the second near infrared window (1000 nm -- 1400 nm, NIR II) is characterized by low endogenous autofluorescence and deep tissue penetration due to reduced tissue scatter. To address the dearth of fluorophores in this window, this work focuses on utilizing the intrinsic near infrared photoluminescence of semiconducting single walled carbon nanotubes (SWNTs) to take advantage of this unique spectral region. First, SWNTs are made bio-inert and applied as fluorescent probes for highly specific cellular targeting using antibodies such as Rituxan and Herceptin. These probes were then used for the first whole animal fluorescent imaging using SWNTs in vivo following tail vein injection, including the observation of high SWNT accumulation in tumors. By implementing a surfactant exchange method to improve the fluorescence yield of SWNTs solubilized by phospholipid-polyethylene glycol, high magnification intravital microscopy of tumor vessels beneath thick skin was achieved. Further improvements were made to improve the fluorescence yield of the SWNT probes by utilizing a density gradient separation method which removed poorly fluorescent short tubes and nanotube bundles. Another separation method, ion-exchange chromatography was applied to isolate single chirality SWNTs and perform multicolor NIR imaging in vitro and in vivo. Finally, these bright, biocompatible nanotube fluorophores were used to achieve video rate imaging of mice in vivo during tail vein injection for dynamic contrast enhanced imaging through principal component analysis. The emission in the NIR II region allowed crisp anatomical resolution, confirmed by mock tissue phantom studies and Monte Carlo simulation.
Spectroscopic and theoretical studies of copper-oxygen intermediates in enzyme model complexes and zeolites [electronic resource] : electronic structure contributions to reactivity
Keywords: Chemistry

Copper-oxygen species catalyze a wide range of biologically and catalytically relevant reactions. In this dissertation a combined spectroscopic and theoretical approach is used to define the geometric and electronic structure of two copper-oxygen intermediates proposed to be activated for H-atom abstraction: an end-on bound mononuclear cupric-superoxo and a zeolitic site activated for methane monooxygenation.
Statistical combination of climate models [electronic resource]
Keywords: Statistics

Atmosphere-ocean general circulation models (AOGCMs) are the primary tool to study how climate responds to increases in the concentration of greenhouse gases in the atmosphere. Outputs from different AOGCM's have been combined using weighting schemes related to how well they reproduce the historical data. Earlier approaches have inferred model weights in the context of a Bayes hierarchical scheme that treats both the historical record and the several model outputs as independent random samples from a distribution of possible weather data centered around the true climate. However, recent work points to evident correlations among model outputs. Our approach is based on optimizing the fit of model output combinations to historical data, allowing for weighting that is location specific with smoothing of both space-time temperature trends and model weight coefficients. Estimated model weights are extrapolated and applied to `future' AOGCM output to produce predictions of future space-time temperature trends. The approach is illustrated using observed summer temperature data for central North America for the
Statistical moment equations for forward and inverse modeling of multiphase flow in porous media [electronic resource]
Keywords: Energy Resources Engineering

A probabilistic framework for dynamic data integration (history matching) has become accepted practice in reservoir engineering applications. The idea is to build an ensemble of reservoir models consistent with the geologic scenario, where each member of the ensemble honors all the available (static and dynamic) information. In addition to data assimilation, the probabilistic framework provides an assessment of the prediction uncertainty due to incomplete knowledge of the reservoir description. Methods based on Monte Carlo Simulation (MCS) are widely used. This is driven by the generality and simplicity of MCS. As a black-box approach, only pre/post processing of conventional flow simulations is needed for MCS. To achieve reasonable accuracy in flow performance predictions; however, large numbers of realizations are usually necessary. Without an adequate number of realizations, it is not possible to quantify, or analyze, the uncertainty space. Here, we develop a Statistical Moment Equations (SME) approach for both the forward (flow-performance predictions) and inverse (conditioning on dynamic data) problems. In the SME method, the equations governing the statistical moments of the quantities of interest (pressure, saturation, travel-time, total- and water-production rates) are derived and solved directly. We study nonlinear, immiscible, two-phase flow problems, where we assume that in addition to statistical information (and a few measurements) about the permeability field, measurements of pressure, saturation, and flow rate are available for a few locations at different times. For the forward problem, the flow (pressure and total-velocity) equations are solved on a regular grid, while a streamline-based strategy is used to solve the nonlinear transport moments. A Kriging-based inversion algorithm, in which the statistical moments of the permeability are conditioned directly, is developed. The computational efficiency of the inversion scheme is discussed. We also analyze the behaviors of the statistical moments of pressure and saturation as a function of the available measurements in both space and time. We also compare the SME inversion scheme with the Kalman filter approach for dynamic data integration. The nature of the prediction uncertainty space and how it changes in the presence of dynamic measurements, such as saturation, are investigated. The analysis helps explain the success of the SME Kriging based inversion scheme in updating the statistical moments of the permeability field in the presence of measurements at different locations and different acquisition times.
Stem cell transcriptomics [electronic resource] : a systems approach to the pluripotent state
Keywords: Bioengineering.

The discovery and isolation of human embryonic stem cells (hESCs), and the more recent generation of induced pluripotent stem cells (iPSCs) from adult cells, has given medical science the tantalizing prospect of one day regenerating organs and tissues in human patients, as well as a revolutionary method for investigating heritable human diseases in a petri dish. This is because hESCs and iPSCs are pluripotent, which enables them to differentiate into virtually any cell type of the human body. However, forcing these cells to change their phenotype is an imperfect science, and is often time-consuming, resource-intensive, and plagued by poor yields. My work over the past four years has therefore attempted to characterize the sets of molecules, both messenger RNAs and microRNAs, that together regulate pluripotency. This has included understanding how the stem cell "transcriptome" changes in the face of external insult (e.g. ionizing radiation), how it changes during differentiation to adult phenotypes such as cardiomyocytes and endothelial cells, and how knowledge from it may be used to induce pluripotency. Taken together, interrogating and ultimately controlling the stem cell transcriptome will be an essential step before we can realize the promise of regenerative therapy.
A stochastic model of cancer progression and screening [electronic resource]
Keywords: Biomedical Informatics.

Cancer screening is critical in clinical practice and public health in order to improve patient prognosis and reduce cancer mortality. In this dissertation, we propose a new approach of assessing the potential of cancer screening, based on estimation of the characteristics of cancer progression. We developed a novel stochastic model of cancer progression and applied this model to lung cancer and breast cancer separately. Model parameters were estimated using data from the Surveillance, Epidemiology and End Results (SEER) cancer registry. The model reproduces SEER, validates against external clinical trials and produces estimates of tumor volume doubling times, likelihood of cure, and mortality reduction that are consistent with empirical data. When applied to lung cancer, the model suggests that under the current treatment regimes, only 6% of patients can be cured in the absence of screening. Despite the high mortality rates from lung cancer, we predict that the majority of lung cancer patients who develop lethal disease could be cured if their primary tumor were detected and treated while it is smaller than 1 cm. To attain a lung cancer mortality reduction of 20% or greater from annual screening, our model estimates that a screen detection threshold of 1.2 cm or lower is necessary, provided there were little to no delay between initial detection and treatment. When applied to breast cancer, our results indicate that likelihood of cure from breast cancer has been improved from 44% in 1975 to 67% in 1993, and a greater fraction of the improvement is attributed to adjuvant therapy than screening. In addition, we found a synergy between adjuvant therapy and screening, which suggests that patients receiving adjuvant therapies would benefit more from screening than those who were not treated by adjuvant therapy, even if there were no improvement in the screening technology. We found that this synergy enables a biannual mammographic screening program to provide benefits that are comparable to an annual program for women age 50 to 69 years. Our model achieves validity and generalizability across different disease types, different cancer characteristics, and different patient cohorts. In this dissertation, we demonstrate the usefulness of this model on estimation of cancer progression timeline and likelihood of cure and its ability to quantify the benefit of screening and treatment. Our approach can be used to provide useful insight for decision making in screening policy, facilitate the design of screening trials, and prioritize novel screening tests based on their potential benefits.
Strained Ge and GeSn Band Engineering for Si Photonic Integrated Circuits [electronic resource]
Keywords: Electrical Engineering

The on-chip interconnect bandwidth limitation is becoming an increasingly critical challenge for integrated circuits (ICs) as device scaling continues to push the speed and density of ICs. Silicon photonics has the ability to solve this emerging problem due to its high speed, high bandwidth, low power consumption, and ability to be monolithically integrated on silicon. Most of the key devices for Si photonic ICs have already been demonstrated. However, a practical CMOS compatible coherent light source is still a major challenge. Germanium (Ge) has already been demonstrated to be a promising material for optoelectronic devices, such as photo-detectors and modulators. However, Ge is an indirect band gap semiconductor, which makes Ge-based light sources very inefficient and limits their practical use. Fortunately, the direct [uppercase Gamma] valley of the Ge conduction band is only 0.14 eV higher than the indirect L valley, suggesting that with band-structure engineering, Ge has the potential to become a direct band gap material and an efficient light emitter. In this dissertation, we first discuss our work on highly biaxial tensile strained Ge grown by molecular beam epitaxy (MBE). Relaxed step-graded InGaAs buffer layers, which are prepared with low temperature growth and high temperature annealing, are used to provide a larger lattice constant substrate to produce tensile strain in Ge epitaxial layers. Up to 2.3% in-plane biaxial tensile strained thin Ge epitaxial layers were achieved with smooth surfaces and low threading dislocation density. A strong increase of photoluminescence with highly tensile strained Ge layers at low temperature suggests that a direct band gap semiconductor has been achieved. This dissertation also presents our work on more than 9% Sn incorporation in epitaxial GeSn alloys using a low temperature MBE growth method. This amount of Sn is 10 times greater than the solid-solubility of Sn in crystalline Ge. Material characterization shows good crystalline quality without Sn precipitation or phase segregation. With increasing Sn percentage, direct band gap narrowing is observed by optical transmission measurements. The studies described in this dissertation will help enable efficient germanium based CMOS compatible coherent light sources. Other possible applications of this work are also discussed in the concluding chapter.
Strategic competitions over networks [electronic resource]
Keywords: Economics

I present three applications of network theory to economic applications. The first chapter studies strategic spending in voting competitions with social networks. It finds that equilibrium spending targets voters whose position in the network has a high eigenvector influence. The second chapter studies how eigenvector influence changes when disconnected components of a network begin interacting. The result has implications for inequality in investment with social spill-overs and for consumption decisions with social influence. The final chapter studies pricing competitions in infrastructure networks. It finds how the structure of the network influences pricing behavior and market surplus.
Strategies and methods for the synthesis of paralytic shellfish poisons [electronic resource]
Keywords: Chemistry

Voltage-gated sodium ion channels are integral membrane proteins most commonly associated with the propagation of action potentials along electrically conducting cells. Nine distinct mammalian isoforms exist, which vary in their primary sequence, gating properties and tissue distribution. Efforts to deconvolute the physiological roles of each isoform through genetic methods, including knockout and gene silencing, are complicated by issues of redundancy and compensatory upregulation of related isoforms. Here we present new strategies and methods for the synthesis of a class of small molecule sodium channel inhibitors, the paralytic shellfish poisons. Methods for the construction of cyclic 5-membered guanidines from acyclic precursors through intramolecular C--H amination and a total synthesis of the paralytic shellfish poison (+)-gonyautoxin 3 are described. It is our vision that these developments will ultimately lead to new small molecule probes designed to help answer fundamental questions regarding sodium ion channel structure and diversity.
String topology and the based loop space [electronic resource]
Keywords: Mathematics

We relate the Batalin-Vilkovisky (BV) algebra structure of the string topology of a manifold to the homological algebra of the singular chains of the based loop space of that manifold, showing that its Hochschild cohomology carries a BV algebra structure isomorphic to that of string topology. Furthermore, this structure is compatible with the usual cup product and Lie bracket on Hochschild cohomology. This isomorphism arises from a derived form of Poincare duality using modules over the based loop space as local coefficient systems. This derived Poincare duality also comes from a form of fibrewise Atiyah duality on the level of fibrewise spectra, and we use this perspective to connect the algebraic constructions to the Chas-Sullivan loop product.
String topology and twisted K-theory [electronic resource]
Keywords: Mathematics

The mathematics in this thesis is motivated by the desire to connect the twisted equivariant K-theory of a compact Lie group G to the string topology of its classifying space BG. The thesis consists of two parts. In the first part, we prove a generalization of the Atiyah--Segal completion theorem to twisted K-theory, a result which Kriz, Westerland and Levin have subsequently used to connect the twisted equivariant K-groups of G to the Gruher--Salvatore string topology of BG. In the second part, we present work towards the construction of a conjectural family of field theories which, on one hand, are closely related to Freed, Hopkins and Teleman's field theories featuring the twisted equivariant K-theory of G, and which on the other hand contain the Chataur--Menichi string topology of BG as a special case. The main result of the second part is the construction of the field-theory operation associated with a fixed cobordism.
Study of high-speed turbulent jet noise using decomposition methods [electronic resource]
Keywords: Mechanical Engineering

Turbulent jet mixing noise is an important component of the overall noise generated by modern aircraft. The mixing noise is dominated by the noise from large scale coherent structures and is observed at shallow exit angles (30[tilde]50deg from axis) with narrow banded spectrum which peaks at St [identical to] fD/U = 0.2 [tilde] 0.3. In this work, we apply a range of theoretical methods to investigate the low frequency noise generation using jet flow data acquired from Large Eddy Simulation database (Bodony & Lele (2005)). Bi-orthogonal relations between regular and adjoint linear stability waves are formulated and applied to detect the amplitude coefficients of instability waves in nonlinear flows. We also apply solutions from Parabolized Stability Equations to the beamforming technique to determine the amplitude coefficients. To separate supersonic and subsonic components of flow variables from LES, we use wavenumber- frequency domain filter then we apply Proper Orthogonal Decomposition method to examine the overall pattern of filtered field. Four jet operating conditions are considered, cold Mj=0.5, 0.9, and 1.95 jets, and a heated Mj =0.97 jet at three frequencies St = 0.1, 0.3 and 0.5 and azimuthal mode numbers n = 0, 1 and 2. Adjoint based amplitude coefficient shows quite promising results for unsteady laminar flow computed using Direct Numerical Simulation. For turbulent flow, this method has limited success, whereas PSE with beamforming technique shows a close resemblance to the turbulent flow data from LES. The near-field norms of the supersonic component of pressure for different jets show a close correlation with the far-field noise intensity and are found to scale well with Lighthill's power law. For heated transonic and cold supersonic jets, the POD projection of the supersonic component resembles the projection of full flow field. However, for subsonic jets, POD projection of supersonic component is drastically different from the POD modes of the full flow field.
Study of Pattern Correlation Between Time Lapse Seismic Data and Saturation Changes
Keywords:  Department of Energy Resources Engineering
School of Earth Energy &amp; Environmental Sciences
Thesis

Time-lapse seismic data has found its applicability in calibrating geological models, history matching, determining well locations and optimizing production. Time-lapse seismic data is used as a reservoir-monitoring tool as it can provide information on fluid dynamics in the reservoir, which is based on the relation between variations of seismic attributes and changes in formation pressure and fluid saturation. In his study Wu (2003) established a correlation between saturation changes and seismic data changes. However his methodology was applied for simple assumptions such as only two wells were operating and one time interval was investigated. The understanding of the correlation could be improved by testing the methodology under different conditions. In this work we addressed those issues. Particularly we investigated the impact of different template sizes on the correlation. After finding the best template we used it to study how the correlation changes under the different fluid flow conditions. Moreover we investigated how the correlation evolves over time for two, four and ten years time interval. The study showed that the template size should be approximately equal to the Fresnel zone to get maximum correlation. The pattern correlation is always higher than the point-to-point correlation. The pattern correlation shows high results (0.7) in the beginning of the production but declines with time. If more than one injectors is used the correlation worsens. The correlation has the same value for two and four years interval. The effect of pressure on the correlation between saturation change and seismic data change has not been studied here. However the pressure change also has some effect on seismic data, thus would be interesting to incorporate the pressure model in the future studies.