Power system operation requires accurate monitoring of electrical quantities and a reliable database of the power system. As the power system operation becomes more competitive, the secure operation becomes highly important and the role of state estimation becomes more critical. Recently, due to the development of new technology in high power electronics, new control and monitoring devices are becoming more popular in power systems. It is therefore necessary to investigate their models and integrate them into the existing state estimation applications. This dissertation is dedicated to exploiting the newly appeared controlling and monitoring devices, such as Flexible AC Transmission System (FACTS) devices and (Phasor Measurement Units) PMUs, and developing new algorithms to include them into power system analysis applications. Another goal is to develop a 3D visualization tool to help power system operators gain an in-depth image of the system operation state and to identify limit violations in a quick and intuitive manner. An algorithm of state estimation of a power system with embedded FACTS devices is developed first. This estimator can be used to estimate the system state quantities and Unified Power Flow Controller (UPFC) controller parameters. Furthermore, it can also to be used to determine the required controller setting to maintain a desired power flow through a given line. In the second part of this dissertation, two methods to determine the optimal locations of PMUs are derived. One is numerical and the other one is topological. The numerical method is more effective when there are very few existing measurements while the topology-based method is more applicable for a system, which has lots of measurements forming several observable islands. To guard against unexpected failures of PMUs, the numerical method is extended to account for single PMU loss. In the last part of this dissertation, a 3D graphic user interface for power system analysis is developed. It supports two basic application functions, power flow analysis and state estimation. Different visualization techniques are used to represent different kinds of system information.

<p>The posttranslation modification of histone proteins within the nucleosomes of chromatin plays important roles in the regulation of gene expression in both normal biological and pathobiological processes. These modifications alter local chromatin structure and subsequently alter the expression profile of associated genes. Histone methylation, which was long thought immutable, is one such modification that plays a dual functionality in both activation and repression of gene expression and can be thought of as an information storage mark. With the initial discovery of lysine-specific demethylase 1A (LSD1/KDM1A), an FAD-dependent enzyme that catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively, the missing counterbalance to dynamic histone methylation was cemented. This discovery further strengthened the link between histone demethylation and transcriptional regulation and the enzyme has since been identified as a target with therapeutic potential.</p><p>Given the significance of KDM1A enzymatic activity, herein we report our efforts to characterize novel binding interactions that dictate the enzymes biological and pathobiological functions. As KDM1A falls into the greater class of flavin-dependent amine oxidases, it contains features that are recurrent within the class, but due to its unique ability to work on histone and non-histone substrates has unprecedented structural elements. Although the active site is expanded compared to the greater amine oxidase superfamily, it is too sterically restricted to encompass the minimal 21-mer peptide substrate footprint of the histone H3 tail. The remainder of the substrate/product is therefore expected to extend along the surface of KDM1A. Using steady-state kinetic analyses, we now show that unmodified histone H3 is a tight-binding, competitive inhibitor of KDM1A demethylation activity with a Ki of 18.9 ± 1.2 nM that is approximately 100-fold higher than the 21-mer peptide product. The relative affinity of dose-response curves is independent of preincubation time suggesting that H3 rapidly reaches equilibrium with KDM1A. Rapid dilution experiments confirmed the increased binding affinity of full-length H3 toward KDM1A was at least partially caused by a slow off-rate with a koff of 0.072 min-1, a half-life (t1/2) of 9.63 min, and residence time (τ) of 13.9 min. Independent affinity capture surface plasmon resonance experiments confirmed the tight-binding nature of the H3/KDM1A interaction revealing a Kd of 9.02 ± 2.27 nM, a kon of 9.26 x 104 ± 1.5 x 104 M-1s-1 and koff of 8.35 x 10-4 ± 3.4 x 105 s-1. Additionally, consistent with H3 being the only histone substrate of KDM1A, no other core histones are inhibitors of demethylation activity. Our data suggests that KDM1A contains a histone H3 secondary specificity recognition element on the enzyme surface and required further characterization.</p><p>In order to characterize this secondary H3 binding site, we turned to the use of cysteine labeling, chemical cross-linking coupled to proteolysis and LC-MS/MS, HDX-MS, and the design of an active, tower domain deletion KDM1A mutant. We now show that the tower domain contributes to the extended binding interface of the KDM1A/H3 interaction. Additionally, we show that the KDM1A tower domain is not required for demethylation activity and that one can functionally uncouple catalytic activity from protein-protein interactions that occur along the KDM1A tower domain interface, a domain unprecedented in the greater amine oxidase family. Furthermore, this towerless mutant will be useful for dissecting molecular contributions to KDM1A function along the tower domain. Our discovery of this secondary binding site within the aforementioned domain points to how pivotal this region is to the control and localization of KDM1A enzymatic activity as it also serves a pivotal role as a protein-protein interaction motif for the nucleation of a multitude of multimeric protein complexes.</p><p>With this in mind, we set out to design a strategy to isolate the core histone demethylase complex from E. coli cellular lysates. With the use of polycistronic vectors that encode both KDM1A and CoREST for coexpression we were able to produce appreciable amounts of chromatographically pure complex. As our CoREST construct in this strategy contains both the ELM2 and SANT2 domain needed for interaction with the HDACs, this core complex will serve as a starting point for future work that will tease apart additional influences on substrate binding and recognition imparted on KDM1A from binding partners. This preparation can therefore be used in a multitude of downstream studies including reconstitution of the core histone demethylase/deactylase complex and in depth kinetic and biophysical analyses and provides an invaluable starting point</p><p>This work provides a foundational understanding of this unprecedented secondary binding site on the surface of the KDM1A tower domain and how it may play an important role in substrate and product recognition. We suspect that this extended interaction interface may control KDM1A localization within specific chromatin loci and allow the enzyme to serve as a docking element for the nucleation of protein complexes or transcriptional machinery. On the other hand, disruption of this point of contact between the KDM1A/H3 binary complex may also facilitate enzyme/product dissociation, thereby tuning the catalytic activity of the demethylase. Additionally, the ability to produce substantial quantities of the core histone demethylase complex is a necessary step in the decoding of the ‘histone code’ hypothesis of KDM1A and its associated complexes. We suspect that the body of this work will prove to be invaluable for future characterization of the enzyme and its role in biology and pathobiology.</p> / Dissertation

Two-phase flow occurs during the production of oil and gas in the wellbores. Modeling this phenomenon is important for monitoring well productivity and designing surface facilities. Since the transient time period in the wellbore is usually shorter than reservoir time steps, stabilized flow is assumed in the wellbore. As such, semi-steady state models are used for modeling wellbore flow dynamics. However, in the case that flow variations happen in a short period of time (i.e., a gas kick during drilling) the use of a transient two-phase model is crucial. Over the last few years, a number of numerical and analytical wellbore simulators have been developed to mimic wellbore-reservoir interaction. However, some issues still remain a concern in these studies. The main issues surrounding a comprehensive wellbore model consist of fluid property calculations, such as black-oil or compositional models, governing equations, such as mechanistic or correlation-based models, effect of temperature variation and non-isothermal assumption, and methods for coupling the wellbore to the reservoir. In most cases, only standalone wellbore models for blackoil have been used to simulate reservoir and wellbore dynamic interactions. Those models are based on simplified assumptions that lead to an unrealistic estimation of pressure and temperature distributions inside the well. In addition, most reservoir simulators use rough estimates for the perforation pressure as a coupling condition between the wellbore and the reservoir, neglecting pressure drops in the horizontal section. In this study, we present an implementation of a compositional, pseudo steady-state, non-isothermal, coupled wellbore-reservoir simulator for fluid flow in wellbores with a vertical section and a horizontal section embedded on the producing reservoir. In addition, we present the implementation of a pseudo-compositional, fully implicit, transient two-fluid model for two-phase flow in wellbores. In this model, we solve gas/liquid mass balance, gas/liquid momentum balance, and two-phase energy equations in order to obtain the five primary variables: liquid velocity, gas velocity, pressure, holdup and temperature. In our simulation, we compared stratified, bubbly, intermittent flow effects on pressure and temperature distributions in either a transient or steady-state condition. We found that flow geometry variation in different regimes can significantly affect the flow parameters. We also observed that there are significant differences in flow rate prediction between a coupled wellbore-reservoir simulator and a stand-alone reservoir simulator, at the early stages of production. The outcome of this research leads to a more accurate and reliable simulation of multiphase flow in the wellbore, which can be applied to surface facility design, well performance optimization, and wellbore damage estimation. / text

A steady-state model for the calculation of temperature and pressure distributions, and heat and work balance for the STAR-LM and the STAR-H2 systems was developed. The STAR-LM system is designed for electricity production and consists of the lead cooled reactor on natural circulation and the supercritical carbon dioxide Brayton cycle. The STAR-H2 system uses the same reactor which is coupled to the hydrogen production plant, the Brayton cycle, and the water desalination plant. The Brayton cycle produces electricity for the on-site needs. Realistic modules for each system component were developed. The model also performs design calculations for the turbine and compressors for the CO2 Brayton cycle. The model was used to optimize the performance of the entire system as well as every system component. The size of each component was calculated. For the 400 MWt reactor power the STAR-LM produces 174.4 MWe (44% efficiency) and the STAR-H2 system produces 7450 kg H2/hr. The steady state model was used to conduct quasi-static passive load follow analysis. The control strategy was developed for each system; no control action on the reactor is required. As a main safety criterion, the peak cladding temperature is used. It was demonstrated that this temperature remains below the safety limit during both normal operation and load follow.

Electrophysiologic responses are used to estimate hearing thresholds and fit hearing aids in young infants, but these estimates are not exact. An objective test of speech encoding could be used to validate infant fittings by showing that speech has been registered in the central auditory system. Such a test could also show the effects of auditory processing problems on the neural representation of speech. This thesis describes techniques for recording electrophysiologic responses to natural speech stimuli from the brainstem and auditory cortex. The first technique uses a Fourier analyzer to measure steady-state brainstem responses to periodicities and envelope changes in vowels, and the second uses a windowed cross-correlation procedure to measure cortical responses to the envelopes of sentences. Two studies were conducted with the Fourier analyzer. The first measured responses to natural vowels with steady and changing fundamentals, and changing formants. Significant responses to the fundamental were detected for all of the vowels, in all of the subjects, in 19 – 73 s (on average). The second study recorded responses to a vowel fundamental and harmonics. Vowels were presented in opposite polarities to distinguish envelope responses from responses to the spectrum. Significant envelope responses were detected in all subjects at the fundamental. Significant spectral responses were detected in most subjects at harmonics near formant peaks. The third study used cross-correlation to measure cortical responses to sentences. Significant envelope responses were detected to all sentences, at delays of roughly 180 ms. Responses were localized to the posterior auditory cortices. A model based on a series of overlapping transient responses to envelope changes could also account for the results, suggesting that the cortex either directly follows the speech envelope or consistently reacts to changes in this envelope. The strengths and weaknesses of both techniques are discussed in relation to their potential clinical applications.

No description available.

Discrete event simulation is well known to be a powerful approach to investigate behaviour of complex dynamic stochastic systems, especially when the system is analytically not tractable. The estimation of mean values has traditionally been the main goal of simulation output analysis, even though it provides limited information about the analysed system's performance. Because of its complexity, quantile analysis is not as frequently applied, despite its ability to provide much deeper insights into the system of interest. A set of quantiles can be used to approximate a cumulative distribution function, providing fuller information about a given performance characteristic of the simulated system. This thesis employs the distributed computing power of multiple computers by proposing new methods for sequential and automated analysis of quantile-based performance measures of such dynamic systems. These new methods estimate steady state quantiles based on replicating simulations on clusters of workstations as simulation engines. A general contribution to the problem of the length of the initial transient is made by considering steady state in terms of the underlying probability distribution. Our research focuses on sequential and automated methods to guarantee a satisfactory level of confidence of the final results. The correctness of the proposed methods has been exhaustively studied by means of sequential coverage analysis. Quantile estimates are used to investigate underlying probability distributions. We demonstrate that synchronous replications greatly assist this kind of analysis.

This thesis describes a new approach to accelerate the simulation of the steady-state response of nonlinear circuits using the Harmonic Balance (HB) technique. The approach presented in this work focuses on direct factorization of the sparse Jacobian matrix of the HB nonlinear equations using a Graphics Processing Unit (GPU) platform. This approach exploits the heterogeneous structure of the Jacobian matrix. The computational core of the proposed approach is based on developing a block-wise version of the KLU factorization algorithm, where scalar arithmetic operations are replaced by block-aware matrix operations. For a large number of harmonics, or excitation tones, or both the Block-KLU (BKLU) approach effectively raises the ratio of floating-point operations to other operations and, therefore, becomes an ideal vehicle for implementation on a GPU-based platform. Motivated by this fact, a GPU-based Hybrid Block KLU framework is developed to implement the BKLU. The proposed approach in this thesis is named Hybrid-BKLU. The Hybrid-BKLU is implemented in two parts, on the host CPU and on the graphic card’s GPU, using the OpenCL heterogeneous parallel programming language. To show the efficiency of the Hybrid-BKLU approach, its performance is compared with BKLU approach performing HB analysis on several test circuits. The Hybrid-BKLU approach yields speedup by up to 89 times over conventional BKLU on CPU.

Electrophysiologic responses are used to estimate hearing thresholds and fit hearing aids in young infants, but these estimates are not exact. An objective test of speech encoding could be used to validate infant fittings by showing that speech has been registered in the central auditory system. Such a test could also show the effects of auditory processing problems on the neural representation of speech. This thesis describes techniques for recording electrophysiologic responses to natural speech stimuli from the brainstem and auditory cortex. The first technique uses a Fourier analyzer to measure steady-state brainstem responses to periodicities and envelope changes in vowels, and the second uses a windowed cross-correlation procedure to measure cortical responses to the envelopes of sentences. Two studies were conducted with the Fourier analyzer. The first measured responses to natural vowels with steady and changing fundamentals, and changing formants. Significant responses to the fundamental were detected for all of the vowels, in all of the subjects, in 19 – 73 s (on average). The second study recorded responses to a vowel fundamental and harmonics. Vowels were presented in opposite polarities to distinguish envelope responses from responses to the spectrum. Significant envelope responses were detected in all subjects at the fundamental. Significant spectral responses were detected in most subjects at harmonics near formant peaks. The third study used cross-correlation to measure cortical responses to sentences. Significant envelope responses were detected to all sentences, at delays of roughly 180 ms. Responses were localized to the posterior auditory cortices. A model based on a series of overlapping transient responses to envelope changes could also account for the results, suggesting that the cortex either directly follows the speech envelope or consistently reacts to changes in this envelope. The strengths and weaknesses of both techniques are discussed in relation to their potential clinical applications.

An attempt was made to calibrate a steady state activated sludge model (ASM2d) for the biological nutrient removal process at the Gold bar wastewater treatment plant. This calibrated model could be used on a regular basis to test various operational strategies and predict effluent quality under different scenario. To achieve this historic data from the plant database was collected based on 24 composite samples. A trial and error method of wastewater characterization of the primary effluent was attempted using the influent advisor module of the GPS-[X] software. Sensitivity analysis of kinetic parameters was carried out and the most important ones identified were calibrated (default values were modified) based on literature. After calibration it was observed that the model was overestimating the concentrations of carbonaceous biological oxygen demand, total suspended solids and orthophosphate in the effluent, compared to the actual value measured at the plant. Similarly the effluent ammonia concentration was underestimated for most days along with the nitrate and nitrite concentration. This clearly indicated the need for a more accurate calibration based on experimental data to improve prediction capabilities and the reliability of the model. / Environmental Science