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Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women. Developing new drugs for the treatment of cancer is both a slow and expensive process. It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market. However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA). The research presented in this document describes the testing, identification, and mechanistic evaluation of novel methods for treating many human carcinomas using drugs previously approved by the FDA. A tissue culture plate-based screening of FDA approved drugs will identify compounds that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells. Identified leads will next be optimized using high-throughput microfluidic devices to determine the most effective treatment conditions. Finally, a rigorous mechanistic analysis will be conducted to understand how the FDA-approved drug mitoxantrone, sensitizes cancer cells to TRAIL-mediated apoptosis.
ContributorsTaylor, David (Author) / Rege, Kaushal (Thesis advisor) / Jayaraman, Arul (Committee member) / Nielsen, David (Committee member) / Kodibagkar, Vikram (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2013
Description
Under the framework of intelligent management of power grids by leveraging advanced information, communication and control technologies, a primary objective of this study is to develop novel data mining and data processing schemes for several critical applications that can enhance the reliability of power systems. Specifically, this study is broadly organized into the following two parts: I) spatio-temporal wind power analysis for wind generation forecast and integration, and II) data mining and information fusion of synchrophasor measurements toward secure power grids. Part I is centered around wind power generation forecast and integration. First, a spatio-temporal analysis approach for short-term wind farm generation forecasting is proposed. Specifically, using extensive measurement data from an actual wind farm, the probability distribution and the level crossing rate of wind farm generation are characterized using tools from graphical learning and time-series analysis. Built on these spatial and temporal characterizations, finite state Markov chain models are developed, and a point forecast of wind farm generation is derived using the Markov chains. Then, multi-timescale scheduling and dispatch with stochastic wind generation and opportunistic demand response is investigated. Part II focuses on incorporating the emerging synchrophasor technology into the security assessment and the post-disturbance fault diagnosis of power systems. First, a data-mining framework is developed for on-line dynamic security assessment by using adaptive ensemble decision tree learning of real-time synchrophasor measurements. Under this framework, novel on-line dynamic security assessment schemes are devised, aiming to handle various factors (including variations of operating conditions, forced system topology change, and loss of critical synchrophasor measurements) that can have significant impact on the performance of conventional data-mining based on-line DSA schemes. Then, in the context of post-disturbance analysis, fault detection and localization of line outage is investigated using a dependency graph approach. It is shown that a dependency graph for voltage phase angles can be built according to the interconnection structure of power system, and line outage events can be detected and localized through networked data fusion of the synchrophasor measurements collected from multiple locations of power grids. Along a more practical avenue, a decentralized networked data fusion scheme is proposed for efficient fault detection and localization.
ContributorsHe, Miao (Author) / Zhang, Junshan (Thesis advisor) / Vittal, Vijay (Thesis advisor) / Hedman, Kory (Committee member) / Si, Jennie (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2013
Description
With the rapid growth of power systems and the concomitant technological advancements, the goal of achieving smart grids is no longer a vision but a foreseeable reality. Hence, the existing grids are undergoing infrastructural modifications to achieve the diverse characteristics of a smart grid. While there are many subjects associated with the operation of smart grids, this dissertation addresses two important aspects of smart grids: increased penetration of renewable resources, and increased reliance on sensor systems to improve reliability and performance of critical power system components. Present renewable portfolio standards are changing both structural and performance characteristics of power systems by replacing conventional generation with alternate energy resources such as photovoltaic (PV) systems. The present study investigates the impact of increased penetration of PV systems on steady state performance as well as transient stability of a large power system which is a portion of the Western U.S. interconnection. Utility scale and residential rooftop PVs are added to replace a portion of conventional generation resources. While steady state voltages are observed under various PV penetration levels, the impact of reduced inertia on transient stability performance is also examined. The simulation results obtained effectively identify both detrimental and beneficial impacts of increased PV penetration both for steady state stability and transient stability performance. With increased penetration of the renewable energy resources, and with the current loading scenario, more transmission system components such as transformers and circuit breakers are subject to increased stress and overloading. This research work explores the feasibility of increasing system reliability by applying condition monitoring systems to selected circuit breakers and transformers. A very important feature of smart grid technology is that this philosophy decreases maintenance costs by deploying condition monitoring systems that inform the operator of impending failures; or the approach can ameliorate problematic conditions. A method to identify the most critical transformers and circuit breakers with the aid of contingency ranking methods is presented in this study. The work reported in this dissertation parallels an industry sponsored study in which a considerable level of industry input and industry reported concerns are reflected.
ContributorsEftekharnejad, Sara (Author) / Heydt, Gerald (Thesis advisor) / Vittal, Vijay (Thesis advisor) / Si, Jennie (Committee member) / Tylavsky, Daniel (Committee member) / Arizona State University (Publisher)
Created2012
Description
Although high performance, light-weight composites are increasingly being used in applications ranging from aircraft, rotorcraft, weapon systems and ground vehicles, the assurance of structural reliability remains a critical issue. In composites, damage is absorbed through various fracture processes, including fiber failure, matrix cracking and delamination. An important element in achieving reliable composite systems is a strong capability of assessing and inspecting physical damage of critical structural components. Installation of a robust Structural Health Monitoring (SHM) system would be very valuable in detecting the onset of composite failure. A number of major issues still require serious attention in connection with the research and development aspects of sensor-integrated reliable SHM systems for composite structures. In particular, the sensitivity of currently available sensor systems does not allow detection of micro level damage; this limits the capability of data driven SHM systems. As a fundamental layer in SHM, modeling can provide in-depth information on material and structural behavior for sensing and detection, as well as data for learning algorithms. This dissertation focusses on the development of a multiscale analysis framework, which is used to detect various forms of damage in complex composite structures. A generalized method of cells based micromechanics analysis, as implemented in NASA's MAC/GMC code, is used for the micro-level analysis. First, a baseline study of MAC/GMC is performed to determine the governing failure theories that best capture the damage progression. The deficiencies associated with various layups and loading conditions are addressed. In most micromechanics analysis, a representative unit cell (RUC) with a common fiber packing arrangement is used. The effect of variation in this arrangement within the RUC has been studied and results indicate this variation influences the macro-scale effective material properties and failure stresses. The developed model has been used to simulate impact damage in a composite beam and an airfoil structure. The model data was verified through active interrogation using piezoelectric sensors. The multiscale model was further extended to develop a coupled damage and wave attenuation model, which was used to study different damage states such as fiber-matrix debonding in composite structures with surface bonded piezoelectric sensors.
ContributorsMoncada, Albert (Author) / Chattopadhyay, Aditi (Thesis advisor) / Dai, Lenore (Committee member) / Papandreou-Suppappola, Antonia (Committee member) / Rajadas, John (Committee member) / Yekani Fard, Masoud (Committee member) / Arizona State University (Publisher)
Created2012
Description
The combined heat and power (CHP)-based distributed generation (DG) or dis-tributed energy resources (DERs) are mature options available in the present energy mar-ket, considered to be an effective solution to promote energy efficiency. In the urban en-vironment, the electricity, water and natural gas distribution networks are becoming in-creasingly interconnected with the growing penetration of the CHP-based DG. Subse-quently, this emerging interdependence leads to new topics meriting serious consideration: how much of the CHP-based DG can be accommodated and where to locate these DERs, and given preexisting constraints, how to quantify the mutual impacts on operation performances between these urban energy distribution networks and the CHP-based DG. The early research work was conducted to investigate the feasibility and design methods for one residential microgrid system based on existing electricity, water and gas infrastructures of a residential community, mainly focusing on the economic planning. However, this proposed design method cannot determine the optimal DG sizing and sit-ing for a larger test bed with the given information of energy infrastructures. In this con-text, a more systematic as well as generalized approach should be developed to solve these problems. In the later study, the model architecture that integrates urban electricity, water and gas distribution networks, and the CHP-based DG system was developed. The pro-posed approach addressed the challenge of identifying the optimal sizing and siting of the CHP-based DG on these urban energy networks and the mutual impacts on operation per-formances were also quantified. For this study, the overall objective is to maximize the electrical output and recovered thermal output of the CHP-based DG units. The electrici-ty, gas, and water system models were developed individually and coupled by the devel-oped CHP-based DG system model. The resultant integrated system model is used to constrain the DG's electrical output and recovered thermal output, which are affected by multiple factors and thus analyzed in different case studies. The results indicate that the designed typical gas system is capable of supplying sufficient natural gas for the DG normal operation, while the present water system cannot support the complete recovery of the exhaust heat from the DG units.
ContributorsZhang, Xianjun (Author) / Karady, George G. (Thesis advisor) / Ariaratnam, Samuel T. (Committee member) / Holbert, Keith E. (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation considers an integrated approach to system design and controller design based on analyzing limits of system performance. Historically, plant design methodologies have not incorporated control relevant considerations. Such an approach could result in a system that might not meet its specifications (or one that requires a complex control architecture to do so). System and controller designers often go through several iterations in order to converge to an acceptable plant and controller design. The focus of this dissertation is on the design and control an air-breathing hypersonic vehicle using such an integrated system-control design framework. The goal is to reduce the number of system-control design iterations (by explicitly incorporate control considerations in the system design process), as well as to influence the guidance/trajectory specifications for the system. Due to the high computational costs associated with obtaining a dynamic model for each plant configuration considered, approximations to the system dynamics are used in the control design process. By formulating the control design problem using bilinear and polynomial matrix inequalities, several common control and system design constraints can be simultaneously incorporated into a vehicle design optimization. Several design problems are examined to illustrate the effectiveness of this approach (and to compare the computational burden of this methodology against more traditional approaches).
ContributorsSridharan, Srikanth (Author) / Rodriguez, Armando A (Thesis advisor) / Mittelmann, Hans D (Committee member) / Si, Jennie (Committee member) / Tsakalis, Konstantinos S (Committee member) / Arizona State University (Publisher)
Created2014
Description
The basal ganglia are four sub-cortical nuclei associated with motor control and reward learning. They are part of numerous larger mostly segregated loops where the basal ganglia receive inputs from specific regions of cortex. Converging on these inputs are dopaminergic neurons that alter their firing based on received and/or predicted rewarding outcomes of a behavior. The basal ganglia's output feeds through the thalamus back to the areas of the cortex where the loop originated. Understanding the dynamic interactions between the various parts of these loops is critical to understanding the basal ganglia's role in motor control and reward based learning. This work developed several experimental techniques that can be applied to further study basal ganglia function. The first technique used micro-volume injections of low concentration muscimol to decrease the firing rates of recorded neurons in a limited area of cortex in rats. Afterwards, an artificial cerebrospinal fluid flush was injected to rapidly eliminate the muscimol's effects. This technique was able to contain the effects of muscimol to approximately a 1 mm radius volume and limited the duration of the drug effect to less than one hour. This technique could be used to temporarily perturb a small portion of the loops involving the basal ganglia and then observe how these effects propagate in other connected regions. The second part applied self-organizing maps (SOM) to find temporal patterns in neural firing rate that are independent of behavior. The distribution of detected patterns frequency on these maps can then be used to determine if changes in neural activity are occurring over time. The final technique focused on the role of the basal ganglia in reward learning. A new conditioning technique was created to increase the occurrence of selected patterns of neural activity without utilizing any external reward or behavior. A pattern of neural activity in the cortex of rats was selected using an SOM. The pattern was then reinforced by being paired with electrical stimulation of the medial forebrain bundle triggering dopamine release in the basal ganglia. Ultimately, this technique proved unsuccessful possibly due to poor selection of the patterns being reinforced.
ContributorsBaldwin, Nathan Aaron (Author) / Helms Tillery, Stephen I (Thesis advisor) / Castaneda, Edward (Committee member) / Buneo, Christopher A (Committee member) / Muthuswamy, Jitendran (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2014
Description
This study focuses on state estimation of nonlinear discrete time systems with constraints. Physical processes have inherent in them, constraints on inputs, outputs, states and disturbances. These constraints can provide additional information to the estimator in estimating states from the measured output. Recursive filters such as Kalman Filters or Extended Kalman Filters are commonly used in state estimation; however, they do not allow inclusion of constraints in their formulation. On the other hand, computational complexity of full information estimation (using all measurements) grows with iteration and becomes intractable. One way of formulating the recursive state estimation problem with constraints is the Moving Horizon Estimation (MHE) approximation. Estimates of states are calculated from the solution of a constrained optimization problem of fixed size. Detailed formulation of this strategy is studied and properties of this estimation algorithm are discussed in this work. The problem with the MHE formulation is solving an optimization problem in each iteration which is computationally intensive. State estimation with constraints can be formulated as Extended Kalman Filter (EKF) with a projection applied to estimates. The states are estimated from the measurements using standard Extended Kalman Filter (EKF) algorithm and the estimated states are projected on to a constrained set. Detailed formulation of this estimation strategy is studied and the properties associated with this algorithm are discussed. Both these state estimation strategies (MHE and EKF with projection) are tested with examples from the literature. The average estimation time and the sum of square estimation error are used to compare performance of these estimators. Results of the case studies are analyzed and trade-offs are discussed.
ContributorsJoshi, Rakesh (Author) / Tsakalis, Konstantinos (Thesis advisor) / Rodriguez, Armando (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2013
Description
This thesis presents approaches to develop micro seismometers and accelerometers based on molecular electronic transducers (MET) technology using MicroElectroMechanical Systems (MEMS) techniques. MET is a technology applied in seismic instrumentation that proves highly beneficial to planetary seismology. It consists of an electrochemical cell that senses the movement of liquid electrolyte between electrodes by converting it to the output current. MET seismometers have advantages of high sensitivity, low noise floor, small size, absence of fragile mechanical moving parts and independence on the direction of sensitivity axis. By using MEMS techniques, a micro MET seismometer is developed with inter-electrode spacing close to 1μm, which improves the sensitivity of fabricated device to above 3000 V/(m/s^2) under operating bias of 600 mV and input acceleration of 400 μG (G=9.81m/s^2) at 0.32 Hz. The lowered hydrodynamic resistance by increasing the number of channels improves the self-noise to -127 dB equivalent to 44 nG/√Hz at 1 Hz. An alternative approach to build the sensing element of MEMS MET seismometer using SOI process is also presented in this thesis. The significantly increased number of channels is expected to improve the noise performance. Inspired by the advantages of combining MET and MEMS technologies on the development of seismometer, a low frequency accelerometer utilizing MET technology with post-CMOS-compatible fabrication processes is developed. In the fabricated accelerometer, the complicated fabrication of mass-spring system in solid-state MEMS accelerometer is replaced with a much simpler post-CMOS-compatible process containing only deposition of a four-electrode MET structure on a planar substrate, and a liquid inertia mass of an electrolyte droplet encapsulated by oil film. The fabrication process does not involve focused ion beam milling which is used in the micro MET seismometer fabrication, thus the cost is lowered. Furthermore, the planar structure and the novel idea of using an oil film as the sealing diaphragm eliminate the complicated three-dimensional packaging of the seismometer. The fabricated device achieves 10.8 V/G sensitivity at 20 Hz with nearly flat response over the frequency range from 1 Hz to 50 Hz, and a low noise floor of 75 μG/√Hz at 20 Hz.
ContributorsHuang, Hai (Author) / Yu, Hongyu (Thesis advisor) / Jiang, Hanqing (Committee member) / Dai, Lenore (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2014
Description
Alzheimer's disease (AD) is the most common type of dementia, affecting one in nine people age 65 and older. One of the most important neuropathological characteristics of Alzheimer's disease is the aggregation and deposition of the protein beta-amyloid. Beta-amyloid is produced by proteolytic processing of the Amyloid Precursor Protein (APP). Production of beta-amyloid from APP is increased when cells are subject to stress since both APP and beta-secretase are upregulated by stress. An increased beta-amyloid level promotes aggregation of beta-amyloid into toxic species which cause an increase in reactive oxygen species (ROS) and a decrease in cell viability. Therefore reducing beta-amyloid generation is a promising method to control cell damage following stress. The goal of this thesis was to test the effect of inhibiting beta-amyloid production inside stressed AD cell model. Hydrogen peroxide was used as stressing agent. Two treatments were used to inhibit beta-amyloid production, including iBSec1, an scFv designed to block beta-secretase site of APP, and DIA10D, a bispecific tandem scFv engineered to cleave alpha-secretase site of APP and block beta-secretase site of APP. iBSec1 treatment was added extracellularly while DIA10D was stably expressed inside cell using PSECTAG vector. Increase in reactive oxygen species and decrease in cell viability were observed after addition of hydrogen peroxide to AD cell model. The increase in stress induced toxicity caused by addition of hydrogen peroxide was dramatically decreased by simultaneously treating the cells with iBSec1 or DIA10D to block the increase in beta-amyloid levels resulting from the upregulation of APP and beta-secretase.
ContributorsSuryadi, Vicky (Author) / Sierks, Michael (Thesis advisor) / Nielsen, David (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2014