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- Genre: Doctoral Dissertation
- Creators: Papandreou-Suppappola, Antonia
Description
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
Distributed inference has applications in a wide range of fields such as source localization, target detection, environment monitoring, and healthcare. In this dissertation, distributed inference schemes which use bounded transmit power are considered. The performance of the proposed schemes are studied for a variety of inference problems. In the first part of the dissertation, a distributed detection scheme where the sensors transmit with constant modulus signals over a Gaussian multiple access channel is considered. The deflection coefficient of the proposed scheme is shown to depend on the characteristic function of the sensing noise, and the error exponent for the system is derived using large deviation theory. Optimization of the deflection coefficient and error exponent are considered with respect to a transmission phase parameter for a variety of sensing noise distributions including impulsive ones. The proposed scheme is also favorably compared with existing amplify-and-forward (AF) and detect-and-forward (DF) schemes. The effect of fading is shown to be detrimental to the detection performance and simulations are provided to corroborate the analytical results. The second part of the dissertation studies a distributed inference scheme which uses bounded transmission functions over a Gaussian multiple access channel. The conditions on the transmission functions under which consistent estimation and reliable detection are possible is characterized. For the distributed estimation problem, an estimation scheme that uses bounded transmission functions is proved to be strongly consistent provided that the variance of the noise samples are bounded and that the transmission function is one-to-one. The proposed estimation scheme is compared with the amplify and forward technique and its robustness to impulsive sensing noise distributions is highlighted. It is also shown that bounded transmissions suffer from inconsistent estimates if the sensing noise variance goes to infinity. For the distributed detection problem, similar results are obtained by studying the deflection coefficient. Simulations corroborate our analytical results. In the third part of this dissertation, the problem of estimating the average of samples distributed at the nodes of a sensor network is considered. A distributed average consensus algorithm in which every sensor transmits with bounded peak power is proposed. In the presence of communication noise, it is shown that the nodes reach consensus asymptotically to a finite random variable whose expectation is the desired sample average of the initial observations with a variance that depends on the step size of the algorithm and the variance of the communication noise. The asymptotic performance is characterized by deriving the asymptotic covariance matrix using results from stochastic approximation theory. It is shown that using bounded transmissions results in slower convergence compared to the linear consensus algorithm based on the Laplacian heuristic. Simulations corroborate our analytical findings. Finally, a robust distributed average consensus algorithm in which every sensor performs a nonlinear processing at the receiver is proposed. It is shown that non-linearity at the receiver nodes makes the algorithm robust to a wide range of channel noise distributions including the impulsive ones. It is shown that the nodes reach consensus asymptotically and similar results are obtained as in the case of transmit non-linearity. Simulations corroborate our analytical findings and highlight the robustness of the proposed algorithm.
ContributorsDasarathan, Sivaraman (Author) / Tepedelenlioğlu, Cihan (Thesis advisor) / Papandreou-Suppappola, Antonia (Committee member) / Reisslein, Martin (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
Electrical neural activity detection and tracking have many applications in medical research and brain computer interface technologies. In this thesis, we focus on the development of advanced signal processing algorithms to track neural activity and on the mapping of these algorithms onto hardware to enable real-time tracking. At the heart of these algorithms is particle filtering (PF), a sequential Monte Carlo technique used to estimate the unknown parameters of dynamic systems. First, we analyze the bottlenecks in existing PF algorithms, and we propose a new parallel PF (PPF) algorithm based on the independent Metropolis-Hastings (IMH) algorithm. We show that the proposed PPF-IMH algorithm improves the root mean-squared error (RMSE) estimation performance, and we demonstrate that a parallel implementation of the algorithm results in significant reduction in inter-processor communication. We apply our implementation on a Xilinx Virtex-5 field programmable gate array (FPGA) platform to demonstrate that, for a one-dimensional problem, the PPF-IMH architecture with four processing elements and 1,000 particles can process input samples at 170 kHz by using less than 5% FPGA resources. We also apply the proposed PPF-IMH to waveform-agile sensing to achieve real-time tracking of dynamic targets with high RMSE tracking performance. We next integrate the PPF-IMH algorithm to track the dynamic parameters in neural sensing when the number of neural dipole sources is known. We analyze the computational complexity of a PF based method and propose the use of multiple particle filtering (MPF) to reduce the complexity. We demonstrate the improved performance of MPF using numerical simulations with both synthetic and real data. We also propose an FPGA implementation of the MPF algorithm and show that the implementation supports real-time tracking. For the more realistic scenario of automatically estimating an unknown number of time-varying neural dipole sources, we propose a new approach based on the probability hypothesis density filtering (PHDF) algorithm. The PHDF is implemented using particle filtering (PF-PHDF), and it is applied in a closed-loop to first estimate the number of dipole sources and then their corresponding amplitude, location and orientation parameters. We demonstrate the improved tracking performance of the proposed PF-PHDF algorithm and map it onto a Xilinx Virtex-5 FPGA platform to show its real-time implementation potential. Finally, we propose the use of sensor scheduling and compressive sensing techniques to reduce the number of active sensors, and thus overall power consumption, of electroencephalography (EEG) systems. We propose an efficient sensor scheduling algorithm which adaptively configures EEG sensors at each measurement time interval to reduce the number of sensors needed for accurate tracking. We combine the sensor scheduling method with PF-PHDF and implement the system on an FPGA platform to achieve real-time tracking. We also investigate the sparsity of EEG signals and integrate compressive sensing with PF to estimate neural activity. Simulation results show that both sensor scheduling and compressive sensing based methods achieve comparable tracking performance with significantly reduced number of sensors.
ContributorsMiao, Lifeng (Author) / Chakrabarti, Chaitali (Thesis advisor) / Papandreou-Suppappola, Antonia (Thesis advisor) / Zhang, Junshan (Committee member) / Bliss, Daniel (Committee member) / Kovvali, Narayan (Committee member) / Arizona State University (Publisher)
Created2013
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
Adaptive processing and classification of electrocardiogram (ECG) signals are important in eliminating the strenuous process of manually annotating ECG recordings for clinical use. Such algorithms require robust models whose parameters can adequately describe the ECG signals. Although different dynamic statistical models describing ECG signals currently exist, they depend considerably on a priori information and user-specified model parameters. Also, ECG beat morphologies, which vary greatly across patients and disease states, cannot be uniquely characterized by a single model. In this work, sequential Bayesian based methods are used to appropriately model and adaptively select the corresponding model parameters of ECG signals. An adaptive framework based on a sequential Bayesian tracking method is proposed to adaptively select the cardiac parameters that minimize the estimation error, thus precluding the need for pre-processing. Simulations using real ECG data from the online Physionet database demonstrate the improvement in performance of the proposed algorithm in accurately estimating critical heart disease parameters. In addition, two new approaches to ECG modeling are presented using the interacting multiple model and the sequential Markov chain Monte Carlo technique with adaptive model selection. Both these methods can adaptively choose between different models for various ECG beat morphologies without requiring prior ECG information, as demonstrated by using real ECG signals. A supervised Bayesian maximum-likelihood (ML) based classifier uses the estimated model parameters to classify different types of cardiac arrhythmias. However, the non-availability of sufficient amounts of representative training data and the large inter-patient variability pose a challenge to the existing supervised learning algorithms, resulting in a poor classification performance. In addition, recently developed unsupervised learning methods require a priori knowledge on the number of diseases to cluster the ECG data, which often evolves over time. In order to address these issues, an adaptive learning ECG classification method that uses Dirichlet process Gaussian mixture models is proposed. This approach does not place any restriction on the number of disease classes, nor does it require any training data. This algorithm is adapted to be patient-specific by labeling or identifying the generated mixtures using the Bayesian ML method, assuming the availability of labeled training data.
ContributorsEdla, Shwetha Reddy (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Chakrabarti, Chaitali (Committee member) / Kovvali, Narayan (Committee member) / Tepedelenlioğlu, Cihan (Committee member) / Arizona State University (Publisher)
Created2012
Description
Immunosignaturing is a medical test for assessing the health status of a patient by applying microarrays of random sequence peptides to determine the patient's immune fingerprint by associating antibodies from a biological sample to immune responses. The immunosignature measurements can potentially provide pre-symptomatic diagnosis for infectious diseases or detection of biological threats. Currently, traditional bioinformatics tools, such as data mining classification algorithms, are used to process the large amount of peptide microarray data. However, these methods generally require training data and do not adapt to changing immune conditions or additional patient information. This work proposes advanced processing techniques to improve the classification and identification of single and multiple underlying immune response states embedded in immunosignatures, making it possible to detect both known and previously unknown diseases or biothreat agents. Novel adaptive learning methodologies for un- supervised and semi-supervised clustering integrated with immunosignature feature extraction approaches are proposed. The techniques are based on extracting novel stochastic features from microarray binding intensities and use Dirichlet process Gaussian mixture models to adaptively cluster the immunosignatures in the feature space. This learning-while-clustering approach allows continuous discovery of antibody activity by adaptively detecting new disease states, with limited a priori disease or patient information. A beta process factor analysis model to determine underlying patient immune responses is also proposed to further improve the adaptive clustering performance by formatting new relationships between patients and antibody activity. In order to extend the clustering methods for diagnosing multiple states in a patient, the adaptive hierarchical Dirichlet process is integrated with modified beta process factor analysis latent feature modeling to identify relationships between patients and infectious agents. The use of Bayesian nonparametric adaptive learning techniques allows for further clustering if additional patient data is received. Significant improvements in feature identification and immune response clustering are demonstrated using samples from patients with different diseases.
ContributorsMalin, Anna (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Bliss, Daniel (Committee member) / Chakrabarti, Chaitali (Committee member) / Kovvali, Narayan (Committee member) / Lacroix, Zoé (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation introduces stochastic ordering of instantaneous channel powers of fading channels as a general method to compare the performance of a communication system over two different channels, even when a closed-form expression for the metric may not be available. Such a comparison is with respect to a variety of performance metrics such as error rates, outage probability and ergodic capacity, which share common mathematical properties such as monotonicity, convexity or complete monotonicity. Complete monotonicity of a metric, such as the symbol error rate, in conjunction with the stochastic Laplace transform order between two fading channels implies the ordering of the two channels with respect to the metric. While it has been established previously that certain modulation schemes have convex symbol error rates, there is no study of the complete monotonicity of the same, which helps in establishing stronger channel ordering results. Toward this goal, the current research proves for the first time, that all 1-dimensional and 2-dimensional modulations have completely monotone symbol error rates. Furthermore, it is shown that the frequently used parametric fading distributions for modeling line of sight exhibit a monotonicity in the line of sight parameter with respect to the Laplace transform order. While the Laplace transform order can also be used to order fading distributions based on the ergodic capacity, there exist several distributions which are not Laplace transform ordered, although they have ordered ergodic capacities. To address this gap, a new stochastic order called the ergodic capacity order has been proposed herein, which can be used to compare channels based on the ergodic capacity. Using stochastic orders, average performance of systems involving multiple random variables are compared over two different channels. These systems include diversity combining schemes, relay networks, and signal detection over fading channels with non-Gaussian additive noise. This research also addresses the problem of unifying fading distributions. This unification is based on infinite divisibility, which subsumes almost all known fading distributions, and provides simplified expressions for performance metrics, in addition to enabling stochastic ordering.
ContributorsRajan, Adithya (Author) / Tepedelenlioğlu, Cihan (Thesis advisor) / Papandreou-Suppappola, Antonia (Committee member) / Bliss, Daniel (Committee member) / Kosut, Oliver (Committee member) / Arizona State University (Publisher)
Created2014
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
Structural integrity is an important characteristic of performance for critical components used in applications such as aeronautics, materials, construction and transportation. When appraising the structural integrity of these components, evaluation methods must be accurate. In addition to possessing capability to perform damage detection, the ability to monitor the level of damage over time can provide extremely useful information in assessing the operational worthiness of a structure and in determining whether the structure should be repaired or removed from service. In this work, a sequential Bayesian approach with active sensing is employed for monitoring crack growth within fatigue-loaded materials. The monitoring approach is based on predicting crack damage state dynamics and modeling crack length observations. Since fatigue loading of a structural component can change while in service, an interacting multiple model technique is employed to estimate probabilities of different loading modes and incorporate this information in the crack length estimation problem. For the observation model, features are obtained from regions of high signal energy in the time-frequency plane and modeled for each crack length damage condition. Although this observation model approach exhibits high classification accuracy, the resolution characteristics can change depending upon the extent of the damage. Therefore, several different transmission waveforms and receiver sensors are considered to create multiple modes for making observations of crack damage. Resolution characteristics of the different observation modes are assessed using a predicted mean squared error criterion and observations are obtained using the predicted, optimal observation modes based on these characteristics. Calculation of the predicted mean square error metric can be computationally intensive, especially if performed in real time, and an approximation method is proposed. With this approach, the real time computational burden is decreased significantly and the number of possible observation modes can be increased. Using sensor measurements from real experiments, the overall sequential Bayesian estimation approach, with the adaptive capability of varying the state dynamics and observation modes, is demonstrated for tracking crack damage.
ContributorsHuff, Daniel W (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Kovvali, Narayan (Committee member) / Chakrabarti, Chaitali (Committee member) / Chattopadhyay, Aditi (Committee member) / Arizona State University (Publisher)
Created2013
Description
This research focuses on the benefits of using nanocomposites in aerospace structural components to prevent or delay the onset of unique composite failure modes, such as delamination. Analytical, numerical, and experimental analyses were conducted to provide a comprehensive understanding of how carbon nanotubes (CNTs) can provide additional structural integrity when they are used in specific hot spots within a structure. A multiscale approach was implemented to determine the mechanical and thermal properties of the nanocomposites, which were used in detailed finite element models (FEMs) to analyze interlaminar failures in T and Hat section stringers. The delamination that first occurs between the tow filler and the bondline between the stringer and skin was of particular interest. Both locations are considered to be hot spots in such structural components, and failures tend to initiate from these areas. In this research, nanocomposite use was investigated as an alternative to traditional methods of suppressing delamination. The stringer was analyzed under different loading conditions and assuming different structural defects. Initial damage, defined as the first drop in the load displacement curve was considered to be a useful variable to compare the different behaviors in this study and was detected via the virtual crack closure technique (VCCT) implemented in the FE analysis.
Experiments were conducted to test T section skin/stringer specimens under pull-off loading, replicating those used in composite panels as stiffeners. Two types of designs were considered: one using pure epoxy to fill the tow region and another that used nanocomposite with 5 wt. % CNTs. The response variable in the tests was the initial damage. Detailed analyses were conducted using FEMs to correlate with the experimental data. The correlation between both the experiment and model was satisfactory. Finally, the effects of thermal cure and temperature variation on nanocomposite structure behavior were studied, and both variables were determined to influence the nanocomposite structure performance.
Experiments were conducted to test T section skin/stringer specimens under pull-off loading, replicating those used in composite panels as stiffeners. Two types of designs were considered: one using pure epoxy to fill the tow region and another that used nanocomposite with 5 wt. % CNTs. The response variable in the tests was the initial damage. Detailed analyses were conducted using FEMs to correlate with the experimental data. The correlation between both the experiment and model was satisfactory. Finally, the effects of thermal cure and temperature variation on nanocomposite structure behavior were studied, and both variables were determined to influence the nanocomposite structure performance.
ContributorsHasan, Zeaid (Author) / Chattopadhyay, Aditi (Thesis advisor) / Dai, Lenore (Committee member) / Jiang, Hanqing (Committee member) / Rajadas, John (Committee member) / Liu, Yongming (Committee member) / Arizona State University (Publisher)
Created2014