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- Genre: Doctoral Dissertation
- Creators: Papandreou-Suppappola, Antonia
- Creators: Tepedelenlioğlu, Cihan
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
Texture analysis plays an important role in applications like automated pattern inspection, image and video compression, content-based image retrieval, remote-sensing, medical imaging and document processing, to name a few. Texture Structure Analysis is the process of studying the structure present in the textures. This structure can be expressed in terms of perceived regularity. Our human visual system (HVS) uses the perceived regularity as one of the important pre-attentive cues in low-level image understanding. Similar to the HVS, image processing and computer vision systems can make fast and efficient decisions if they can quantify this regularity automatically. In this work, the problem of quantifying the degree of perceived regularity when looking at an arbitrary texture is introduced and addressed. One key contribution of this work is in proposing an objective no-reference perceptual texture regularity metric based on visual saliency. Other key contributions include an adaptive texture synthesis method based on texture regularity, and a low-complexity reduced-reference visual quality metric for assessing the quality of synthesized textures. In order to use the best performing visual attention model on textures, the performance of the most popular visual attention models to predict the visual saliency on textures is evaluated. Since there is no publicly available database with ground-truth saliency maps on images with exclusive texture content, a new eye-tracking database is systematically built. Using the Visual Saliency Map (VSM) generated by the best visual attention model, the proposed texture regularity metric is computed. The proposed metric is based on the observation that VSM characteristics differ between textures of differing regularity. The proposed texture regularity metric is based on two texture regularity scores, namely a textural similarity score and a spatial distribution score. In order to evaluate the performance of the proposed regularity metric, a texture regularity database called RegTEX, is built as a part of this work. It is shown through subjective testing that the proposed metric has a strong correlation with the Mean Opinion Score (MOS) for the perceived regularity of textures. The proposed method is also shown to be robust to geometric and photometric transformations and outperforms some of the popular texture regularity metrics in predicting the perceived regularity. The impact of the proposed metric to improve the performance of many image-processing applications is also presented. The influence of the perceived texture regularity on the perceptual quality of synthesized textures is demonstrated through building a synthesized textures database named SynTEX. It is shown through subjective testing that textures with different degrees of perceived regularities exhibit different degrees of vulnerability to artifacts resulting from different texture synthesis approaches. This work also proposes an algorithm for adaptively selecting the appropriate texture synthesis method based on the perceived regularity of the original texture. A reduced-reference texture quality metric for texture synthesis is also proposed as part of this work. The metric is based on the change in perceived regularity and the change in perceived granularity between the original and the synthesized textures. The perceived granularity is quantified through a new granularity metric that is proposed in this work. It is shown through subjective testing that the proposed quality metric, using just 2 parameters, has a strong correlation with the MOS for the fidelity of synthesized textures and outperforms the state-of-the-art full-reference quality metrics on 3 different texture databases. Finally, the ability of the proposed regularity metric in predicting the perceived degradation of textures due to compression and blur artifacts is also established.
ContributorsVaradarajan, Srenivas (Author) / Karam, Lina J (Thesis advisor) / Chakrabarti, Chaitali (Committee member) / Li, Baoxin (Committee member) / Tepedelenlioğlu, Cihan (Committee member) / Arizona State University (Publisher)
Created2014
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
Description
LTE-Advanced networks employ random access based on preambles
transmitted according to multi-channel slotted Aloha principles. The
random access is controlled through a limit W on the number of
transmission attempts and a timeout period for uniform backoff after a
collision. We model the LTE-Advanced random access system by formulating
the equilibrium condition for the ratio of the number of requests
successful within the permitted number of transmission attempts to those
successful in one attempt. We prove that for W≤8 there is only one
equilibrium operating point and for W≥9 there are three operating
points if the request load ρ is between load boundaries ρ1
and ρ2. We analytically identify these load boundaries as well as
the corresponding system operating points. We analyze the throughput and
delay of successful requests at the operating points and validate the
analytical results through simulations. Further, we generalize the
results using a steady-state equilibrium based approach and develop
models for single-channel and multi-channel systems, incorporating the
barring probability PB. Ultimately, we identify the de-correlating
effect of parameters O, PB, and Tomax and introduce the
Poissonization effect due to the backlogged requests in a slot. We
investigate the impact of Poissonization on different traffic and
conclude this thesis.
transmitted according to multi-channel slotted Aloha principles. The
random access is controlled through a limit W on the number of
transmission attempts and a timeout period for uniform backoff after a
collision. We model the LTE-Advanced random access system by formulating
the equilibrium condition for the ratio of the number of requests
successful within the permitted number of transmission attempts to those
successful in one attempt. We prove that for W≤8 there is only one
equilibrium operating point and for W≥9 there are three operating
points if the request load ρ is between load boundaries ρ1
and ρ2. We analytically identify these load boundaries as well as
the corresponding system operating points. We analyze the throughput and
delay of successful requests at the operating points and validate the
analytical results through simulations. Further, we generalize the
results using a steady-state equilibrium based approach and develop
models for single-channel and multi-channel systems, incorporating the
barring probability PB. Ultimately, we identify the de-correlating
effect of parameters O, PB, and Tomax and introduce the
Poissonization effect due to the backlogged requests in a slot. We
investigate the impact of Poissonization on different traffic and
conclude this thesis.
ContributorsTyagi, Revak (Author) / Reisslein, Martin (Thesis advisor) / Tepedelenlioğlu, Cihan (Committee member) / McGarry, Michael (Committee member) / Zhang, Yanchao (Committee member) / Arizona State University (Publisher)
Created2014
Description
Damage detection in heterogeneous material systems is a complex problem and requires an in-depth understanding of the material characteristics and response under varying load and environmental conditions. A significant amount of research has been conducted in this field to enhance the fidelity of damage assessment methodologies, using a wide range of sensors and detection techniques, for both metallic materials and composites. However, detecting damage at the microscale is not possible with commercially available sensors. A probable way to approach this problem is through accurate and efficient multiscale modeling techniques, which are capable of tracking damage initiation at the microscale and propagation across the length scales. The output from these models will provide an improved understanding of damage initiation; the knowledge can be used in conjunction with information from physical sensors to improve the size of detectable damage. In this research, effort has been dedicated to develop multiscale modeling approaches and associated damage criteria for the estimation of damage evolution across the relevant length scales. Important issues such as length and time scales, anisotropy and variability in material properties at the microscale, and response under mechanical and thermal loading are addressed. Two different material systems have been studied: metallic material and a novel stress-sensitive epoxy polymer.
For metallic material (Al 2024-T351), the methodology initiates at the microscale where extensive material characterization is conducted to capture the microstructural variability. A statistical volume element (SVE) model is constructed to represent the material properties. Geometric and crystallographic features including grain orientation, misorientation, size, shape, principal axis direction and aspect ratio are captured. This SVE model provides a computationally efficient alternative to traditional techniques using representative volume element (RVE) models while maintaining statistical accuracy. A physics based multiscale damage criterion is developed to simulate the fatigue crack initiation. The crack growth rate and probable directions are estimated simultaneously.
Mechanically sensitive materials that exhibit specific chemical reactions upon external loading are currently being investigated for self-sensing applications. The "smart" polymer modeled in this research consists of epoxy resin, hardener, and a stress-sensitive material called mechanophore The mechanophore activation is based on covalent bond-breaking induced by external stimuli; this feature can be used for material-level damage detections. In this work Tris-(Cinnamoyl oxymethyl)-Ethane (TCE) is used as the cyclobutane-based mechanophore (stress-sensitive) material in the polymer matrix. The TCE embedded polymers have shown promising results in early damage detection through mechanically induced fluorescence. A spring-bead based network model, which bridges nanoscale information to higher length scales, has been developed to model this material system. The material is partitioned into discrete mass beads which are linked using linear springs at the microscale. A series of MD simulations were performed to define the spring stiffness in the statistical network model. By integrating multiple spring-bead models a network model has been developed to represent the material properties at the mesoscale. The model captures the statistical distribution of crosslinking degree of the polymer to represent the heterogeneous material properties at the microscale. The developed multiscale methodology is computationally efficient and provides a possible means to bridge multiple length scales (from 10 nm in MD simulation to 10 mm in FE model) without significant loss of accuracy. Parametric studies have been conducted to investigate the influence of the crosslinking degree on the material behavior. The developed methodology has been used to evaluate damage evolution in the self-sensing polymer.
For metallic material (Al 2024-T351), the methodology initiates at the microscale where extensive material characterization is conducted to capture the microstructural variability. A statistical volume element (SVE) model is constructed to represent the material properties. Geometric and crystallographic features including grain orientation, misorientation, size, shape, principal axis direction and aspect ratio are captured. This SVE model provides a computationally efficient alternative to traditional techniques using representative volume element (RVE) models while maintaining statistical accuracy. A physics based multiscale damage criterion is developed to simulate the fatigue crack initiation. The crack growth rate and probable directions are estimated simultaneously.
Mechanically sensitive materials that exhibit specific chemical reactions upon external loading are currently being investigated for self-sensing applications. The "smart" polymer modeled in this research consists of epoxy resin, hardener, and a stress-sensitive material called mechanophore The mechanophore activation is based on covalent bond-breaking induced by external stimuli; this feature can be used for material-level damage detections. In this work Tris-(Cinnamoyl oxymethyl)-Ethane (TCE) is used as the cyclobutane-based mechanophore (stress-sensitive) material in the polymer matrix. The TCE embedded polymers have shown promising results in early damage detection through mechanically induced fluorescence. A spring-bead based network model, which bridges nanoscale information to higher length scales, has been developed to model this material system. The material is partitioned into discrete mass beads which are linked using linear springs at the microscale. A series of MD simulations were performed to define the spring stiffness in the statistical network model. By integrating multiple spring-bead models a network model has been developed to represent the material properties at the mesoscale. The model captures the statistical distribution of crosslinking degree of the polymer to represent the heterogeneous material properties at the microscale. The developed multiscale methodology is computationally efficient and provides a possible means to bridge multiple length scales (from 10 nm in MD simulation to 10 mm in FE model) without significant loss of accuracy. Parametric studies have been conducted to investigate the influence of the crosslinking degree on the material behavior. The developed methodology has been used to evaluate damage evolution in the self-sensing polymer.
ContributorsZhang, Jinjun (Author) / Chattopadhyay, Aditi (Thesis advisor) / Dai, Lenore (Committee member) / Jiang, Hanqing (Committee member) / Papandreou-Suppappola, Antonia (Committee member) / Rajadas, John (Committee member) / Arizona State University (Publisher)
Created2014
Description
Tracking a time-varying number of targets is a challenging
dynamic state estimation problem whose complexity is intensified
under low signal-to-noise ratio (SNR) or high clutter conditions.
This is important, for example, when tracking
multiple, closely spaced targets moving in the same direction such as a
convoy of low observable vehicles moving through a forest or multiple
targets moving in a crisscross pattern. The SNR in
these applications is usually low as the reflected signals from
the targets are weak or the noise level is very high.
An effective approach for detecting and tracking a single target
under low SNR conditions is the track-before-detect filter (TBDF)
that uses unthresholded measurements. However, the TBDF has only been used to
track a small fixed number of targets at low SNR.
This work proposes a new multiple target TBDF approach to track a
dynamically varying number of targets under the recursive Bayesian framework.
For a given maximum number of
targets, the state estimates are obtained by estimating the joint
multiple target posterior probability density function under all possible
target
existence combinations. The estimation of the corresponding target existence
combination probabilities and the target existence probabilities are also
derived. A feasible sequential Monte Carlo (SMC) based implementation
algorithm is proposed. The approximation accuracy of the SMC
method with a reduced number of particles is improved by an efficient
proposal density function that partitions the multiple target space into a
single target space.
The proposed multiple target TBDF method is extended to track targets in sea
clutter using highly time-varying radar measurements. A generalized
likelihood function for closely spaced multiple targets in compound Gaussian
sea clutter is derived together with the maximum likelihood estimate of
the model parameters using an iterative fixed point algorithm.
The TBDF performance is improved by proposing a computationally feasible
method to estimate the space-time covariance matrix of rapidly-varying sea
clutter. The method applies the Kronecker product approximation to the
covariance matrix and uses particle filtering to solve the resulting dynamic
state space model formulation.
dynamic state estimation problem whose complexity is intensified
under low signal-to-noise ratio (SNR) or high clutter conditions.
This is important, for example, when tracking
multiple, closely spaced targets moving in the same direction such as a
convoy of low observable vehicles moving through a forest or multiple
targets moving in a crisscross pattern. The SNR in
these applications is usually low as the reflected signals from
the targets are weak or the noise level is very high.
An effective approach for detecting and tracking a single target
under low SNR conditions is the track-before-detect filter (TBDF)
that uses unthresholded measurements. However, the TBDF has only been used to
track a small fixed number of targets at low SNR.
This work proposes a new multiple target TBDF approach to track a
dynamically varying number of targets under the recursive Bayesian framework.
For a given maximum number of
targets, the state estimates are obtained by estimating the joint
multiple target posterior probability density function under all possible
target
existence combinations. The estimation of the corresponding target existence
combination probabilities and the target existence probabilities are also
derived. A feasible sequential Monte Carlo (SMC) based implementation
algorithm is proposed. The approximation accuracy of the SMC
method with a reduced number of particles is improved by an efficient
proposal density function that partitions the multiple target space into a
single target space.
The proposed multiple target TBDF method is extended to track targets in sea
clutter using highly time-varying radar measurements. A generalized
likelihood function for closely spaced multiple targets in compound Gaussian
sea clutter is derived together with the maximum likelihood estimate of
the model parameters using an iterative fixed point algorithm.
The TBDF performance is improved by proposing a computationally feasible
method to estimate the space-time covariance matrix of rapidly-varying sea
clutter. The method applies the Kronecker product approximation to the
covariance matrix and uses particle filtering to solve the resulting dynamic
state space model formulation.
ContributorsEbenezer, Samuel P (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Chakrabarti, Chaitali (Committee member) / Bliss, Daniel (Committee member) / Kovvali, Narayan (Committee member) / Arizona State University (Publisher)
Created2015
Description
This work considers the problem of multiple detection and tracking in two complex time-varying environments, urban terrain and underwater. Tracking multiple radar targets in urban environments is rst investigated by exploiting multipath signal returns, wideband underwater acoustic (UWA) communications channels are estimated using adaptive learning methods, and multiple UWA communications users are detected by designing the transmit signal to match the environment. For the urban environment, a multi-target tracking algorithm is proposed that integrates multipath-to-measurement association and the probability hypothesis density method implemented using particle filtering. The algorithm is designed to track an unknown time-varying number of targets by extracting information from multiple measurements due to multipath returns in the urban terrain. The path likelihood probability is calculated by considering associations between measurements and multipath returns, and an adaptive clustering algorithm is used to estimate the number of target and their corresponding parameters. The performance of the proposed algorithm is demonstrated for different multiple target scenarios and evaluated using the optimal subpattern assignment metric. The underwater environment provides a very challenging communication channel due to its highly time-varying nature, resulting in large distortions due to multipath and Doppler-scaling, and frequency-dependent path loss. A model-based wideband UWA channel estimation algorithm is first proposed to estimate the channel support and the wideband spreading function coefficients. A nonlinear frequency modulated signaling scheme is proposed that is matched to the wideband characteristics of the underwater environment. Constraints on the signal parameters are derived to optimally reduce multiple access interference and the UWA channel effects. The signaling scheme is compared to a code division multiple access (CDMA) scheme to demonstrate its improved bit error rate performance. The overall multi-user communication system performance is finally analyzed by first estimating the UWA channel and then designing the signaling scheme for multiple communications users.
ContributorsZhou, Meng (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Tepedelenlioğlu, Cihan (Committee member) / Kovvali, Narayan (Committee member) / Berisha, Visar (Committee member) / Arizona State University (Publisher)
Created2014
Description
Three dimensional (3-D) ultrasound is safe, inexpensive, and has been shown to drastically improve system ease-of-use, diagnostic efficiency, and patient throughput. However, its high computational complexity and resulting high power consumption has precluded its use in hand-held applications.
In this dissertation, algorithm-architecture co-design techniques that aim to make hand-held 3-D ultrasound a reality are presented. First, image enhancement methods to improve signal-to-noise ratio (SNR) are proposed. These include virtual source firing techniques and a low overhead digital front-end architecture using orthogonal chirps and orthogonal Golay codes.
Second, algorithm-architecture co-design techniques to reduce the power consumption of 3-D SAU imaging systems is presented. These include (i) a subaperture multiplexing strategy and the corresponding apodization method to alleviate the signal bandwidth bottleneck, and (ii) a highly efficient iterative delay calculation method to eliminate complex operations such as multiplications, divisions and square-root in delay calculation during beamforming. These techniques were used to define Sonic Millip3De, a 3-D die stacked architecture for digital beamforming in SAU systems. Sonic Millip3De produces 3-D high resolution images at 2 frames per second with system power consumption of 15W in 45nm technology.
Third, a new beamforming method based on separable delay decomposition is proposed to reduce the computational complexity of the beamforming unit in an SAU system. The method is based on minimizing the root-mean-square error (RMSE) due to delay decomposition. It reduces the beamforming complexity of a SAU system by 19x while providing high image fidelity that is comparable to non-separable beamforming. The resulting modified Sonic Millip3De architecture supports a frame rate of 32 volumes per second while maintaining power consumption of 15W in 45nm technology.
Next a 3-D plane-wave imaging system that utilizes both separable beamforming and coherent compounding is presented. The resulting system has computational complexity comparable to that of a non-separable non-compounding baseline system while significantly improving contrast-to-noise ratio and SNR. The modified Sonic Millip3De architecture is now capable of generating high resolution images at 1000 volumes per second with 9-fire-angle compounding.
In this dissertation, algorithm-architecture co-design techniques that aim to make hand-held 3-D ultrasound a reality are presented. First, image enhancement methods to improve signal-to-noise ratio (SNR) are proposed. These include virtual source firing techniques and a low overhead digital front-end architecture using orthogonal chirps and orthogonal Golay codes.
Second, algorithm-architecture co-design techniques to reduce the power consumption of 3-D SAU imaging systems is presented. These include (i) a subaperture multiplexing strategy and the corresponding apodization method to alleviate the signal bandwidth bottleneck, and (ii) a highly efficient iterative delay calculation method to eliminate complex operations such as multiplications, divisions and square-root in delay calculation during beamforming. These techniques were used to define Sonic Millip3De, a 3-D die stacked architecture for digital beamforming in SAU systems. Sonic Millip3De produces 3-D high resolution images at 2 frames per second with system power consumption of 15W in 45nm technology.
Third, a new beamforming method based on separable delay decomposition is proposed to reduce the computational complexity of the beamforming unit in an SAU system. The method is based on minimizing the root-mean-square error (RMSE) due to delay decomposition. It reduces the beamforming complexity of a SAU system by 19x while providing high image fidelity that is comparable to non-separable beamforming. The resulting modified Sonic Millip3De architecture supports a frame rate of 32 volumes per second while maintaining power consumption of 15W in 45nm technology.
Next a 3-D plane-wave imaging system that utilizes both separable beamforming and coherent compounding is presented. The resulting system has computational complexity comparable to that of a non-separable non-compounding baseline system while significantly improving contrast-to-noise ratio and SNR. The modified Sonic Millip3De architecture is now capable of generating high resolution images at 1000 volumes per second with 9-fire-angle compounding.
ContributorsYang, Ming (Author) / Chakrabarti, Chaitali (Thesis advisor) / Papandreou-Suppappola, Antonia (Committee member) / Karam, Lina (Committee member) / Frakes, David (Committee member) / Ogras, Umit Y. (Committee member) / Arizona State University (Publisher)
Created2015
Description
Analysis of social networks has the potential to provide insights into wide range of applications. As datasets continue to grow, a key challenge is the lack of a widely applicable algorithmic framework for detection of statistically anomalous networks and network properties. Unlike traditional signal processing, where models of truth or empirical verification and background data exist and are often well defined, these features are commonly lacking in social and other networks. Here, a novel algorithmic framework for statistical signal processing for graphs is presented. The framework is based on the analysis of spectral properties of the residuals matrix. The framework is applied to the detection of innovation patterns in publication networks, leveraging well-studied empirical knowledge from the history of science. Both the framework itself and the application constitute novel contributions, while advancing algorithmic and mathematical techniques for graph-based data and understanding of the patterns of emergence of novel scientific research. Results indicate the efficacy of the approach and highlight a number of fruitful future directions.
ContributorsBliss, Nadya Travinin (Author) / Laubichler, Manfred (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Papandreou-Suppappola, Antonia (Committee member) / Arizona State University (Publisher)
Created2015
Description
The healthcare system in this country is currently unacceptable. New technologies may contribute to reducing cost and improving outcomes. Early diagnosis and treatment represents the least risky option for addressing this issue. Such a technology needs to be inexpensive, highly sensitive, highly specific, and amenable to adoption in a clinic. This thesis explores an immunodiagnostic technology based on highly scalable, non-natural sequence peptide microarrays designed to profile the humoral immune response and address the healthcare problem. The primary aim of this thesis is to explore the ability of these arrays to map continuous (linear) epitopes. I discovered that using a technique termed subsequence analysis where epitopes could be decisively mapped to an eliciting protein with high success rate. This led to the discovery of novel linear epitopes from Plasmodium falciparum (Malaria) and Treponema palladium (Syphilis), as well as validation of previously discovered epitopes in Dengue and monoclonal antibodies. Next, I developed and tested a classification scheme based on Support Vector Machines for development of a Dengue Fever diagnostic, achieving higher sensitivity and specificity than current FDA approved techniques. The software underlying this method is available for download under the BSD license. Following this, I developed a kinetic model for immunosignatures and tested it against existing data driven by previously unexplained phenomena. This model provides a framework and informs ways to optimize the platform for maximum stability and efficiency. I also explored the role of sequence composition in explaining an immunosignature binding profile, determining a strong role for charged residues that seems to have some predictive ability for disease. Finally, I developed a database, software and indexing strategy based on Apache Lucene for searching motif patterns (regular expressions) in large biological databases. These projects as a whole have advanced knowledge of how to approach high throughput immunodiagnostics and provide an example of how technology can be fused with biology in order to affect scientific and health outcomes.
ContributorsRicher, Joshua Amos (Author) / Johnston, Stephen A. (Thesis advisor) / Woodbury, Neal (Committee member) / Stafford, Phillip (Committee member) / Papandreou-Suppappola, Antonia (Committee member) / Arizona State University (Publisher)
Created2014