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Description
Sparsity has become an important modeling tool in areas such as genetics, signal and audio processing, medical image processing, etc. Via the penalization of l-1 norm based regularization, the structured sparse learning algorithms can produce highly accurate models while imposing various predefined structures on the data, such as feature groups

Sparsity has become an important modeling tool in areas such as genetics, signal and audio processing, medical image processing, etc. Via the penalization of l-1 norm based regularization, the structured sparse learning algorithms can produce highly accurate models while imposing various predefined structures on the data, such as feature groups or graphs. In this thesis, I first propose to solve a sparse learning model with a general group structure, where the predefined groups may overlap with each other. Then, I present three real world applications which can benefit from the group structured sparse learning technique. In the first application, I study the Alzheimer's Disease diagnosis problem using multi-modality neuroimaging data. In this dataset, not every subject has all data sources available, exhibiting an unique and challenging block-wise missing pattern. In the second application, I study the automatic annotation and retrieval of fruit-fly gene expression pattern images. Combined with the spatial information, sparse learning techniques can be used to construct effective representation of the expression images. In the third application, I present a new computational approach to annotate developmental stage for Drosophila embryos in the gene expression images. In addition, it provides a stage score that enables one to more finely annotate each embryo so that they are divided into early and late periods of development within standard stage demarcations. Stage scores help us to illuminate global gene activities and changes much better, and more refined stage annotations improve our ability to better interpret results when expression pattern matches are discovered between genes.
ContributorsYuan, Lei (Author) / Ye, Jieping (Thesis advisor) / Wang, Yalin (Committee member) / Xue, Guoliang (Committee member) / Kumar, Sudhir (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Continuous monitoring in the adequate temporal and spatial scale is necessary for a better understanding of environmental variations. But field deployments of molecular biological analysis platforms in that scale are currently hindered because of issues with power, throughput and automation. Currently, such analysis is performed by the collection of large

Continuous monitoring in the adequate temporal and spatial scale is necessary for a better understanding of environmental variations. But field deployments of molecular biological analysis platforms in that scale are currently hindered because of issues with power, throughput and automation. Currently, such analysis is performed by the collection of large sample volumes from over a wide area and transporting them to laboratory testing facilities, which fail to provide any real-time information. This dissertation evaluates the systems currently utilized for in-situ field analyses and the issues hampering the successful deployment of such bioanalytial instruments for environmental applications. The design and development of high throughput, low power, and autonomous Polymerase Chain Reaction (PCR) instruments, amenable for portable field operations capable of providing quantitative results is presented here as part of this dissertation. A number of novel innovations have been reported here as part of this work in microfluidic design, PCR thermocycler design, optical design and systems integration. Emulsion microfluidics in conjunction with fluorinated oils and Teflon tubing have been used for the fluidic module that reduces cross-contamination eliminating the need for disposable components or constant cleaning. A cylindrical heater has been designed with the tubing wrapped around fixed temperature zones enabling continuous operation. Fluorescence excitation and detection have been achieved by using a light emitting diode (LED) as the excitation source and a photomultiplier tube (PMT) as the detector. Real-time quantitative PCR results were obtained by using multi-channel fluorescence excitation and detection using LED, optical fibers and a 64-channel multi-anode PMT for measuring continuous real-time fluorescence. The instrument was evaluated by comparing the results obtained with those obtained from a commercial instrument and found to be comparable. To further improve the design and enhance its field portability, this dissertation also presents a framework for the instrumentation necessary for a portable digital PCR platform to achieve higher throughputs with lower power. Both systems were designed such that it can easily couple with any upstream platform capable of providing nucleic acid for analysis using standard fluidic connections. Consequently, these instruments can be used not only in environmental applications, but portable diagnostics applications as well.
ContributorsRay, Tathagata (Author) / Youngbull, Cody (Thesis advisor) / Goryll, Michael (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in

Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in the encoding gradient waveforms. This causes sampling discrepancies between the actual and the ideal k-space trajectory. Reconstruction assuming an ideal trajectory can result in shading and blurring artifacts in spiral images. Current methods to estimate such hardware errors require many modifications to the pulse sequence, phantom measurements or specialized hardware. This work presents a new method to estimate time-varying system delays for spiral-based trajectories. It requires a minor modification of a conventional stack-of-spirals sequence and analyzes data collected on three orthogonal cylinders. The method is fast, robust to off-resonance effects, requires no phantom measurements or specialized hardware and estimate variable system delays for the three gradient channels over the data-sampling period. The initial results are presented for acquired phantom and in-vivo data, which show a substantial reduction in the artifacts and improvement in the image quality.
ContributorsBhavsar, Payal (Author) / Pipe, James G (Thesis advisor) / Frakes, David (Committee member) / Kodibagkar, Vikram (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After

Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After developing an algorithm for obtaining calcium scores from a CTA exam, a dual energy CTA exam was performed on patients at dose levels equivalent to levels for single energy CTA with a calcium scoring exam. Calcium Agatston scores obtained from the dual energy CTA exam were within ±11% of scores obtained with conventional calcium scoring exams. In the presence of highly attenuating coronary calcium plaques, the virtual non-calcium images obtained with dual energy CTA were able to successfully measure percent coronary stenosis within 5% of known stenosis values, which is not possible with single energy CTA images due to the presence of the calcium blooming artifact. After fabricating an anthropomorphic beating heart phantom with coronary plaques, characterization of soft plaque vulnerability to rupture or erosion was demonstrated with measurements of the distance from soft plaque to aortic ostium, percent stenosis, and percent lipid volume in soft plaque. A classification model was developed, with training data from the beating heart phantom and plaques, which utilized support vector machines to classify coronary soft plaque pixels as lipid or fibrous. Lipid versus fibrous classification with single energy CTA images exhibited a 17% error while dual energy CTA images in the classification model developed here only exhibited a 4% error. Combining the calcium blooming correction and the percent lipid volume methods developed in this work will provide physicians with metrics for increasing the positive predictive value of coronary CTA as well as expanding the use of coronary CTA to patients with highly attenuating calcium plaques.
ContributorsBoltz, Thomas (Author) / Frakes, David (Thesis advisor) / Towe, Bruce (Committee member) / Kodibagkar, Vikram (Committee member) / Pavlicek, William (Committee member) / Bouman, Charles (Committee member) / Arizona State University (Publisher)
Created2013
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Description
This work presents two complementary studies that propose heuristic methods to capture characteristics of data using the ensemble learning method of random forest. The first study is motivated by the problem in education of determining teacher effectiveness in student achievement. Value-added models (VAMs), constructed as linear mixed models, use students’

This work presents two complementary studies that propose heuristic methods to capture characteristics of data using the ensemble learning method of random forest. The first study is motivated by the problem in education of determining teacher effectiveness in student achievement. Value-added models (VAMs), constructed as linear mixed models, use students’ test scores as outcome variables and teachers’ contributions as random effects to ascribe changes in student performance to the teachers who have taught them. The VAMs teacher score is the empirical best linear unbiased predictor (EBLUP). This approach is limited by the adequacy of the assumed model specification with respect to the unknown underlying model. In that regard, this study proposes alternative ways to rank teacher effects that are not dependent on a given model by introducing two variable importance measures (VIMs), the node-proportion and the covariate-proportion. These VIMs are novel because they take into account the final configuration of the terminal nodes in the constitutive trees in a random forest. In a simulation study, under a variety of conditions, true rankings of teacher effects are compared with estimated rankings obtained using three sources: the newly proposed VIMs, existing VIMs, and EBLUPs from the assumed linear model specification. The newly proposed VIMs outperform all others in various scenarios where the model was misspecified. The second study develops two novel interaction measures. These measures could be used within but are not restricted to the VAM framework. The distribution-based measure is constructed to identify interactions in a general setting where a model specification is not assumed in advance. In turn, the mean-based measure is built to estimate interactions when the model specification is assumed to be linear. Both measures are unique in their construction; they take into account not only the outcome values, but also the internal structure of the trees in a random forest. In a separate simulation study, under a variety of conditions, the proposed measures are found to identify and estimate second-order interactions.
ContributorsValdivia, Arturo (Author) / Eubank, Randall (Thesis advisor) / Young, Dennis (Committee member) / Reiser, Mark R. (Committee member) / Kao, Ming-Hung (Committee member) / Broatch, Jennifer (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The objective of this research is to investigate the relationship among key process design variables associated with the development of nanoscale electrospun polymeric scaffolds capable of tissue regeneration. To date, there has been no systematic approach toward understanding electrospinning process parameters responsible for the production of 3-D nanoscaffold architectures with

The objective of this research is to investigate the relationship among key process design variables associated with the development of nanoscale electrospun polymeric scaffolds capable of tissue regeneration. To date, there has been no systematic approach toward understanding electrospinning process parameters responsible for the production of 3-D nanoscaffold architectures with desired levels quality assurance envisioned to satisfy emerging regenerative medicine market needs. , As such, this study encompassed a more systematic, rational design of experiment (DOE) approach toward the identification of electrospinning process conditions responsible for the production of dextran-polyacrylic acid (DEX-PAA) nanoscaffolds with desired architectures and tissue engineering properties. The latter includes scaffold fiber diameter, pore size, porosity, and degree of crosslinking that together can provide a range of scaffold nanomechanical properties that closely mimics the cell microenvironment. The results obtained from this preliminary DOE study indicate that there exist electrospinning operation conditions capable of producing Dex-PAA nanoarchitecture having potential utility for regenerative medicine applications.
ContributorsEspinoza, Roberta (Author) / Pizziconi, Vincent (Thesis advisor) / Massia, Stephen (Committee member) / Garcia, Antonio (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The overall goal of this research project was to assess the feasibility of investigating the effects of microgravity on mineralization systems in unit gravity environments. If possible to perform these studies in unit gravity earth environments, such as earth, such systems can offer markedly less costly and more concerted research

The overall goal of this research project was to assess the feasibility of investigating the effects of microgravity on mineralization systems in unit gravity environments. If possible to perform these studies in unit gravity earth environments, such as earth, such systems can offer markedly less costly and more concerted research efforts to study these vitally important systems. Expected outcomes from easily accessible test environments and more tractable studies include the development of more advanced and adaptive material systems, including biological systems, particularly as humans ponder human exploration in deep space. The specific focus of the research was the design and development of a prototypical experimental test system that could preliminarily meet the challenging design specifications required of such test systems. Guided by a more unified theoretical foundation and building upon concept design and development heuristics, assessment of the feasibility of two experimental test systems was explored. Test System I was a rotating wall reactor experimental system that closely followed the specifications of a similar test system, Synthecon, designed by NASA contractors and thus closely mimicked microgravity conditions of the space shuttle and station. The latter includes terminal velocity conditions experienced by both innate material systems, as well as, biological systems, including living tissue and humans but has the ability to extend to include those material test systems associated with mineralization processes. Test System II is comprised of a unique vertical column design that offered more easily controlled fluid mechanical test conditions over a much wider flow regime that was necessary to achieving terminal velocities under free convection-less conditions that are important in mineralization processes. Preliminary results indicate that Test System II offers distinct advantages in studying microgravity effects in test systems operating in unit gravity environments and particularly when investigating mineralization and related processes. Verification of the Test System II was performed on validating microgravity effects on calcite mineralization processes reported earlier others. There studies were conducted on calcite mineralization in fixed-wing, reduced gravity aircraft, known as the `vomit comet' where reduced gravity conditions are include for very short (~20second) time periods. Preliminary results indicate that test systems, such as test system II, can be devised to assess microgravity conditions in unit gravity environments, such as earth. Furthermore, the preliminary data obtained on calcite formation suggest that strictly physicochemical mechanisms may be the dominant factors that control adaptation in materials processes, a theory first proposed by Liu et al. Thus the result of this study may also help shine a light on the problem of early osteoporosis in astronauts and long term interest in deep space exploration.
ContributorsSeyedmadani, Kimia (Author) / Pizziconi, Vincent (Thesis advisor) / Towe, Bruce (Committee member) / Alford, Terry (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering

Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering highly specific targets is the application of phage display utilizing single chain variable fragment antibodies (scFv). The aim of this research was to employ phage display to identify pathologies related to traumatic brain injury (TBI), particularly astrogliosis. A unique biopanning method against viable astrocyte cultures activated with TGF-β achieved this aim. Four scFv clones of interest showed varying relative affinities toward astrocytes. One of those four showed the ability to identify reactive astroctyes over basal astrocytes through max signal readings, while another showed a statistical significance in max signal reading toward basal astrocytes. Future studies will include further affinity characterization assays. This work contributes to the development of targeting therapeutics and diagnostics for TBI.
ContributorsMarsh, William (Author) / Stabenfeldt, Sarah (Thesis advisor) / Caplan, Michael (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response

The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response characteristics, inter-subject variability, consistency of effect across outcome measures, and day-to-day variability. Eight subjects with PD and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS) and at three reduced amplitude conditions: approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively). Overall symptom severity and performance on a battery of motor tasks - gait, postural control, single-joint flexion-extension, postural tremor, and tapping - were assessed at each condition using the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and quantitative measures. Data were analyzed to determine whether subjects demonstrated a threshold response (one decrement in stimulation resulted in ≥ 70% of the maximum change) or a graded response to reduced stimulation. Day-to-day variability was assessed using the CDS data from the three testing sessions. Although the cohort as a whole demonstrated a graded response on several measures, there was high variability across subjects, with subsets exhibiting graded, threshold, or minimal responses. Some subjects experienced greater variability in their CDS performance across the three days than the change induced by reducing stimulation. For several tasks, a subset of subjects exhibited improved performance at one or more of the reduced conditions. Reducing stimulation did not affect all subjects equally, nor did it uniformly affect each subject's performance across tasks. These results indicate that altered recruitment of neural structures can differentially affect motor capabilities and demonstrate the need for clinical consideration of the effects on multiple symptoms across several days when selecting DBS parameters.
ContributorsConovaloff, Alison (Author) / Abbas, James (Thesis advisor) / Krishnamurthi, Narayanan (Committee member) / Mahant, Padma (Committee member) / Jung, Ranu (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
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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

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