Matching Items (356)
Description
In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
Description
Functional magnetic resonance imaging (fMRI) has been widely used to measure the retinotopic organization of early visual cortex in the human brain. Previous studies have identified multiple visual field maps (VFMs) based on statistical analysis of fMRI signals, but the resulting geometry has not been fully characterized with mathematical models. This thesis explores using concepts from computational conformal geometry to create a custom software framework for examining and generating quantitative mathematical models for characterizing the geometry of early visual areas in the human brain. The software framework includes a graphical user interface built on top of a selected core conformal flattening algorithm and various software tools compiled specifically for processing and examining retinotopic data. Three conformal flattening algorithms were implemented and evaluated for speed and how well they preserve the conformal metric. All three algorithms performed well in preserving the conformal metric but the speed and stability of the algorithms varied. The software framework performed correctly on actual retinotopic data collected using the standard travelling-wave experiment. Preliminary analysis of the Beltrami coefficient for the early data set shows that selected regions of V1 that contain reasonably smooth eccentricity and polar angle gradients do show significant local conformality, warranting further investigation of this approach for analysis of early and higher visual cortex.
ContributorsTa, Duyan (Author) / Wang, Yalin (Thesis advisor) / Maciejewski, Ross (Committee member) / Wonka, Peter (Committee member) / Arizona State University (Publisher)
Created2013
Description
In blindness research, the corpus callosum (CC) is the most frequently studied sub-cortical structure, due to its important involvement in visual processing. While most callosal analyses from brain structural magnetic resonance images (MRI) are limited to the 2D mid-sagittal slice, we propose a novel framework to capture a complete set of 3D morphological differences in the corpus callosum between two groups of subjects. The CCs are segmented from whole brain T1-weighted MRI and modeled as 3D tetrahedral meshes. The callosal surface is divided into superior and inferior patches on which we compute a volumetric harmonic field by solving the Laplace's equation with Dirichlet boundary conditions. We adopt a refined tetrahedral mesh to compute the Laplacian operator, so our computation can achieve sub-voxel accuracy. Thickness is estimated by tracing the streamlines in the harmonic field. We combine areal changes found using surface tensor-based morphometry and thickness information into a vector at each vertex to be used as a metric for the statistical analysis. Group differences are assessed on this combined measure through Hotelling's T2 test. The method is applied to statistically compare three groups consisting of: congenitally blind (CB), late blind (LB; onset > 8 years old) and sighted (SC) subjects. Our results reveal significant differences in several regions of the CC between both blind groups and the sighted groups; and to a lesser extent between the LB and CB groups. These results demonstrate the crucial role of visual deprivation during the developmental period in reshaping the structural architecture of the CC.
ContributorsXu, Liang (Author) / Wang, Yalin (Thesis advisor) / Maciejewski, Ross (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2013
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 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
Description
Accumulating evidence implicates exposure to adverse childhood experiences in the development of hypocortisolism in the long-term, and researchers are increasingly examining individual-level mechanisms that may underlie, exacerbate or attenuate this relation among at-risk populations. The current study takes a developmentally and theoretically informed approach to examining episodic childhood stressors, inherent and voluntary self-regulation, and physiological reactivity among a longitudinal sample of youth who experienced parental divorce. Participants were drawn from a larger randomized controlled trial of a preventive intervention for children of divorce between the ages of 9 and 12. The current sample included 159 young adults (mean age = 25.5 years; 53% male; 94% Caucasian) who participated in six waves of data collection, including a 15-year follow-up study. Participants reported on exposure to negative life events (four times over a 9-month period) during childhood, and mothers rated child temperament. Six years later, youth reported on the use of active and avoidant coping strategies, and 15 years later, they participated in a standardized psychosocial stress task and provided salivary cortisol samples prior to and following the task. Path analyses within a structural equation framework revealed that a multiple mediation model best fit the data. It was found that children with better mother-rated self-regulation (i.e. low impulsivity, low negative emotionality, and high attentional focus) exhibited lower total cortisol output 15 years later. In addition, greater self-regulation in childhood predicted greater use of active coping in adolescence, whereas a greater number of negative life events predicted increased use of avoidant coping in adolescence. Finally, a greater number of negative events in childhood predicted marginally lower total cortisol output, and higher levels of active coping in adolescence were associated with greater total cortisol output in young adulthood. Findings suggest that children of divorce who exhibit better self-regulation evidence lower cortisol output during a standardized psychosocial stress task relative to those who have higher impulsivity, lower attentional focus, and/or higher negative emotionality. The conceptual significance of the current findings, including the lack of evidence for hypothesized relations, methodological issues that arose, and issues in need of future research are discussed.
ContributorsHagan, Melissa (Author) / Luecken, Linda (Thesis advisor) / MacKinnon, David (Committee member) / Wolchik, Sharlene (Committee member) / Doane, Leah (Committee member) / Arizona State University (Publisher)
Created2013
Description
Over 2 billion people are using online social network services, such as Facebook, Twitter, Google+, LinkedIn, and Pinterest. Users update their status, post their photos, share their information, and chat with others in these social network sites every day; however, not everyone shares the same amount of information. This thesis explores methods of linking publicly available data sources as a means of extrapolating missing information of Facebook. An application named "Visual Friends Income Map" has been created on Facebook to collect social network data and explore geodemographic properties to link publicly available data, such as the US census data. Multiple predictors are implemented to link data sets and extrapolate missing information from Facebook with accurate predictions. The location based predictor matches Facebook users' locations with census data at the city level for income and demographic predictions. Age and relationship based predictors are created to improve the accuracy of the proposed location based predictor utilizing social network link information. In the case where a user does not share any location information on their Facebook profile, a kernel density estimation location predictor is created. This predictor utilizes publicly available telephone record information of all people with the same surname of this user in the US to create a likelihood distribution of the user's location. This is combined with the user's IP level information in order to narrow the probability estimation down to a local regional constraint.
ContributorsMao, Jingxian (Author) / Maciejewski, Ross (Thesis advisor) / Farin, Gerald (Committee member) / Wang, Yalin (Committee member) / Arizona State University (Publisher)
Created2012
Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (Committee member) / Arizona State University (Publisher)
Created2012
Description
In order to analyze data from an instrument administered at multiple time points it is a common practice to form composites of the items at each wave and to fit a longitudinal model to the composites. The advantage of using composites of items is that smaller sample sizes are required in contrast to second order models that include the measurement and the structural relationships among the variables. However, the use of composites assumes that longitudinal measurement invariance holds; that is, it is assumed that that the relationships among the items and the latent variables remain constant over time. Previous studies conducted on latent growth models (LGM) have shown that when longitudinal metric invariance is violated, the parameter estimates are biased and that mistaken conclusions about growth can be made. The purpose of the current study was to examine the impact of non-invariant loadings and non-invariant intercepts on two longitudinal models: the LGM and the autoregressive quasi-simplex model (AR quasi-simplex). A second purpose was to determine if there are conditions in which researchers can reach adequate conclusions about stability and growth even in the presence of violations of invariance. A Monte Carlo simulation study was conducted to achieve the purposes. The method consisted of generating items under a linear curve of factors model (COFM) or under the AR quasi-simplex. Composites of the items were formed at each time point and analyzed with a linear LGM or an AR quasi-simplex model. The results showed that AR quasi-simplex model yielded biased path coefficients only in the conditions with large violations of invariance. The fit of the AR quasi-simplex was not affected by violations of invariance. In general, the growth parameter estimates of the LGM were biased under violations of invariance. Further, in the presence of non-invariant loadings the rejection rates of the hypothesis of linear growth increased as the proportion of non-invariant items and as the magnitude of violations of invariance increased. A discussion of the results and limitations of the study are provided as well as general recommendations.
ContributorsOlivera-Aguilar, Margarita (Author) / Millsap, Roger E. (Thesis advisor) / Levy, Roy (Committee member) / MacKinnon, David (Committee member) / West, Stephen G. (Committee member) / Arizona State University (Publisher)
Created2013
Description
This document presents a new implementation of the Smoothed Particles Hydrodynamics algorithm using DirectX 11 and DirectCompute. The main goal of this document is to present to the reader an alternative solution to the largely studied and researched problem of fluid simulation. Most other solutions have been implemented using the NVIDIA CUDA framework; however, the proposed solution in this document uses the Microsoft general-purpose computing on graphics processing units API. The implementation allows for the simulation of a large number of particles in a real-time scenario. The solution presented here uses the Smoothed Particles Hydrodynamics algorithm to calculate the forces within the fluid; this algorithm provides a Lagrangian approach for discretizes the Navier-Stockes equations into a set of particles. Our solution uses the DirectCompute compute shaders to evaluate each particle using the multithreading and multi-core capabilities of the GPU increasing the overall performance. The solution then describes a method for extracting the fluid surface using the Marching Cubes method and the programmable interfaces exposed by the DirectX pipeline. Particularly, this document presents a method for using the Geometry Shader Stage to generate the triangle mesh as defined by the Marching Cubes method. The implementation results show the ability to simulate over 64K particles at a rate of 900 and 400 frames per second, not including the surface reconstruction steps and including the Marching Cubes steps respectively.
ContributorsFigueroa, Gustavo (Author) / Farin, Gerald (Thesis advisor) / Maciejewski, Ross (Committee member) / Wang, Yalin (Committee member) / Arizona State University (Publisher)
Created2012
Description
Research shows that general parenting practices (e.g., support and discipline), influence adolescent substance use. However, socialization theory suggests that parental socialization occurs not only through general parenting practices, but also through parents' attempts to influence specific behaviors and values. A growing literature supports links between substance-specific parenting and adolescent substance use. For adolescent alcohol use, there are considerable limitations and gaps within this literature. To address these limitations, the present study examined the factor structure of alcohol-specific parenting, investigated the determinants of alcohol-specific parenting, and explored its association with nondrinking adolescents' attitudes about alcohol use. Using a high-risk sample of nondrinking adolescents and their parents, the current study found three dimensions of alcohol-specific parenting using both adolescent and parent reports, but also found evidence of non-invariance across reporters. Results also revealed complex roles of parental alcohol use disorder (AUD; including recovered and current AUD), family history of AUD, and current drinking as determinants of the three dimensions of anti-alcohol parenting behaviors. Moreover, the current study showed that the effects of these determinants varied by the reporter of the parenting behavior. Finally, the current study found the dimensions of alcohol-specific parenting to be unique and significant predictors of nondrinking adolescents' attitudes about alcohol, over and above general parenting practices, parent AUD, and parent current drinking. Given its demonstrated distinctness from general parenting practices, its link with adolescent alcohol attitudes, and its potential malleability, alcohol-specific parenting may be an important complement to interventions targeting parents of adolescents.
ContributorsHandley, Elizabeth D (Author) / Chassin, Laurie (Thesis advisor) / MacKinnon, David (Committee member) / Crnic, Keith (Committee member) / Sandler, Irwin (Committee member) / Arizona State University (Publisher)
Created2012