Matching Items (91)
Description
Despite the safe and effective use of attenuated vaccines for over fifty years, measles virus (MV) remains an insidious threat to global health. Problematically, infants less than one year of age, who are the most prone to severe infection and death by measles, cannot be immunized using current MV vaccines. For this dissertation, I generated and performed preclinical evaluation of two novel MV vaccine candidates. Based on data from clinical trials that showed increasing the dosage of current MV vaccines improved antibody responses in six-month-old recipients, I hypothesized that increasing the relevant antigenic stimulus of a standard titer dose would allow safe and effective immunization at a younger age. I generated two modified MVs with increased expression of the hemagglutinin (H) protein, the most important viral antigen for inducing protective neutralizing immunity, in the background of a current vaccine-equivalent. One virus, MVvac2-H2, expressed higher levels of full-length H, resulting in a three-fold increase in H incorporation into virions, while the second, MVvac2-Hsol, expressed and secreted truncated, soluble H protein to its extracellular environment. The alteration to the virion envelope of MVvac2-H2 conferred upon that virus a measurable resistance to in vitro neutralization. In initial screening in adult mouse models of vaccination, both modified MVs proved more immunogenic than their parental strain in outbred mice, while MVvac2-H2 additionally proved more immunogenic in the gold standard MV-susceptible mouse model. Remarkably, MVvac2-H2 better induced protective immunity in the presence of low levels of artificially introduced passive immunity that mimic the passive maternal immunity that currently limits vaccination of young infants, and that strongly inhibited responses to the current vaccine-equivalent. Finally, I developed a more physiological infant-like mouse model for MV vaccine testing, in which MV-susceptible dams vaccinated with the current vaccine-equivalent transfer passive immunity to their pups. This model will allow additional preclinical evaluation of the performance of MVvac2-H2 in pups of immune dams. Altogether, in this dissertation I identify a promising candidate, MVvac2-H2, for a next generation measles vaccine.
ContributorsJulik, Emily (Author) / Reyes del Valle, Jorge (Thesis advisor) / Chang, Yung (Committee member) / Blattman, Joseph (Committee member) / Hogue, Brenda (Committee member) / Nickerson, Cheryl (Committee member) / Arizona State University (Publisher)
Created2016
Description
Understanding the complexity of temporal and spatial characteristics of gene expression over brain development is one of the crucial research topics in neuroscience. An accurate description of the locations and expression status of relative genes requires extensive experiment resources. The Allen Developing Mouse Brain Atlas provides a large number of in situ hybridization (ISH) images of gene expression over seven different mouse brain developmental stages. Studying mouse brain models helps us understand the gene expressions in human brains. This atlas collects about thousands of genes and now they are manually annotated by biologists. Due to the high labor cost of manual annotation, investigating an efficient approach to perform automated gene expression annotation on mouse brain images becomes necessary. In this thesis, a novel efficient approach based on machine learning framework is proposed. Features are extracted from raw brain images, and both binary classification and multi-class classification models are built with some supervised learning methods. To generate features, one of the most adopted methods in current research effort is to apply the bag-of-words (BoW) algorithm. However, both the efficiency and the accuracy of BoW are not outstanding when dealing with large-scale data. Thus, an augmented sparse coding method, which is called Stochastic Coordinate Coding, is adopted to generate high-level features in this thesis. In addition, a new multi-label classification model is proposed in this thesis. Label hierarchy is built based on the given brain ontology structure. Experiments have been conducted on the atlas and the results show that this approach is efficient and classifies the images with a relatively higher accuracy.
ContributorsZhao, Xinlin (Author) / Ye, Jieping (Thesis advisor) / Wang, Yalin (Thesis advisor) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2016
Description
The rapid growth of social media in recent years provides a large amount of user-generated visual objects, e.g., images and videos. Advanced semantic understanding approaches on such visual objects are desired to better serve applications such as human-machine interaction, image retrieval, etc. Semantic visual attributes have been proposed and utilized in multiple visual computing tasks to bridge the so-called "semantic gap" between extractable low-level feature representations and high-level semantic understanding of the visual objects.
Despite years of research, there are still some unsolved problems on semantic attribute learning. First, real-world applications usually involve hundreds of attributes which requires great effort to acquire sufficient amount of labeled data for model learning. Second, existing attribute learning work for visual objects focuses primarily on images, with semantic analysis on videos left largely unexplored.
In this dissertation I conduct innovative research and propose novel approaches to tackling the aforementioned problems. In particular, I propose robust and accurate learning frameworks on both attribute ranking and prediction by exploring the correlation among multiple attributes and utilizing various types of label information. Furthermore, I propose a video-based skill coaching framework by extending attribute learning to the video domain for robust motion skill analysis. Experiments on various types of applications and datasets and comparisons with multiple state-of-the-art baseline approaches confirm that my proposed approaches can achieve significant performance improvements for the general attribute learning problem.
Despite years of research, there are still some unsolved problems on semantic attribute learning. First, real-world applications usually involve hundreds of attributes which requires great effort to acquire sufficient amount of labeled data for model learning. Second, existing attribute learning work for visual objects focuses primarily on images, with semantic analysis on videos left largely unexplored.
In this dissertation I conduct innovative research and propose novel approaches to tackling the aforementioned problems. In particular, I propose robust and accurate learning frameworks on both attribute ranking and prediction by exploring the correlation among multiple attributes and utilizing various types of label information. Furthermore, I propose a video-based skill coaching framework by extending attribute learning to the video domain for robust motion skill analysis. Experiments on various types of applications and datasets and comparisons with multiple state-of-the-art baseline approaches confirm that my proposed approaches can achieve significant performance improvements for the general attribute learning problem.
ContributorsChen, Lin (Author) / Li, Baoxin (Thesis advisor) / Turaga, Pavan (Committee member) / Wang, Yalin (Committee member) / Liu, Huan (Committee member) / Arizona State University (Publisher)
Created2016
Description
In many fields one needs to build predictive models for a set of related machine learning tasks, such as information retrieval, computer vision and biomedical informatics. Traditionally these tasks are treated independently and the inference is done separately for each task, which ignores important connections among the tasks. Multi-task learning aims at simultaneously building models for all tasks in order to improve the generalization performance, leveraging inherent relatedness of these tasks. In this thesis, I firstly propose a clustered multi-task learning (CMTL) formulation, which simultaneously learns task models and performs task clustering. I provide theoretical analysis to establish the equivalence between the CMTL formulation and the alternating structure optimization, which learns a shared low-dimensional hypothesis space for different tasks. Then I present two real-world biomedical informatics applications which can benefit from multi-task learning. In the first application, I study the disease progression problem and present multi-task learning formulations for disease progression. In the formulations, the prediction at each point is a regression task and multiple tasks at different time points are learned simultaneously, leveraging the temporal smoothness among the tasks. The proposed formulations have been tested extensively on predicting the progression of the Alzheimer's disease, and experimental results demonstrate the effectiveness of the proposed models. In the second application, I present a novel data-driven framework for densifying the electronic medical records (EMR) to overcome the sparsity problem in predictive modeling using EMR. The densification of each patient is a learning task, and the proposed algorithm simultaneously densify all patients. As such, the densification of one patient leverages useful information from other patients.
ContributorsZhou, Jiayu (Author) / Ye, Jieping (Thesis advisor) / Mittelmann, Hans (Committee member) / Li, Baoxin (Committee member) / Wang, Yalin (Committee member) / Arizona State University (Publisher)
Created2014
Description
Many learning models have been proposed for various tasks in visual computing. Popular examples include hidden Markov models and support vector machines. Recently, sparse-representation-based learning methods have attracted a lot of attention in the computer vision field, largely because of their impressive performance in many applications. In the literature, many of such sparse learning methods focus on designing or application of some learning techniques for certain feature space without much explicit consideration on possible interaction between the underlying semantics of the visual data and the employed learning technique. Rich semantic information in most visual data, if properly incorporated into algorithm design, should help achieving improved performance while delivering intuitive interpretation of the algorithmic outcomes. My study addresses the problem of how to explicitly consider the semantic information of the visual data in the sparse learning algorithms. In this work, we identify four problems which are of great importance and broad interest to the community. Specifically, a novel approach is proposed to incorporate label information to learn a dictionary which is not only reconstructive but also discriminative; considering the formation process of face images, a novel image decomposition approach for an ensemble of correlated images is proposed, where a subspace is built from the decomposition and applied to face recognition; based on the observation that, the foreground (or salient) objects are sparse in input domain and the background is sparse in frequency domain, a novel and efficient spatio-temporal saliency detection algorithm is proposed to identify the salient regions in video; and a novel hidden Markov model learning approach is proposed by utilizing a sparse set of pairwise comparisons among the data, which is easier to obtain and more meaningful, consistent than tradition labels, in many scenarios, e.g., evaluating motion skills in surgical simulations. In those four problems, different types of semantic information are modeled and incorporated in designing sparse learning algorithms for the corresponding visual computing tasks. Several real world applications are selected to demonstrate the effectiveness of the proposed methods, including, face recognition, spatio-temporal saliency detection, abnormality detection, spatio-temporal interest point detection, motion analysis and emotion recognition. In those applications, data of different modalities are involved, ranging from audio signal, image to video. Experiments on large scale real world data with comparisons to state-of-art methods confirm the proposed approaches deliver salient advantages, showing adding those semantic information dramatically improve the performances of the general sparse learning methods.
ContributorsZhang, Qiang (Author) / Li, Baoxin (Thesis advisor) / Turaga, Pavan (Committee member) / Wang, Yalin (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2014
Description
In this thesis, the application of pixel-based vertical axes used within parallel coordinate plots is explored in an attempt to improve how existing tools can explain complex multivariate interactions across temporal data. Several promising visualization techniques are combined, such as: visual boosting to allow for quicker consumption of large data sets, the bond energy algorithm to find finer patterns and anomalies through contrast, multi-dimensional scaling, flow lines, user guided clustering, and row-column ordering. User input is applied on precomputed data sets to provide for real time interaction. General applicability of the techniques are tested against industrial trade, social networking, financial, and sparse data sets of varying dimensionality.
ContributorsHayden, Thomas (Author) / Maciejewski, Ross (Thesis advisor) / Wang, Yalin (Committee member) / Runger, George C. (Committee member) / Mack, Elizabeth (Committee member) / Arizona State University (Publisher)
Created2014
Description
Sparse learning is a powerful tool to generate models of high-dimensional data with high interpretability, and it has many important applications in areas such as bioinformatics, medical image processing, and computer vision. Recently, the a priori structural information has been shown to be powerful for improving the performance of sparse learning models. A graph is a fundamental way to represent structural information of features. This dissertation focuses on graph-based sparse learning. The first part of this dissertation aims to integrate a graph into sparse learning to improve the performance. Specifically, the problem of feature grouping and selection over a given undirected graph is considered. Three models are proposed along with efficient solvers to achieve simultaneous feature grouping and selection, enhancing estimation accuracy. One major challenge is that it is still computationally challenging to solve large scale graph-based sparse learning problems. An efficient, scalable, and parallel algorithm for one widely used graph-based sparse learning approach, called anisotropic total variation regularization is therefore proposed, by explicitly exploring the structure of a graph. The second part of this dissertation focuses on uncovering the graph structure from the data. Two issues in graphical modeling are considered. One is the joint estimation of multiple graphical models using a fused lasso penalty and the other is the estimation of hierarchical graphical models. The key technical contribution is to establish the necessary and sufficient condition for the graphs to be decomposable. Based on this key property, a simple screening rule is presented, which reduces the size of the optimization problem, dramatically reducing the computational cost.
ContributorsYang, Sen (Author) / Ye, Jieping (Thesis advisor) / Wonka, Peter (Thesis advisor) / Wang, Yalin (Committee member) / Li, Jing (Committee member) / Arizona State University (Publisher)
Created2014
Description
Tessellation and Screen-Space Ambient Occlusion are algorithms which have been widely-used in real-time rendering in the past decade. They aim to enhance the details of the mesh, cast better shadow effects and improve the quality of the rendered images in real time. WebGL is a web-based graphics library derived from OpenGL ES used for rendering in web applications. It is relatively new and has been rapidly evolving, this has resulted in it supporting a subset of rendering features normally supported by desktop applications. In this thesis, the research is focusing on evaluating Curved PN-Triangles tessellation with Screen Space Ambient Occlusion (SSAO), Horizon-Based Ambient Occlusion (HBAO) and Horizon-Based Ambient Occlusion Plus (HBAO+) in WebGL-based real-time application and comparing its performance to desktop based application and to discuss the capabilities, limitations and bottlenecks of WebGL 1.0.
ContributorsLi, Chenyang (Author) / Amresh, Ashish (Thesis advisor) / Wang, Yalin (Thesis advisor) / Kobayashi, Yoshihiro (Committee member) / Arizona State University (Publisher)
Created2017
Description
Many Fic domain proteins, through catalyzing post translational modifications (PTM) of protein substrates, functionally contribute to bacterial pathogenesis and the regulation of bacterial growth. Furthermore, one form of Fic-mediated regulation is the Fic toxin-antitoxin system, whereby an antitoxin interacts with and inhibits the Fic toxin. This study sought to determine the functional importance of Mycobacterium tuberculosis Fic and its putative antitoxin protein, Rv3642c. Using M. tuberculosis H37Rv genetic deletion mutants, fic and Rv3642c were demonstrated to promote intracellular survival in human THP-1 macrophage-like cells. Unlike other Fic toxins, of Fic toxin-antitoxin systems, Fic did not inhibit bacterial growth in vitro in the absence of Rv3642c. Notably, Fic demonstrated in vitro AMPylation of a THP-1 cell extract protein as shown by immunodetection. Fic also exhibited auto-AMPylation activity. Interestingly, a mutation of the conserved histidine in the Fic domain motif, a residue previously shown to be critical for AMPylation, had no effect on Fic-mediated ATP hydrolysis or AMPylation activity. Rv3642c was demonstrated to form a complex with Fic when co-expressed in Escherichia coli, indicating a toxin-antitoxin interaction. Screening M. tuberculosis protein fractions and culture filtrate with α-Fic and α-Rv3642c rabbit antisera did not detect monomers of Fic or Rv3642c, thus the cellular localization of Fic and the Rv3642c-Fic complex remains unclear. The results of this study provide insight into the function of M. tuberculosis Fic, and suggest that Fic and Rv3642c are important for M. tuberculosis survival in the intracellular macrophage environment. Furthermore, these findings challenge the current dogma that Fic domain catalysis is dependent on the conserved histidine of the Fic motif.
ContributorsLaMarca, Ryan (Author) / Haydel, Shelley (Thesis advisor) / Lake, Douglas (Committee member) / Nickerson, Cheryl (Committee member) / Arizona State University (Publisher)
Created2017
Description
While techniques for reading DNA in some capacity has been possible for decades,
the ability to accurately edit genomes at scale has remained elusive. Novel techniques
have been introduced recently to aid in the writing of DNA sequences. While writing
DNA is more accessible, it still remains expensive, justifying the increased interest in
in silico predictions of cell behavior. In order to accurately predict the behavior of
cells it is necessary to extensively model the cell environment, including gene-to-gene
interactions as completely as possible.
Significant algorithmic advances have been made for identifying these interactions,
but despite these improvements current techniques fail to infer some edges, and
fail to capture some complexities in the network. Much of this limitation is due to
heavily underdetermined problems, whereby tens of thousands of variables are to be
inferred using datasets with the power to resolve only a small fraction of the variables.
Additionally, failure to correctly resolve gene isoforms using short reads contributes
significantly to noise in gene quantification measures.
This dissertation introduces novel mathematical models, machine learning techniques,
and biological techniques to solve the problems described above. Mathematical
models are proposed for simulation of gene network motifs, and raw read simulation.
Machine learning techniques are shown for DNA sequence matching, and DNA
sequence correction.
Results provide novel insights into the low level functionality of gene networks. Also
shown is the ability to use normalization techniques to aggregate data for gene network
inference leading to larger data sets while minimizing increases in inter-experimental
noise. Results also demonstrate that high error rates experienced by third generation
sequencing are significantly different than previous error profiles, and that these errors can be modeled, simulated, and rectified. Finally, techniques are provided for amending this DNA error that preserve the benefits of third generation sequencing.
the ability to accurately edit genomes at scale has remained elusive. Novel techniques
have been introduced recently to aid in the writing of DNA sequences. While writing
DNA is more accessible, it still remains expensive, justifying the increased interest in
in silico predictions of cell behavior. In order to accurately predict the behavior of
cells it is necessary to extensively model the cell environment, including gene-to-gene
interactions as completely as possible.
Significant algorithmic advances have been made for identifying these interactions,
but despite these improvements current techniques fail to infer some edges, and
fail to capture some complexities in the network. Much of this limitation is due to
heavily underdetermined problems, whereby tens of thousands of variables are to be
inferred using datasets with the power to resolve only a small fraction of the variables.
Additionally, failure to correctly resolve gene isoforms using short reads contributes
significantly to noise in gene quantification measures.
This dissertation introduces novel mathematical models, machine learning techniques,
and biological techniques to solve the problems described above. Mathematical
models are proposed for simulation of gene network motifs, and raw read simulation.
Machine learning techniques are shown for DNA sequence matching, and DNA
sequence correction.
Results provide novel insights into the low level functionality of gene networks. Also
shown is the ability to use normalization techniques to aggregate data for gene network
inference leading to larger data sets while minimizing increases in inter-experimental
noise. Results also demonstrate that high error rates experienced by third generation
sequencing are significantly different than previous error profiles, and that these errors can be modeled, simulated, and rectified. Finally, techniques are provided for amending this DNA error that preserve the benefits of third generation sequencing.
ContributorsFaucon, Philippe Christophe (Author) / Liu, Huan (Thesis advisor) / Wang, Xiao (Committee member) / Crook, Sharon M (Committee member) / Wang, Yalin (Committee member) / Sarjoughian, Hessam S. (Committee member) / Arizona State University (Publisher)
Created2017