Matching Items (123)
Description
The RNA editing enzyme adenosine deaminase acting on double stranded RNA 2 (ADAR2) converts adenosine into inosine in regions of double stranded RNA. Here, it was discovered that this critical function of ADAR2 was dysfunctional in amyotrophic lateral sclerosis (ALS) mediated by the C9orf72 hexanucleotide repeat expansion, the most common genetic abnormality associated with ALS. Typically a nuclear protein, ADAR2 was localized in cytoplasmic accumulations in postmortem tissue from C9orf72 ALS patients. The mislocalization of ADAR2 was confirmed using immunostaining in a C9orf72 mouse model and motor neurons differentiated from C9orf72 patient induced pluripotent stem cells. Notably, the cytoplasmic accumulation of ADAR2 coexisted in neurons with cytoplasmic accumulations of TAR DNA binding protein 43 (TDP-43). Interestingly, ADAR2 overexpression in mammalian cell lines induced nuclear depletion and cytoplasmic accumulation of TDP-43, reflective of the pathology observed in ALS patients. The mislocalization of TDP-43 was dependent on the catalytic activity of ADAR2 and the ability of TDP-43 to bind directly to inosine containing RNA. In addition, TDP-43 nuclear export was significantly elevated in cells with increased RNA editing. Together these results describe a novel cellular mechanism by which alterations in RNA editing drive the nuclear export of TDP-43 leading to its cytoplasmic mislocalization. Considering the contribution of cytoplasmic TDP-43 to the pathogenesis of ALS, these findings represent a novel understanding of how the formation of pathogenic cytoplasmic TDP-43 accumulations may be initiated. Further research exploring this mechanism will provide insights into opportunities for novel therapeutic interventions.
ContributorsMoore, Stephen Philip (Author) / Sattler, Rita (Thesis advisor) / Zarnescu, Daniela (Committee member) / Brafman, David (Committee member) / Van Keuren-Jensen, Kendall (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2021
Description
Communicating with computers through thought has been a remarkable achievement in recent years. This was made possible by the use of Electroencephalography (EEG). Brain-computer interface (BCI) relies heavily on Electroencephalography (EEG) signals for communication between humans and computers. With the advent ofdeep learning, many studies recently applied these techniques to EEG data to perform various tasks like emotion recognition, motor imagery classification, sleep analysis, and many more.
Despite the rise of interest in EEG signal classification, very few studies have explored the MindBigData dataset, which collects EEG signals recorded at the stimulus of seeing a digit and thinking about it. This dataset takes us closer to realizing the idea of mind-reading or communication via thought. Thus classifying these signals into the respective digit that the user thinks about is a challenging task. This serves as a motivation to study this dataset and apply existing deep learning techniques to study it.
Given the recent success of transformer architecture in different domains like Computer Vision and Natural language processing, this thesis studies transformer architecture for EEG signal classification. Also, it explores other deep learning
techniques for the same. As a result, the proposed classification pipeline achieves comparable performance with the existing methods.
ContributorsMuglikar, Omkar Dushyant (Author) / Wang, Yalin (Thesis advisor) / Liang, Jianming (Committee member) / Venkateswara, Hemanth (Committee member) / Arizona State University (Publisher)
Created2021
Description
Statistical Shape Modeling is widely used to study the morphometrics of deformable objects in computer vision and biomedical studies. There are mainly two viewpoints to understand the shapes. On one hand, the outer surface of the shape can be taken as a two-dimensional embedding in space. On the other hand, the outer surface along with its enclosed internal volume can be taken as a three-dimensional embedding of interests. Most studies focus on the surface-based perspective by leveraging the intrinsic features on the tangent plane. But a two-dimensional model may fail to fully represent the realistic properties of shapes with both intrinsic and extrinsic properties. In this thesis, severalStochastic Partial Differential Equations (SPDEs) are thoroughly investigated and several methods are originated from these SPDEs to try to solve the problem of both two-dimensional and three-dimensional shape analyses. The unique physical meanings of these SPDEs inspired the findings of features, shape descriptors, metrics, and kernels in this series of works. Initially, the data generation of high-dimensional shapes, here, the tetrahedral meshes, is introduced. The cerebral cortex is taken as the study target and an automatic pipeline of generating the gray matter tetrahedral mesh is introduced. Then, a discretized Laplace-Beltrami operator (LBO) and a Hamiltonian operator (HO) in tetrahedral domain with Finite Element Method (FEM) are derived. Two high-dimensional shape descriptors are defined based on the solution of the heat equation and Schrödinger’s equation. Considering the fact that high-dimensional shape models usually contain massive redundancies, and the demands on effective landmarks in many applications, a Gaussian process landmarking on tetrahedral meshes is further studied. A SIWKS-based metric space is used to define a geometry-aware Gaussian process. The study of the periodic potential diffusion process further inspired the idea of a new kernel call the geometry-aware convolutional kernel. A series of Bayesian learning methods are then introduced to tackle the problem of shape retrieval and classification. Experiments of every single item are demonstrated. From the popular SPDE such as the heat equation and Schrödinger’s equation to the general potential diffusion equation and the specific periodic potential diffusion equation, it clearly shows that classical SPDEs play an important role in discovering new features, metrics, shape descriptors and kernels. I hope this thesis could be an example of using interdisciplinary knowledge to solve problems.
ContributorsFan, Yonghui (Author) / Wang, Yalin (Thesis advisor) / Lepore, Natasha (Committee member) / Turaga, Pavan (Committee member) / Yang, Yezhou (Committee member) / Arizona State University (Publisher)
Created2021
Description
Graph matching is a fundamental but notoriously difficult problem due to its NP-hard nature, and serves as a cornerstone for a series of applications in machine learning and computer vision, such as image matching, dynamic routing, drug design, to name a few. Although there has been massive previous investigation on high-performance graph matching solvers, it still remains a challenging task to tackle the matching problem under real-world scenarios with severe graph uncertainty (e.g., noise, outlier, misleading or ambiguous link).In this dissertation, a main focus is to investigate the essence and propose solutions to graph matching with higher reliability under such uncertainty. To this end, the proposed research was conducted taking into account three perspectives related to reliable graph matching: modeling, optimization and learning. For modeling, graph matching is extended from typical quadratic assignment problem to a more generic mathematical model by introducing a specific family of separable function, achieving higher capacity and reliability. In terms of optimization, a novel high gradient-efficient determinant-based regularization technique is proposed in this research, showing high robustness against outliers. Then learning paradigm for graph matching under intrinsic combinatorial characteristics is explored. First, a study is conducted on the way of filling the gap between discrete problem and its continuous approximation under a deep learning framework. Then this dissertation continues to investigate the necessity of more reliable latent topology of graphs for matching, and propose an effective and flexible framework to obtain it. Coherent findings in this dissertation include theoretical study and several novel algorithms, with rich experiments demonstrating the effectiveness.
ContributorsYu, Tianshu (Author) / Li, Baoxin (Thesis advisor) / Wang, Yalin (Committee member) / Yang, Yezhou (Committee member) / Yang, Yingzhen (Committee member) / Arizona State University (Publisher)
Created2021
Description
Graph matching is a fundamental but notoriously difficult problem due to its NP-hard nature, and serves as a cornerstone for a series of applications in machine learning and computer vision, such as image matching, dynamic routing, drug design, to name a few. Although there has been massive previous investigation on high-performance graph matching solvers, it still remains a challenging task to tackle the matching problem under real-world scenarios with severe graph uncertainty (e.g., noise, outlier, misleading or ambiguous link).In this dissertation, a main focus is to investigate the essence and propose solutions to graph matching with higher reliability under such uncertainty. To this end, the proposed research was conducted taking into account three perspectives related to reliable graph matching: modeling, optimization and learning. For modeling, graph matching is extended from typical quadratic assignment problem to a more generic mathematical model by introducing a specific family of separable function, achieving higher capacity and reliability. In terms of optimization, a novel high gradient-efficient determinant-based regularization technique is proposed in this research, showing high robustness against outliers. Then learning paradigm for graph matching under intrinsic combinatorial characteristics is explored. First, a study is conducted on the way of filling the gap between discrete problem and its continuous approximation under a deep learning framework. Then this dissertation continues to investigate the necessity of more reliable latent topology of graphs for matching, and propose an effective and flexible framework to obtain it. Coherent findings in this dissertation include theoretical study and several novel algorithms, with rich experiments demonstrating the effectiveness.
ContributorsYu, Tianshu (Author) / Li, Baoxin (Thesis advisor) / Wang, Yalin (Committee member) / Yang, Yezhou (Committee member) / Yang, Yingzhen (Committee member) / Arizona State University (Publisher)
Created2021
Description
This dissertation describes a series of four studies on cognitive aging, working memory, and cognitive flexibility in dogs (Canis lupus familiaris) and their wild relatives. In Chapters 2 and 3, I designed assessments for age-related cognitive deficits in pet dogs which can be deployed rapidly using inexpensive and accessible materials. These novel tests can be easily implemented by owners, veterinarians, and clinicians and therefore, may improve care for elderly dogs by aiding in the diagnosis of dementia. In addition, these widely deployable tests may facilitate the use of dementia in pet dogs as a naturally occurring model of Alzheimer’s Disease in humans.In Chapters 4 and 5, I modified one of these tests to demonstrate for the first time that coyotes (Canis latrans) and wolves (Canis lupus lupus) develop age-related deficits in cognitive flexibility. This was an important first step towards differentiating between the genetic and environmental components of dementia in dogs and in turn, humans. Unexpectedly, I also detected cognitive deficits in young, adult dogs and wolves but not coyotes. These finding add to a recent shift in understanding cognitive development in dogs which may improve cognitive aging tests as well as training, care, and use of working and pet dogs. These findings also suggest that the ecology of coyotes may select for flexibility earlier in development.
In Chapter 5, I piloted the use of the same cognitive flexibility test for red and gray foxes so that future studies may test for lifespan changes in the cognition of small-bodied captive canids. More broadly, this paradigm may accommodate physical and behavioral differences between diverse pet and captive animals. In Chapters 4 and 5, I examined which ecological traits drive the evolution of behavioral flexibility and in turn, species resilience. I found that wolves displayed less flexibility than dogs and coyotes suggesting that species which do not rely heavily on unstable resources may be ill-equipped to cope with human habitat modification. Ultimately, this comparative work may help conservation practitioners to identify and protect species that cannot cope with rapid and unnatural environmental change.
ContributorsVan Bourg, Joshua (Author) / Wynne, Clive D (Thesis advisor) / Aktipis, C. Athena (Committee member) / Gilby, Ian C (Committee member) / Young, Julie K (Committee member) / Arizona State University (Publisher)
Created2022
Description
Alzheimer's disease (AD) is a neurodegenerative disease that damages the cognitive abilities of a patient. It is critical to diagnose AD early to begin treatment as soon as possible which can be done through biomarkers. One such biomarker is the beta-amyloid (Aβ) peptide which can be quantified using the centiloid (CL) scale. For identifying the Aβ biomarker, A deep learning model that can model AD progression by predicting the CL value for brain magnetic resonance images (MRIs) is proposed. Brain MRI images can be obtained through the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Open Access Series of Imaging Studies (OASIS) datasets, however a single model cannot perform well on both datasets at once. Thus, A regularization-based continuous learning framework to perform domain adaptation on the previous model is also proposed which captures the latent information about the relationship between Aβ and AD progression within both datasets.
ContributorsTrinh, Matthew Brian (Author) / Wang, Yalin (Thesis advisor) / Liang, Jianming (Committee member) / Su, Yi (Committee member) / Arizona State University (Publisher)
Created2022
Description
The partitioning of photosynthates between their sites of production (source) and their sites of utilization (sink) is a major determinant of crop yield and the potential of regulating this translocation promises substantial opportunities for yield increases. Ubiquitous overexpression of the plant type I proton pyrophosphatase (H+-PPase) in crops improves several valuable traits including salt tolerance and drought resistance, nutrient and water use efficiencies, and increased root biomass and yield. Originally, type I H+-PPases were described as pyrophosphate (PPi)-dependent proton pumps localized exclusively in vacuoles of mesophyll and meristematic tissues. It has been proposed that in the meristematic tissues, the role of this enzyme would be hydrolyzing PPi originated in biosynthetic reactions and favoring sink strength. Interestingly, this enzyme has been also localized at the plasma membrane of companion cells in the phloem which load and transport photosynthates from source leaves to sinks. Of note, the plasma membrane-localized H+-PPase could only function as a PPi-synthase in these cells due to the steep proton gradient between the apoplast and cytosol. The generated PPi would favor active sucrose loading through the sucrose/proton symporter in the phloem by promoting sucrose hydrolysis through the Sucrose Synthase pathway and providing the ATP required to maintain the proton gradient. To better understand these two different roles of type I H+-PPases, a series of Arabidopsis thaliana transgenic plants were generated. By expressing soluble pyrophosphatases in companion cells of Col-0 ecotype and H+-PPase mutants, impaired photosynthates partitioning was observed, suggesting phloem-localized H+-PPase could generate the PPi required for sucrose loading. Col-0 plants expressed with either phloem- or meristem-specific AVP1 overexpression cassette and the cross between the two tissue specific lines (Cross) were generated. The results showed that the phloem-specific AVP1-overexpressing plants had increased root hair elongation under limited nutrient conditions and both phloem- and meristem-overexpression of AVP1 contributed to improved rhizosphere acidification and drought resistance. It was concluded that H+-PPases localized in both sink and source tissues regulate plant growth and performance under stress through its versatile enzymatic functions (PPi hydrolase and synthase).
ContributorsLi, Lin (Author) / Park, Yujin (Thesis advisor) / Mangone, Marco (Committee member) / Roberson, Robert (Committee member) / Vermaas, Willem (Committee member) / Arizona State University (Publisher)
Created2022
Description
The Population Receptive Field (pRF) model is widely used to predict the location (retinotopy) and size of receptive fields on the visual space. Doing so allows for the creation of a mapping from locations in the visual field to the associated groups of neurons in the cortical region (within the visual cortex of the brain). However, using the pRF model is very time consuming. Past research has focused on the creation of Convolutional Neural Networks (CNN) to mimic the pRF model in a fraction of the time, and they have worked well under highly controlled conditions. However, these models have not been thoroughly tested on real human data. This thesis focused on adapting one of these CNNs to accurately predict the retinotopy of a real human subject using a dataset from the Human Connectome Project. The results show promise towards creating a fully functioning CNN, but they also expose new challenges that must be overcome before the model could be used to predict the retinotopy of new human subjects.
ContributorsBurgard, Braeden (Author) / Wang, Yalin (Thesis director) / Ta, Duyan (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / Computer Science and Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2022-05
Description
MicroRNAs (miRNAs) are 17-22 nucleotide non-coding RNAs that regulate gene expression by targeting non-complementary elements in the 3’ untranslated regions (3’UTRs) of mRNAs. miRNAs, which form complex networks of interaction that differ by tissue and developmental stage, display conservation in their function across metazoan species. Yet much remains unknown regarding their biogenesis, localization, strand selection, and their absolute abundance due to the difficulty of detecting and amplifying such small molecules. Here, I used an updated HT qPCR-based methodology to follow miRNA expression of 5p and 3p strands for all 190 C. elegans miRNAs described in miRBase throughout all six developmental stages in triplicates (total of 9,708 experiments), and studied their expression levels, tissue localization, and the rules underlying miRNA strand selection. My study validated previous findings and identified novel, conserved patterns of miRNA strand expression throughout C. elegans development, which at times correlate with previously observed developmental phenotypes. Additionally, my results highlighted novel structural principles underlying strand selection, which can be applied to higher metazoans.
Though optimized for use in C. elegans, this method can be easily adapted to other eukaryotic systems, allowing for more scalable quantitative investigation of miRNA biology and/or miRNA diagnostics.
ContributorsMeadows, Dalton Alexander (Author) / Mangone, Marco (Thesis advisor) / LaBaer, Joshua (Committee member) / Murugan, Vel (Committee member) / Wilson-Rawls, Jeanne (Committee member) / Arizona State University (Publisher)
Created2023