Matching Items (5)
Description
Solution conformations and dynamics of proteins and protein-DNA complexes are often difficult to predict from their crystal structures. The crystal structure only shows a snapshot of the different conformations these biological molecules can have in solution. Multiple different conformations can exist in solution and potentially have more importance in the biological activity. DNA sliding clamps are a family of proteins with known crystal structures. These clamps encircle the DNA and enable other proteins to interact more efficiently with the DNA. Eukaryotic PCNA and prokaryotic β clamp are two of these clamps, some of the most stable homo-oligomers known. However, their solution stability and conformational equilibrium have not been investigated in depth before. Presented here are the studies involving two sliding clamps: yeast PCNA and bacterial β clamp. These studies show that the β clamp has a very different solution stability than PCNA. These conclusions were reached through various different fluorescence-based experiments, including fluorescence correlation spectroscopy (FCS), Förster resonance energy transfer (FRET), single molecule fluorescence, and various time resolved fluorescence techniques. Interpretations of these, and all other, fluorescence-based experiments are often affected by the properties of the fluorophores employed. Often the fluorescence properties of these fluorophores are influenced by their microenvironments. Fluorophores are known to sometimes interact with biological molecules, and this can have pronounced effects on the rotational mobility and photophysical properties of the dye. Misunderstanding the effect of these photophysical and rotational properties can lead to a misinterpretation of the obtained data. In this thesis, photophysical behaviors of various organic dyes were studied in the presence of deoxymononucleotides to examine more closely how interactions between fluorophores and DNA bases can affect fluorescent properties. Furthermore, the properties of cyanine dyes when bound to DNA and the effect of restricted rotation on FRET are presented in this thesis. This thesis involves studying fluorophore photophysics in various microenvironments and then expanding into the solution stability and dynamics of the DNA sliding clamps.
ContributorsRanjit, Suman (Author) / Levitus, Marcia (Thesis advisor) / Lindsay, Stuart (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
Description
Over the past few decades, medical imaging is becoming important in medicine for disease diagnosis, prognosis, treatment assessment and health monitoring. As medical imaging has progressed, imaging biomarkers are being rapidly developed for early diagnosis and staging of disease. Detecting and segmenting objects from images are often the first steps in quantitative measurement of these biomarkers. While large objects can often be automatically or semi-automatically delineated, segmenting small objects (blobs) is challenging. The small object of particular interest in this dissertation are glomeruli from kidney magnetic resonance (MR) images. This problem has its unique challenges. First of all, the size of glomeruli is extremely small and very similar with noises from images. Second, there are massive of glomeruli in kidney, e.g. over 1 million glomeruli in human kidney, and the intensity distribution is heterogenous. A third recognized issue is that a large portion of glomeruli are overlapping and touched in images. The goal of this dissertation is to develop computational algorithms to identify and discover glomeruli related imaging biomarkers. The first phase is to develop a U-net joint with Hessian based Difference of Gaussians (UH-DoG) blob detector. Joining effort from deep learning alleviates the over-detection issue from Hessian analysis. Next, as extension of UH-DoG, a small blob detector using Bi-Threshold Constrained Adaptive Scales (BTCAS) is proposed. Deep learning is treated as prior of Difference of Gaussian (DoG) to improve its efficiency. By adopting BTCAS, under-segmentation issue of deep learning is addressed. The second phase is to develop a denoising convexity-consistent Blob Generative Adversarial Network (BlobGAN). BlobGAN could achieve high denoising performance and selectively denoise the image without affecting the blobs. These detectors are validated on datasets of 2D fluorescent images, 3D synthetic images, 3D MR (18 mice, 3 humans) images and proved to be outperforming the competing detectors. In the last phase, a Fréchet Descriptors Distance based Coreset approach (FDD-Coreset) is proposed for accelerating BlobGAN’s training. Experiments have shown that BlobGAN trained on FDD-Coreset not only significantly reduces the training time, but also achieves higher denoising performance and maintains approximate performance of blob identification compared with training on entire dataset.
ContributorsXu, Yanzhe (Author) / Wu, Teresa (Thesis advisor) / Iquebal, Ashif (Committee member) / Yan, Hao (Committee member) / Beeman, Scott (Committee member) / Arizona State University (Publisher)
Created2022
Description
Deep learning is a sub-field of machine learning in which models are developed to imitate the workings of the human brain in processing data and creating patterns for decision making. This dissertation is focused on developing deep learning models for medical imaging analysis of different modalities for different tasks including detection, segmentation and classification. Imaging modalities including digital mammography (DM), magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) are studied in the dissertation for various medical applications. The first phase of the research is to develop a novel shallow-deep convolutional neural network (SD-CNN) model for improved breast cancer diagnosis. This model takes one type of medical image as input and synthesizes different modalities for additional feature sources; both original image and synthetic image are used for feature generation. This proposed architecture is validated in the application of breast cancer diagnosis and proved to be outperforming the competing models. Motivated by the success from the first phase, the second phase focuses on improving medical imaging synthesis performance with advanced deep learning architecture. A new architecture named deep residual inception encoder-decoder network (RIED-Net) is proposed. RIED-Net has the advantages of preserving pixel-level information and cross-modality feature transferring. The applicability of RIED-Net is validated in breast cancer diagnosis and Alzheimer’s disease (AD) staging. Recognizing medical imaging research often has multiples inter-related tasks, namely, detection, segmentation and classification, my third phase of the research is to develop a multi-task deep learning model. Specifically, a feature transfer enabled multi-task deep learning model (FT-MTL-Net) is proposed to transfer high-resolution features from segmentation task to low-resolution feature-based classification task. The application of FT-MTL-Net on breast cancer detection, segmentation and classification using DM images is studied. As a continuing effort on exploring the transfer learning in deep models for medical application, the last phase is to develop a deep learning model for both feature transfer and knowledge from pre-training age prediction task to new domain of Mild cognitive impairment (MCI) to AD conversion prediction task. It is validated in the application of predicting MCI patients’ conversion to AD with 3D MRI images.
ContributorsGao, Fei (Author) / Wu, Teresa (Thesis advisor) / Li, Jing (Committee member) / Yan, Hao (Committee member) / Patel, Bhavika (Committee member) / Arizona State University (Publisher)
Created2019
Description
High-dimensional data is omnipresent in modern industrial systems. An imaging sensor in a manufacturing plant a can take images of millions of pixels or a sensor may collect months of data at very granular time steps. Dimensionality reduction techniques are commonly used for dealing with such data. In addition, outliers typically exist in such data, which may be of direct or indirect interest given the nature of the problem that is being solved. Current research does not address the interdependent nature of dimensionality reduction and outliers. Some works ignore the existence of outliers altogether—which discredits the robustness of these methods in real life—while others provide suboptimal, often band-aid solutions. In this dissertation, I propose novel methods to achieve outlier-awareness in various dimensionality reduction methods. The problem is considered from many different angles depend- ing on the dimensionality reduction technique used (e.g., deep autoencoder, tensors), the nature of the application (e.g., manufacturing, transportation) and the outlier structure (e.g., sparse point anomalies, novelties).
ContributorsSergin, Nurettin Dorukhan (Author) / Yan, Hao (Thesis advisor) / Li, Jing (Committee member) / Wu, Teresa (Committee member) / Tsung, Fugee (Committee member) / Arizona State University (Publisher)
Created2021
Description
Deoxyribonucleic acid (DNA), a biopolymer well known for its role in preserving genetic information in biology, is now drawing great deal of interest from material scientists. Ease of synthesis, predictable molecular recognition via Watson-Crick base pairing, vast numbers of available chemical modifications, and intrinsic nanoscale size makes DNA a suitable material for the construction of a plethora of nanostructures that can be used as scaffold to organize functional molecules with nanometer precision. This dissertation focuses on DNA-directed organization of metallic nanoparticles into well-defined, discrete structures and using them to study photonic interaction between fluorophore and metal particle. Presented here are a series of studies toward this goal. First, a novel and robust strategy of DNA functionalized silver nanoparticles (AgNPs) was developed and DNA functionalized AgNPs were employed for the organization of discrete well-defined dimeric and trimeric structures using a DNA triangular origami scaffold. Assembly of 1:1 silver nanoparticle and gold nanoparticle heterodimer has also been demonstrated using the same approach. Next, the triangular origami structures were used to co-assemble gold nanoparticles (AuNPs) and fluorophores to study the distance dependent and nanogap dependencies of the photonic interactions between them. These interactions were found to be consistent with the full electrodynamic simulations. Further, a gold nanorod (AuNR), an anisotropic nanoparticle was assembled into well-defined dimeric structures with predefined inter-rod angles. These dimeric structures exhibited unique optical properties compared to single AuNR that was consistent with the theoretical calculations. Fabrication of otherwise difficult to achieve 1:1 AuNP- AuNR hetero dimer, where the AuNP can be selectively placed at the end-on or side-on positions of anisotropic AuNR has also been shown. Finally, a click chemistry based approach was developed to organize sugar modified DNA on a particular arm of a DNA origami triangle and used them for site-selective immobilization of small AgNPs.
ContributorsPal, Suchetan (Author) / Liu, Yan (Thesis advisor) / Yan, Hao (Thesis advisor) / Lindsay, Stuart (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2012