90 research outputs found

    A Novel Function of Apolipoprotein E: Upregulation of ATP-Binding Cassette Transporter A1 Expression

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    Despite the well known importance of apolipoprotein (Apo) E in cholesterol efflux, the effect of ApoE on the expression of ATP-binding cassette transporter A1 (ABCA1) has never been investigated. The objective of this study was to determine the effect of ApoE on ApoB-carrying lipoprotein-induced expression of ABCA1, a protein that mediates cholesterol efflux. Our data demonstrate that ApoB-carrying lipoproteins obtained from both wild-type and ApoE knockout mice induced ApoAI-mediated cholesterol efflux in mouse macrophages, which was associated with an enhanced ABCA1 promoter activity, and an increased ABCA1 mRNA and protein expression. In addition, these lipoproteins increased the level of phosphorylated specificity protein 1 (Sp1) and the amount of Sp1 bound to the ABCA1 promoter. However, all these inductions were significantly diminished in cells treated with ApoE-free lipoproteins, when compared to those treated with wild-type lipoproteins. Enrichment with human ApoE3 reversed the reduced inducibility of ApoE-free lipoproteins. Moreover, we observed that inhibition of Sp1 DNA-binding by mithramycin A diminished ABCA1 expression and ApoAI-mediated cholesterol efflux induced by ApoB-carrying lipoproteins, and that mutation of the Sp1-binding motif in the ABCA1 promoter region diminished ApoB-carrying lipoprotein-induced ABCA1 promoter activity. Collectively, these data suggest that ApoE associated with ApoB-carrying lipoproteins has an upregulatory role on ABCA1 expression, and that induction of Sp1 phosphorylation is a mechanism by which ApoE upregulates ABCA1 expression

    The role of rock joint frictional strength in the containment of fracture propagation

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    The fracturing phenomenon within the reservoir environment is a complex process that is controlled by several factors and may occur either naturally or by artificial drivers. Even when deliberately induced, the fracturing behaviour is greatly influenced by the subsurface architecture and existing features. The presence of discontinuities such as joints, artificial and naturally occurring faults and interfaces between rock layers and microfractures plays an important role in the fracturing process and has been known to significantly alter the course of fracture growth. In this paper, an important property (joint friction) that governs the shear behaviour of discontinuities is considered. The applied numerical procedure entails the implementation of the discrete element method to enable a more dynamic monitoring of the fracturing process, where the joint frictional property is considered in isolation. Whereas fracture propagation is constrained by joints of low frictional resistance, in non-frictional joints, the unrestricted sliding of the joint plane increases the tendency for reinitiation and proliferation of fractures at other locations. The ability of a frictional joint to suppress fracture growth decreases as the frictional resistance increases; however, this phenomenon exacerbates the influence of other factors including in situ stresses and overburden conditions. The effect of the joint frictional property is not limited to the strength of rock formations; it also impacts on fracturing processes, which could be particularly evident in jointed rock masses or formations with prominent faults and/or discontinuities

    Network Modeling Identifies Molecular Functions Targeted by miR-204 to Suppress Head and Neck Tumor Metastasis

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    Due to the large number of putative microRNA gene targets predicted by sequence-alignment databases and the relative low accuracy of such predictions which are conducted independently of biological context by design, systematic experimental identification and validation of every functional microRNA target is currently challenging. Consequently, biological studies have yet to identify, on a genome scale, key regulatory networks perturbed by altered microRNA functions in the context of cancer. In this report, we demonstrate for the first time how phenotypic knowledge of inheritable cancer traits and of risk factor loci can be utilized jointly with gene expression analysis to efficiently prioritize deregulated microRNAs for biological characterization. Using this approach we characterize miR-204 as a tumor suppressor microRNA and uncover previously unknown connections between microRNA regulation, network topology, and expression dynamics. Specifically, we validate 18 gene targets of miR-204 that show elevated mRNA expression and are enriched in biological processes associated with tumor progression in squamous cell carcinoma of the head and neck (HNSCC). We further demonstrate the enrichment of bottleneckness, a key molecular network topology, among miR-204 gene targets. Restoration of miR-204 function in HNSCC cell lines inhibits the expression of its functionally related gene targets, leads to the reduced adhesion, migration and invasion in vitro and attenuates experimental lung metastasis in vivo. As importantly, our investigation also provides experimental evidence linking the function of microRNAs that are located in the cancer-associated genomic regions (CAGRs) to the observed predisposition to human cancers. Specifically, we show miR-204 may serve as a tumor suppressor gene at the 9q21.1–22.3 CAGR locus, a well established risk factor locus in head and neck cancers for which tumor suppressor genes have not been identified. This new strategy that integrates expression profiling, genetics and novel computational biology approaches provides for improved efficiency in characterization and modeling of microRNA functions in cancer as compared to the state of art and is applicable to the investigation of microRNA functions in other biological processes and diseases

    The recognition of 2D partially occluded objects using curve moment invariants

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    10.1109/ICADIWT.2008.46643751st International Conference on the Applications of Digital Information and Web Technologies, ICADIWT 2008372-37

    Classifications of Image Features: A Survey

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    Computer imaging is a complex multi-discipline science with broad application and well developed theory. A briefknowledge of computer imaging is presented in this paper. An image feature is a descriptor of an image, which canavoid redundant data and reduce the effects of noise and variance. In computer imaging, feature selection is vitalfor researchers and processors. Feature extraction and image processing are based on the mathematical selection,computation and manipulation of image features with high efficiency, robustness and invariance. Common imagefeatures are expressed under definitions of feature measurements, which is stated in this paper. This paper mainlybrings an overall presentation of different sorts of image features and classifies them into specified types. Basedon different purposes of application, three main ways are put forward in this paper to categorize image features.The first one is based on the nature of the image. The features applied to a binary image are different from theones applied to a gray-level image or a color image. The second classification separates visible features frominvisible features. The last one classifies image features into global image features and local image features. Aclear statement is given for each way of classification and each type of image feature. Every image feature hasboth merits and defects, hence when selecting features for further image application, a clear cognition of differentfeatures is required. Well applied image features and the algorithms related to them are highlighted in this paperwith analysis and comparison

    Image recognition of occluded objects based on improved curve moment invariants

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    Journal of Digital Information Management73152-15
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