Ezetimibe therapy: mechanism of action and clinical update.

The lowering of low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy in the primary and secondary prevention of cardiovascular events. Although statin therapy is the mainstay for LDL-C lowering, a significant percentage of patients prescribed these agents either do not achieve targets with statin therapy alone or have partial or complete intolerance to them. For such patients, the use of adjuvant therapy capable of providing incremental LDL-C reduction is advised. One such agent is ezetimibe, a cholesterol absorption inhibitor that targets uptake at the jejunal enterocyte brush border. Its primary target of action is the cholesterol transport protein Nieman Pick C1 like 1 protein. Ezetimibe is an effective LDL-C lowering agent and is safe and well tolerated. In response to significant controversy surrounding the use and therapeutic effectiveness of this drug, we provide an update on the biochemical mechanism of action for ezetimibe, its safety and efficacy, as well as the results of recent randomized studies that support its use in a variety of clinical scenarios

Symbolic Quantitative Information Flow

acmid: 2382791 issue_date: November 2012 keywords: algorithms, security, verification numpages: 5acmid: 2382791 issue_date: November 2012 keywords: algorithms, security, verification numpages: 5acmid: 2382791 issue_date: November 2012 keywords: algorithms, security, verification numpages: 5acmid: 2382791 issue_date: November 2012 keywords: algorithms, security, verification numpages: 5acmid: 2382791 issue_date: November 2012 keywords: algorithms, security, verification numpages:

Low-Complexity Iterative Detection for Orthogonal Time Frequency Space Modulation

We elaborate on the recently proposed orthogonal time frequency space (OTFS) modulation technique, which provides significant advantages over orthogonal frequency division multiplexing (OFDM) in Doppler channels. We first derive the input--output relation describing OTFS modulation and demodulation (mod/demod) for delay--Doppler channels with arbitrary number of paths, with given delay and Doppler values. We then propose a low-complexity message passing (MP) detection algorithm, which is suitable for large-scale OTFS taking advantage of the inherent channel sparsity. Since the fractional Doppler paths (i.e., not exactly aligned with the Doppler taps) produce the inter Doppler interference (IDI), we adapt the MP detection algorithm to compensate for the effect of IDI in order to further improve performance. Simulations results illustrate the superior performance gains of OTFS over OFDM under various channel conditions.Comment: 6 pages, 7 figure

Importance Sketching of Influence Dynamics in Billion-scale Networks

The blooming availability of traces for social, biological, and communication networks opens up unprecedented opportunities in analyzing diffusion processes in networks. However, the sheer sizes of the nowadays networks raise serious challenges in computational efficiency and scalability. In this paper, we propose a new hyper-graph sketching framework for inflence dynamics in networks. The central of our sketching framework, called SKIS, is an efficient importance sampling algorithm that returns only non-singular reverse cascades in the network. Comparing to previously developed sketches like RIS and SKIM, our sketch significantly enhances estimation quality while substantially reducing processing time and memory-footprint. Further, we present general strategies of using SKIS to enhance existing algorithms for influence estimation and influence maximization which are motivated by practical applications like viral marketing. Using SKIS, we design high-quality influence oracle for seed sets with average estimation error up to 10x times smaller than those using RIS and 6x times smaller than SKIM. In addition, our influence maximization using SKIS substantially improves the quality of solutions for greedy algorithms. It achieves up to 10x times speed-up and 4x memory reduction for the fastest RIS-based DSSA algorithm, while maintaining the same theoretical guarantees.Comment: 12 pages, to appear in ICDM 2017 as a regular pape

Cardioprotective Extracellular Vesicles Derived-Micrornas: Sorting Mechanisms and Functions

Extracellular vesicles (EVs) are nano-size membrane bound vesicles that are derived from the fusion of multivesicular endosomes with the plasma membranes. EVs have important roles in intercellular communication through the transfer of their unique cargoes including RNA, DNA and protein molecules to recipient cells. Mesenchymal stem cell (MSC)-derived EVs have been shown to reduce infarct size and reduce the progress of heart failure after cardiac ischemia/reperfusion (I/R) injury in animal models. Small non-coding RNAs such as microRNA (miRNA) have been indicated as one of the active components that mediate the beneficial effects of MSC-derived EVs. However, the selective packaging mechanisms of these EV-enriched miRNAs as well as their specific functions in recipient cardiomyocytes are still incompletely understood.Regarding the sorting mechanisms of miRNAs into MSC-derived EVs, we characterized the role of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in controlling the distribution of the miRNA population to EVs. We showed that disruption of the gene encoding hnRNPA2B1 prevented much of the loading of miR-486-5p into MSC-derived EVs. Based on RNA immunoprecipitation, gel-shift and biotinylated RNA pull-down assays, we confirmed the interaction of miR-486-5p and hnRNPA2B1. Because miR-486-5p was the predominant miRNA in EVs and almost absent in producer cells, we focused on the function of miR-486-5p in cardioprotection against I/R injury. Using different in vitro and in vivo functional assays, we demonstrated that miR-486-5p is protective against I/R injury by inhibition of PDCD4-induced apoptosis in cardiomyocytes. The findings represented here indicated that hnRNPA2B1 interacts with miRNAs and mediates packing of miRNAs into MSC-derived EVs via a specific nucleotide motif in the miRNAs. One of the most highly EV-packaged miRNAs, miR-486-5p is cardioprotective in cardiomyocytes and in the heart

On the 3-D structure and dissipation of reconnection-driven flow-bursts

The structure of magnetic reconnection-driven outflows and their dissipation are explored with large-scale, 3-D particle-in-cell (PIC) simulations. Outflow jets resulting from 3-D reconnection with a finite length x-line form fronts as they propagate into the downstream medium. A large pressure increase ahead of this ``reconnection jet front'' (RJF), due to reflected and transmitted ions, slows the front so that its velocity is well below the velocity of the ambient ions in the core of the jet. As a result, the RJF slows and diverts the high-speed flow into the direction perpendicular to the reconnection plane. The consequence is that the RJF acts as a thermalization site for the ion bulk flow and contributes significantly to the dissipation of magnetic energy during reconnection even though the outflow jet is subsonic. This behavior has no counterpart in 2-D reconnection. A simple analytic model predicts the front velocity and the fraction of the ion bulk flow energy that is dissipated