INHIBITION OF CHOLESTEROL SYNTHESIS BY POLICOSANOL

Cholesterol is an essential component of the cell, but excessive blood levels are a major risk factor for the development of atherosclerotic plaques that can lead to heart disease and stroke, the foremost cause of premature death in Western societies. Policosanol, a mixture of very long chain alcohols derived from sugarcane, has gained considerable attention among the public as safe and effective means to reduce blood cholesterol levels, a belief based on some early clinical studies. My research investigates one possible mechanism by which policosanol might decrease blood cholesterol levels: the inhibition of cholesterol synthesis in the liver. Previous studies with cultured hepatoma cells have indicated that policosanol suppresses HMG-CoA reductase activity, the regulatory step in cholesterol synthesis, by activation of AMP-kinase, which then inactivates HMG-CoA reductase by phosphorylation. My studies have confirmed this activation of AMP-kinase both in hepatoma cells and in whole animals after intragastric administration of policosanol. The present studies were also undertaken to identify the upstream signaling mechanism by which policosanol activates AMP-kinase. Treatment of rat hepatoma cells with policosanol increased the amount of phosphorylated CaMKK, which can directly activate AMP-kinase, but had only a small effect on LKB1, the principal activator of AMP-kinase. Intragastric administration to mice similarly activated CaMKK, but not LKB1, in the liver. To determine if metabolism of policosanol was necessary for activation of AMP-kinase, siRNA-mediated suppression of fatty aldehyde dehydrogenase, fatty acyl CoA synthase-4, or β-ketothiolase in hepatoma cells prevented the phosphorylation of AMP-kinase and HMG-CoA reductase by policosanol, indicating that metabolism of these very long chain alcohols to fatty acids and subsequent peroxisomal β-oxidation is necessary for the suppression of cholesterol synthesis. As the principal product of fatty acid -oxidation is acetyl-CoA, further studies demonstrated that addition of acetate to cells similarly activated AMP-kinase and inactivated HMG-CoA reductase. This finding argues that the activation of AMP-kinase by policosanol results from the generation of excess acetyl-CoA via peroxisomal metabolism. Finally, although the intestine is a significant source of circulating cholesterol, policosanol was unable to activate AMP-kinase in the small intestine. These findings open new perspectives for the control of cholesterol synthesis by activators of AMP-kinase

A Joint 3D-2D based Method for Free Space Detection on Roads

In this paper, we address the problem of road segmentation and free space detection in the context of autonomous driving. Traditional methods either use 3-dimensional (3D) cues such as point clouds obtained from LIDAR, RADAR or stereo cameras or 2-dimensional (2D) cues such as lane markings, road boundaries and object detection. Typical 3D point clouds do not have enough resolution to detect fine differences in heights such as between road and pavement. Image based 2D cues fail when encountering uneven road textures such as due to shadows, potholes, lane markings or road restoration. We propose a novel free road space detection technique combining both 2D and 3D cues. In particular, we use CNN based road segmentation from 2D images and plane/box fitting on sparse depth data obtained from SLAM as priors to formulate an energy minimization using conditional random field (CRF), for road pixels classification. While the CNN learns the road texture and is unaffected by depth boundaries, the 3D information helps in overcoming texture based classification failures. Finally, we use the obtained road segmentation with the 3D depth data from monocular SLAM to detect the free space for the navigation purposes. Our experiments on KITTI odometry dataset, Camvid dataset, as well as videos captured by us, validate the superiority of the proposed approach over the state of the art.Comment: Accepted for publication at IEEE WACV 201

Reusing view-dependent animation

In this paper we present techniques for reusing view-dependent animation. First, we provide a framework for representing view-dependent animations. We formulate the concept of a view space, which is the space formed by the key views and their associated character poses. Tracing a path on the view space generates the corresponding view-dependent animation in real time. We then demonstrate that the framework can be used to synthesize new stylized animations by reusing view-dependent animations. We present three types of novel reuse techniques. In the first we show how to animate multiple characters from the same view space. Next, we show how to animate multiple characters from multiple view spaces. We use this technique to animate a crowd of characters. Finally, we draw inspiration from cubist paintings and create their view-dependent analogues by using different cameras to control different body parts of the same characte