Hongyang Li

TarFisDock is a web-based tool for automating the procedure of searching for small molecule-protein interactions over a large repertoire of protein structures. It offers PDTD (potential drug target database), a target database containing 698 protein structures covering 15 therapeutic areas and a reverse ligand-protein docking program. In contrast to conventional ligand-protein docking, reverse ligand-protein docking aims to seek potential protein targets by screening an appropriate protein database. The input file of this web server is the small molecule to be tested, in standard mol2 format; TarFisDock then searches for possible binding proteins for the given small molecule by use of a docking approach. The ligand-protein interaction energy terms of the program DOCK are adopted for ranking the proteins. To test the reliability of the TarFisDock server, we searched the PDTD for putative binding proteins for vitamin E and 4H-tamoxifen. The top 2 and 10% candidates of vitamin E binding proteins identified by TarFisDock respectively cover 30 and 50% of reported targets verified or implicated by experiments; and 30 and 50% of experimentally confirmed targets for 4H-tamoxifen appear amongst the top 2 and 5% of the TarFisDock predicted candidates, respectively. Therefore, TarFisDock may be a useful tool for target identification, mechanism study of old drugs and probes discovered from natural products. TarFisDock and PDTD are available at http://www.dddc.ac.cn/tarfisdock/.

Scalable video coding is an ongoing standard, and the current working draft (WD) is an extension of H.264/AVC. In the WD, an exhaustive search technique is employed to select the best coding mode for each macroblock. This technique achieves the highest possible coding efficiency, but it results in extremely large encoding time which obstructs it from practical use. This paper proposes a fast mode decision algorithm for inter-frame coding for spatial, coarse grain signal-to-noise ratio, and temporal scalability. It makes use of the mode-distribution correlation between the base layer and enhancement layers. Specifically, after the exhaustive search technique is performed at the base layer, the candidate modes for enhancement layers can be reduced to a small number based on the correlation. Experimental results show that the fast mode decision scheme reduces the computational complexity significantly with negligible coding loss and bit-rate increases

Abstract—With the rapid increase in Android device pop-ularity, the capabilities that the diverse user base demands from Android have significantly exceeded its original design. As a result, people have to seek ways to obtain the permissions not directly offered to ordinary users. A typical way to do that is using the Android Debug Bridge (ADB), a developer tool that has been granted permissions to use critical system resources. Apps adopting this solution have combined tens of millions of downloads on Google Play. However, we found that such ADB-level capabilities are not well guarded by Android. A prominent example we investigated is the apps that perform programmatic screenshots, a much-needed capability Android fails to support. We found that all such apps in the market inadvertently expose this ADB capability to any party with the INTERNET permission on the same device. With this exposure, a malicious app can be built to stealthily and intelligently collect sensitive user data through screenshots. To understand the threat, we built Screenmilker, an app that can detect the right moment to monitor the screen and pick up a user’s password when she is typing in real time. We show that this can be done efficiently by leveraging the unique design of smartphone user interfaces and its public resources. Such an understanding also informs Android developers how to protect this screenshot capability, should they consider providing an interface to let third-party developers use it in the future, and more generally the security risks of the ADB workaround, a standard technique gaining popularity in app development. Based on the understanding, we present a mitigation mechanism that controls the exposure of the ADB capabilities only to authorized apps. I.

Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period is enhanced permeability of mitochondrial membranes. The precise mechanisms by which mitochondrial function is disrupted are, as yet, unclear. Here we show that global ischemia promotes alterations in mitochondrial membrane contact points, a rise in intramitochondrial Zn2+, and activation of large, multi-conductance channels in mitochondrial outer membranes by 1 h after insult. Mitochondrial channel activity was associated with enhanced protease activity and proteolytic cleavage of BCL-xL to generate its pro-death counterpart, deltaN-BCL-xL. The findings implicate deltaN-BCL-xL in large, multi-conductance channel activity. Consistent with this, large channel activity was mimicked by introduction of recombinant deltaN-BCL-xL to control mitochondria and blocked by introduction of a functional BCL-xL antibody to post-ischemic mitochondria via the patch pipette. Channel activity was also inhibited by nicotinamide adenine dinucleotide, indicative of a role for the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. In vivo administration of the membrane-impermeant Zn2+ chelator CaEDTA before ischemia or in vitro application of the membrane-permeant Zn2+ chelator tetrakis-(2-pyridylmethyl) ethylenediamine attenuated channel activity, suggesting a requirement for Zn2+. These findings reveal a novel mechanism by which ischemic insults disrupt the functional integrity of the outer mitochondrial membrane and implicate deltaN-BCL-xL and VDAC in the large, Zn2+-dependent mitochondrial channels observed in post-ischemic hippocampal mitochondria.

In the developing CNS, neurons and glia are sequentially produced from the ventricular neural progenitor cells. One fundamental question in developmental neurobiology is what signals or factors control the developmental switch from neurogenesis to gliogenesis. Here we report that microRNAs (miRNAs) play an essential role in this important developmental process. Inhibition of miRNA formation in Olig1(Cre)-mediated Dicer conditional knock-out mice disrupted both oligodendrogenesis and astrogliogenesis in the ventral neuroepithelial cells. By contrast, the early patterning and development of motor neurons were not affected in the mutant spinal cord tissue.