Space microgravity condition has great physiological influence on astronauts’ health. The interaction of endothelial cells, which control vascular permeability and immune responses, is sensitive to mechanical stress. However, whether microgravity has significant effects on the physiological function of the endothelium has not been investigated. In order to address such a question, a clinostat-based culture model with a HUVEC monolayer being inside the culture vessel under the simulated microgravity (SMG) was established. The transmittance of FITC-tagged dextran was used to estimate the change of integrity of the adherens junction of the HUVEC monolayer. Firstly, we found that the permeability of the HUVEC monolayer was largely increased after SMG treatment. To elucidate the mechanism of the increased permeability of the HUVEC monolayer under SMG, the levels of total expression and activated protein levels of Rap1 and Rap2 in HUVEC cells, which regulate the adherens junction of endothelial cells, were detected by WB and GST pull-down after SMG. As the activation of both Rap1 and Rap2 was significantly decreased under SMG, the expression of Rap1GEF1 (C3G) and Rap1GAP in HUVECs, which regulate the activation of them, was further determined. The results indicate that both C3G and Rap1GAP showed a time-dependent increase with the expression of Rap1GAP being dominant at 48 h after SMG. The down-regulation of the expression of junctional proteins, VE-cadherin and β-catenin, in HUVEC cells was also confirmed by WB and immunofluorescence after SMG. To clarify whether up-regulation of Rap1GAP is necessary for the increased permeability of the HUVEC monolayer after SMG, the expression of Rap1GAP was knocked down by Rap1GAP-shRNA, and the change of permeability of the HUVEC monolayer was detected. The results indicate that knock-down of Rap1GAP reduced SMG-induced leaking of the HUVEC monolayer in a time-dependent manner. In total, our results indicate that the Rap1GAP-Rap signal axis was necessary for the increased permeability of the HUVEC monolayer along with the down-regulation of junctional molecules including VE-cadherin and β-catenin. 相似文献
This study investigates pressure loss and compensation in the combustion process of Al–CuO metastable intermolecular composite (MIC) on a microheater chip. A ball cell model of pressure change in the combustion process is proposed to show the effects of pressure loss on the reaction rate and efficiency of energy output at microscale. An effective compensation method for pressure loss is then developed by integrating Al–CuO MIC with CL-20 (2,4,6,8,10,12-hexanitrohexaazaisowurtzitane) onto a SiO2/Cr/Pt/Au microheater chip. The combustion processes of Al–CuO MIC with different weight percentages of fine CL-20 particles on the microheater chips are observed by high-speed video recording. Results indicate that the reaction of Al–CuO MIC is a slow combustion process that turns into intense deflagration after adding fine CL-20 particles to Al–CuO MIC. The pressure–time characteristics indicate higher maximum pressure and pressurization rate for Al–CuO/CL-20 because the pressure loss at microscale is well compensated by the addition of fine CL-20. This study proves the importance of pressure loss in the combustion process of MIC at microscale and provides an efficient compensation strategy for pressure loss to improve the reaction rate and efficiency of energy output at microscale environment. 相似文献
Kernel callback queues (KQs) are the established mechanism for event handling in modern kernels. Unfortunately, real-world malware has abused KQs to run malicious logic, through an attack called kernel queue injection (KQI). Current kernel-level defense mechanisms have difficulties with KQI attacks, since they work without necessarily changing legitimate kernel code or data. In this paper, we present the design, implementation, and evaluation of KQguard, an efficient and effective protection mechanism of KQs. KQguard employs static and dynamic analysis of kernel and device drivers to learn specifications of legitimate event handlers. At runtime, KQguard rejects all the unknown KQ requests that cannot be validated. We implement KQguard on the Windows Research Kernel (WRK), Windows XP, and Linux, using source code instrumentation or binary patching. Our extensive experimental evaluation shows that KQguard is effective (i.e., it can have zero false positives against representative benign workloads after enough training and very low false negatives against 125 real-world malware), and it incurs a small overhead (up to ~5%). We also present the result of an automated analysis of 1,528 real-world kernel-level malware samples aiming to detect their KQ Injection behaviors. KQguard protects KQs in both Windows and Linux kernels, can accommodate new device drivers, and can support closed source device drivers through dynamic analysis of their binary code.
