Real-Time Monitoring the Effect of Cytopathic Hypoxia on Retinal Pigment Epithelial Barrier Functionality Using Electric Cell-Substrate Impedance Sensing (ECIS) Biosensor Technology

Disruption of retinal pigment epithelial (RPE barrier integrity is a hallmark feature of various retinal blinding diseases, including diabetic macular edema and age-related macular degeneration, but the underlying causes and pathophysiology are not completely well-defined. One of the most conserved phenomena in biology is the progressive decline in mitochondrial function with aging leading to cytopathic hypoxia, where cells are unable to use oxygen for energy production. Therefore, this study aimed to thoroughly investigate the role of cytopathic hypoxia in compromising the barrier functionality of RPE cells. We used Electric Cell-Substrate Impedance Sensing (ECIS) system to monitor precisely in real time the barrier integrity of RPE cell line (ARPE-19) after treatment with various concentrations of cytopathic hypoxia-inducing agent, Cobalt(II) chloride (CoCl₂). We further investigated how the resistance across ARPE-19 cells changes across three separate parameters: R_b (the electrical resistance between ARPE-19 cells), α (the resistance between the ARPE-19 and its substrate), and C_m (the capacitance of the ARPE-19 cell membrane). The viability of the ARPE-19 cells and mitochondrial bioenergetics were quantified with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and seahorse technology, respectively. ECIS measurement showed that CoCl₂ reduced the total impedance of ARPE-19 cells in a dose dependent manner across all tested frequencies. Specifically, the ECIS program’s modelling demonstrated that CoCl₂ affected R_b as it begins to drastically decrease earlier than α or C_m, although ARPE-19 cells’ viability was not compromised. Using seahorse technology, all three concentrations of CoCl₂ significantly impaired basal, maximal, and ATP-linked respirations of ARPE-19 cells but did not affect proton leak and non-mitochondrial bioenergetic. Concordantly, the expression of a major paracellular tight junction protein (ZO-1) was reduced significantly with CoCl_2-treatment in a dose-dependent manner. Our data demonstrate that the ARPE-19 cells have distinct dielectric properties in response to cytopathic hypoxia in which disruption of barrier integrity between ARPE-19 cells precedes any changes in cells’ viability, cell-substrate contacts, and cell membrane permeability. Such differences can be used in screening of selective agents that improve the assembly of RPE tight junction without compromising other RPE barrier parameters.     

基于采样尺度自适应的多尺度量子谐振子优化算法并行化

多尺度量子谐振子优化算法MQHOA是基于量子波函数理论提出的元启发式算法,传统MQHOA寻优过程中不同个体的采样尺度不具有差异性,这种机制限制了解的多样性。针对适应度不同的采样个体,提出采样尺度自适应策略,将采样情况差的个体采样尺度合理扩大,增加迭代过程中不同采样个体所使用采样尺度的多样性,并基于采样尺度的差异性提出并行化框架。选取7组测试函数将改进后的算法（MQHOA-PS）与MQHOA在华为鲲鹏920和AMD EPYC 7452处理器上进行测试实验,实验结果表明,改进后的算法寻优具有较高的精度和成功率,并且所需时间更短。     

High Performance MPI over the Slingshot Interconnect

Journal of Computer Science and Technology - The Slingshot interconnect designed by HPE/Cray is becoming more relevant in high-performance computing with its deployment on the upcoming exascale...     

可信执行环境软件侧信道攻击研究综述

为保护计算设备中安全敏感程序运行环境的安全,研究人员提出了可信执行环境(TEE)技术,通过对硬件和软件进行隔离为安全敏感程序提供一个与通用计算环境隔离的安全运行环境.侧信道攻击从传统的需要昂贵设备发展到现在仅基于微体系结构状态就能通过软件方式获取机密信息的访问模式,从而进一步推测出机密信息.TEE架构仅提供隔离机制,无法抵抗这类新出现的软件侧信道攻击.深入调研了ARM TrustZone、Intel SGX和AMD SEV这3种TEE架构的软件侧信道攻击及相应防御措施,并探讨其攻击和防御机制的发展趋势.首先,介绍了ARM TrustZone、Intel SGX和AMD SEV的基本原理,并详细阐述了软件侧信道攻击的定义以及缓存侧信道攻击的分类、方法和步骤;之后从处理器指令执行的角度,提出一种TEE攻击面分类方法,利用该方法对TEE软件侧信道攻击进行分类,并阐述了软件侧信道攻击与其他攻击相结合的组合攻击;然后详细讨论TEE软件侧信道攻击的威胁模型;最后全面总结业界对TEE软件侧信道攻击的防御措施,并从攻击和防御两方面探讨TEE软件侧信道攻击未来的研究趋势.     

基于OpenCL的图像模糊化算法优化研究

现代GPU一般都提供特定硬件(如纹理部件、光栅化部件及各种片上缓存)以加速二维图像的处理和显示过程,相应的编程模型(CUDA、OpenCL)都定义了特定程序设计接口(CUDA的纹理内存,OpenCL的图像对象)以便图像应用能利用相关硬件支持。以典型图像模糊化处理算法在AMD平台GPU的优化为例,探讨了OpenCL的图像对象在图像算法优化上的适用范围,尤其是分析了其相对于更通用的基于全局内存加片上局部存储进行性能优化的方法的优劣。实验结果表明,图像对象只有在图像为四通道且计算过程中需要缓存的数据量较小时才能带来较好的性能改善,其余情况采用全局内存加局部存储都能获得较好性能。优化后的算法性能相对于精心实现的CPU版加速比为200～1000;相对于NVIDIA NPP库相应函数的性能加速比为1.3～5。     

集装箱吊具有阻尼AMD防摇装置的试验研究

为了检验集装箱吊具有阻尼AM D防摇装置的控制效果,设计了一套基于主动质量阻尼（AM D）控制原理的电子主动防摇试验装置。进行了AM D防摇控制理论分析,应用M atlab/S im u link软件建模仿真,并做了相应的防摇模拟试验。对比理论仿真和试验数据给出了阻尼对试验装置防摇效果的影响。     

Thin natural gelatin/chitosan nanofibrous scaffolds for retinal pigment epithelium cells

Damage of the retinal pigmented epithelial cells causes various diseases such as age-related macular degeneration in retinal tissue. Nowadays, scientists are attempting to replace lost retinal cells with healthy and efficient cells that provide better conditions for recovering and preventing blindness. In this study, gelatin/chitosan nanofibrous scaffolds with mean diameters of 180?nm were fabricated for subretinal space through electrospinning. Thickness and morphology of the gelatin–chitosan scaffolds were analyzed by scanning electron microscopy (SEM). The results showed that the high rate of degradation, i.e., 90% damage was obtained after 1 month. The cell viability of gelatin/chitosan nanofibers were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The SEM results of cultured RPE on gelatin/chitosan scaffolds showed the appropriate adhesion of cells on the substrate. The results of the identity of RPE cells cultured on the scaffolds indicated that a large number of cells strongly expressed RPE65 and cytokeratin 8/18.     

Genetic Variability in DNA Repair Proteins in Age-Related Macular Degeneration

The pathogenesis of age-related macular degeneration (AMD) is complex and involves interactions between environmental and genetic factors, with oxidative stress playing an important role inducing damage in biomolecules, including DNA. Therefore, genetic variability in the components of DNA repair systems may influence the ability of the cell to cope with oxidative stress and in this way contribute to the pathogenesis of AMD. However, few reports have been published on this subject so far. We demonstrated that the c.977C>G polymorphism (rs1052133) in the hOGG1 gene and the c.972G>C polymorphism (rs3219489) in the MUTYH gene, the products of which play important roles in the repair of oxidatively damaged DNA, might be associated with the risk of AMD. Oxidative stress may promote misincorporation of uracil into DNA, where it is targeted by several DNA glycosylases. We observed that the g.4235T>C (rs2337395) and c.–32A>G (rs3087404) polymorphisms in two genes encoding such glycosylases, UNG and SMUG1, respectively, could be associated with the occurrence of AMD. Polymorphisms in some other DNA repair genes, including XPD (ERCC2), XRCC1 and ERCC6 (CSB) have also been reported to be associated with AMD. These data confirm the importance of the cellular reaction to DNA damage, and this may be influenced by variability in DNA repair genes, in AMD pathogenesis.     

Squamosamide Derivative FLZ Protects Retinal Pigment Epithelium Cells from Oxidative Stress through Activation of Epidermal Growth Factor Receptor (EGFR)-AKT Signaling

Reactive oxygen species (ROS)-mediated retinal pigment epithelium (RPE) cell apoptosis is attributed to age-related macular degeneration (AMD) pathogenesis. FLZ, a novel synthetic squamosamide derivative from a Chinese herb, Annona glabra, has displayed significant cyto-protective activity. In the current study, we explored the pro-survival effect of FLZ in oxidative stressed-RPE cells and studied the underlying signaling mechanisms. Our results showed that FLZ attenuated hydrogen peroxide (H₂O₂)-induced viability decrease and apoptosis in the RPE cell line (ARPE-19 cells) and in primary mouse RPE cells. Western blotting results showed that FLZ activated AKT signaling in RPE cells. The AKT-specific inhibitor, MK-2206, the phosphoinositide 3-kinase (PI3K)/AKT pan inhibitor, wortmannin, and AKT1-shRNA (short hairpin RNA) depletion almost abolished FLZ-mediated pro-survival/anti-apoptosis activity. We discovered that epidermal growth factor receptor (EGFR) trans-activation mediated FLZ-induced AKT activation and the pro-survival effect in RPE cells, and the anti-apoptosis effect of FLZ against H₂O₂ was inhibited by the EGFR inhibitor, PD153035, or by EGFR shRNA-knockdown. In conclusion, FLZ protects RPE cells from oxidative stress through activation of EGFR-AKT signaling, and our results suggest that FLZ might have therapeutic values for AMD.     

On the role of deterioration of structures in their performance; with a focus on mining industry equipment and structures

Some examples of materials performance of civil materials such as steel and concrete in mining industry are considered. These examples are about structural steels (either as support for the structure or the equipment) and concrete structures. Also, it is mentioned that in mine sites that contain sulphide minerals, the formation of acid mine drainage (AMD) may also contribute to decreasing the integrity of civil and supportive structures. Using these examples, an effort has been made to emphasise that in order to extend the service life of structures in very aggressive environments such as those encountered in mining industry, a sound knowledge of deterioration and corrosion‐enhancing factors in addition to standardised application of measures against deterioration (such as painting) can be very applicative.