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.     

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.     

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.     

AMD蚀化砂岩的性征及其机理研究

为研究矿山酸性水(Ac id M ine D rainage,AMD)对矿山边坡的破坏作用,在不同时间步长条件下,用pH=1.07,3.26的两种H2SO4溶液蚀化砂岩,然后对蚀化的砂岩试样进行抗压试验和细观结构观察。试验结果表明,在AMD作用后,砂岩的单轴抗压强度降低幅值达30%~50%,弹性模量降低25%~45%,粘聚力和内摩擦角降低,泊松比在0.20~0.29范围内波动。节理越发育,试件过峰后的残余应力值越大,破坏时间越长。细观研究表明,AMD作用后,砂岩中的Fe、A l等金属元素被稀释、溶解,质量百分比大幅下降。机理分析表明,AMD作用过程中,砂岩内节理和裂隙间的充填物频繁发生分解和聚合反应,改变岩体内部分子结构和骨架组成,降低岩体层面间的粘聚力和内摩擦角。     

基于单片机模糊控制器的AMD主动控制试验研究

模糊控制是结构主动控制的一种很有前途的控制算法。本文针对顶层设置AMD控制装置的5层钢框架模型结构,首先由已有主动控制训练样本提取了模糊规则;其次,将模糊逻辑推理与单片机技术结合起来,开发了单片机模糊控制器。在此基础上,完成了1∶4缩尺的5层钢框架模型结构的AMD模糊控制模拟地震振动台试验研究。试验结果表明:模糊AMD控制可以有效地减小地震作用下模型结构的反应,对顶层位移反应峰值的控制效果达到50%。本文研究成果可为AMD模糊控制走向工程应用提供参考。     

基于LQG/LTR方法的结构主动控制的研究

将LQG/LTR(Linear Quadratic Gaussian/Loop Transfer Recovery)方法引入到结构控制领域中,针对AMD(Active Mass Damper)Benchmark模型进行主动控制策略的研究。首先建立AMD试验结构的LQG/LTR控制系统模型,并采用近似法确定模型不确定性,引入速度反馈来降低模态峰值以设计理想的目标回路;然后根据LQG/LTR理论设计了控制器,使得全状态LQR(linear quadratic regulator)调节器自然拥有的鲁棒特性在系统的输入端得到基本恢复。最后仿真结果证明了LQG/LTR控制器的有效性和鲁棒性。