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41.
Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.  相似文献   
42.
防碰装置是起重机械重要的安全防护装置,其性能质量直接关系到人员和设备安全。常规的防碰装置性能试验方法难以保证试验数据的精度和可靠性。针对防碰装置的工作特点和试验要求,从试验原理、系统结构、运行逻辑等方面入手,设计一套能模拟防碰装置实际运行工况,自动进行性能试验和数据采集处理,精度高、重复性好的试验系统,可以有效提升防碰装置检测能力。  相似文献   
43.
The present paper tests experimentally the through-thickness electrical conductivity of carbon fiber-reinforced polymer (CFRP) composites laminates for aircraft applications. Two types of samples were prepared: Type A samples with carbon nanotubes (CNTs) and Type B samples without CNTs. During the electrical experiments, electrical currents of several mA were injected through the specimens. Electrical resistance was monitored simultaneously in order to deduce the changes in the through-the-thickness electrical conductivity caused by the addition of CNTs. Improvement of electrical conduction by two orders of magnitude was achieved through the addition of 1 wt% carbon nanotubes as compared to classic CFRP without CNTs. For moisture saturated samples, the influence of moisture absorption on such measures was found to be negligible.  相似文献   
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It is important to take contact temperatures into account when developing friction and wear tests for potential tribomaterials and when analyzing the results of those tests. This paper presents some of the most useful analytical and numerical methods that can be used to predict surface temperature rises in dry or boundary lubricated pin-on-disk tribotests. The objective is the development of relatively simple, accurate, and easy-to-use expressions that can be used to predict contact temperatures in pin-on-disk sliding contacts. Results of the methods are compared for several different cases, and experimental verification of the predictions are also presented. The resulting expressions are applied to investigate wear of a ceramic (zirconia), metal (stainless steel) and polymer (polyethylene) in pin-on-disk tests.  相似文献   
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针对矫直速度对重轨矫后残余应力的影响进行研究,利用Pro/E建立60kg·m-1重轨九辊水平矫直模型,采用ANSYS Workbench对重轨矫直过程进行有限元数值模拟,通过现场矫直规程对采用现场矫直速度以及假定矫直速度得到的重轨矫后残余应力进行分析比较,得出了在其余条件不变的情况下重轨的矫直速度在1.4~1.6m·s-1的范围内其轨底矫后纵向残余拉应力小于250MPa,且残余应力分布合理,满足矫直要求,相比于现场采用的1.2m·s-1的矫直速度其生产效率最大能够提高16.7%~33.3%。  相似文献   
49.
Isothermal nucleic-acid amplification methods such as Loop-Mediated isothermal AMPlification (LAMP) are increasingly appealing alternatives to PCR for use in portable diagnostic system due to the low cost, weight, and power requirements of the instrumentation. As such, interest in developing new probes and other functionality based on the LAMP reaction has been intense. Here, we report on the development of duplexed LAMP assays for pathogen detection using spectrally unique Assimilating Probes. As proof of principle, we used a reaction for Salmonella enterica as a model coupled with a reaction for λ-phage DNA as an internal control, as well as a duplexed assay to sub-type specific quarantine strains of the bacterial wilt pathogen Ralstonia solanacearum. Detection limits for bacterial DNA analyzed in individual reactions was less than 100 genomic equivalents in all cases, and increased by one to two orders of magnitude when reactions were coupled in duplexed formats. Even so, due to the more robust activity of newly available strand-displacing polymerases, the duplexed assays reported here were more powerful than analogous individual reactions reported only a few years ago, and represent a significant advance for incorporation of internal controls to validate assay results in the field.  相似文献   
50.
对AP1000压水堆核电站安全壳贯穿件的非径向管板焊接接头结构特点进行了介绍,并分析其超声检测工艺的重点和难点。通过建立统一的缺陷定位坐标系并结合被检构件的几何特点进行综合分析,推导得出了h值(缺陷回波最高点距套管外壁的距离)的计算方法。为超声检测对这类焊接接头缺陷的准确识别和定位提供了行之有效的方法,为解决这类焊接接头的超声检测技术受限区提供了行之有效的措施。  相似文献   
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