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1.
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.  相似文献   
2.
边界识别是位场数据解释中一项重要任务,可用于资源探测等领域,是目前研究的热点问题之一。对于深部异常体目标,采用传统的边界识别方法易出现模糊、发散、变形等问题,而改进的方法大多采用高阶导数,虽然能够很好地识别出深部异常体边界,但是计算复杂,易受噪声干扰。为了改善以上问题,提出了一种稳定的快速边界识别方法,仅利用符号函数和重磁垂直导数数据,即可均衡识别不同深度的目标,且避免了高阶导数的计算。通过理论模型的实验与对比,验证了方法的便捷性、有效性、抗斜磁化能力以及抗噪能力。同时,应用实测数据验证了方法在复杂重磁环境下,能够准确清晰地分辨出异常体,可节约相关研究人员的大量时间与精力,具有很好地应用前景。  相似文献   
3.
Carbon monoxide (CO)—gaseous or released by CO-RMs—both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO—delivered by gaseous CO–saturated buffer (COG) and generated by CORM-A1—on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of COG on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, COG did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by COG or CORM-A1, was dependent on sGC. We conclude that the source (COG vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.  相似文献   
4.
Growing interest in extracellular vesicles (EVs) has prompted the advancements of protocols for improved EV characterization. As a high-throughput, multi-parameter, and single particle technique, flow cytometry is widely used for EV characterization. The comparison of data on EV concentration, however, is hindered by the lack of standardization between different protocols and instruments. Here, we quantified EV counts of platelet-derived EVs, using two flow cytometers (Gallios and CytoFLEX LX) and nanoparticle tracking analysis (NTA). Phosphatidylserine-exposing EVs were identified by labelling with lactadherin (LA). Calibration with silica-based fluorescent beads showed detection limits of 300 nm and 150 nm for Gallios and CytoFLEX LX, respectively. Accordingly, CytoFLEX LX yielded 40-fold higher EV counts and 13-fold higher counts of LA+CD41+ EVs compared to Gallios. NTA in fluorescence mode (F-NTA) demonstrated that only 9.5% of all vesicles detected in scatter mode exposed phosphatidylserine, resulting in good agreement of LA+ EVs for CytoFLEX LX and F-NTA. Since certain functional characteristics, such as the exposure of pro-coagulant phosphatidylserine, are not equally displayed across the entire EV size range, our study highlights the necessity of indicating the size range of EVs detected with a given approach along with the EV concentration to support the comparability between different studies.  相似文献   
5.
6.
砂卵石地层是一种典型的力学不稳定地层及强磨蚀性地层,盾构在该类地层中掘进通常会面临刀盘、刀具磨损严重,盾构推力与刀盘扭矩偏高且波动幅度大、地层变形不易控制等问题。砂卵石地层盾构掘进效率的高低及地层控制的好坏,刀盘选型及刀具配置是关键。以北京地铁新机场线“磁各庄站~1#风井”盾构区间为工程依托,利用PFC3D数值模拟及现场测试相结合的手段,研究刀盘开口率、刀具组合高差、先行刀刀间距等参数对盾构掘进效率及地层变形的影响。研究结果表明:相同掘进参数下大开口率辐条式刀盘比小开口率辐板式刀盘具有更好的掘进速度,小开口率辐板式刀盘掘进时引起的地表变形更小,对周围地层的扰动范围也更小;先行刀与切削刀的组合高差为70 mm时盾构掘进效率较高且扭矩较低;先行刀刀间距设定为300 mm时,盾构有较好的掘进效率和较低的刀盘扭矩。工程实践表明;要实现砂卵石地层盾构长距离高效掘进,大开口率辐条式刀盘设计及大高差梯次化刀具布置是基础,高贯入度、低转速的掘进控制是关键。研究结果可为类似工程的盾构刀盘选型与刀具布设提供借鉴。  相似文献   
7.
This work describes the procedure used to define the measurement uncertainties of horizontal two-phase air-water flow experiments conducted to determine influences due to pipe diameter on pressure gradient on such flows. These experiments were performed with 4 different pipe diameters, always using the same test section length, therefore varying the length-to-diameter (L/D) ratio. Several parameters were measured, such as volumetric/mass flow rate, pressures, temperatures and pressure drop; other parameters were calculated, such as the superficial velocities of each fluid, as well as their corresponding properties. The main parameters studied were the flow patterns for different velocity configurations and the two-phase pressure drop to be used for model improvement, thus the importance of uncertainties analysis. The sources of uncertainty were defined, detailed, systematically studied and quantified. Also, the reproducibility capacity of the experimental setups were analysed through the uncertainty analysis and proving them to be able for future similar studies. The flow maps with their uncertainties could help understand the thresholds for each defined flow pattern region, and the plots of two-phase pressure drop variation with diameter confirmed the homogeneous model as a possible approach to calculate pressure drop if the uncertainties are considered.  相似文献   
8.
拉臂机构作为拉臂式垃圾车的关键部位,直接决定整车的可靠运行与人员操作体验,文中在分析拉臂机构的力学特性基础上,计算出在装卸工况下的载荷,利用有限元分析软件,对拉臂机构关键部位进行静态有限元分析与模态分析,分析结果表明拉臂机构符合动态性能要求,但其工作时强度不足,需对此进行结构优化。通过对拉臂机构进行局部修改,采取必要的辅助措施,使其达到符合静态性能要求的目的。在满足拉臂机构静动态性能要求上,装箱工况最大应力降低了23.3%,卸箱工况最大应力降低了24.9%,较好地达到了提高拉臂机构安全性能的目的。  相似文献   
9.
针对塔式起重机起重量限制器现场检验的约束条件,提出了一种利用夹绳器及施力装置配合的无载荷试重系统模型,拟解决现场难以配备标准重物及检验成本过高的问题,并通过模拟塔式起重机钢结构受力情况,分析了该理论模型系统的安全性。  相似文献   
10.
唐伦    姚力  肖畅  张弛  孙毅  过夏明  刘巍  邓扶摇 《陕西电力》2021,(2):47-53
发电机故障停运是电力系统运行中的不确定事件。目前在含风电鲁棒机组组合中考虑机组故障停运的方法,不同程度地忽略了机组故障停运的概率特征,难以较好描述机组故障停运风险。在含风电鲁棒机组组合模型的基础上,引入电量不足期望以量化机组故障停运风险,基于成本收益分析建立了考虑风电不确定性和机组故障停运风险的两阶段鲁棒机组组合模型,并提出计算电量不足期望的简化模型以提升计算效率。基于改进的IEEE-RTS 26机系统验证所提模型和方法,结果表明该方法能较好考虑风电不确定性和机组故障停运风险的影响,该简化模型能显著减小问题求解规模、缩短计算时间。  相似文献   
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