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1.
Peter K. Windsor Stephen P. Plassmeyer Dominic S. Mattock Jonathan C. Bradfield Erika Y. Choi Bill R. Miller III Byung Hee Han 《International journal of molecular sciences》2021,22(6)
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.
针对目前工业CT图像转换为3D打印G代码方法效率低的问题,提出一种基于邻层数据匹配的工业CT图像直接转换成G代码的方法。首先采用Canny算子提取工业CT图像的轮廓,然后处理轮廓分叉问题,实现邻层间几何信息数据匹配,其次进行邻层间轮廓插值以满足3D打印层间厚度要求,从而避免"阶梯效应",最后通过填充编码得到用于3D打印的G代码。使用本文提出的方法,轮毂CT图像转换为G代码的时间为10.5 s,耗时远小于其他间接转换方法;3D打印出的轮毂无"阶梯效应",平均尺寸误差率为0.25%。实验结果表明,该方法不涉及中间格式,转换效率高,转换误差与传统方法相当,适用于具有复杂内腔结构的零件。 相似文献
3.
Sobha Karuthedom George Lucia Laukov Ren Weiss Vladislav Semak Birgit Fendl Victor U. Weiss Stephanie Steinberger Günter Allmaier Carla Tripisciano Viktoria Weber 《International journal of molecular sciences》2021,22(8)
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
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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
6.
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
7.
为解决系统模型误差、外部干扰以及执行器故障引起的双星编队轨道控制精度低、稳定性差问题,设计一种基于观测器的抗干扰容错线性二次型调节器(LQR)控制策略。首先,根据编队双星相对运动动力学模型,设计基于双比例积分自适应律的增广观测器,同时实现对系统状态、间歇故障与快速时变故障、可建模干扰的快速精确估计,并采用H∞优化技术抑制不可建模干扰对控制系统的影响。其次,采用Lyapunov稳定性理论,保证动态误差系统渐近稳定。然后,在控制器中引入未知动态估计信息的前馈补偿项,设计闭环反馈抗干扰容错LQR控制律。最后实验结果表明,相比文献中控制方法,本文所提方法的编队卫星相对位置控制精度提高49.93%,验证了所设计的抗干扰容错LQR控制律的优越性,能够为双星编队构形保持提供精确控制策略。 相似文献
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10.
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