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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   
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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   
4.
输油泵机组作为管道输油系统的主要设备,其运行状态影响着油田正常的生产。传统的针对泵机组的“预防为主,计划检修”检修模式由于缺乏实时性、灵活性,已无法满足设备安全稳定运行的要求。基于这种缺陷,通过“预测性维修”的方式实时掌握输油泵组运行状态趋势能够及时察觉设备故障,为企业计划性备品备件、提高生产效率、确保生产安全提供有力保障。因此,本文提出了一种基于ARMA模型的输油泵振动特征值趋势预测方案。通过对某输油站车间输油泵进行在线监测,得到测点振动信号特征值的历史数据。使用历史时间数据进行建模,进行当前时间数据预测。通过实际数据与预测数据对比,发现ARMA模型可以较好地拟合输油泵振动信号特征值,满足当下预测趋势的需求。该方案较于其他传统趋势预测方法准确率高、计算迅速、易于理解,填补了输油泵振动信号趋势预测方面的空白。  相似文献   
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在电力信息化战略的不断深入下,电力巡检机器人日益普及,为完善机器人功能,拓宽其应用前景,提出一种挂空异物智能检测方法。根据光照强度、天气状况等因素,基于不同颜色空间变量值与背景特征关联,合理利用对应滤波方式去除图像内噪声杂质。面向模糊不清的采集图像,依据前景与背景的分割阈值和平均灰度值,改变分段区间与拉伸区间,增强图像对比度。结合输电线路的直线特征与点线对偶特性,以霍夫变换直线提取法为基础识别出输电线路;通过设计的拟合恢复方法,获取完整的输电线路由局部二值模式图像特征点匹配策略,建立矩形兴趣范围,遍历像素点,检测出线路上的挂空异物。实验环节分别通过检测图像与评估指标数据,从主客观角度全面分析了检测效果,经实验结果验证,所提方法具有良好的可行性与适用性,能够较为准确地检测出多种异物。  相似文献   
6.
通过按照相关标准设计并制作校准试块及认证试块,研发针对船体结构焊缝的检测工艺,实现对船体结构焊缝的检测。通过同RT对比结果表明,PAUT技术检测结果与传统RT检测结果相对应,无漏检情况发生,且检测精度较高。该成果可对今后船体结构焊缝的检测提供技术支持,降低辐射风险,提高作业效率。  相似文献   
7.
针对直流配电网母线电压稳定性问题,设计了一种变增益线性扩张状态观测器(variable gain linear extended state observer,VGLESO),有效地解决了传统高增益线性扩张状态观测器(linear extended state observer extended state observer,LESO)在运行初始阶段输出存在峰值的问题。在此基础上进一步提出了一种变增益滑模自抗扰控制策略,将其应用到直流配电网AC-DC双向变流器控制系统中的电压外环。变增益滑模自抗扰控制策略在不需要增加额外电流传感器的情况下,就能够实现对系统总扰动的快速跟踪和补偿,有效地抑制了母线电压波动,提高了系统的动态响应。从理论上证明了VGLESO和变增益滑模自抗扰控制策略的稳定性。最后通过MATLAB/Simulink验证了该控制策略的可行性与正确性。  相似文献   
8.
The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.  相似文献   
9.
In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE2) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.  相似文献   
10.
Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.  相似文献   
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