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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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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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针对中性点不接地系统单相接地故障选线困难的问题,通过母线故障相接地故障转移与中性点接入小电阻的方式来增强故障信息从而选出故障线路。建立了故障转移阶段、并联电阻投入前后各个阶段的零序网络模型,分析了健全线路和故障线路各自的零序电流幅值的变化特征。在中性点小电阻投入、母线开关分闸前后各馈线零序电流幅值变化明显,健全线路零序电流在母线开关分闸后显著减小而故障线路零序电流增大。利用故障线路与健全线路的零序电流变化特征构建了不接地系统故障选线判据。大量的仿真计算验证了该方法对于不接地系统单相接地故障良好的适应性,有助于进一步提高故障选线准确率。  相似文献   
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硅橡胶复合绝缘子因其优异的憎水性及憎水迁移性而具备较好的防污闪能力,往往作为应对污闪事故的首选方案。但在部分特殊工业粉尘地区,复合绝缘子在短时间运行后会出现爬电及蚀损现象,并发展为绝缘失效。为研究特殊工业粉尘地区复合绝缘子的腐蚀失效过程,测试了某特殊工业园区内运行的复合绝缘子的表面污秽度及污秽成分、污闪电压梯度、憎水性能及微观性能,并分析了其腐蚀失效过程。主要结论如下:绝缘子表面等值盐密为0.1~0.2 mg/cm2,其污秽成分与化工污源类似;存在自然污秽时绝缘子表面憎水性良好,但其憎水性的减弱、恢复及迁移特性均不能满足运行要求;绝缘失效的起因是电晕放电导致憎水性降低,进而导致伞裙电蚀损,最后发展为绝缘失效。  相似文献   
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目前在集成电路测试中,测试时间长、测试效率低是影响测试成本的关键问题之一,针对此问题提出了一种基于测试性能估算的测试集重排序方法。首先针对不同的故障类型进行分类建模,然后对每种故障类型进行仿真,通过在每个逻辑门注入故障,统计测试向量命中故障门的面积之和来估算测试向量的测试性能,最后根据测试性能的优劣对测试集进行重新排序。实验表明,对于单固定故障使用排序后的测试集测试可以减少5329%的故障检测时间。该方法是通过对电路的逻辑结构进行分析和统计然后对测试集进行优化,对ISCAS 89标准电路进行试验,与其他测试集重排序对比,有着明显的优化。算法运行完全是基于软件的,不需要增加任何硬件开销,可以直接相容于传统的集成电路测试流程。  相似文献   
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介绍光伏电站的充油箱变色谱普测情况,通过统计分析氢气、总烃等指标超标率及故障类型,从设备、施工、运维等方面进行原因分析,提出了增加出厂前局部放电试验、加强工艺施工控制、有针对性的检修等整改措施和预防策略,对此类箱变的运行维护有一定的借鉴意义。  相似文献   
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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.
Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.  相似文献   
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