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1.
Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1G227R and NEU1V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1G227R- and NEU1V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1G227R- and NEU1V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy–lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs. 相似文献
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根据剪切解络-超滤过程中金属离子的动态浓度关系和质量守恒定律,采用CodeBlocks17.12软件编写程序,建立了剪切解络-超滤工艺关键指标预测模型,实现了金属离子浓度、回收率、体积稀释倍数等指标的预测,并用实验加以验证。依次在转速800 r/min、1 400 r/min、3 000 r/min下回收模拟废水中43 μg/L的Co2+、995 μg/L的Ni2+和88 μg/L的La3+,3种金属的回收率均达99.8%以上时,超滤过程体积稀释倍数的预测值分别为7.0、7.5、5.75,实验值分别为7.5、7.25、6.25,可见预测值与实验值基本一致。本模型对研究方案制定和调整有实际指导意义。 相似文献
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诱导式卫星欺骗干扰可诱导航空器逐渐偏离预定航迹,难以被发现,因此及时有效地检测干扰是飞行安全的保障。在现有紧组合导航体制基础上,设计了一种基于误差估值累加开环校正的紧组合导航结构,并证明了其性能与传统闭环校正紧组合导航性能等效。在此结构中,将紧组合导航系统与自适应序贯概率比检测方法结合,提出了一种基于误差估值累加开环校正的诱导式欺骗检测方法,融合紧组合导航信息与其他不受欺骗影响的导航信息,构建欺骗检测统计量进行诱导式欺骗检测。仿真结果表明,开环校正结构可避免随时间累加的惯性导航系统误差所导致的组合导航滤波器发散问题,同时欺骗检测方法可进一步提高算法对“最坏”情形下微小诱导式欺骗的检测效果。 相似文献
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《岩石力学与岩土工程学报(英文版)》2022,14(5):1556-1567
Wind erosion is one of the significant natural calamities worldwide, which degrades around one-third of global land. The eroded and suspended soil particles in the environment may cause health hazards, i.e. allergies and respiratory diseases, due to the presence of harmful contaminants, bacteria, and pollens. The present study evaluates the feasibility of microbially induced calcium carbonate precipitation (MICP) technique to mitigate wind-induced erosion of calcareous desert sand (Thar desert of Rajasthan province in India). The temperature during biotreatment was kept at 36 °C to stimulate the average temperature of the Thar desert. The spray method was used for bioaugmentation of Sporosarcina (S.) pasteurii and further treatment using chemical solutions. The chemical solution of 0.25 pore volume was sprayed continuously up to 5 d, 10 d, 15 d, and 20 d, using two different concentration ratios of urea and calcium chloride dihydrate viz 2:1 and 1:1. The biotreated samples were subjected to erosion testing (in the wind tunnel) at different wind speeds of 10 m/s, 20 m/s, and 30 m/s. The unconfined compressive strength of the biocemented crust was measured using a pocket penetrometer. The variation in calcite precipitation and microstructure (including the presence of crystalline minerals) of untreated as well as biotreated sand samples were determined through calcimeter, scanning electron microscope (SEM), and energy-dispersive X-ray spectroscope (EDX). The results demonstrated that the erosion of untreated sand increases with an increase in wind speeds. When compared to untreated sand, a lower erosion was observed in all biocemented sand samples, irrespective of treatment condition and wind speed. It was observed that the sample treated with 1:1 cementation solution for up to 5 d, was found to effectively resist erosion at a wind speed of 10 m/s. Moreover, a significant erosion resistance was ascertained in 15 d and 20 d treated samples at higher wind speeds. The calcite content percentage, thickness of crust, bulk density, and surface strength of biocemented sand were enhanced with the increase in treatment duration. The 1:1 concentration ratio of cementation solution was found effective in improving crust thickness and surface strength as compared to 2:1 concentration ratio of cementation solution. The calcite crystals formation was observed in SEM analysis and calcium peaks were observed in EDX analysis for biotreated sand. 相似文献
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Hui-Yung Song Yi-Ping Yang Yueh Chien Wei-Yi Lai Yi-Ying Lin Shih-Jie Chou Mong-Lien Wang Chien-Ying Wang Hsin-Bang Leu Wen-Chung Yu Chian-Shiu Chien 《International journal of molecular sciences》2021,22(5)
The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications. 相似文献
8.
为了在腔磁力系统中实现可控的磁子诱导透明、磁力诱导透明以及快慢光传播,建立了一个混合腔磁力系统.该系统由一个含有YIG球的微波腔和在z方向对球施加一个均匀的偏置磁场组成,并用强泵浦场驱动磁子和弱探测场驱动微波腔.研究表明,通过调节腔与磁子之间的相互作用强度和微波腔与磁子的耗散比,可以增加磁子诱导透明(MIT)、磁力诱导透明(MMIT)的效果和提高快慢光传播的速度.该研究结果可为磁力诱导放大、量子光学操纵和量子信息存储以及灵敏光开关的研究提供参考. 相似文献
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马尔可夫跳变线性系统(MJLS)是一种具有多个模态的随机系统,系统在各个模态之间的跳变转移由一组马尔可夫链来决定。MJLS模型因其在表示过程中可以产生突变而更能精确的描述实际工程应用中的系统。近年来,MJLS的最优控制问题成为了研究的热点,动态规划、极大值原理以及线性矩阵不等式等成为了解决此类问题的主流方法。本文对MJLS最优控制领域的研究现状进行了综述。分别对一般情况下、带有噪声的情况下、带有时滞的情况下以及某些特定情况下的MLJS最优控制问题的国内外研究现状进行论述。最后进行了总结并提出MJLS最优控制领域未来值得关注的研究方向。 相似文献
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This paper presents a physics-based compact gate delay model that includes all short-channel phenomena prevalent at the ultra-deep submicron technology node of 32 nm. To simplify calculations, the proposed model is connected to a compact α-power law-based (Sakurai-Newton) model. The model has been tested on a wide range of supply voltages. The model accurately predicts nominal delays and the delays under process variations. It has been shown that at lower technology nodes, the delay is more sensitive to threshold voltage variations, specifically at the sub-threshold operating region as compared with effective channel length variations above the threshold region. 相似文献