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Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.  相似文献   
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The realization of liquid metal-based wearable systems will be a milestone toward high-performance, integrated electronic skin. However, despite the revolutionary progress achieved in many other components of electronic skin, liquid metal-based flexible sensors still suffer from poor sensitivity due to the insufficient resistance change of liquid metal to deformation. Herein, a nacre-inspired architecture composed of a biphasic pattern (liquid metal with Cr/Cu underlayer) as “bricks” and strain-sensitive Ag film as “mortar” is developed, which breaks the long-standing sensitivity bottleneck of liquid metal-based electronic skin. With 2 orders of magnitude of sensitivity amplification while maintaining wide (>85%) working range, for the first time, liquid metal-based strain sensors rival the state-of-art counterparts. This liquid metal composite features spatially regulated cracking behavior. On the one hand, hard Cr cells locally modulate the strain distribution, which avoids premature cut-through cracks and prolongs the defect propagation in the adjacent Ag film. On the other hand, the separated liquid metal cells prevent unfavorable continuous liquid-metal paths and create crack-free regions during strain. Demonstrated in diverse scenarios, the proposed design concept may spark more applications of ultrasensitive liquid metal-based electronic skins, and reveals a pathway for sensor development via crack engineering.  相似文献   
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Images with hazy scene suffer from low-contrast, which reduces the visible quality of the scene, thus making object detection a more challenging task. Low-contrast can result from foggy weather conditions during image acquisition. Dehazing is a process of removal of haze from the photography of a hazy scene. Single-image dehazing based on dark channel priors are well-known techniques in this field. However, the performance of such techniques is limited to priors or constraints. Moreover, this type of method fails when images have sky-region. So, a method is proposed, which can restore the visibility of hazy images. First, a hazy image is divided into blocks of size 32 × 32, then the score of each block is calculated to select a block having the highest score. Atmospheric light is calculated from the selected block. A new color channel is considered to remove atmospheric scattering, obtained channel value and atmospheric light are then used to calculate the transmission map in the second step. Third, radiance is computed using a transmission map and atmospheric light. The illumination scaling factor is adopted to enhance the quality of a dehazed image in the final step. Experiments are performed on six datasets namely, I-HAZE, O-HAZE, BSDS500, FRIDA, RESIDE dataset and natural images from Google. The proposed method is compared against 11 state-of-the-art methods. The performance is analyzed using fourteen quantitative evaluation metrics. All the results demonstrate that the proposed method outperforms 11 state-of-the-art methods in most of the cases.  相似文献   
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基于GA-BP的汽车风振噪声声品质预测模型   总被引:1,自引:1,他引:0  
目前对于汽车风振噪声的优化研究主要以声压级(Sound pressure level,SPL)作为单一评价指标,既不能全面反映噪声的物理属性,也无法考虑人耳对噪声的主观认知过程。为准确评价风振噪声,引入声品质,运用大涡模拟(Large eddy simulation,LES)对风振噪声进行数值仿真,根据实车道路试验判断仿真的准确性;对仿真结果进行声品质客观评价与主观评价,综合声品质客观评价参数与声品质主观评价试验结果建立BP神经网络预测模型;利用遗传算法(Genetic algorithm,GA),进一步对BP神经网络的结构参数进行优化,建立GA-BP声品质预测模型。研究结果表明,GA-BP声品质预测模型在训练速度和预测精度上都优于BP神经网络预测模型。预测模型基于声品质主客观评价结果,其预测值可以代替传统的声压级评价指标,为风振噪声提供更为准确合理的评价。  相似文献   
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杨春燕  宾冬梅  黎新 《电信科学》2021,37(2):144-153
提出了一种基于实用拜占庭容错(PBFT)算法的区块链技术,首先对传统的实用拜占庭容错算法原理进行了阐述,该传统算法包含前期、需求、预准备、准备、确认、答复6个阶段,但传统算法具有实时性差、缺乏惩罚机制、带宽高的缺点。针对出现的这些问题,又对传统算法进行了改进,具体涉及记账节点、共识过程以及视图切换过程。通过测试进一步证明了该改进算法的实用性,并将该算法应用于电网企业中,构建的虚拟仓库实现了联储联备,降低了库存资金的耗费,并且提高了电网企业库存管理的效率。  相似文献   
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This paper develops a novel approach to the parameterisation of high temperature exchange membrane fuel cells (HTPEMFC) with limited and non-invasive measurements. The proposed method allows an effective identification of electrochemical parameters for three-dimensional fuel cell models by combining computational simulation tools and genetic algorithms. To avoid each evaluation undertaken by the optimisation method involving a complete computational simulation of the 3D model, a strategy has been designed that, thanks to an iterative process, makes it possible to decouple the fluid dynamic resolution from the electrochemistry one.Two electrochemical models have been incorporated into these tools to describe the behaviour of the catalyst layer, Butler-Volmer and spherical aggregate. For each one, a case study has been carried out to validate the results by comparing them with empirical data in the first model and with data generated by numerical simulation in the second. Results show that, from a set of measured operating conditions, it is possible to identify a unique set of electrochemical parameters that fits the 3D model to the target polarisation curve. The extension of this framework can be used to systematically estimate any model parameter in order to reduce the uncertainty in 3D simulation predictions.  相似文献   
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