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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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Wire arc additive manufacturing(WAAM)has been investigated to deposit large-scale metal parts due to its high deposition efficiency and low material cost.However,in the process of automatically manufacturing the high-quality metal parts by WAAM,several problems about the heat build-up,the deposit-path optimization,and the stability of the process parameters need to be well addressed.To overcome these issues,a new WAAM method based on the double electrode micro plasma arc welding(DE-MPAW)was designed.The circuit principles of different metal-transfer models in the DE-MPAW deposition process were analyzed theoretically.The effects between the parameters,wire feed rate and torch stand-off distance,in the process of WAAM were investigated experimentally.In addition,a real-time DE-MPAW control system was developed to optimize and stabilize the deposition process by self-adaptively changing the wire feed rate and torch stand-off distance.Finally,a series of tests were performed to evaluate the con-trol system's performance.The results show that the capability against interferences in the process of WAAM has been enhanced by this self-adaptive adjustment system.Further,the deposition paths about the metal part's layer heights in WAAM are simplified.Finally,the appearance of the WAAM-deposited metal layers is also improved with the use of the control system.  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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The energy management and trajectory tracking control are crucial to realize long-endurance autonomous flight for hybrid electric UAVs. This study aims to comprehensively consider energy management and trajectory tracking for hybrid electric fixed wing UAVs with photovoltaic panel/fuel cell/battery. A double-layer fuzzy adaptive nonlinear model predictive control method (DFNMPC) is proposed. Separated by the surplus demand power, energy management and trajectory tracking problem are decoupled into the high-layer fuzzy adaptive nonlinear model predictive controll problem (H-FNMPC) and low-layer fuzzy adaptive nonlinear model predictive controll problem (L-FNMPC). H-FNMPC solves the trajectory tracking and navigation control probelm for the greatest benefit of solar energy. L-FNMPC solves the power allocation problem of hybrid energy system for minimum equivalent hydrogen consumption. A fuzzy adaptive prediction horizon adjustment method based on UAV maneuvering degree is proposed to effectively improve proposed method adaptability to different mission profiles. Analogously, a fuzzy adaptive equivalent hydrogen consumption factor adjustment method in L-FNMPC is proposed to ensure the flexible utilization of battery. In addition, an equivalent hydrogen flow rate calculation method based on the real-time current ratio is proposed for PV/FC/Battery hybrid energy system. Numerical simulation results including a spiral trajectory tracking and a quadrilateral trajectory tracking, demonstrate that DFNMPC can simultaneously handle energy management and trajectory tracking problem for hybrid electric UAVs. Compared to hierarchical fuzzy state machine strategy, DFNMPC can save 13.3% hydrogen for the spiral trajectory tracking, and 56.9% for the quadrilateral trajectory tracking. It indicates that the energy efficiency can be improved from both levels of energy management and flight motion. The proposed method prospected for exploring high-energy-efficiency autonomous flight of hybrid electric UAVs in the future.  相似文献   
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为探索生物活性未知的双对苯醌(2,7-dihydroxy-3,6,9-trimethyl-9H-xanthene-1,4,5,8-tetraone,DTXT)的抗氧化活性,并提高其发酵产量,考察DTXT的还原力以及对超氧阴离子自由基、羟自由基、1,1-二苯基-2-三硝基苯肼(1,1-diphenyl-2-picrylhydrazyl,DPPH)自由基的清除效果,在单因素试验基础上,采用响应面法优化了DTXT产生菌瓶生顶孢霉(Acremonium cavaraeanum)CA022菌株的固体发酵培养基。结果表明:在200 μg/mL质量浓度下,DTXT的还原力与芦丁差异不显著,高于VE和2,6-二叔丁基-4甲基苯酚,对超氧阴离子自由基清除率达到67.00%,对羟自由基清除率达到78.83%,对DPPH自由基清除率达到76.53%。通过响应面试验,得到最佳培养基配方为葡萄糖0.773%、硝酸钠0.185%、H3BO3 0.032%、VB1 100 μg/100 g,在此条件下实际获得的DTXT产量为4 150.8 mg/kg,是优化前产量的(2 864.83 mg/kg)1.45 倍。  相似文献   
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