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The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents.  相似文献   
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《Ceramics International》2022,48(13):18151-18156
The electrical properties and domain reversal in BiFeO3 ferroelectric films were studied using sandwiched heterostructures and piezoresponse force microscopy. A robust polarization state was observed, combined with a switchable domain pattern and a remanent polarization of approximately 100 μC cm?2. In addition, domain reversal was explored using scanning probe microscopy. The results show that dipoles could be reversed along the direction of the electric field under a negative tip bias, leading to carrier gathering near the domain walls. The enhanced conductivity near the domain walls was owing to the discontinuous polarization boundary conditions. In addition, typical diode-like current transport properties are sensitive to various temperature conditions, which is attributed to the Schottky barriers at the contact interface. These findings extend the current understanding of domain texture reversal in ferroelectric films and shed light on their potential applications for future ferroelectric random-access memory operations over a wide temperature range.  相似文献   
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Hexagonal rare-earth ferrites (h-RFeO3) have attracted much scientific attention due to their room-temperature multiferroicity. However, it is still a hard job to obtain h-RFeO3 bulk materials because of the meta-stability of such hexagonal phase, and the evaluation of room-temperature ferroelectric and magnetoelectric characteristics in such materials is also a challengeable issue. In the present work, Yb1−xInxFeO3 ceramics with the stable hexagonal structure were obtained by introducing chemical pressure, where the unique ferroelectric domain structures of sixfold vortex combined with tenfold vortex with a typical size of ~400 nm were determined. Symmetry of the present system evolved from centrosymmetric orthorhombic Pbnm (x = 0–0.4) to non-centrosymmetric hexagonal P63cm (x = 0.5 and 0.6) with a ferroelectric polarization up to 3.2 μC/cm2, and finally to centrosymmetric hexagonal P63/mmc (x = 0.7 and 0.8). The Curie point decreased monotonically from 723 K to a temperature below room temperature with increasing x, and the antiferromagnetic phase transition above room temperature was determined for all compositions. Meanwhile, a large linear magnetoelectric coefficient (αME) up to 0.96 mV/cm Oe was obtained at room temperature, and this indicated the great application potential for magnetoelectric devices.  相似文献   
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Professor Utkin proposed an example showing that the amplitude of chattering caused by the presence of parasitic dynamics (stable actuators) in some systems governed by the First‐Order Sliding‐Mode Controller is lower than that produced by the Super‐Twisting Algorithm. This example served to motivate this paper reconsidering the problem of comparison of chattering in systems with stable actuators, and driven by Discontinuous Sliding‐Mode Controllers (DSMCs) and Continuous Sliding‐Mode Controllers (CSMCs). Comparison of chattering produced by DSMC and CSMC taking into account their amplitudes, frequencies, and average power (AP) needed to maintain the system into real‐sliding modes, allowing to conclude the following: (i) for systems with slow actuators, the amplitude of oscillations and AP produced by DSMC be smaller than those caused by CSMC; (ii) for bounded disturbances with fixed Lipschitz constant, there exist sufficiently fast actuators for which the amplitude of oscillations and AP produced by CSMC be smaller than those caused by DSMC.  相似文献   
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《工程(英文)》2019,5(4):624-636
An intelligent manufacturing system is a composite intelligent system comprising humans, cyber systems, and physical systems with the aim of achieving specific manufacturing goals at an optimized level. This kind of intelligent system is called a human–cyber–physical system (HCPS). In terms of technology, HCPSs can both reveal technological principles and form the technological architecture for intelligent manufacturing. It can be concluded that the essence of intelligent manufacturing is to design, construct, and apply HCPSs in various cases and at different levels. With advances in information technology, intelligent manufacturing has passed through the stages of digital manufacturing and digital-networked manufacturing, and is evolving toward new-generation intelligent manufacturing (NGIM). NGIM is characterized by the in-depth integration of new-generation artificial intelligence (AI) technology (i.e., enabling technology) with advanced manufacturing technology (i.e., root technology); it is the core driving force of the new industrial revolution. In this study, the evolutionary footprint of intelligent manufacturing is reviewed from the perspective of HCPSs, and the implications, characteristics, technical frame, and key technologies of HCPSs for NGIM are then discussed in depth. Finally, an outlook of the major challenges of HCPSs for NGIM is proposed.  相似文献   
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域名具有重要的品牌价值,研究域名管理体系有利于开展域名注册与保护。现行域名注册规则容易导致域名与字号、商标、姓名等传统权利的冲突。互联网域种类繁多、层级结构复杂,企业应当建立域名注册评估机制、抢注侵权监测机制,加强域名注册与维权保护。  相似文献   
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以适用于中等水深(50~200 m)的新型潜式浮式风力机为研究对象,该风力机基础综合Spar式、半潜式及张力腿(TLP)3类浮式风力机基础的优点,运行时基础主体淹没在水下,具有较小的水线面(如同Spar平台),受波浪影响较小;平台通过张紧式系泊线与海床相连(如同TLP平台),具有良好的垂荡和摇摆运动特性;拖航状态下,浮式平台处于半潜状态,水线面面积大(如同半潜式平台),具有良好的浮稳性。通过分析不同波况下的潜式浮式风力机耦合动力响应得到潜式浮式基础的横荡、纵荡、垂荡及纵摇运动响应,以及发电功率、叶片根部弯矩、塔筒顶部和底部弯矩、锚链张力时程曲线。研究结果表明:波浪对于结构的纵摇运动的影响最为明显,对发电功率、叶片根部弯矩和塔筒顶部弯矩影响较小,对塔筒底部弯矩和系泊线张力影响较大。  相似文献   
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