Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

Enhanced graphitic domains of unreduced graphene oxide and the interplay of hydration behaviour and catalytic activity

Previous studies indicate that the properties of graphene oxide (GO) can be significantly improved by enhancing its graphitic domain size through thermal diffusion and clustering of functional groups. Remarkably, this transition takes place below the decomposition temperature of the functional groups and thus allows fine tuning of graphitic domains without compromising with the functionality of GO. By studying the transformation of GO under mild thermal treatment, we directly observe this size enhancement of graphitic domains from originally ≤40 nm² to >200 nm² through an extensive transmission electron microscopy (TEM) study. Additionally, we confirm the integrity of the functional groups during this process by a comprehensive chemical analysis. A closer look into the process confirms the theoretical predicted relevance for the room temperature stability of GO and the development of the composition of functional groups is explained with reaction pathways from theoretical calculations. We further investigate the influence of enlarged graphitic domains on the hydration behaviour of GO and the catalytic performance of single atom catalysts supported by GO. Additionally, we show that the sheet resistance of GO is reduced by several orders of magnitude during the mild thermal annealing process.     

Traffic video‐based intelligent traffic control system for smart cities using modified ant colony optimizer

Road traffic congestion is a serious problem in today's world and it happens because of urbanization and population growth. The traffic reduces the transport efficiency in the city, increases the waiting time and travel time, and also increases the usage of fuel and air pollution. To overcome these issues this papers propose an intelligent traffic control system using the Internet of Vehicles (IoV). The vehicles or nodes present in the IoV can communicate between themselves. This technique helps in determining the traffic intensity and the best route to reach the destination. The area of study used in this paper is Vellore city in Tamilnadu, India. The city map is separated into many segments of equal size and Ant Colony Algorithm (AOC) is applied to the separated maps to find the optimal route to reach the destination. Further, Support Vector Machine (SVM) is used to calculate the traffic density and to model the heavy traffic. The proposed algorithm performs better in finding the optimal route when compared to that of the existing path selection algorithms. From the results, it is evident that the proposed IoV‐based route selection method provides better performance.     

Observations of Membrane Domain Reorganization in Mechanically Compressed Artificial Cells

Giant unilamellar vesicles (GUVs) are considered to be the gold standard for assembling artificial cells from the bottom up. In this study, we investigated the behavior of such biomimetic vesicles as they were subjected to mechanical compression. A microfluidic device is presented that comprises a trap to capture GUVs and a microstamp that is deflected downwards to mechanically compress the trapped vesicle. After characterization of the device, we show that single-phase GUVs can be controllably compressed to a high degree of deformation (D=0.40) depending on the pressure applied to the microstamp. A permeation assay was implemented to show that vesicle bursting is prevented by water efflux. Next, we mechanically compressed GUVs with co-existing liquid-ordered and liquid-disordered membrane phases. Upon compression, we observed that the normally stable lipid domains reorganized themselves across the surface and fused into larger domains. This phenomenon, observed here in a model membrane system, not only gives us insights into how the multicomponent membranes of artificial cells behave, but might also have interesting consequences for the role of lipid rafts in biological cells that are subjected to compressive forces in a natural environment.     

浅析智能网联汽车感知系统电磁兼容性

本文将就智能网联汽车感知系统中的电子兼容技术进行深入的分析和探究。     

Images of a First‐Order Spin‐Reorientation Phase Transition in a Metallic Kagome Ferromagnet

First‐order phase transitions, where one phase replaces another by virtue of a simple crossing of free energies, are best known between solids, liquids, and vapors, but they also occur in a wide range of other contexts, including even elemental magnets. The key challenges are to establish whether a phase transition is indeed first order, and then to determine how the new phase emerges because this will determine thermodynamic and electronic properties. Here it is shown that both challenges are met for the spin reorientation transition in the topological metallic ferromagnet Fe₃Sn₂. The magnetometry and variable temperature magnetic force microscopy experiments reveal that, analogous to the liquid–gas transition in the temperature–pressure plane, this transition is centered on a first‐order line terminating in a critical end point in the field‐temperature plane. The nucleation and growth associated with the transition is directly imaged, indicating that the new phase emerges at the most convoluted magnetic domain walls for the high temperature phase and then moves to self‐organize at the domain centers of the high temperature phase. The dense domain patterns and phase coexistence imply a complex inhomogenous electronic structure, which can yield anomalous contributions to the electrical conductivity.     

智能网联汽车APP中控制模块的视觉设计与应用

目的研究智能网联汽车手机APP中控制模块的视觉设计与应用,强化视觉设计过程的合理性,为智能汽车HMI设计实践工作提供启示与借鉴。方法首先从用户体验的角度分析APP控制模块存在的视觉设计问题,主要是视觉结构单一、视觉层级混乱、视觉特征缺失,再从行为逻辑的角度思考视觉设计方法,"由面及点"地提出控制模块的视觉设计思路,并结合设计应用案例论证其可行性。结果从合理视觉布局、明确视觉层级和提炼视觉语言的角度提出APP控制模块的视觉设计思路。结论智能网联汽车APP控制模块的视觉设计应该重视行为逻辑的影响。从任务角度思考视觉布局、从行为逻辑的角度思考视觉层级、从行为特征的角度思考视觉语言,提高视觉设计工作的合理性,减少与交互设计工作脱节的现象,强化控制求助的高效性和安全性。     

Failure load prediction and optimisation for adhesively bonded joints enabled by deep learning and fruit fly optimisation

Adhesively bonded joints have been extensively employed in the aeronautical and automotive industries to join thin-layer materials for developing lightweight components. To strengthen the structural integrity of joints, it is critical to estimate and improve joint failure loads effectually. To accomplish the aforementioned purpose, this paper presents a novel deep neural network (DNN) model-enabled approach, and a single lap joint (SLJ) design is used to support research development and validation. The approach is innovative in the following aspects: (i) the DNN model is reinforced with a transfer learning (TL) mechanism to realise an adaptive prediction on a new SLJ design, and the requirement to re-create new training samples and re-train the DNN model from scratch for the design can be alleviated; (ii) a fruit fly optimisation (FFO) algorithm featured with the parallel computing capability is incorporated into the approach to efficiently optimise joint parameters based on joint failure load predictions. Case studies were developed to validate the effectiveness of the approach. Experimental results demonstrate that, with this approach, the number of datasets and the computational time required to re-train the DNN model for a new SLJ design were significantly reduced by 92.00% and 99.57% respectively, and the joint failure load was substantially increased by 9.96%.     

华电集团华中总部基地主楼抗震性能设计

华电集团华中总部基地主楼的两个塔楼在顶部8层(47~54层)连为一体,为"门"形复杂连体超限高层建筑。结构存在楼板不连续、刚度和承载力突变、构件间断、局部不规则等5项不规则项。对主楼进行了抗震性能分析,确定了结构构件抗震性能目标。对主楼进行了小震静力弹性和弹性时程分析、中震和大震等效弹性分析及大震弹塑性时程分析,重点对比了单塔模型与整体模型统计的力学和变形指标的差异、加强层及连体桁架屈服情况,验算了墙肢受力状态,并根据分析结果采取相应的抗震措施,抗震性能达到预期的性能目标C类要求。最后针对地下室顶板开大洞、连体层楼板受力性能、结构抗连续倒塌等做了专门的计算分析与构造设计,结果满足要求。     

相连两结构体系的动力特性和抗震性能

不同动力特性的子结构通过某种方式连接后，体系的动力特性不仅取决于独立结构和连接构件本身的性能，而且还取决于它们之间的相互作用，其相互作用的影响程度主要是取决于连接构件的刚度以及连接方式。研究了此类结构体系的动力特性随着连接构件刚度的变化规律。对于利用天桥相连的两实际结构三雏模型的时程分析结果显示：（1）子结构的各项反应有着不同的变化规律，因此不能仅从一项反应的结果得出一般的结论；（2）利用非耗能元件相连结构动力特性的变化非常大，设计时不能忽视。