Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets

Introduction

Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials and methods

GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.

Results

We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.

Discussion

The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.

     

Mechanical and corrosion properties of low-carbon steel prepared by friction stir processing

Low-carbon steel plates were successfully subjected to normal friction stir processing(NFSP) in air and submerged friction stir processing(SFSP) under water, and the microstructure, mechanical properties, and corrosion behavior of the NFSP and SFSP samples were investigated. Phase transformation and dynamic recrystallization resulted in fine-grained ferrite and martensite in the processed zone. The SFSP samples had smaller ferrites(5.1 μm), finer martensite laths(557 nm), and more uniform distribution of martensite compared to the NFSP samples. Compared to the base material(BM), the microhardness of the NFSP and SFSP samples increased by 19.8% and 27.1%, respectively because of the combined strengthening effects of grain refinement, phase transformation, and dislocation. The ultimate tensile strengths(UTSs) of the NFSP and SFSP samples increased by 27.1% and 38.7%, respectively. Grain refinement and martensite transformation also improved the electrochemical corrosion properties of the low-carbon steel. Overall, the SFSP samples had better mechanical properties and electrochemical corrosion resistance than the NFSP samples.     

干湿循环和吸力对非饱和下蜀土力学特性影响的试验研究

为研究干湿循环和吸力共同作用对非饱和下蜀土力学特性的影响,选取镇江某边坡的下蜀土为研究对象,通过非饱和直剪试验,对不同干湿循环次数及吸力水平下下蜀土力学特性的变化规律进行了研究.结果 表明:随着干湿循环次数的增加,下蜀土表面裂隙明显增加并具有不可逆性;下蜀土的抗剪强度经短暂增大后逐渐降低,并在第4次干湿循环作用后趋于稳定;下蜀土的黏聚力在经历短暂提高后逐渐降低并趋于稳定,而其内摩擦角则随干湿循环次数的增加变化幅度较小,呈上下波动态势;相同干湿循环次数下,吸力的存在对于下蜀土的黏聚力具有提升作用,而对土体内摩擦角的影响则不明显.研究结果可为干湿循环作用下下蜀土边坡的稳定性分析提供计算参数,具有实际工程意义.     

Side-Channel Attacks in a Real Scenario

Existing Side-Channel Attacks(SCAs) have several limitations and, rather than to be real attack methods,can only be considered to be security evaluation methods. Their limitations are mainly related to the sampling conditions, such as the trigger signal embedded in the source code of the encryption device, and the acquisition device that serves as the encryption-device controller. Apart from it being very difficult for an attacker to add a trigger into the original design before making an attack or to control the encryption device, there is a big gap in the capacity of existing SCAs to pose real threats to cipher devices. In this paper, we propose a new method, the sliding window SCA(SW-SCA), which can be applied in scenarios in which the acquisition device is independent of the encryption device and for which the encryption source code requires no trigger signal or modification. First,we describe the main issues in existing SCAs, then we theoretically analyze the effectiveness and complexity of our proposed SW-SCA —a method that can incorporate a sliding-window mechanism into almost all of the existing non-profiled SCAs. The experimental results for both simulated and physical traces verify the effectiveness of the SW-SCA and the appropriateness of its theoretical complexity.     

The Life-Cycle Model with Optimal Retiring Age and Simulation

In this paper, a life-cycle model with retirement is set up to study how an individual chooses the optimal retiring age on account of wage growth rate, longevity and healthy state. It is proved that there exists optimal retiring age under given conditions. The numerical simulations are given to show how wage growth rate, longevity and healthy state affect retiring age.     

螺栓连接大变形梁非线性振动特性的实验研究

柔性机械臂、大型可展开天线等机械结构的动作精度受运动过程中大变形几何非线性和连接处接触非线性的影响十分显著。以含螺栓连接结构的大变形梁作为研究对象，针对动力学建模和振动特性开展了实验研究，通过数值计算验证了实验发现的非线性振动特性。搭建了含螺栓连接柔性大变形梁的实验台架，开展了敲击和正弦激振的实验测试。实验结果表明，螺栓连接的柔性梁较连续梁的（无螺栓连接）模态频率降低，阻尼增加，反映出随着激励能量增大，模态频率降低的非线性模态特征。改变螺栓连接位置会显著影响结构的模态频率，其变化规律可由求解线性矩阵特征值定性反映。     

基于漫水填充的图像骨架提取方法

针对当前图像骨架提取存在毛刺现象和骨架冗余的问题,提出基于漫水填充的图像骨架提取方法。对目标图像预处理,得到阈值化二值图像,分割出前景和背景;构建掩模图像和轴线图,为后续运算过程提供数据来源和判断依据;通过遍历水平面灰度直方图,模拟漫水过程,收缩掩膜图像的前景轮廓,根据邻域连通分量变化,确定是否为骨架特征点,待轮廓收缩完毕,得到图像骨架。实验验证表明,该方法可以有效地提取图像骨架,毛刺现象和冗余结构明显减少,执行速度快。     

自动化码头运输设备充电策略优化的仿真研究

随着自动化集装箱码头成为当今码头的发展趋势,AGV(automated guided vehicle) 作为自动化码头中使用最为广泛的水平运输工具,合理制定其充电策略至关重要。针对当前自动化集装箱码头中AGV充电策略的不足,提出一种以离线充电为主在线充电为辅的充电策略,并且针对在线充电站点位置选择问题提出一种利用热区图选择有效在线充电站点的快捷方法。在使用该种充电策略情况下,通过大量仿真实验得出在码头工作任务量不变的前提下可减少AGV数量配置的结果,说明自动化集装箱码头水平搬运效率得到提高,证明该充电策略具有有效性。