A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Regulation of sensory nerve conduction velocity of human bodies responding to annual temperature variations in natural environments

The extensive research interests in environmental temperature can be linked to human productivity / performance as well as comfort and health; while the mechanisms of physiological indices responding to temperature variations remain incompletely understood. This study adopted a physiological sensory nerve conduction velocity (SCV) as a temperature‐sensitive biomarker to explore the thermoregulatory mechanisms of human responding to annual temperatures. The measurements of subjects’ SCV (over 600 samples) were conducted in a naturally ventilated environment over all four seasons. The results showed a positive correlation between SCV and annual temperatures and a Boltzmann model was adopted to depict the S‐shaped trend of SCV with operative temperatures from 5°C to 40°C. The SCV increased linearly with operative temperatures from 14.28°C to 20.5°C and responded sensitively for 10.19°C‐24.59°C, while tended to be stable beyond that. The subjects’ thermal sensations were linearly related to SCV, elaborating the relation between human physiological regulations and subjective thermal perception variations. The findings reveal the body SCV regulatory characteristics in different operative temperature intervals, thereby giving a deeper insight into human autonomic thermoregulation and benefiting for built environment designs, meantime minimizing the temperature‐invoked risks to human health and well‐being.     

锦纶长丝染色均匀度判色新方法

锦纶长丝的染色均匀度测试方法一直是采用人工判色方法,其判色结果会因人眼目光的不同导致经常会存在一定的误差,对企业节约成本和实际生产应用相当不利。本文提出了一种利用测试锦纶DTY长丝热收缩应力的方法,用热应力测试结果对锦纶染色性能进行预判,不需要进行织袜染色,为企业节约大量的人工成本。     

Stick-Breaking Dependent Beta Processes with Variational Inference

Neural Processing Letters - The beta processes (BP) is a powerful nonparametric tool in feature learning, which is often used as the prior of Bernoulli process for choosing features from a feature...     

浅谈客运机车走行部风险调研及对策

针对机车走行部关键部位存在的风险及日常机车运用和检修存在的问题,进行了调查分析并提出预防对策,保证了机车走行部的运行安全。     

Study of MW-scale biogas-fed SOFC-WGS-TSA-PEMFC hybrid power technology as distributed energy system: Thermodynamic,exergetic and thermo-economic evaluation

Advanced biogas power generation technology has been attracting attentions, which contributes to the waste disposal and the mitigation of greenhouse gas emissions. This work proposes and models a novel biogas-fed hybrid power generation system consisting of solid oxide fuel cell, water gas shift reaction, thermal swing adsorption and proton exchange membrane fuel cell (SOFC-WGS-TSA-PEMFC). The thermodynamic, exergetic, and thermo-economic analyses of this hybrid system for power generation were conducted to comprehensively evaluate its performance. It was found that the novel biogas-fed hybrid system has a gross energy conversion efficiency of 68.63% and exergy efficiency of 65.36%, indicating high efficiency for this kind of hybrid power technology. The market sensitivity analysis showed that the hybrid system also has a low sensitivity to market price fluctuation. Under the current subsidy level for the distributed biogas power plant, the levelized cost of energy can be lowered to 0.02942 $/kWh for a 1 MW scale system. Accordingly, the payback period and annual return on investment can reach 1.4 year and about 20%, respectively. These results reveal that the proposed hybrid system is promising and economically feasible as a distributed power plant, especially for the small power scale (no more than 2 MW).     

三门峡地区黄土工程特性

三门峡地区广泛分布第四纪黄土及黄土状土,通过分析该地区黄土的颗粒成分、矿物成分、化学成分、微观结构特征,分析了黄土的工程特性,结果表明:该地区Q3黄土的组成与中更新统黄土的矿物组成基本相近,颗粒组成以粉粒为主,黏粒含量大于我国西北地区,粉粒含量小于西北地区;全新统黄土、晚更新统黄土为中等、强湿陷性黄土,湿陷性系数为0.020~0.098,中更新统黄土一般不具有湿陷性。     

A computer aided design method for car form and its application based on shape parameters

In the early design stage, automotive modeling should both meet the requirements of aesthetics and engineering. Therefore, a vehicle CAD (computer aided design) model that can be easily adjusted by feedbacks is necessary. Based on CE-Bézier surface, this paper presents a set of algorithms for parametric segmentation and fairing surface generation in a car model. This model is defined by a simplified automotive template and relevant control points, shape parameters and segmentation parameters, which can be modified to alter the car form efficiently. With this model and the corresponding adjustment method, more than fifty various vehicle models are established in this research according to different parameters. And two methods for calculating similarity index between car models are constructed, which are suitable for brand design trend analysis and modelling design decisionmaking.