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.     

电磁精细探测法在隐伏型导水地质裂缝勘探中的应用

针对传统隐伏型导水地质裂缝勘探方法存在勘测精度较差的问题,提出电磁精细探测法探析隐伏型导水地质裂缝。依照屏蔽系数、实测场强和理论场强数据绘制综合曲线图,通过该图获取隐伏型导水地质裂缝所处位置几何阴影范围,采用层析成像法得到网格化的工作面,获取隐伏型导水地质图像。通过图像直接观测隐伏型导水地质工作面裂缝所处位置,在此基础上,观测四个电磁场分量,采用正交电磁场分量计算介质视电阻率,依据计算视电阻率数值和视电阻率分布状态研究裂缝发育情况和裂缝富水程度。结果表明:采用该方法能较为精准地获取隐伏型导水地质裂缝位置。通过裂缝位置进一步检测出隐伏型导水地质裂缝最大发育高度为63.5 m。当视电阻数值不断增加时,隐伏型导水地质裂缝和裂缝富水性逐渐减小,与实际情况较为相符,说明该种方法探析效果较好。     

Correlation between instrumental texture and colour quality attributes with sensory analysis of selected cheeses as affected by fat contents

This study evaluated several physical and sensory parameters of different types of cheese available in the Polish market. The measurements of textural properties were conducted in an Instron universal testing machine, while the colour properties of cheeses were measured using a Minolta chromameter. The chemical composition was determined by means of the near‐infrared spectroscopy (NIRs). Moreover, a trained sensory panel was invited to assess the cheese texture‐related properties. Generally, cheeses with reduced fat content were characterised by higher hardness, adhesiveness, cohesiveness and elasticity. Texture‐related parameters of cheese with canola oil were comparable to that of most of full‐fat cheeses. The correlation analysis between physical and sensory attributes related to cheese textural properties indicated the potential applications of TPA, shear and penetration tests (r = 0.766, r = 0.75 and r = 0.765, respectively) for the evaluation of sensory properties related to the hardness. Meanwhile, the elasticity of cheese obtained from sensory evaluation was strongly correlated with the elasticity determined from the shear test (r = 0.722) and moderately correlated with the elasticity from penetration test (r = 0.588), indicating a need to refine the method of penetration test. In addition, cheeses exhibited higher meltability during convection heating at 230 °C than microwave heating. The values of meltability for cheese with reduced fat content were lower than those of full‐fat cheese.     

内插法在相关干涉仪测向体制中的应用

测向误差的减小一直以来都是无线电测向精度提高的一个难点,对于不同的测向体制所采用的减小测向误差的方法都不尽相同。本文主要介绍的是相关干涉仪测向体制的基本原理以及通过内插法的应用来减小测向误差的方法。     

课程群案例嵌入协同教学模式的探索

在课程群的教学中由于每门课程各自独立开展教学,缺乏知识的融合和衔接,导致学生运用综合知识解决问题的能力较弱。在课程群的教学中采用案例嵌入协同教学模式,将完整的工程案例嵌入到课程群各门课程的教学中,协同规划各门课程的教学任务,每门课程再围绕案例展开研究性教学。通过嵌入的工程案例衔接各门课程的知识点,帮助学生建构完整的知识体系,强化工程应用的概念；同时通过研究性教学,培养学生分析问题和解决问题的能力,两部分相结合,提高了学生运用综合知识解决复杂问题的能力。