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.     

Microstructures and mechanical properties of B4C-TiB2-SiC composites fabricated by ball milling and hot pressing

B₄C-TiB₂-SiC composites were fabricated via hot pressing using ball milled B₄C, TiB₂, and SiC powder mixtures as the starting materials. The impact of ball milling on the densification behaviors, mechanical properties, and microstructures of the ceramic composites were investigated. The results showed that the refinement of the powder mixtures and the removal of the oxide impurities played an important role in the improvement of densification and properties. Moreover, the formation of the liquid phases during the sintering was deemed beneficial for densification. The typical values of relative density, hardness, bending strength, and fracture toughness of the composites reached 99.20%, 32.84?GPa, 858?MPa and 8.21?MPa?m^1/2, respectively. Crack deflection, crack bridging, crack branching, and microcracking were considered to be the potential toughening mechanisms in the composites. Furthermore, numerous nano-sized intergranular/intragranular phases and twin structures were observed in the B₄C-TiB₂-SiC composite.     

安家岭露天矿过采空区危险源辨识及安全措施研究

危险源辨识对提高煤矿安全生产具有重要的现实意义。研究建立了基于层次分析法的安家岭露天矿危险源辨识模型,确定了危险源指标的权重。依据危险源辨识的权重研究了安家岭露天矿过采空区安全开采存在的主要危险源,并把采空区分为高温明火采空区、积水采空区、存在有毒气体的采空区、未冒实采空区,针对不同的类别的采空区提出了相应的安全开采措施。     

马钢张庄矿高压辊磨机装配工艺研究

针对马钢张庄矿高压辊磨机辊套疲劳断裂严重、对辊精度不能满足生产要求等问题，马钢重机公司根据张庄矿实际生产要求对对辊进行国产化，国产化内容包括辊轴、辊套等零部件的新制以及装配工艺攻关，通过技术研发同时结合实际生产经验，成功对高压辊磨机辊套与辊轴以及辊轴与轴承进行装配，完成了张庄矿高压辊磨机整对对辊的国产化，为该型设备后续生产及优化提供了理论和实践参考依据。     

关于当前钢材市场形势的看法

从今年3月初以来,钢材市场行情呈现明显恢复性上扬态势。据中国钢铁工业协会财务资产部和冶金价格信息中心发布的钢材价格指数,5月15日-5月19日板材平均已恢复到110.34点,比去年末上升17.92点,价格恢复性上涨19.38%,但比去年5月份的146.1点仍低24.5%;长材价格指数略有同升,在94.37点,比去年末只回升3.56点,价格只恢复性上涨3.92%,比去年5月份的102.19点仍低7.65。掘国家统计局数据,一季度全国规模以上工业企业销售收入同比增长25.3%,实现利润同比增长21.3%,但钢铁企业由于去年下半年价格大幅度下降,今年一季度钢协会员企业(钢产量占全国81.8%)销售收入同比下降5.18%,实现利润同比下降     

辐射型漏泄同轴电缆的设计

总结了漏泄同轴电缆的理论研究现状。围绕使用频带和耦合损耗这两个重要电气参数，讨论辐射型漏泄同轴电缆的设计方法。基于周期性槽孔结构的空间谐波的分析，讨论了抑制高次谐波以拓展使用频带的方法。利用时域有限差分方法和Matlab软件计算耦合损耗。     

WC/Cu复合材料制备及其高温性能

用机械合金化法结合冷变形，制备了WC／Cu复合材料，研究了冷变形后复合材料的组织特征和高温退火时韵性能变化。结果表明：烧结后的材料经冷变形，组织呈显著纤维状，WC颗粒弥散分布，密度明显提高，达到理论密度的99．2％；复合材料经600～900℃高温退火，强度和硬度略有下降，塑性则有大幅提高；900℃退火时未发生明显的再结晶，界面结合良好；所制备的WC／Cu复合材料有优良的综合性能。     

一种CMOS静态双沿顺序脉冲发生器的设计

提出一种基于CMOS技术的静态双沿顺序脉冲发生器结构。他是由以基于CMOS二选一选择器的电平型触发器构成的记忆单元和一个与门阵列组成的转译单元构成的。与门阵列的转译单元使顺序脉冲发生器在时钟上升沿和下降沿处均能输出移位脉冲,从而形成双沿触发的功能。仿真验证其功能正确,且根据分析该结构不仅能够节省芯片面积,还可以大大减小芯片的功耗。