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.     

Elucidation of colour development and microstructural characteristics of Allium sativum fumigated with acetic acid

It has been well known that the greening of Allium sativum cloves could be formed after immersed in acetic acid solution. Nonetheless, no investigation was reported on colour development of A. sativum in response to acetic acid vapour until now. In this study, the brief exposure of A. sativum to acetic acid vapour (200–400 ppm) was combined with controlled atmosphere (5%, 20% and 80% CO₂) packaging storage to break cell membrane and green garlic. The garlic bulbs were fumigated with acetic acid before controlled CO₂ atmosphere packaging for 25 days at 4 °C. Fumigation with 200 ppm acetic acid followed by high CO₂ atmosphere packaging (80% CO₂) facilitated the garlic greening. It was also verified that γ‐glutamyl transpeptidase was involved in garlic greening in present study, and the compromise of glacial acetic acid vapour fumigation and CO₂ gas atmosphere in package stored at low temperature could result in garlic greening as well.     

Semantic word shifts in a scientific domain

Understanding semantic word shifts in scientific domains is essential for facilitating interdisciplinary communication. Using a data set of published papers in the field of information retrieval (IR), this paper studies the semantic shifts of words in IR based on mining per-word topic distribution over time. We propose that semantic word shifts not only occur over time, but also over topics. The shifts are examined from two perspectives, the topic-level and the context-level. According to the over-time word-topic distribution, stable words and unstable words are recognized. The diverging and converging trends in the unstable type reveal characteristics of the topic evolution process. The context-level shifts are further detected by similarities between word vectors. Our work associates semantic word shifts with the evolving of topics, which facilitates a better understanding of semantic word shifts from both topics and contexts.     

Nb和时效时间对热轧中锰TRIP钢中P偏聚的影响

热轧态中锰TRIP钢首先经650 ℃退火2 h,随后在550 ℃进行等温时效热处理,采用场发射扫描电镜(FE-SEM)研究该钢中P的偏聚和时效析出行为的变化情况。结果表明,中锰TRIP钢中P在晶界的偏聚是一种非平衡偏聚现象,临界时间约为50 h,与理论计算结果48 h较为吻合。在局部偏聚区域内,C与P存在共偏聚的关系,即P偏聚量高的地方,C含量也高。而合金元素Nb具有抑制P偏聚的效果,在20~70 h时效时间内,可以相对降低6.57%~19.5%的最大P偏聚量。根据电子背散射衍射(EBSD)菊池线分析,P偏聚量低于2.28at%时,P为固溶状态,高于2.28at.%时,P为析出状态。     

A dynamic SVR–ARMA model with improved fruit fly algorithm for the nonlinear fiber stretching process

Natural Computing - The fiber stretching process plays the key role in the process of fiber production and its effects is measured by the stretching ratio. The stretching ratio is determined by the...     

中原油田集中供热锅炉房改扩建工程设计

阐述了中原油田基地北区锅炉房改扩建工程的工艺流程、DCS控制系统等设计特点,依据中原油田燃料种类、特性及环保要求,确定了设备的合理选型,针对节能和环境保护,提出了设计中应采取的技术措施.工程投产后,系统运行平稳,各项指标均达到设计要求,保证了锅炉安全、经济地运行.     

轧制始极片

本文介绍了轧制法生产始极片的工艺，比较了轧制法和传统的钛种板生产始极片的优缺点，讨论了采用轧制始极片的经济效益和应用前景。