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.     

快速灵敏的LC-MS/MS法测定人血浆中阿莫西林并应用于两种制剂的一致性评价

目的: 建立快速灵敏的LC-MS/MS法测定人血浆中阿莫西林浓度，并用于两种阿莫西林胶囊的一致性评价。方法: 采用岛津公司LCMS-8060型LC-MS/MS仪，以MRM模式测定阿莫西林（m/z 366.00/114.00）的浓度，d4-阿莫西林作内标（m/z 370.10/114.05），离子源为ESI源。色谱柱选用Waters ACQUITY BEH C18（2.1×50 mm，1.7 μm），梯度洗脱。血浆样本加入内标，经甲醇沉淀蛋白后取上清液进样检测。结果: 所建方法经验证，其线性、准确度、精密度、最低定量限、提取回收率、特异性、基质效应、稳定性等各项指标均符合CFDA的指导原则及最新核查标准要求，并较文献报道中的方法有处理简单、灵敏度高、色谱峰形好的优点。结论: 所建方法快速、灵敏，适用于人血浆中阿莫西林浓度的检测。用于一致性评价的样本实测，两种制剂生物等效。     

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...     

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。     

塔河油田成藏期次的地球化学示踪研究

应用油藏地球化学的方法对塔河油田的成藏期次进行了探讨。塔河油田稠油正构烷烃分布完整,但色谱基线不同程度抬升;原油非烃和沥青质碳同位素偏轻,族组成碳同位素发生倒转;原油中普遍含有25-降藿烷。这些特征表明该区油藏经历了至少两期成藏过程,早期充注原油遭受生物降解作用后又受到高成熟原油充注。塔河油田天然气为典型的油型气,成熟度较高,为成熟—过成熟阶段产物,亦显示了两期充注的特征:早期充注的为典型的原油伴生气,充注时间与后期原油的充注时间相同;晚期充注的为高温裂解气,充注方向为自东向西。因此,塔河油田至少存在着3次油气充注过程。