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.     

水泥厂堆取料机轨道梁设计优化及安装

正0前言近年来苏州中材建设有限公司承建了多条海外5 000 t/d水泥熟料生产线EPC总承包项目。原燃料堆场多采用圆型堆场或长型堆场,例如400 m长型辅助原料堆场有约1 600 m轨道梁、4 200多支螺栓,直径Φ90 m圆型堆场有约282 m轨道梁、1150支螺栓,合计共有约5 350多支螺栓需要安装,燃料为煤的生产线,工作量更是庞大。堆取料机轨道行程较长,对固定轨道螺栓的安     

Distributed learning consensus control based on neural networks for heterogeneous nonlinear multiagent systems

This paper considers a novel distributed iterative learning consensus control algorithm based on neural networks for the control of heterogeneous nonlinear multiagent systems. The system's unknown nonlinear function is approximated by suitable neural networks; the approximation error is countered by a robust term in the control. Two types of control algorithms, both of which utilize distributed learning laws, are provided to achieve consensus. In the provided control algorithms, the desired reference is considered to be an unknown factor and then estimated using the associated learning laws. The consensus convergence is proven by the composite energy function method. A numerical simulation is ultimately presented to demonstrate the efficacy of the proposed control schemes.     

我公司延长耐火砖寿命的工艺管理措施

正0引言我公司有两条2 500 t/d的熟料生产线,于2000年先后投产,现正常生产,随着近年来对耐火材料使用的技术攻关和精心管控,烧成带窑砖使用寿命超过40个月。下面就我公司的延长耐火砖寿命的工艺管理措施进行介绍,供借鉴研讨。     

基于步冷试验的2.25Cr-1Mo-0.25V钢母材及焊缝回火脆化研究

对原始态、步冷态、脱脆态和脱脆步冷态2.25Cr-1Mo-0.25V钢母材及焊缝冲击试验结果进行分析,得到了母材和焊缝在不同状态下的韧脆转变温度vTr54.2和FATT以及脆化度ΔvTr54.2和ΔFATT。试验结果表明,步冷试验之后,母材发生较低程度脆化或脱脆现象,但是脆化度或脱脆度较低,表明母材具有良好的抗回火脆化性能;经脱脆试验后,母材和焊缝都发生较高程度的脱脆,表明材料的脆化主要是由于回火脆化引起的,脱脆试验使得材料的韧脆转变温度降低;脱脆步冷试验后,焊缝发生较高程度的脆化,焊缝对脱脆步冷试验的敏感性较高,脱脆步冷试验有效促进了焊缝的脆化。在相同脆化条件下,母材的脆化敏感性低于焊缝,焊缝更易发生脆化。     

山东栖霞—大柳行地区金矿找矿靶区地质评价及优选

栖霞—大柳行地区位于胶东中部栖霞—蓬莱金矿成矿带内，是胶东重要的金成矿区，成矿条件优越。为了对圈定靶区进行优选分类，通过对该区地质背景、找矿靶区评价、找矿靶区优选方面展开综合研究，并结合勘查工作程度和矿业权设置情况，划分出3类预测区，选定了5个靶区为今后优先部署勘查工作的方向。     

Single-Crystalline TiO2(B) Nanobelts with Unusual Large Exposed {100} Facets and Enhanced Li-Storage Capacity

The {100} facet of single-crystalline TiO₂(B) is an ideal platform for inserting Li ions, but it is hard to be obtained due to its high surface energy. Here, the single-crystalline TiO₂(B) nanobelts from H₂Ti₃O₇ with nearly 70% {100} facets exposed are synthesized, which significantly enhances Li-storage capacity. The first-principle calculations demonstrate an ab in-plane 2D diffusion through the exposed {100} facets. As a consequence, the nanobelts can significantly accommodate Li ions in LiTiO₂ formula with specific capacity up to 335 mAh g⁻¹, which is in good agreement with the electrochemical characterizations. Coating with conductive and protective poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), the cut-off discharge voltage is as low as 0.5 V, leading to a capacity of 160.7 mAh g⁻¹ after 1500 cycles with a retention rate of 66% at 1C. This work provides a practical strategy to increase the Li-ion capacity and cycle stability by tailoring the crystal orientation and nanostructures.