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     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

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。     

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.