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     

Visual Detection of Adenosine Triphosphate by Taylor Rising: A Simple Point-of-Care Testing Method Based on Rolling Circle Amplification

Rapid and sensitive point-of-care testing (POCT) is an extremely critical mission in practical applications, especially for rigorous military medicine, home health care, and in the third world. Here, we report a visual POCT method for adenosine triphosphate (ATP) detection based on Taylor rising in the corner of quadratic geometries between two rod surfaces. We discuss the principle of Taylor rising, demonstrating that it is significantly influenced by contact angle, surface tension, and density of the sample, which are controlled by ATP-dependent rolling circle amplification (RCA). In the presence of ATP, RCA reaction effectively suppresses Taylor-rising behavior, due to the increased contact angle, density, and decreased surface tension. Without addition of ATP, untriggered RCA reaction is favorable for Taylor rising, resulting in a significant height. With this proposed method, visual sensitive detection of ATP without the aid of other instruments is realized with only a 5 μL droplet, which has good selectivity and a low detection limit (17 nM). Importantly, this visual method provides a promising POCT tool for user-friendly molecular diagnostics.     

Structural dependence of microwave dielectric properties of spinel structured Mg2(Ti1-xSnx)O4 solid solutions: Crystal structure refinement,Raman spectra study and complex chemical bond theory

Mg₂(Ti_1-xSn_x)O₄ (x?=?0–1) ceramics were prepared through conventional solid-state method. This paper focused on the dependence of microwave dielectric properties on crystal structural characteristics via crystal structure refinement, Raman spectra study and complex chemical bond theory. XRD spectrums delineated the phase information of a spinel structure, and structural characteristic of these compositions were achieved with the help of Rietveld refinements. Raman spectrums were used to depict the correlations between vibrational phonon modes and dielectric properties. The variation of permittivity is ascribed to the Mg₂(Ti_1-xSn_x)O₄ average bond covalency. The relationship among the B-site octahedral bond energy, tetrahedral bond energy and temperature coefficient are discussed by defining on the change rate of bond energy and the contribution rate of octahedral bond energy. The quality factor is affected by systematic total lattice energy, and the research of XPS patterns illustrated that oxygen vacancies can be effectively restrained in rich oxygen sintering process. Obviously, the microwave dielectric properties of Mg₂(Ti_1-xSn_x)O₄ compounds were obtained (${\epsilon }_r$= 12.18, $Q\times f$?=?170,130?GHz, ${\tau }_f$?=??53.1?ppm/°C, x?=?0.2).     

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。     

Image Encryption Application of Chaotic Sequences Incorporating Quantum Keys

Machine Intelligence Research - This paper proposes an image encryption algorithm LQBPNN (logistic quantum and back propagation neural network) based on chaotic sequences incorporating quantum...