Design,synthesis and biological evaluation of pyridyl substituted benzoxazepinones as potent and selective inhibitors of aldosterone synthase

Exorbitant aldosterone is closely associated with various severe diseases, including congestive heart failure and chronic kidney disease. As aldosterone synthase is the pivotal enzyme in aldosterone biosynthesis, its inhibition constitutes a promising treatment for these diseases. Via a structure-based approach, a series of pyridyl substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-ones were designed as inhibitors of aldosterone synthase. Six compounds (5j, 5l, 5m 5w, 5x and 5y) distinguished themselves with potent inhibition (IC₅₀ <100 nmol/L) and high selectivity over homogenous 11β-hydroxylase. As the most promising compound, 5x exhibited an IC₅₀ of 12 nmol/L and an excellent selectivity factor (SF) of 157, which are both superior to those of the reference fadrazole (IC₅₀ = 21 nmol/L, SF = 7). Importantly, 5x showed no inhibition against steroidogenic CYP17, CYP19 and a panel of hepatic CYP enzymes indicating an outstanding safety profile. As it manifested satisfactory pharmacokinetic properties in rats, compound 5x was considered as a drug candidate for further development.     

Adaptive Laser Aiming Through 2 km Horizontal Atmosphere with Precise-Delayed SPGD Algorithm

Journal of Russian Laser Research - Laser aiming is one of the key technologies of laser atmospheric transmission. The beam actually is affected by atmospheric turbulence and mechanical vibration;...     

IVDAS: an interactive visual design and analysis system for image data symmetry detection of CNN models

Journal of Visualization - Convolutional neural networks (CNNs) have achieved breakthrough performance in image recognition and classification. However, it is still a challenge for CNNs to classify...     

Chemical Constituents of the Roots of Phlomis betonicoides and Their Anti-Rotavirus Activity

Chemistry of Natural Compounds - Two new isobenzofuranone derivatives (1 and 2) together with six known compounds (3–8) were isolated from the roots of Phlomis betonicoides, a highly sweet...     

百kV级纳秒脉冲源的设计与实验研究

GW级Tesla型脉冲源在触发开关技术研究中作为触发脉冲源使用,抖动较大,触发开关工作不稳定,需要为其研制一台触发器以解决这一问题。结合其他使用需求,设计了一台百kV级纳秒脉冲源,该脉冲源采用Tesla变压器结合单筒脉冲形成线结构,进行了Tesla变压器结构、Tesla变压器初次级参数、Tesla开路磁芯与初级电路设计,调试结果为：最高输出电压100 kV,峰值功率250 MW,重复频率1~100 Hz,输出脉冲宽度约4 ns,前沿约1 ns。该脉冲源作为触发器使用,可以将GW级Tesla型纳秒脉冲源抖动由500 ns降低至150 ns,满足触发开关研究需求,还可用于产生超宽谱短脉冲进行辐射。     

电磁轨道发射装置隔离式分压器

研制了一套用于测量电磁发射装置轨道电压信号的隔离式分压器,实现了测量回路与被测回路之间的电隔离,简化了电磁发射装置测试系统的复杂性。并对影响隔离式分压器频率响应的元件参数进行了参数扫描,结果表明：研制的分压器在-3 dB区间的频率响应范围为14 Hz~18 MHz,满足电磁发射装置轨道电压信号的测试要求。使用P6015A高压探头进行比对标定,输出信号的前沿约1s,频率响应满足电磁轨道发射装置轨道电压信号的测量要求。同时用隔离式分压器及电阻分压器测量轨道电压信号,两者波形符合较好。     

Notable shift of ultraviolet intensity on Sn-doped ZnO nanostructure fabricated by sol–gel method

Sn-doped ZnO (SZO) thin films are deposited by sol–gel dip-coating method with Sn content at 0 at.% and 1–15 at.% with an increment of 2 at.%. The structure and luminescence of the films are investigated. X-ray diffraction results indicate that all the SZO samples show preferential orientation along the (002) direction, and the scanning electron microscope exhibits that the surface morphology of the films change from nanoparticles to nanorods with increasing Sn concentration. X-ray photoelectron spectroscopy reveals that Sn exists as valence of +4 in the matrix. The photoluminescence peaks at 381 and 398 nm are observed in all the samples. The ratio of intensity of peak at 381 nm to that of peak at 398 nm differed markedly. The intensity of peak at 398 nm might be due to the response for the Sn atoms, while the intensity of peak at 381 nm is probably related to the quantum size effect.     

The intersection marker method for 3D interface tracking of deformable surfaces in finite volumes

Currently, the majority of computational fluid dynamics (CFD) codes use the finite volume method to spatially discretise the computational domain, sometimes as an array of cubic control volumes. The Finite volume method works well with single‐phase flow simulations, but two‐phase flow simulations are more challenging because of the need to track the surface interface traversing and deforming within the 3D grid. Surface area and volume fraction details of each interface cell must be accurately accounted for, in order to calculate for the momentum exchange and rates of heat and mass transfer across the interface. To attain a higher accuracy in two‐phase flow CFD calculations, the intersection marker (ISM) method is developed. The ISM method is a hybrid Lagrangian–Eulerian front‐tracking algorithm that can model an arbitrary 3D surface within an array of cubic control volumes. The ISM method has a cell‐by‐cell remeshing capability that is volume conservative and is suitable for the tracking of complex interface deformation in transient two‐phase CFD simulations. Copyright © 2015 John Wiley & Sons, Ltd.     

非低温法的稀有气体纯化技术概述

稀有气体广泛应用于工业生产中,如离子刻蚀、检漏等。但是它们在地球上的含量比较少,属于稀有资源,因此需要对它们进行纯化以循环再利用。首先介绍了不同气体纯化的原理,然后以实际生产中的不同稀有气体使用范围为例,说明纯化装置的设计方法和需要考虑的问题。为以后气体纯化装置的设计提供借鉴。