Design and Analysis of the 4-Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure-Activity Relationships

The 4-anilinoquinoline and 4-anilinoquinazoline ring systems have been the focus of significant efforts in prior kinase drug discovery programs, which have led to approved medicines. Broad kinome profiles of these compounds have now been assessed with the advent of advanced screening technologies. These ring systems, while originally designed for specific targets including epidermal growth factor receptor (EGFR), but actually display a number of potent collateral kinase targets, some of which have been associated with negative clinical outcomes. We have designed and synthesized a series of 4-anilinoquin(az)olines in order to better understand the structure-activity relationships of three main collateral kinase targets of quin(az)oline-based kinase inhibitors: cyclin G associated kinase (GAK), STE20-like serine/threonine-protein kinase (SLK) and serine/threonine-protein kinase 10 (STK10). This was achieved through a series of quantitative structure-activity relationship (QSAR) analysis, water mapping of the kinase ATP binding sites and extensive small-molecule X-ray structural analysis.     

MIMO Detector for LTE/LTE-A Uplink Receiver

Journal of Signal Processing Systems - We propose a carefully selected receiver structure, detector and detector implementation architecture for multiple-input multiple-output (MIMO) uplink base...     

Electromagnetic and mechanical design aspects of a high-speed solid-rotor induction machine with no separate copper electric circuit in the megawatt range

The most crucial electro-magnetic and mechanical design aspects of an integrated electrical-motor–gas-compressor system in high speed and high power operation are presented. The electric motor type considered is a solid-rotor induction motor with properties of which are particularly well suited in high-speed operation. The effect of the electro-magnetic material properties of the solid rotor core material on the performance of the machine is discussed. Guidelines to improve the performance of the solid-rotor induction motor are given. Thermal design aspects of a solid-rotor induction motor are presented. The mechanical properties of a solid rotor are discussed. Bearing arrangements as well as the rotor dynamics of an integrated system are presented.     

多层柔性衬底电路板的低成本丝网印刷

当大批量生产多层聚合物基厚膜电路板时需要低成本的印刷技术.对于有超过6层导电层且不平滑的表面来说,丝网印刷是一个便宜、便捷的选择.为了研究丝网印刷技术的可行性,本研究在不同衬底材料的表面,如聚碳酸酯(PC)、聚酯(PET)、聚酰亚胺(PI)和液晶聚合物(LCP),使用同样的印刷分辨率,常规的厚膜网版印刷,通过丝网的网孔在衬底上形成精细图形.最后,研究在双层PI衬底(拥有2层导体层,在导体层的两侧有1层绝缘层覆盖板基孔)上的印刷.丝网印刷的导体材料是银基纳米颗粒油墨,介质层是聚酰亚胺基材料.许多变量是妨碍这种经济适用技术大规模生产应用的影响因素.例如,如果固化温度超过200℃,聚酰亚胺基板的稳定性就成为大问题.在本实验中,如果印刷面积小,层与层之间的对齐公差是允许的.然而,在印刷进行一段时间后,层与层之间的平整度会变差.测试用纳米粒子油墨是一种很好的导电系统,但是,当固化温度从230℃降低到200℃时,生产效率会受到极大影响.另一种实现多层结构的方法是层压法.本研究选择PET和PC层,重点是处理沉积胶层的PET层和片材的复合过程.多层结构中的板基孔和导线通过常规厚膜网印解决.先打孔,然后采用厚膜网印填补,最后印刷表面.层与层之间的黏合精度和对准精度<±15μm.     

Black carbon-inclusive modeling approaches for estimating the aquatic fate of dibenzo-p-dioxins and dibenzofurans

A novel black carbon (BC) inclusive modeling tool is applied to estimate the distribution and long-term fate of dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the Norwegian Grenland Fjords. Three versions of the model were developed in which sediment-water partitioning was described using (i) an amorphous organic carbon (AOC) partitioning sorption model without BC sorption, (ii) a combined AOC and BC sorption model based on the Freundlich isotherm, and (iii) a combined BC-AOC model based on the Langmuir isotherm. The predictive ability of the three different models was evaluated for 17 PCDD/Fs by comparison of model predictions with observed organic carbon normalized sediment-water partition coefficients (K(TOC)) and with measured concentrations. All three versions of the model were able to predict concentrations that were in reasonable agreement with measured particulate concentrations (i.e., within a factor of 4 of median values). Estimated particulate concentrations were less sensitive to the model choice because the majority of the mass of these hydrophobic chemicals is associated with particulates regardless. However, for estimation of K(TOC) or dissolved water concentrations, both versions of the combined AOC and BC sorption models provided greatly improved estimates compared to the AOC-only model.     

Cavity-ring-down principle for fiber-optic resonators: experimental realization of bending loss and evanescent-field sensing

A novel measurement principle for fiber-optic sensing is presented. Use of a cavity-ring-down scheme enables measurements of minute optical losses in high-finesse fiber-optic cavities. The loss may be induced by evanescent-field absorption, fiber bending, fiber degradation, Bragg gratings, or any other effect that might change the fiber transmission or cavity reflector properties. The principle is proved to be rather insensitive to ambient perturbations such as temperature changes. A high-sensitivity measurement of loss due to bending is presented as a proof-of-principle. With a cavity finesse of 627 a sensitivity for induced loss of 108 ppm (4.68 x 10(-4) dB) is achieved. Preliminary measurements of evanescent-field absorption are also discussed.     

Impact of different forest densities on atmospheric boundary‐layer development and wind‐turbine wake

The aim of this work is to investigate the atmospheric boundary‐layer (ABL) flow and the wind turbine wake over forests with varying leaf area densities (LAD). The forest LAD profile used in this study is based on a real forest site, Ryningsnäs, located in Sweden. The reference turbine used to model the wake is a well‐documented 5‐MW turbine, which is implemented in the simulations using an actuator line model (ALM). All simulations are carried out with openFOAM using the Reynolds averaged Navier‐Stokes (RANS) approach. Twelve forest cases with leaf area index (LAI) ranging from 0.42 to 8.5 are considered. Results show that the mean velocity decreases with increasing LAI within the forest canopy, but increases with LAI above the hub height. Meanwhile, the turbulent kinetic energy (TKE) varies nonmonotonically with forest density. The TKE increases with forest density and reaches to its maximum at an average LAI of 1.70, afterwards, it decreases gradually as the density increases. It is also observed that the forest density has a clear role in the wake development and recovery. Comparisons between no‐forest and forest cases show that the forest characteristics help in damping the added turbulence from the turbine. As a consequence, the forest with the highest upstream turbulence has the shortest wake downstream of the turbine.     

Role of Polyamine-Induced Dimerization of Antizyme in Its Cellular Functions

The polyamines, spermine (Spm) and spermidine (Spd), are important for cell growth and function. Their homeostasis is strictly controlled, and a key downregulator of the polyamine pool is the polyamine-inducible protein, antizyme 1 (OAZ1). OAZ1 inhibits polyamine uptake and targets ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, for proteasomal degradation. Here we report, for the first time, that polyamines induce dimerization of mouse recombinant full-length OAZ1, forming an (OAZ1)₂-Polyamine complex. Dimerization could be modulated by functionally active C-methylated spermidine mimetics (MeSpds) by changing the position of the methyl group along the Spd backbone—2-MeSpd was a poor inducer as opposed to 1-MeSpd, 3-MeSpd, and Spd, which were good inducers. Importantly, the ability of compounds to inhibit polyamine uptake correlated with the efficiency of the (OAZ1)₂-Polyamine complex formation. Thus, the (OAZ1)₂-Polyamine complex may be needed to inhibit polyamine uptake. The efficiency of polyamine-induced ribosomal +1 frameshifting of OAZ1 mRNA could also be differentially modulated by MeSpds—2-MeSpd was a poor inducer of OAZ1 biosynthesis and hence a poor downregulator of ODC activity unlike the other MeSpds. These findings offer new insight into the OAZ1-mediated regulation of polyamine homeostasis and provide the chemical tools to study it.     

Evaluation of Substituted 1,2,3‐Dithiazoles as Inhibitors of the Feline Immunodeficiency Virus (FIV) Nucleocapsid Protein via a Proposed Zinc Ejection Mechanism

A diverse library of 5‐thieno‐, 5‐oxo‐, and 5‐imino‐1,2,3‐dithiazole derivatives was synthesized and evaluated for efficacy against the feline immunodeficiency virus (FIV) as a model for HIV in cells. Several diverse compounds from this series displayed nanomolar activity and low toxicity, representing a potential new class of compounds for the treatment of FIV and HIV.