Het(aryl)isatin to het(aryl)aminoindoline scaffold hopping: A route to selective inhibitors of matrix metalloproteinases

Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression. A variety of chemical classes have been explored for targeting individual MMP isoforms. In the present study, we further developed our isatin based scaffold BB0223107 capable of binding to and inactivating MMP-2 in a zinc-independent manner (Agamennone et al., 2016). Forty four new compounds were synthesized based on the modified BB0223107. All compounds were tested in enzyme inhibition assays against MMP-2, ?8 and ?13. SAR studies demonstrated that 5-het(aryl)-3-aminoindolin-2-ones (37–39) were active toward MMP-2 and MMP-13. The most potent compounds 33 and 37 displayed an IC₅₀ of 3 µM against MMP-13 and showed a negligible activity toward MMP-8; almost all new compounds were inactive toward MMP-8. Replacement of the isatin ring with a biaryl system (compound 33) did not decrease the potency against MMP-13 but reduced the selectivity. Structure-based computational studies were carried out to rationalize the inhibitory activity data. The analysis of binding geometries confirmed that all fragments occupied the S1′ site in the three enzymes while no ligand was able to bind the catalytic zinc ion. To the best of our knowledge, this is the first example of 3-aminoindolin-2-one-based MMP inhibitors that, based on the computer modeling study, do not coordinate the zinc ion. Thus, the het(aryl)-3-aminoindolin-2-one derivatives emerge as a drug-like and promising chemotype that, along with the hetaryl variations, represents an alternative and thrifty tool for chemical space exploration aimed at MMP inhibitor design.     

Determination of sulfa antibiotic residues in river and particulate matter by field-amplified sample injection-capillary zone electrophoresis

In the present research, field-amplified sample injection–CZE (FASI–CZE) coupled with a diode array detector was established to determine trace level sulfa antibiotic. Sulfathiazole, sulfadiazine, sulfamethazine, sulfadimethoxine, sulfamethoxazole, and sulfisoxazole were selected as analytes for the experiments. The background electrolyte solution consisted of 70.0 mmol/L borax and 60.0 mmol/L boric acid (including 10% methanol, pH 9.1). The plug was 2.5 mmol/L borax, which was injected into the capillary at a pressure of 0.5 psi for 5 s. Then the sample was injected into the capillary at an injection voltage of –10 kV for 20 s. The electrophoretic separation was carried out under a voltage of +19 kV. The capillary temperature was maintained at 20˚C throughout the analysis, and six sulfonamides were completely separated within 35 min. Compared with pressure injection-CZE, the sensitivity of FASI-CZE was increased by 6.25–10.0 times, and the LODs were reduced from 0.2–0.5 to 0.02–0.05 μg/mL. The method was applied to the determination of sulfonamides in river water and particulate matter samples. The recoveries were 78.59–106.59%. The intraday and interday precisions were 2.89–7.35% and 2.77–7.09%, respectively. This provides a simpler and faster method for the analysis of sulfa antibiotic residues in environmental samples.     

Off‐grid DoA estimation method of wideband signals

In this paper, an off‐grid direction of arrival (DoA) estimation method is proposed for wideband signals. This method is based on the sparse representation (SR) of the array covariance matrix. Similar to the time domain DoA estimation methods, the correlation function of the sources was assumed to be the same and known. A new measurement vector is obtained using the lower‐left triangular elements of the covariance matrix. The DoAs are estimated by quantizing the entire range of continuous angle space into discrete grid points. However, the exact DoAs may be located between two grid points; therefore, this estimation has errors. The accuracy of DoA estimation is improved by the minimization of the difference between the new measurement vector and its estimated values. Simulation results revealed that the proposed method can enhance the DoA estimation accuracy of wideband signals.     

干扰条件下的“北斗”信号解扩重构DOA估计

在干扰条件下，卫星导航抗干扰波束形成算法往往需要卫星信号波达方向（Direction-of-Arrival，DOA）的先验信息。但当存在低信噪比信号或主动干扰源时，常规的DOA估计算法性能急剧下降甚至失效。针对此问题，提出了一种被干扰信号压制的低信噪比“北斗”信号的DOA估计算法。该算法首先通过对接收信号进行子空间投影抑制干扰信号，然后对抑制干扰后的信号进行解扩重构处理，最后通过多重信号分类算法完成对“北斗”信号的DOA估计。仿真结果表明，在干扰信号干信比80 dB条件下，“北斗”信号DOA估计误差在5°以内，为下一步进行波束形成计算提供了高精度的入射角信息。     

On the performance of improved quadrature spatial modulation

Quadrature spatial modulation (QSM) utilizes the in‐phase and quadrature spatial dimensions to transmit the real and imaginary parts of a single signal symbol, respectively. The improved QSM (IQSM) transmits two signal symbols per channel use through a combination of two antennas for each of the real and imaginary parts. The main contributions of this study can be summarized as follows. First, we derive an upper bound for the error performance of the IQSM. We then design constellation sets that minimize the error performance of the IQSM for several system configurations. Second, we propose a double QSM (DQSM) that transmits the real and imaginary parts of two signal symbols through any available transmit antennas. Finally, we propose a parallel IQSM (PIQSM) that splits the antenna set into equal subsets and performs IQSM within each subset using the same two signal symbols. Simulation results demonstrate that the proposed constellations significantly outperform conventional constellations. Additionally, DQSM and PIQSM provide a performance similar to that of IQSM while requiring a smaller number of transmit antennas and outperform IQSM with the same number of transmit antennas.     

Concurrent multiresponse non-linear screening: Robust profiling of webpage performance

Profiling engineered data with robust mining methods continues attracting attention in knowledge engineering systems. The purpose of this article is to propose a simple technique that deals with non-linear multi-factorial multi-characteristic screening suitable for knowledge discovery studies. The method is designed to proactively seek and quantify significant information content in engineered mini-datasets. This is achieved by deploying replicated fractional-factorial sampling schemes. Compiled multi-response data are converted to a single master-response effectuated by a series of distribution-free transformations and multi-compressed data fusions. The resulting amalgamated master response is deciphered by non-linear multi-factorial stealth stochastics intended for saturated schemes. The stealth properties of our method target processing datasets which might be overwhelmed by a lack of knowledge about the nature of reference distributions at play. Stealth features are triggered to overcome restrictions regarding the data normality conformance, the effect sparsity assumption and the inherent collapse of the ‘unexplainable error’ connotation in saturated arrays. The technique is showcased by profiling four ordinary controlling factors that influence webpage content performance by collecting data from a commercial browser monitoring service on a large scale web host. The examined effects are: (1) the number of Cascading Style Sheets files, (2) the number of JavaScript files, (3) the number of Image files, and (4) the Domain Name System Aliasing. The webpage performance level was screened against three popular characteristics: (1) the time to first visual, (2) the total loading time, and (3) the customer satisfaction. Our robust multi-response data mining technique is elucidated for a ten-replicate run study dictated by an L₉(3⁴) orthogonal array scheme where any uncontrolled noise embedded contribution has not been necessarily excluded.     

Molecular design of ambipolar redox-active molecules II: closed-shell systems

This mini-review highlights key structural features that should be taken into account when creating ambipolar redox-active closed-shell metal-free molecules. This type of compound is strongly required for the fabrication of all-organic ‘poleless’ batteries and semiconductors. The suggested strategies aimed at stabilization of both oxidized (cationic) and reduced (anionic) redox-states are based on the comprehensive analysis of the most successful structures taken from the recent publications.     

面向航空通信应用的边沿触发器教学设计

研究和分析了面向航空通信应用的边沿触发器教学设计。以边沿触发电路实现原理为核心,引导边沿触发机制的探究式学习；以航空机载网络通信为具体应用背景,引入科学研究和工程实现中实际问题,设计曼切斯特码检测系统实验；使得边沿触发器教学成为“知识再创造”的过程和创新实践的新载体,以期培养新工科背景下的独立、创新和实践精神。     

Response surface methodology toward the optimization of high-energy carotenoid extraction from Aristeus antennatus shrimp

High-energy assisted extraction techniques, like ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE), are widely applied over the last years for the recovery of bioactive compounds such as carotenoids, antioxidants and phenols from foods, animals and herbal natural sources. Especially for the case of xanthophylls, the main carotenoid group of crustaceans, they can be extracted in a rapid and quantitative way with the use of UAE and MAE.     

Pure tetrahedral quadruple systems with index two

An oriented tetrahedron defined on four vertices is a set of four cyclic triples with the property that any ordered pair of vertices is contained in exactly one of the cyclic triples. A tetrahedral quadruple system of order $n$ with index $\lambda$, denoted by ${\text{TQS}}_{\lambda }\left(n\right)$, is a pair $\left(X,\mathrm{?}\right)$, where $X$ is an $n$‐set and $\mathrm{?}$ is a set of oriented tetrahedra (blocks) such that every cyclic triple on $X$ is contained in exactly $\lambda$ members of $\mathrm{?}$. A ${\text{TQS}}_{\lambda }\left(n\right)$ is pure if there do not exist two blocks with the same vertex set. When $\lambda =1$, the spectrum of a pure TQS $\left(n\right)$ has been completely determined by Ji. In this paper, we show that there exists a pure ${\text{TQS}}_2\left(n\right)$ if and only if $n\equiv 1,2\left(\mathrm{mod}3\right)$ and $n\ge 7$. A corollary is that a simple ${\text{QS}}_4\left(n\right)$ also exists if and only if $n\equiv 1,2\left(\mathrm{mod}3\right)$ and $n\ge 7$.