A human-like visual-attention-based artificial vision system for wildland firefighting assistance

In this work we contribute to development of a “Human-like Visual-Attention-based Artificial Vision” system for boosting firefighters’ awareness about the hostile environment in which they are supposed to move along. Taking advantage from artificial visual-attention, the investigated system’s conduct may be adapted to firefighter’s way of gazing by acquiring some kind of human-like artificial visual neatness supporting firefighters in interventional conditions’ evaluation or in their appraisal of the rescue conditions of people in distress dying out within the disaster. We achieve such a challenging goal by combining a statistically-founded bio-inspired saliency detection model with a Machine-Learning-based human-eye-fixation model. Hybridization of the two above-mentioned models leads to a system able to tune its parameters in order to fit human-like gazing of the inspected environment. It opens appealing perspectives in computer-aided firefighters’ assistance boosting their awareness about the hostile environment in which they are supposed to evolve. Using as well various available wildland fires images’ databases as an implementation of the investigated concept on a 6-wheeled mobile robot equipped with communication facilities, we provide experimental results showing the plausibility as well as the efficiency of the proposed system.     

响应面法优化香圆皮柠檬烯提取工艺

在单因素实验基础上,采用响应面法对香圆皮柠檬烯提取工艺进行优化。以香圆成熟果皮为主要原料,采用水蒸气蒸馏法进行柠檬烯提取工艺研究。通过单因素实验,确定以碳酸钠为盐析组分,选择料液比、盐用量、提取时间这3个因素作为自变量,应用响应面法来优化柠檬烯的提取工艺。分离得到的柠檬烯产品经GC-MS和红外表征鉴定。结果表明,柠檬烯提取的最佳工艺参数为:液料比4.6:1,碳酸钠用量1.05 g,提取时间63 min,在此条件下,柠檬稀得率理论值可达2.75%,验证值为2.76%,与理论值十分接近。表明该模型能较好地预测柠檬烯得率。     

Synthesis and application of the first radioligand targeting the allosteric binding pocket of chemokine receptor CXCR3

Strategies for the identification of allosteric modulators of chemokine receptors largely rely on various cell‐based functional assays. Radioligand binding assays are typically not available for allosteric binding sites. We synthesized, purified, and applied the first tritium‐labeled allosteric modulator of the human chemokine receptor CXCR3 (RAMX3, [³H]N‐{1‐[3‐(4‐ethoxyphenyl)‐4‐oxo‐3,4‐dihydropyrido[2,3‐d]pyrimidin‐2‐yl]ethyl}‐2‐[4‐fluoro‐3‐(trifluoromethyl)phenyl]‐N‐[(1‐methylpiperidin‐4‐yl)methyl]acetamide). RAMX3 is chemically derived from 8‐azaquinazolinone‐type allosteric modulators and binds to the CXCR3 receptor with a K_d value of 1.08 nM (specific activity: 80.4 Ci mmol^?1). Radioligand displacement assays showed potent negative cooperativity between RAMX3 and chemokine CXCL11, providing a basis for the use of RAMX3 to investigate other potential allosteric modulators. Additionally, the synthesis and characterization of a number of other full and truncated 8‐azaquinazoline analogues were used to validate the binding properties of RAMX3. We demonstrate that RAMX3 can be efficiently used to facilitate the discovery and characterization of small molecules as allosteric modulators of the CXCR3 receptor.     

金花茶花总黄酮双水相提取工艺优化及其抗氧化活性分析

研究了超声波辅助聚乙二醇(PEG)/(NH4)2SO4双水相提取金花茶花总黄酮工艺及其抗氧化活性.以黄酮萃取率为指标,在单因素实验的基础上,采用正交试验优化提取工艺.通过DPPH·和OH·清除率的测定,评价其抗氧化效果.采用HPLC分析对金花茶花中的芦丁、槲皮素和山奈酚等黄酮化合物进行了确认.实验结果表明,最佳提取条件...     

Development of Photoactivatable Allosteric Modulators for the Chemokine Receptor CXCR3

The CXCR3 receptor, a class A G protein‐coupled receptor (GPCR), is involved in the regulation and trafficking of various immune cells. CXCR3 antagonists have been proposed to be beneficial for the treatment of a wide range of disorders including but not limited to inflammatory and autoimmune diseases. The structure‐based design of CXCR3 ligands remains, however, hampered by a lack of structural information describing in detail the interactions between an allosteric ligand and the receptor. We designed and synthesized photoactivatable probes for the structural and functional characterization, using photoaffinity labeling followed by mass spectrometry, of the CXCR3 allosteric binding pocket of AMG 487 and RAMX3, two potent and selective CXCR3 negative allosteric modulators. Photoaffinity labeling is a common approach to elucidate binding modes of small‐molecule ligands of GPCRs through the aid of photoactivatable probes that convert to extremely reactive intermediates upon photolysis. The photolabile probe N‐[({1‐[3‐(4‐ethoxyphenyl)‐4‐oxo‐3,4‐dihydropyrido[2,3‐d]pyrimidin‐2‐yl]ethyl}‐2‐[4‐fluoro‐3‐(trifluoromethyl)phenyl]‐N‐{1‐[4‐(3‐(trifluoromethyl)‐3H‐diazirin‐3‐yl]benzyl}piperidin‐4‐yl)methyl]acetamide ( 10 ) showed significant labeling of the CXCR3 receptor (80 %) in a [³H]RAMX3 radioligand displacement assay. Compound 10 will serve as an important tool compound for the detailed investigation of the binding pocket of CXCR3 by mass spectrometry.     

Ligand‐Biased and Probe‐Dependent Modulation of Chemokine Receptor CXCR3 Signaling by Negative Allosteric Modulators

Over the last decade, functional selectivity (or ligand bias) has evolved from being a peculiar phenomenon to being recognized as an essential feature of synthetic ligands that target G protein‐coupled receptors (GPCRs). The CXC chemokine receptor 3 (CXCR3) is an outstanding platform to study various aspects of biased signaling, because nature itself uses functional selectivity to manipulate receptor signaling. At the same time, CXCR3 is an attractive therapeutic target in the treatment of autoimmune diseases and cancer. Herein we report the discovery of an 8‐azaquinazolinone derivative (N‐{1‐[3‐(4‐ethoxyphenyl)‐4‐oxo‐3,4‐dihydropyrido[2,3‐d]pyrimidin‐2‐yl]ethyl}‐4‐(4‐fluorobutoxy)‐N‐[(1‐methylpiperidin‐4‐yl)methyl]butanamide, 1 b ) that can inhibit CXC chemokine 11 (CXCL11)‐dependent G protein activation over β‐arrestin recruitment with 187‐fold selectivity. This compound also demonstrates probe‐dependent activity, that is, it inhibits CXCL11‐ over CXCL10‐mediated G protein activation with 12‐fold selectivity. Together with a previously reported biased negative allosteric modulator from our group, the present study provides additional information on the molecular requirements for allosteric modulation of CXCR3.     

乙醇-硫酸铵双水相体系提取桃花总黄酮及其抗氧化性能

以桃花为主要原料,采用乙醇-硫酸铵双水相体系进行总黄酮提取工艺研究。在单因素实验基础上,以硫酸铵质量分数、液料比、提取温度、提取时间这4个因素作为自变量,以黄酮得率为指标,通过响应面法对桃花总黄酮提取工艺进行优化。以DPPH·、OH·和O₂^?·清除率为指标,对桃花总黄酮的抗氧化能力进行评价。结果表明,黄酮提取的最佳工艺参数为:硫酸铵质量分数15.2%,提取时间26 min,液料比27.8:1(mL/g),提取温度51℃。在此条件下,黄酮得率理论值可达45.64%,验证值为45.65%,与理论值十分接近。抗氧化实验结果表明,桃花总黄酮表现出较强的自由基清除能力,当浓度为0.56 mg/mL时,DPPH·清除率为94.21%,当浓度为0.672 mg/mL时,OH·和O₂^?清除率分别为91.23%和80.65%。响应面法优化双水相提取桃花总黄酮工艺合理可行,模型能较好地预测黄酮得率,得到的黄酮具有良好的抗氧化性能,可进一步开发利用。