Design, synthesis, and biological evaluation of AHPN derivatives as RARγ agonists

RARγ是核受体超家族的重要成员，可以参与调控细胞生长、分化、凋亡、代谢和胚胎发育等许多重要生理过程。RARγ表达水平和功能的改变将可能导致肿瘤的发生，因而被认为是肿瘤治疗中的一个重要靶点。 6-{3'-(1-金刚烷基)-4'-羟基苯基}-2-萘甲酸(AHPN)是已经报道的选择性RARγ激动剂，可以通过调控RARγ的功能从而发挥诱导细胞凋亡的作用，对急性和慢性淋巴细胞白血病有潜在的治疗作用，然而在使用的过程中出现了视黄酸类化合物常见的不良反应，限制了其成药。 本课题以AHPN母环为结构基础，以RARγ-LBD为靶点，结合计算机辅助药物设计，通过7步合成反应，得到39个AHPN衍生物，所有的...Retinoic acid receptor-γ (RARγ) is a unique member of the nuclear receptor (NR) superfamily, playing an important role in many biological processes ranging from apoptosis, cell differentiation and growth to lipid metabolism. The changes of RARγ expression level or itself may lead to the occurrence of tumor. Therefore, it serve as an crucial drug target of cancer therapy in modern drug discovery. ...学位：医学硕士院系专业：药学院_药物化学学号：3232013115340

AHPN衍生物的合成及其与RARγ的结合活性研究

目的本实验以6-{3’-(1-金刚烷基)-4’-羟基苯基}-2-萘甲酸(AHPN)母核为结构基础,设计、合成一系列AHPN衍生物,并对这些衍生物做初步的活性筛选,期望找到活性显著的衍生物。方法以对溴苯酚和1-金刚烷醇为原料经取代、缩合、氧化、还原等反应合成AHPN衍生物,经过1H-NMR、13C-NMR、HR-MS表征,并利用Biacore技术检测衍生物与蛋白质之间的结合能力。结果衍生物7c、6c、6e、6h显示出了显著优于先导化合物AHPN与视黄酸核受体γ(RARγ)的结合能力,亚磷酸二甲酯基与氮杂环的引入提高了该类化合物的活性。结论该类AHPN衍生物与RARγ结合能力显著,有进一步研究的价值。扬州市邗江区科技计划项目资助;;福建省基金项目资助(2014Y0044);;国家海洋局第三海洋研究所基本科研业务费专项资金资助项目(海三科2016044

Effects of four typical brominated flame retardants on hepatic antioxidant system of Mossambica tilapia in vitro

以罗非鱼(MOSSAMbICA TIlAPIA)为实验生物,研究了离体条件下其肝脏抗氧化系统中谷胱甘肽(gSH)含量、谷胱甘肽硫转移酶(gST)和超氧化物歧化酶(SOd)活性对4种溴代阻燃剂(brOMInATEd flAME rETArdAnTS,bfrS)——四溴联苯醚(bdE-47)、十溴联苯醚(bdE-209)、六溴环十二烷(HbCd)和四溴双酚A(TbbPA)的响应.研究结果表明:离体暴露于4种bfrS 1 H后,罗非鱼肝脏上清液中gSH含量和SOd活性随暴露剂量升高均呈现先升高后回落的趋势,但总体均高于对照组水平;gST活性则被抑制.上述3种抗氧化参数中,同一参数对4种bfrS响应均呈现一致的变化趋势,其中gST和SOd活性响应更为灵敏.gST活性对bdE-47、bdE-209和HbCd的最低响应浓度均低于1 ng·l-1,且与TbbPA和bdE-209在一定浓度范围内存在较好的剂量-效应关系;SOd活性对4种bfrS暴露较为敏感,最低响应浓度均低于10 ng·l-1,并且与除bdE-209外的上述3种污染物在一定的浓度范围内具有良好的剂量-效应关系.因此,gST和SOd活性指标是值得进一步研究的溴代阻燃剂污染候选生物标志物.The present work aims to investigate the responses of glutathione(GSH),glutathione S-transferase(GST) and superoxide dismutase(SOD)in Mossambica tilapia liver supernatant exposed in vitro to four kinds of brominated flame retardants(BFRs)(BDE-47,BDE-209,HBCD and TBBPA)for 1 h at different doses.The results showed that hepatic GSH content and SOD activity increased at lower concentrations,and then decreased at higher concentrations,while GSH content and SOD activity in the exposed groups were higher than that in the control at all mentioned concentrations.The GST activity was inhibited by the four types of BFRs.The results indicated that the same antioxidant parameter had the similar response trend to the 4 BFRs.Moreover,the responses of the activity of GST and SOD to the BFRs were more sensitive than that of GSH content.The lowest observed effect concentration(LOEC) of GST activity to BDE-47,BDE-209 and HBCD was less than 1 ng·L-1and GST activity values had a good linear relationship with the certain concentrations of TBBPA and BDE-209.The SOD activity was sensitive to all four types of BFRs and the LOEC was less than 10 ng·L-1.The values of SOD activity had a good linear relationship with the certain concentrations of BDE-47,HBCD and TBBPA.Our results suggested that the parameters of GST and SOD in Mossambica tilapia liver antioxidant system had the potential to serve as biomarkers to evaluate the adverse effects of BFRs pollution.海洋公益性项目(No.201105013); 国家海洋局第三海洋研究所基本科研业务费专项基金项目(No.201221); 福建省重大专项/专题项目(No.2011YZ0001-1); 福建省自然科学基金项目(No.2013J01386)~

Plasma-assisted ignition for a kerosene fueled scramjet at Mach 1.8

By using a plasma jet (PJ) torch with 1.5 kW input power as an igniter, successful ignition for liquid-kerosene fueled combustion experiment was conducted in a direct-connected supersonic test facility. The incoming flow has total temperature of 950 K and local Mach number of 1.8, corresponding to Mach 4 flight condition. In this study, several optical techniques, including high speed photography, high speed schlieren photography, and planar laser scattering (PLS) technique, were combined to study the ignition process, flame propagation, and mixing features of liquid kerosene fuel with air around the cavity. The effect of fuel injection position, injection pressure, and feedstock gas on ignition performance has been analyzed. The results indicate that local mixing is a critical factor for ignition. It is also shown that the PJ torch with N-2 + H-2 feedstock is superior to the PJ torch with N-2 feedstock for the ignition of liquid-kerosene fuel. These results are valuable for the future optimization of kerosene-fueled scramjet engine when using a PJ torch as an igniter

游戏智能中的AI——从多角色博弈到平行博弈

总结了国内外人工智能技术在游戏领域的研究进展，分析了游戏领域的研究进步对于现实社会的意义。针对强化学习中免模型方法存在的仿真与真实的鸿沟、基于模型的方法缺乏通用性的问题，提出平行博弈的思想和方法，介绍了平行博弈在解决现有单角色博弈和多角色博弈问题上的先进之处。认为虚实结合的平行博弈方法将成为迈向通用人工智能的奠基石

西湖湖西浮游与着生藻类季节变化及相互关系

2014年11月至2015年8月调查了西湖湖西沿岸带浮游藻类和不同基质（植物、石块和底泥）上着生藻类的群落结构及季节变化, 分析了着生丝状藻与浮游丝状藻的相互关系以及它们与环境因子的相关性, 探讨湖西生态修复过程中季节性暴发的丝状藻水华的原因.结果表明浮游藻类和植物、底泥、石头上着生藻类中均以硅藻门种类数（分别占52.5%、60.4%、86.7%和72.7%）最多, 蓝藻门（分别占10.1%、8.9%、6.7%和15.2%）和绿藻门（分别占26.3%、19.8%、5.6%和10.6%）次之, 其他门类相对较少, 浮游藻类与着生藻类优势种季节差异较大.附植丝状藻密度显著高于附泥和附石丝状藻, 且狐尾藻上着生丝状藻密度与浮游丝状藻密度呈显著正相关, 表明狐尾藻着生丝状藻可能是浮游丝状藻较重要的来源之-, 该结果可为西湖丝状藻水华的控制提供-些参考.相关性分析表明, 着生藻类和丝状藻与各理化因子（水深、透明度、溶解氧、水温、pH、TN、SRP、TP等）均无显著相关性

file fuzzing test based on file format description

针对传统文件测试效率不高、存在功能遗漏的缺点,提出一种基于文件规范描述的文件模糊测试方法。给出基于文件规范的文件推导规则,用于描述文件中结构的组织形式、结构与结构之间的依赖关系,生成同一格式下不同类型的文件并对每类文件进行模糊测试。实验结果表明,该方法能有效找到文件处理软件的脆弱点

automatic software input data construction based on evolve algorithm

在软件二进制补丁比对结果的基础上,提出一种基于目标的适应值函数模型。该模型对同一种群中所有个体评估,寻找优秀个体以遗传到子代中,产生能够到达或接近到达可疑函数的个体数据。该算法不需要源码。实验结果表明,该算法简化了逆向分析人员构造软件畸形数据的过程,为其快速触发软件脆弱点创造了条件

Assessing in vivo toxicity of graphene materials: current methods and future outlook

<span lang="EN-US" style="font-family: &quot;Calibri&quot;,&quot;sans-serif&quot;; font-size: 10.5pt; mso-bidi-font-size: 11.0pt; mso-ascii-theme-font: minor-latin; mso-fareast-font-family: 宋体; mso-fareast-theme-font: minor-fareast; mso-hansi-theme-font: minor-latin; mso-bidi-font-family: &quot;Times New Roman&quot;; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: ZH-CN; mso-bidi-language: AR-SA;"><font color="#000000">Graphene, a novel 2D carbon nanomaterial with unique properties, has attracted massive attention. Evaluating its toxicity is of great significance due to its potential applications in many fields, especially in biomedicine. In this review, the toxicity of graphene-based nanomaterials (GNMs) and related mechanisms at the molecular and cellular level, various approaches to evaluation of the in vivo toxicity of GNMs and major factors defining their toxicity will be discussed and summarized. This review will allow better understanding of the in vitro and in vivo toxicity of GNMs, which, we believe, may facilitate design and fabrication of novel, biocompatible and efficient GNM-based systems for biomedical applications.</font></span

基于量子级联激光器的ADN 基发动机燃烧室内CO 浓度和温度测量系统的设计

ADN（二硝酰胺铵）作为一种绿色推进剂已在固体推进剂以及液体推进剂领域得到一定程度的应用，是未来化学推进技术的一个新方向。目前我国正处于ADN 推进剂研究的起始阶段，燃烧过程的研究是当前研究的一个重要问题。由于ADN 基推进剂催化分解及燃烧反应过程复杂，相关的实验数据无法从国外公开文献获得，因此有必要开展ADN 发动机催化分解及燃烧反应的实验研究。本实验采用基于量子级联激光器吸收光谱诊断技术对ADN 基发动机燃烧室内燃烧过程进行探究。CO 是ADN基燃烧反应特征产物之一，通过测量ADN 基发动机不同工况下CO 的浓度和燃烧室内温度，可以获得ADN 基的催化效率及燃烧反应进行的程度