Discharge characteristics of the DUHOCAMIS with a high magnetic bottle-shaped field

For the purpose of producing high intensity, multiply charged metal ion beams, the dual hollow cathode ion source for metal ions (DUHOCAMIS) was derived from the hot cathode Penning ion source combined with the hollow cathode sputtering experiments in 2007. To investigate the behavior of this discharge geometry in a stronger magnetic bottle-shaped field, a new test bench for DUHOCAMIS with a high magnetic bottle-shaped field up to 0.6 T has been set up at the Peking University. The experiments with magnetic fields from 0.13 T to 0.52 T have indicated that the discharge behavior is very sensitive to the magnetic flux densities. The slope of discharge curves in a very wide range can be controlled by changing the magnetic field as well as regulated by adjusting the cathode heating power; the production of metallic ions would be much greater than gas ions with the increased magnetic flux density; and the magnetic field has a much higher influence on the DHCD mode than on the PIG mode.     

HCV复制抑制剂的定量构效关系的研究

选用60个结构多样的HCV复制抑制剂分子作为数据集,随机选择其中46个分子作为训练集,剩余14个分子作为验证集.采用多元线性回归(MLR)和主成分分析(PCA)方法对每个分子的646个理化和结构参数进行了线性回归分析,并分别建立各自的最优模型.结果表明MLR中的逐步和向前法所建模型最佳,模型结果为:训练集R2=0.827,验证集R2=0.850,模型能够直观地反映影响化合物活性的主要因素.该模型将有助于筛选和开发新的HCV复制抑制.     

Discharge characteristics of the DUHOCAMIS with a high magnetic bottle-shaped field

For the purpose of producing high intensity, multiply charged metal ion beams, the dual hollow cathode ion source for metal ions （DUHOCAMIS） was derived from the hot cathode Penning ion source combined with the hollow cathode sputtering experiments in 2007. To investigate the behavior of this discharge geometry in a stronger magnetic bottle-shaped field, a new test bench for DUHOCAMIS with a high magnetic bottle-shaped field up to 0.6 T has been set up at the Peking University. The experiments with magnetic fields from 0.13 T to 0.52 T have indicated that the discharge behavior is very sensitive to the magnetic flux densities. The slope of discharge curves in a very wide range can be controlled by changing the magnetic field as well as regulated by adjusting the cathode heating power; the production of metallic ions would be much greater than gas ions with the increased magnetic flux density; and the magnetic field has a much higher influence on the DHCD mode than on the PIG mode.     

广谱沙粒病毒抑制剂的3D-QSAR分析

沙粒病毒(Arenaviruses)遍布全球,其中的拉沙热病毒可引起致命的拉沙热.通过应用比较分子场分析(CoMFA)和比较相似性指数分析法(CoMSIA)对47个广谱沙粒病毒抑制剂进行了三维定量构效关系(3D-QSAR)分析.使用立体场、静电场、疏水场和氢键受体场组合获得最优模型CoMSIA的统计结果为Q2=0.518,R2ncv=0.972,R2pre=0.911,说明该模型的可靠性和较好预测能力.此外,模型等势线图直观地解释了分子结构与其活性的关系,为进一步设计新型高效的沙粒病毒抑制剂提供了理论依据.     

3C-like蛋白酶抑制剂的构效关系、分子对接和分子动力学

3C-like蛋白酶是中东呼吸综合征冠状病毒（MERS-CoV）等其它冠状病毒的繁殖过程中极为重要的蛋白酶。它已成为人类在抗冠状病毒领域中的研究热点。本文基于计算生物学方法对与MERS-CoV同属的蝙蝠冠状病毒HKU4（HKU4-CoV）的43个肽类3C-like蛋白酶抑制剂分子,建立三维定量构效关系（3D-QSAR）模型。在基于配体叠合的基础上,发现比较分子相似性指数分析法（CoMSIA）中的四个场组合（位阻场、静电场、氢键供体场与氢键受体场）为最优的模型（Q²=0.522,R_ncv²=0.996,R_pre²=0.904;Q²：交叉验证相关系数,R_ncv²：非交叉验证相关系数,R_pre²：验证集分子的预测值相关系数）,并借助该模型通过分子对接（docking）与分子动力学（MD）方法阐明了配受体结合作用。实验结果表明：（1）基于最优的CoMSIA模型基础上的三维等势图形象地说明了分子基团的位阻作用、静电作用、氢键供体与氢键受体作用对分子生物活性的影响;（2）分子对接研究结果显示了疏水性以及结晶水、氨基酸His166和Glu169在配体和受体结合过程中产生重要作用;（3）分子动力学模拟进一步验证了分子对接模型的可靠性,并发现了两个新的关键氨基酸Ser24与Gln192,它们与配体产生了两个较强的氢键。此外,根据这些结果,一些新的具有潜在抑制活性的肽类化合物作为3C-like蛋白酶抑制剂被获得。以上结果能够帮助深入了解3C-like蛋白酶与肽类抑制剂的作用机理,并且能够为今后的抗MERS-CoV药物设计提供有价值的参考。     

P2Y12受体拮抗剂定量构效关系的研究

P2Y12受体拮抗剂是一类重要的抗血小板药物,研究分子活性与其结构参数的关系,对于合成新的P2Y12受体拮抗剂具有一定指导作用.选用178个结构多样的P2Y12受体拮抗剂分子作为数据集,随机选取了143个P2Y12受体拮抗剂作为训练集,剩余分子作为检验集.采用多元线性回归(MLR)方法和主成分回归分析(PCA)方法对每个分子的636个分子参数进行线性回归分析.MLR所建模型的结果为:训练集R2=0.800,检验集R2=0.834;PCA模型结果为:训练集R2=0.545,检验集R2=0.665.相比之下MLR法所建模型具有良好的预测性和可靠性.通过模型分析,确定了影响分子活性的关键因素.以上模型对筛选和合成新型高效P2Y12受体拮抗剂提供了一定理论指导.     

Design of triode extraction system for a dual hollow cathode ion source

A triode extraction system is designed for a dual hollow cathode ion source being developed at the Institute of Heavy Ion Physics, Peking University. Basic parameters of the plasma are selected after examining the operation principle of the ion source, then the triode extraction system is designed and optimized by using software PBGUNS (for Particle Beam GUN Simulations). The physical design of the system is given in this paper.     

Theoretical analysis of a new extraction system for a DUHOCAMIS operating in a high magnetic field

A new extraction system is designed for a penning ion source DUHOCAMIS （dual hollow cathode ion source for metal ion beams） being installed at the Institute of Heavy Ion Physics,Peking University.We have analyzed theoretically the central particle trajectories in the extraction region for ions having different q/m ratios and then compared our results with the simulation results of CST （Computer Simulation Technology） software.The validity of the system is verified and some analytical formulas are obtained which will be used for the optimization of the extraction system as well as the experimental setup.     

系统药理学法研究“上火”与氧化应激之间的关系

运用中药系统药理学来分析黄连解毒汤,进而研究"上火"与氧化应激之间的关系.运用系统药理学中的靶点预测和网络药理学部分用来研究黄连解毒汤的抗氧化机制.具体来说,对黄连解毒汤的22个活性组分做靶点预测,发现有38个靶点与之相互作用,其中10个靶点与其抗氧化机制有关.且黄连解毒汤的抗氧化机制在组分水平、靶点水平、靶点对细胞因子水平上都有体现.从药理学角度,黄连解毒汤的抗氧化作用显著,与其在中药中强大的"清火"功能相对照后,就可以看出"上火"与氧化应激密切相关.将系统药理学应用于中药的方法,为"上火"的研究提供了一条新的思路.     

基于糖皮质激素受体调节剂波尼松龙的定量构效关系研究

为了探讨糖皮质激素受体调节剂波尼松龙系列的结构和活性之间的关系,首次使用比较分子力场(CoMFA)和比较分子相似性指数分析(CoMSIA)方法对77个靶标分子建立三维定量构效关系(3D-QSAR)模型.在基于配体叠合的基础上,得到了最好的CoMSIA模型(Q2=0.504,R2ncv=0.849,SEE=0.283,F=56.365和R2pred=0.792).模型的三维等势线图分析说明了疏水性基团在R1取代基位置有利于提高活性,亲水性基团在R2取代基位置有利于提高活性.此外,分子对接分析结果显示了与波尼松龙形成一些氢键的氨基酸Asn564,Gln642,Thr739在糖皮质激素受体调节剂中有重要作用.本文得到的结果能够更好地帮助理解糖皮质激素受体调节剂作用机理,并为今后的药物设计与合成提供了新思路.