基于分子对接和QSAR方法预测B-Raf II型抑制剂活性

B-Raf激酶在促分裂素原活化蛋白激酶(MAPK)信号转导通路中起着重要作用,已被确定为癌症治疗非常有吸引力的靶标.新型高效B-Raf抑制剂的开发成为癌症治疗的一个热门研究领域.本文以结构多样的B-Raf II型抑制剂为研究对象,联合应用分子对接和定量构效关系(QSAR)模型研究其定量构效关系去探讨抑制活性的起源.两个主题作为研究重点:生物活性构象和描述符.首先对分子对接方法(Glide、Gold、LigandFit、Cdocker和Libdock)进行准确性评价,后将研究的对象分子对接到B-Raf活性位点并获得生物活性构象.基于准确的对接结果,计算得到16个打分评价函数和21个能量描述符,以此构建定量构效关系模型. QSAR结果表明模型具有高度精确的拟合和强的预测能力(模型M1: r² = 0.852, r_(CV)² = 0.790, r_pre² = 0.864;模型M2: r² = 0.738, r_(CV)² = 0.812, r_pre² = 0.8605).同时探讨了对抑制活性有重要影响的描述符,结果表明打分评价函数(G_Score, -ECD, Dock_Score, PMF)与能量描述符(S(hb_ext), DE(int), Emodel)对抑制活性影响非常大.通过虚拟筛选和QSAR模型理论预测,一些新的具有潜在抑制活性的化合物作为B-Raf II型抑制剂被获得.上述信息对于进一步设计新颖高效的B-Raf II型抑制剂提供了有用的指导.     

LaAlO3衬底高温超导线性相位滤波器

报道了带宽为10 MHz,80%以上带宽内群时延失真小于20 ns的高温超导线性相位滤波器.该滤波器制作于LaAlO3衬底上,采用了一种新的谐振器结构以消除寄生耦合的影响,使得滤波器不仅具有很好的线性相位特性,而且具有对称的幅频响应特性.滤波器实测带宽为9.85 MHz,回波损耗约16 dB,带外抑制大于80 dB,群时延失真(80%以上带宽内)约20 ns,其他实测指标也与仿真结果符合很好.     

基于红色荧光染料3-(dicyanomethylene)-5, 5-dimethyl-1-(4-dimethylamino-styryl) cyclohexene的高性能白色有机电致发光器件

研究了基于红色荧光染料3-（dicyanomethylene）-5, 5-dimethyl-1-（4-dimethylamino-styryl） cyclohexene（DCDDC）的白色有机电致发光器件的性能,分别制备了基于DCDDC超薄层和DCDDC掺杂主体材料的两种器件结构: 1）indium-tin oxide（ITO）/N, N′-diphenyl-N, N′-bis（1-naphthyl-pheny1）-1, 1′-biphenyl-4, 关键词： 有机电致发光器件 白色发光 红色荧光染料 掺杂     

约瑟夫森结的混沌行为及其在保密通信中的应用(英文)

约瑟夫森结的混沌行为在研究和应用方面都具有重要的价值。电阻-电容-电感并联约瑟夫森结在直流电流的驱动下会出现混沌行为,采用数值计算的方法,对混沌行为进行了研究。通过电压波形、频谱、对初始条件的敏感依赖以及奇怪吸引子,证实了混沌的存在,在此基础上首次提出了基于约瑟夫森结混沌行为的保密通信方案。     

Phase Locking and Chaos in a Josephson Junction Array Shunted by a Common Resistance

The dynamics of a Josephson junction array shunted by a common resistance are investigated by using numerical methods. Coexistence of phase locking and chaos is observed in the system when the resistively and capacitively shunted junction model is adopted. The corresponding parameter ranges for phase locking and chaos are presented. When there are three resistively shunted junctions in the array, chaos is found for the first time and the parameter range for chaos is also presented. According to the theory of Chernikov and Schmidt, when there are four or more junctions in the array, the system exhibits chaotic behavior. Our results indicate that the theory of Chernikov and Schmidt is not exactly appropriate.     

Properties of Graphene Based Parametric Pump

The adiabatic parametric electron pump of the infinite zigzag graphene ribbons and the infinite armchair graphene ribbons is investigated by the tight binding method. The pumping signals are added by two gates around the ribbons. It is shown that the de current can be pumped out by cyclically varying the two gate voltages and the pumped current strongly depends on the driving frequency, the pumping amplitude and the phase difference of the gate voltages. The pumped current is mediated by the graphene energy levels and its peaks occur around the energies where transmission coefficients and density of states are large. The pump current may give one peak or two opposite peaks corresponding to each transmission peak or transmission pair peaks. The height and width of the current peaks increase with the amplitude of the pumping driving voltages. The pumped current is antisymmetric about the phase difference Ф=π and for small pumping amplitude the pumped current is a sinusoidal function of the phase difference. Some graphene ribbons, although with different widths, have very similar contours of the transmission coefficients and give the same pumped current figures.     

Heat Transport of Non-Local Effect with Modulated SMBI on HL-2A

Modulated supersonic molecular beam （SMB） injection is introduced to study transport features of non-local transport phenomenon on HL-2A. Repetitive non-local effect induced by modulated SMBI allows Fourier trans-formation of the temperature perturbation, yielding detailed investigation of the pulse propagation. Fourier analysis provides evidence for existence of internal transport barriers. Meanwhile, experimental progress of nonlocal effect was made in the HL-2A Tokamak in 200Z The core electron temperature Te rise increases from 18% to more than 40% and the duration of the Te rise could be prolonged by changing the conditions of SMB injection.     

系列Cr（Ⅲ）配合物的晶体结构和表面光电性能

采用常规方法合成了3种Cr（Ⅲ）配合物：[Cr(en)₂ox][Cr(en)(ox)₂]•2H₂O (1)、[Co(NH₂NHCSNH₂)₃][Cr(ox)₃]•7H₂O (2)和Cr(acac)₃ (3) (en=ethylenediamine, ox=oxalic acid, acac=acetylacetone)。通过X射线单晶衍射、紫外可见吸收光谱（UV-Vis）及表面光电压光谱（SPS）对配合物进行了表征。通过SPS光谱对3种配合物的表面光电性能与其相应的UV-Vis吸收光谱进行了对比。结果表明,配合物在300~600 nm范围内均可呈现较好的光伏响应,而且测得的表面光电压光谱峰位置和紫外吸收光谱有较好的对应关系。     

3D-QSAR和分子对接研究吲哚咔唑类细胞周期蛋白激酶抑制剂的选择性

细胞周期蛋白激酶(cyclin-dependent kinases, CDKs)是近年来治疗肿瘤的重要靶标. 由于大多数激酶ATP结合位点的保守性, CDK选择性激酶抑制剂的开发成为当前的研发难点和热点. 针对吲哚咔唑类CDK抑制剂, 我们采用比较分子力场分析方法(CoMFA)建立了CDK2-QSAR(quantitative structure-activity relationship)和CDK4-QSSR(quantitative structure-selectivity relationship)模型. 所建模型的交叉验证系数q2分别为0.722和0.703; 非交叉验证系数r2分别为0.977和0.946, 表明其具有较好的预测能力. 同时, 用分子对接的方法分析了这类化合物与CDK4同源模建结构的作用模式, 根据这两个模型发现, 吲哚咔唑类化合物的R5和R6位长链取代对CDK4的选择性具有一定的影响, 而且结合其作用模式比较合理地解释了这类抑制剂的选择性原因, 这对CDKs的选择性研究具有一定的指导意义.     

关于定积分概念的数列化

讨论定积分概念的数列化及其相关问题．使用经典的精确分析方法,得到一个数列化的可积的充要条件．探索微元法表述后续相关概念与证明相关结果．同时举例说明定积分概念数列化的优越性与微元法处理后续相关问题的可行性．