碳离子辐射诱导秀丽隐杆线虫生殖细胞凋亡研究

重离子辐射具有独特的深度剂量分布和较高的相对生物学效应,被认为是理想的放疗手段。重离子的生物学效应在径迹形成过程中由多个物理参量共同决定,而这些物理参量和离子入射深度紧密相关,因此明确离子不同入射深度的生物学效应对重离子肿瘤放疗方案的设计和优化有着重要的理论和应用价值。使用兰州重离子研究装置HIRFL-CSRe 终端的碳离子束作为辐射源,以活体模式动物线虫作为实验对象,以线虫生殖细胞的凋亡水平作为生物学检测终点,研究了10 和20 Gy 碳离子辐射在辐射的入口、坪区和峰区的当代生物学效应和对后代个体基因组不稳定性的影响。结果表明:10 和20 Gy 碳离子辐射在三个不同的辐照区域内均显著增加了辐射当代的线虫生殖腺细胞的凋亡水平,并表现出一定的辐射区域和辐射剂量依赖性。同时,辐射诱导的后代个体基因组不稳定性也表现出一定的辐射区域和辐射剂量相关性。Heavy ion irradiation is a perfect means in radio-therapy due to its special depth dose distribution and high relative biological effects. The biological effects of heavy ion irradiation are determined by some major physical parameters, and vary along the tracks of heavy ions. Therefore, it is very significant for the tumor radio-therapy to investigate the biological effects along whole range of heavy ion radiation. In the present study, Caenorhabditis elegans, a model in vivo, was irradiated by carbon ion beams from HCRFL-CSRe, The level of germ cell apoptosis of worms was used as a checking endpoint for DNA damage, the effects of carbon irradiation located in the entrance, plateau and peak regions on the genomic instability of the irradiated worm and their progeny were detected. The results showed that the 10 and 20 Gy of carbon ion radiations led to the increased germ cell apoptosis in irradiated worms and these effects depend on the worm location along the range of carbon ions and the irradiation dosage. The results also suggested that heavy ion irradiation induced the up-regulated genomic instability in their progeny, and might be related to both the irradiation dose and the irradiated location.     

秀丽隐杆线虫对声表面波刺激的行为响应

利用频率为8.8 MHz的声表面波, 刺激位于压电基底上琼脂表面秀丽隐杆线虫, 研究其对超声作用的行为响应。具体地, 分析了超声刺激后线虫的转向和后退行为与声表面波辐照时长、基底振动幅度及脉冲重复频率的关系, 发现线虫对高频声表面波脉冲刺激的响应与此前低频体波刺激所得规律一致, 即类似于可感知脉冲重复频率的带通滤波器。通过比较温度感知缺陷突变体线虫与野生型线虫的行为, 明确了机械振动在诱发线虫响应中占据主导地位, 而超声热效应并非主要因素。在此基础上, 尝试通过信号时−空分布的调节改变声场形态, 研究线虫在声场中的趋避性, 进而实现对线虫转向行为的初步干预。     

应用CoMFA研究抗菌肽的三维定量构效关系

采用比较分子场分析(CoMFA)方法对抗菌九肽、抗菌十四肽、抗菌十八肽进行三维定量构效关系(3D-QSAR)分析,建立了预测力强的3D-QSAR模型.结果表明,所建立的3D-QSAR模型对三种抗菌肽均有较好的统计学稳定性及预测能力(抗菌九肽:交叉验证系数q~2=0.537,非交叉验证相关系数r~2=0.961,外部样本检验复相关系数Q_(ext)~2=0.883;抗菌十四肽:q~2=0.502,r~2=0.718,Q_(ext)~2=0.645;抗菌十八肽:q~2=0.550,r~2=0.967,Q_(ext)~2=0.989).三维等势图不仅解释了抗菌肽结构与活性的关系,而且为抗菌肽的进一步合成提供了理论依据.     

抗癌性苯并噻唑类衍生物三维定量构效关系研究

应用比较分子场分析法(CoMFA)对一系列抗癌性苯并噻唑类衍生物进行了三维定量构效关系(3D-QSAR)研究,建立了交叉验证的CoMFA模型,并在此基础上建立了非交叉验证的偏最小二乘分析模型．所建最佳模型的交叉验证相关系数为0.642,非交叉验证相关系数为0.976,估算的标准误差S＝0.161,统计方差比F(3;20)＝111.4,表明该模型是合理有效的．同时对该系列抗癌化合物的3D-QSAR进行了深入研究．结果表明,在R取代基的第一个原子上引入吸电子基团或原子,如F等,便可增强与它直接相连的C19的正电荷,从而增强C19ˉ位上处于静电场蓝色区域的原子的正电荷．同时,选择适当体积大小的取代基R,使之落入立体场绿色区域,就能有效地改善这类化合物的抗癌活性．     

定量构效关系研究中图论方法:烷烃13C NMR化学位移

系统研究了图论方法在定量构效(性)关系(QSAR/QSPR)中的应用.本文研究提出了一种新的指数L,并发现它与烷烃¹³C NMR有良好线性相关性.     

HIV蛋白酶抑制剂的定量构效关系研究及其指导下的修饰

HIV蛋白酶是一类用于治疗艾滋病具有潜在价值的关键酶,很多此类酶的抑制剂已经上市.一系列由AHPBA分子的基本骨架进行改造并合成的25个α-羟基β-氨基酸类似物对于HIV蛋白酶具有很高的活性和选择性.我们筛选合适的描述子建立一个二维定量构效关系的模型,模型的均方根误差RMSE=0.09823、相关性系数R=0.97461、F值=30.763、交叉验证的相关系数RCV=0.7071、交叉验证的预测误差平方PRESS=0.588,该模型为HIV蛋白酶抑制剂修饰和设计提供了比较可靠的预测.并且根据“变形钥匙”理论,分别用“杂化肽键”Ψ[CH2NH]、Ψ[CF2NH]、Ψ[COCF2]、替换掉这组类似物中易水解的肽键-CO=NH-,使得这个共轭π键就变成一个较强的单键,变得不易被HIV蛋白酶所水解,从而得到抗AIDS的有效的抑制剂.然后通过原子电荷分布对比、分子对接等方法检验修饰的可能性和合理性.预先设想都在计算结果中得到验证,并且用QSAR模型预测了修饰后分子的活性.     

基于酪氨酸端基的ACE三肽抑制剂定量构效关系研究

固定酪氨酸为端基对ACE三肽抑制剂进行构效关系研究,采用多元线性回归方法,基于不同描述符建立模型,比较模型的可靠性和准确性.结果表明Z描述子建立的模型最好.定量构效关系研究表明ACE抑制三肽第二位氨基酸的电性参数是抑制活性的最大影响因素.     

基于酪氨酸端基的ACE三肽抑制剂定量构效关系研究

固定酪氨酸为端基对ACE三肽抑制剂进行构效关系研究,采用多元线性回归方法,基于不同描述符建立模型,比较模型的可靠性和准确性。结果表明Z描述子建立的模型最好。定量构效关系研究表明ACE抑制三肽第一位氨基酸的疏水性是抑制活性的最大影响因素。     

抗癌新药德氮吡格及其衍生物的定量构效关系

按氢分类的分子电性距离矢量（Hydrogen-association classified molecular electronegafivity-distance vector,H-MEDV）是由4种类型原子间的相互作用得到的一种描述分子二维结构的拓扑描述子.本文根据H-MEDV来研究创新构型抗肿瘤药物德氮吡格（TNBG）及其衍生物活性与其结构之间的关系,利用多元线性回归和逐步回归,建立的4变量模型的相关系数R=0.862.对筛选后建立的模型用留一法交互检验的结果为Rcv=0.713,结果表明模型具有较好的预测能力和稳定性.     

抗癌药物铂络合物构效关系的物理方法研究

本文用Ｘ射线衍射、傅里叶变换红外光谱、差热分析等物理方法研究了抗癌药物铂络合物特性、结构以及构效关系．研究结果表明：ｃｉｓ－［Ｐｔ（ＮＨ３）２Ｃｌ２］属简单斜方晶系,晶格常数ａ＝０．９２２１ｎｍ,ｂ＝０．８７７１ｎｍ,ｃ＝０．６８９０ｎｍ．草酸二氨合铂的结构为斜方晶系,其晶格常数为：ａ１＝１．０７２１ｎｍ,ａ２＝０．６４０２ｎｍ,ａ３＝１．８５７０ｎｍ,并用傅里叶变换红外光谱、差热分析、元素分析等方法对它们理化特性进行了研究     

In vivo imaging of cell morphology and cellular processes in Caenorhabditis elegans, using non-linear phenomena

We present the detailed imaging of structures and processes of the nematode Caenorhabditis elegans (C. elegans) using non-linear microscopy. Complementary information about the anatomy of the nematode was collected by implementing a combination of two photon excitation fluorescence (TPEF), second and third harmonic generation (SHG and THG) image contrast modes on the same microscope. Three-dimensional (3D) reconstructions of TPEF, SHG and THG images were also performed. Moreover, THG imaging technique has been tested as a potential, novel, non-destructive diagnostic tool for monitoring cellular processes in vivo, such as neuronal degeneration.     

MAP kinase cascades regulating axon regeneration in C. elegans

Mitogen-activated protein kinase (MAPK) signaling cascades are activated by diverse stimuli such as growth factors, cytokines, neurotransmitters and various types of cellular stress. Our evolving understanding of these signal cascades has been facilitated by genetic analyses and physiological characterization in model organisms such as the nematode Caenorhabditis elegans. Genetic and biochemical studies in C. elegans have shed light on the physiological roles of MAPK cascades in the control of cell fate decision, neuronal function and immunity. Recently it was demonstrated that MAPK signaling is also important for axon regeneration in C. elegans, and the use of C. elegans as a model system has significantly advanced our understanding of the largely conserved molecular mechanisms underlying axon regeneration. This review summarizes our current understanding of the role and regulation of MAPK signaling in C. elegans axon regeneration.     

The odyssey of Orpheus: The evolution of solo singing

Notated sacred solo song dates from 1,000 B.C. Early secular song exhibits modest vocal demands of chant-like character. Popular song and liturgical solo song share common origins. Western European secular song notation began in the early Medieval Age. Compositional writing for solo voice took a dramatic turn toward virtuosity about 1600. By the mid-17th century, the modern solo voice emerged. “Classical” solo vocal literature is not static but is constantly evolving, requiring skills far in excess of those of speech or of early solo song literature; this is equally the case with ethnomusicological and popular singing styles. Efficient use of the singing instrument is essential to the healthy accomplishment of all of these literatures.     

核因子κB活性抑制剂定量构效关系

用量子化学密度泛函及分子力学方法,计算了一系列喹唑啉衍生物分子的电子结构、几何结构及分子性质(广义结构)的各种参数,用以探讨该类药物分子的结构与对核因子抑制活性的关系.通过逐步回归分析,筛选出主要因素,建立了定量构效关系方程.结果表明,化合物的环D上17位碳原子上的取代基X的疏水参数、环A中R1取代基上第一个原子的净电荷及该取代基的立体参数,以及环A上3位碳原子的净电荷与化合物的抑制活性紧密相关,它们是影响化合物抑制活性的主要因素.采用“leaveoneout”法进行预报检验,其交叉检验相关系数较大,表明所得的模型有较强的预报能力.方程入选的都是可计算参数,这有利于计算机辅助该类NFκB活性抑制剂的分子设计.     

Structural and ultrastructural characterization of male reproductive tracts and spermatozoa in fig wasps of the genus Pegoscapus (Hymenoptera, Chalcidoidea)

The three Pegoscapus species present the same internal reproductive tract features comprising testes with a single testicular tubule, seminal vesicles, vasa deferentia, accessory glands and an ejaculatory duct. The seminal vesicle shows two morphologically distinct portions although they do not resemble the separate chambers found in other Chalcidoidea. The anterior portion of the seminal vesicle shows a prominent epithelium and stores the mature spermatozoa, while the posterior region is formed by a thicker muscular sheath that participates on ejaculation. The sexual maturation in Pegoscapus is achieved at emergence, when the testicular degeneration occurs. The spermatozoa of Pegoscapus reveal a basic structure similar to that of other Chalcidoidea. In Pegoscapus sp1. and Pegoscapus sp2. they present the same features, whereas Pegoscapus tonduzi comprises some different characteristics. It measures approximately 160 μm in Pegoscapus sp1. and Pegoscapus sp2., while in P. tonduzi the spermatozoa measure about 360 μm. The extracellular sheath thickness is another difference among the species. While Pegoscapus sp1. and Pegoscapus sp2. show a thick extracellular sheath, in P. tonduzi this sheath is very thin resulting in a large space intervening between the extracellular sheath and the nucleus. Despite these differences, the three species analyzed share some characteristics that allow the establishment of an identity to the spermatozoon of the genus Pegoscapus: the seminal vesicle not divided in chambers; the absence of acrosomal structures in the spermatozoa; the length of the extracellular sheath; the central microtubules being the firsts to terminate in the sequence of microtubular cutoff at the final axonemal portion.     

快离子导体AgxTiS2中Ag+离子－空位的二维基态结构与能量性质研究

根据Ag⁺离子-空位的二维有序结构建立了三维晶胞模型.采用局域密度近似下的平面波赝势方法,对有序Ag_xTiS₂(x=0,1/4,1/3,1/2,2/3,3/4,1)系列进行了几何结构优化和总能量计算,并与Li_xTiS₂系列进行了对比研究.有序Ag_xTiS₂系统的晶格参量增量Δa关键词：xTiS₂')\" href=\"#\">Ag_xTiS₂有序—无序相变离子扩散第一性原理计算     

Application of quantitative structure-activity relationship to the determination of binding constant based on fluorescence quenching

Quantitative structure-activity relationship (QSAR) model was used to predict and explain binding constant (log K) determined by fluorescence quenching. This method allowed us to predict binding constants of a variety of compounds with human serum albumin (HSA) based on their structures alone. Stepwise multiple linear regression (MLR) and nonlinear radial basis function neural network (RBFNN) were performed to build the models. The statistical parameters provided by the MLR model (R²=0.8521, RMS=0.2678) indicated satisfactory stability and predictive ability while the RBFNN predictive ability is somewhat superior (R²=0.9245, RMS=0.1736). The proposed models were used to predict the binding constants of two bioactive components in traditional Chinese medicines (isoimperatorin and chrysophanol) whose experimental results were obtained in our laboratory and the predicted results were in good agreement with the experimental results. This QSAR approach can contribute to a better understanding of structural factors of the compounds responsible for drug-protein interactions, and can be useful in predicting the binding constants of other compounds.     

Luminescence of O2−-vacancy centers in BaFBr and BaFCl

Irkutsk State University, 20, Gagarin Av., Irkutsk, 664003, Russia. Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 62, No. 3, pp. 215–217, May–June, 1995.