12C6+束和Mitomycin C 诱导的DNA损伤效应

本文旨在分别研究重离子束及MMC在诱导细胞的DNA损伤效应中一些具体的分子机制，为治疗的进行以及相关辅助药物的开发提供理论依据。本文探索的重点有两个，第一个是重离子束辐射诱导的DNA损伤效应及p53在其中的激活，第二个是MMC诱导的DNA损伤效应及p53和BRCA1、H2AX等分子在其中的角色。 1. 12C6+离子束诱导HeLa细胞DNA损伤效应为了研究HeLa细胞经过12C6+ 束辐照之后的DNA损伤效应，及这个过程中p53激活的分子机制。我们运用中性单细胞电泳技术，检测了HeLa细胞经过4Gy 12C6+ 束辐照0h、3h、6h和12h之后DNA的损伤情况，以及0.5Gy、1Gy、2Gy和4Gy 12C6+ 束辐照0h后的DNA损伤情况。同时运用细胞生长实时监测仪监测了HeLa细胞在经过0Gy、0.5Gy和1Gy 12C6+ 束辐照之后的生长变化，并运用AO/EB双染检测了辐照24小时后的凋亡情况。另外，利用8mmol/L的caffeine（抑制ATM和ATR）和20μmol/L的wortmannin（抑制ATM和DNA-PK）处理HeLa细胞后再进行1Gy 12C6+ 束辐照，通过western blot检测p53的表达。结果显示，12C6+ 束辐照可造成HeLa细胞的DNA损伤，损伤随剂量升高而升高但随时间降低；并诱导HeLa细胞发生凋亡；而且辐照后p53表达升高，但经过caffeine或者wortmannin预先处理的细胞p53均没有显著升高。我们的结论是：12C6+ 束辐照可造成HeLa细胞的DNA损伤并诱导损伤修复及凋亡等效应，损伤效应相关的分子p53被激活，并且激活依赖于ATM。 2. MMC诱导的DNA损伤效应在这一部分研究中，首先，我们利用与上面相同的研究方法，探讨了p53在MMC诱导的DNA损伤效应中的激活情况，结果显示，MMC诱导的DNA损伤效应并不依赖于p53。另外，我们还探讨了， BRCA1在FANCD2的γ-H2AX依赖性转移中的作用。MMC可造成DNA的ICL（interstrand cross-link）损伤，ICL可通过FA(Fanconi Anemia)通路进行修复。FANCD2是FA通路的核心分子，在DNA产生ICL时被各种分子修饰然后转移到损伤部分，这个过程的涉及到ATR、γ-H2AX及BRCA1等，本文试图探讨BRCA1在其中的作用方式。研究中，我们监测了不同处理（包括对照、caffeine（可抑制ATR）、MMC及MMC ＋caffeine）的HCC1937(BRCA1缺陷型)和MCF7（BRCA1野生型）细胞的生长；并用Western blot检测MMC处理之后HCC1937细胞γ-H2AX的表达情况。结果表明，MMC和caffeine均可以抑制HCC1937的生长，但caffeine和MMC+caffeine的抑制效果是一样的；MMC和caffeine均可以抑制MCF7的生长，且MMC+caffeine处理比仅进行caffeine处理的抑制作用强；MMC处理之后，HCC1937的γ-H2AX表达显著升高。我们的结论是，在FANCD2的γ-H2AX依赖性转移中，H2AX的磷酸化并不依赖于BRCA1，不过，BRCA1和ATR应该参与一个相同的分子事件，可能是FANCD2的磷酸化。这个有待进一步的实验验证

草鱼体内肾细胞姐妹染色单体分化及交换的初步研究

本文确立了一个以草鱼体内肾细胞姐妹染色单体交换频率为指标的检测环境诱变或致癌物质的短期试验系统。采用硫堇-UV-Giemsa染色法,分析了草鱼体内肾细胞的SCD-2(注射BrdU后第二个细胞周期的中期分裂相的SCD)频率和SCE频率。用500微克/克体重BrdU体内标记5天,草鱼肾细胞SCD-2频率为8.58±0.22%;SCE频率为3.05±2.523 SCE_5/细胞。以丝裂霉素C(Mitomycin C,MMC)作为阳性对照,分析了化合物亚硝基胍(N-methyl-N~1-nitro-N-nitro

Induction and preliminary characterization of a novel halophage SNJ1 from lysogenic Natrinema sp F5

Halophage SNJ1 was induced with mitomycin C from Natrinema sp. strain F5. The phage produces plaques on Natrinema sp. strain J7 only. The phage has a head of about 67 nm in diameter and a tail of 570 nm in length and belongs morphologically to the family Siphoviridae. The phage is strongly salt dependent; NaCl concentration affects the integrity of SNJ1, phage adsorption, and plaque formation. The optimal NaCl concentration for phage adsorption and plaque formation is 30% and 25%, respectively.

Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing

In this study, an in vitro multicellular tumor spheroid model was developed using microencapsulation, and the feasibility of using the microencapsulated. multicellular tumor spheroid (MMTS) to test the effect of chemotherapeutic drugs was investigated. Human MCF-7 breast cancer cells were encapsulated in alginate-poly-L-lysine-alginate (APA) microcapsules, and a single multicellular spheroid 150 mu m in diameter was formed in the microcapsule after 5 days of cultivation. The cell morphology, proliferation, and viability of the MMTS were characterized using phase contrast microscopy, BrdU-Iabeling, MTT stain, calcein AM/ED-2 stain, and H&E stain. It demonstrated that the MMTS was viable and that the proliferating cells were mainly localized to the periphery of the cell spheroid and the apoptotic cells were in the core. The MCF-7 MMTS was treated with mitomycin C (MC) at a concentration of 0.1, 1, or 10 times that of peak plasma concentration (ppc) for up to 72 h. The cytotoxicity was demonstrated. clearly by the reduction in cell spheroid size and the decrease in cell viability. The MMTS was further used to screen the anticancer effect of chemotherapeutic drugs, treated with MC, adriamycin (ADM) and 5-fluorouracil (5-FU) at concentrations of 0.1, 1, and 10 ppc for 24, 48, and 72 h. MCF-7 monolayer culture was used as control. Similar to monolayer culture, the cell viability of MMTS was reduced after treatment with anticancer drugs. However, the inhibition rate of cell viability in MMTS was much lower than that in monolayer culture. The MMTS was more resistant to anticancer drugs than monolayer culture. The inhibition rates of cell viability were 68.1%, 45.1%, and 46.8% in MMTS and 95.1%, 86.8%, and 91.6% in monolayer culture treated with MC, ADM, and 5-FU at 10 ppc for 72 h, respectively. MC showed the strongest cytotoxicity in both MMTS and monolayer, followed by 5-FU and ADM. It demonstrated that the MMTS has the potential to be a rapid and valid in vitro model to screen chemotherapeutic drugs with a feature to mimic in vivo three-dimensional (3-D) cell growth pattern.

Nonequilibrium microstructures and their evolution in a Fe-Cr-W-Ni-C laser clad coating

The laser-solidified microstructural and compositional characterization and phase evolution during tempering at 963 K were investigated using an analytical transmission electron microscope with energy dispersive X-ray analysis. The cladded alloy, a powder mixture of Fe, Cr, W, Ni, and C with a weight ratio of 10:5:1:1:1, was processed with a 3 kW continuous wave CO2 laser. The processing parameters were 16 mm/s beam scanning speed, 3 mm beam diameter. 2 kW laser power, and 0.3 g/s feed rate. The coating was metallurgically bonded to the substrate, with a maximum thickness of 730 mu m, a microhardness of about 860 Hv and a volumetric dilution ratio of about 6%. Microanalyses revealed that the cladded coating possessed the hypoeutectic microstructure comprising the primary dendritic gamma-austenite and interdendritic eutectic consisted of gamma-austenite and M7C3 carbide. The gamma-austenite was a non-equilibrium phase with extended solid solution of alloying elements and a great deal of defect structures, i.e. a high density of dislocations, twins, and stacking faults existed in gamma phase. During high temperature aging, in situ carbide transformation occurred of M7C3 to M23C6 and M6C. The precipitation of M23C6, MC and M2C carbides from austenite was also observed.

铁基抗高温磨损激光熔覆涂层强韧设计和研究II:Fe-Cr-C-W-Ni激光熔覆层的微观组织及性能

本文以对热工模具进行失效分析的基础上，利用激光熔覆技术，在５ＣｒＭｎＭｏ基础上设计并制备强韧兼备的抗高温磨损涂层。

裂纹顶端位错的运动和小范围屈服的K_(Ⅱc)

本文从裂纹顶端位错运动的简化模型估计形成塑性区所消耗的功;从而计算临界裂纹扩展力。由于Ⅰ型加载和Ⅱ型加载的应力状态有所不同,裂纹顶端塑性功耗也会不一样。基于上述思想,考虑了小范围屈服的K_(Ⅰc)和K_(Ⅱc)的关系,得出K(Ⅱc)>K(Ⅰc)的结论,符合实验结果;并就K(Ⅱc)/K(Ⅰc)的比值与材料性能和温度的关系作了讨论。

铁基抗高温磨损激光熔覆涂层强韧设计和研究 Ⅱ:Fe-Cr-C-W-Ni激光熔覆层的微观组织及性能

利用ＯＭ、ＳＥＭ、ＴＥＭ研究了Ｆｅ－Ｃｒ－Ｃ－Ｗ－Ｎｉ激光熔覆涂层熔覆态及其高温时效态的微观组织结构。结果表明激光熔覆层组织细小，具有强韧两相组成（奥氏体和Ｍ_７Ｃ_３碳化物）的微观结构特征，高温时效处理组织中有Ｍ_（２３）Ｃ_６、Ｍ_６Ｃ、Ｍ_２Ｃ等新碳化物形成。显微硬度和冲击磨损实验证实了激光熔覆态和峰值时效态熔覆层均具有良好的力学性能。

钾离子通道Kir2.1/C-末端功能区的分子动力学模拟

<正>内向整流型钾离子通道(Kir,inwardlyrectifyingpotassium)在细胞激活、细胞内外钾离子K~+的动态平衡、胰岛素分泌等细胞生理过程中起重要作用。而细胞内各种不同因素和第二信使对Kir的调控则是实现其不同生理功能的途径。已有实验结果表明,4,5二磷酸磷脂酰肌醇(PIP2,phosphatidylinositol4,5-bisphosphate)与Kir相互作用的强弱决定了Kir对各种调控因素的响应程度。根据Kir2.1与Kir3.1胞内C-末端X-ray

Visual C++ 6.0学习教程

c="http://img3.douban.com/mpic/s1281493.jpg" border="0" alt="" hspace="8" width="102" height="144" align="left" />MicrosoftVisualC十十6.0作为Microsoft Visual Studio的重要组成部分，包含了迄今为止功能最为强大的基于Windows的应用框架，在同类产品中处于领先地位。VisualC十十6.0是Microsoft迄今为止最全面、最完善的程序开发工具，为了适应各种编程风格，该软件提供了各种各样的辅助工具，在发挥编程能力和提高灵活性方面达到了空前的水平。与以往VisualC十十的各种版本相比较，VisualC十十6.0在编程环境、程序语言技术等方面做了许多改进，从而使VisualC十十更加适合专业程序员快速进行应用程序的开发。

本书内容丰富、图文并茂，是一本适合各种读者学习VisualC十十6.0的优秀参考书。

目 录
第一章 VisualC十十6.0简介及安装
1.1VisualC十十6.0新特性
1.2viSualC十十6.0开发环境简介
1.3如何学习使用VisualC十十6.0
1.4VisualC十十6.0的安装
第二章 走进C十十的世界
2.1类和对象的简介
2.2继承和多态性――一个具体的例子
2.3内嵌对象
2.4在栈中申请对象
2.5全程对象的申请
2.6对象之间的相互关系――指针数据成员
2.7this指针的使用
2.8对指针的引用
2.9友元类和友元函数
2.10静态类成员
2.11重载运算符
2.12从代码中分离出类定义
2.13匈牙利表示法
第三章 VisualC十十6.0的编程环境
3.1VisualC十十6.0主窗口
3.2VisualC十十6.0工具栏
3.3VisualC十十6.0菜单栏
3.4项目与项目工作区
3.5资源与资源编辑器
第四章 编一个最简单的VC十十程序
4.1什么是AppWizard？
4.2迎接你的第一个AppWizard程序
4.3“Iamaprogrammer.”在哪儿？
第五章 程序框架入门
5.1一个简化过的程序框架
5.2WinMain（）：第一个动作
5.3登记窗口类
5.4创建一个窗口
5.5显示窗口
5.6显示出那条消息
5.7窗口类与窗口对象
第六章 消息循环
6.1在消息循环中兜圈子
6.2对事件做出响应：WindowFun（）
6.3响应不同的消息
6.4现在你还跟得上吗？
6.5设备界面进行交互
第七章 精通程序框架
7.1WinMain（）函数在哪儿？
7.2应用程序框架和源文件
7.3工具条、状态条和打印等选项
7.4程序的控制流程
第八章 使用classWizard编程
8.1使用ClassWizard添加消息处理函数
8.2classWizard功能介绍
8.3传送鼠标消息
8.4保存鼠标绘图的信息
第九章 视图与文档
9.1Document－View模式
9.2从视图中分离出文档
9.3保存文档
9.4再访MyProg2.cpp
第十章 对象连接与嵌入（OLE）及其自动化
10.1公共对象模式（COM）
10.2类厂（classfactory）
10.3OLE自动化
10.4IDispatch接口
第十一章 动态连接库（DLLs）
11.1为什么使用DLL
11.2传统的DLL
11.3MFC库DLL
11.4MyProg4A――编写自己的类库扩展DLL
11.5MyProg4B――使用MFC库扩展DLL
11.6资源访问
第十二章 图形设备接口
12.1设备环境类
12.2GDI对象
12.3Windows的颜色映射
12.4映射方式
12.5字体
12.6MyProg3例程序
12.7MyProg3B程序
12.8MyPr0g3C例程序――使用CScrollView
第十三章 对话框
13.1在状态条上显示对话控件的帮助信息
13.2利用Fi1eOpen通用对话框打开多个文件
13.3定制通用文件对话框
13.4扩展和缩减一个对话框
13.5显示一个模式或无模式对话框
13.6编写定制的DDX/DDV例程
第十四章 剖析工具Spy十＋
14.1窗体
14.2消息
14.3进程与线程
第十五章 代码调试
15.1TRACE
15.2调试框架
15.3自我诊断
15.4调试代码的作用
15.5用Dump（）显示对象的信息
15.6检查内存

Development And Characterization Of Composite Ni-Cr-C-Caf2 Laser Cladding On Gamma-Tial Intermetallic Alloy

A process of laser cladding Ni-CF-C-CaF2 mixed powders to form a multifunctional composite coatingd on gamma-TiAl substrate was carried out. The microstructure of the coating was examined using XRD, SEM and EDS. The coating has a unique microstructure consisting of primary dendrite or short-stick TiC and block Al4C3 carbides reinforcement as well as fine isolated spherical CaF2 solid lubrication particles uniformly dispersed in the NiCrAlTi (gamma) matrix. The average microhardness of the composite coatings is approximately HV 650 and it is 2-factor greater than that of the TiAl substrate. (C) 2008 Elsevier B.V. All rights reserved.

Improved fluorescence from Tm3+/Er3+/Ce3+ triply doped bismuth-silicate glasses for S+C-bands amplifiers

Fluorescence of Tm3+/Er3+ codoped bismuth-silica (BS) glasses and the sensitization of Ce3+ are investigated. It shows that Ce3+ codoping with Tm3+/Er3+ in BS glasses results in a quenching of Tm3+ ion emission from F-3(4) to the H-3(6) level. Consequently, the 1.47 mu m emission occurs after the population inversion between the H-3(4) and F-3(4) levels. Furthermore, the codoped glasses show the broad emission spectra over the whole S and C bands with full-width at half-maximum (FWHM) up to about 119nm, as it combines 1.55 mu m emission band of Er3+ with 1.47 mu m emission band of Tm3+ under 800nm excitation.