Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines

Objective:To characterize the infection patterns and growth characteristics of the Zika virus(ZIKV)strain JMB-185 from Indonesia in various mammalian cell lines.Methods:ZIKV was grown in human(A549,HEK293,HepG2,Huh7,Jurkat,and THP-1)and non-human mammalian(RAW264.7,Vero,and Vero76)cell lines.Viral replication kinetics were measured using plaque assay,while intra-and extracellular viral RNA concentrations were assessed using RT-PCR.Flow cytometry was used to quantify the infected cells and cell viability was measured using an MTT assay.The ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining assay.Results:This ZIKV strain preferentially infected the lung,kidney,and liver cell lines A549,HEK293,Huh7,Vero,and Vero76,but not the immune cells Jurkat,RAW264.7,and THP-1.By contrast,the ZIKV showed no sign of infection in HepG2 cells,while maintaining viral titer over 3 days post-infection,with no infection recorded in immunostaining,no increase in viral RNA,and no indication of cell deterioration.Conclusions:The Indonesian ZIKV strain has a similar infection profile as other strains,except for its poor infectivity on HepG2 cells.Information on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS

The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

网络中ACCESS数据库同步问题研究

介绍用VB6.0实现ACCESS数据库在网络中同步的几个属性和方法。

Isolation and Chromosomal Mapping of a Corn B Chromosome Specific RAPDs

B染色体存在于多种动植物中 ,具有很多独特的性状。B染色体与正常染色体在DNA组成方面十分相似 ,寻找B染色体特异序列一直是B染色体研究的难点和热点。通过对含有和不含有B染色体的两种玉米 (ZeamaysL .)基因组进行了RAPD分析 ,筛选到一个B染色体特异性分子标记B480。该标记与玉米的自主复制起始序列ARS1和ARS2同源 ,特别是该序列中的 2 5bp出现在多种模式生物基因组中。FISH的结果显示 。

基于多模型的能源组件维修性建模与仿真研究

某激光装置能源组件是其关键组件,该组件具有随机劣化失效特点,其部件失效类型多,维修类型和维修策略也比较复杂,现有的基于单一模型和解析方法的系统维修性建模与分析方法难以解决其维修性设计与分析问题。本文采用多模型集成的维修性建模与仿真方法,解决能源组件维修性建模与分析问题。其中,采用故障树模型描述能源组件系统级可靠性,采用SPNAT模型描述各部件的失效过程和维修决策,并基于"Join/Replicate"操作进行模型集成,通过报酬结构定义组件的维修性指标。仿真结果表明,基于多模型集成的维修性建模与仿真方法,是解决能源组件这样的复杂产品维修方案设计与分析的有效途径。

SQL Server CE在手持设备上的开发应用

本文对SQL Server CE在Wince设备上的应用开发进行了介绍(主要是RDA和Replication的使用)

A Novel Replication-competent Adenovirus CNHK500 in the Treatment of Heptocellular Carcinoma In Vitro

Objective: To evaluate the therapeutic efficacy of replicative adenovirus CNHK500 in the treatment of hepatocellular carcinoma. Methods: Virus proliferation assay, cell viability assay and Western blot were performed to assess the selective replication and cytolysis of CNHK500 in telomerase positive liver cancer cells Hep3B, HepGII, SMMC7721 and in normal cells. Results: The replicative multiples of CNHK500 in HepGII, Hep3B and SMMC7221 after 96 h of virus proliferation were 52 000, 396 984.9 and 632 911.3 fold respectively, similar to those of wtAd5. However, CNHK500 demonstrated more significant attenuated replicative ability in normal cell lines than wtAd5. CNHK500 replicated only 3.1-100 fold at 96 h, while the wtAd5 still reached 3160-17 357 fold. CNHK500 could cause half of HepGII cells death within 7 days at MOI 2, in Hep3B cell lines the IC50 was as low as MOI 0.01, whereas the IC50 in BJ cell was as high as MOI 1000. CNHK500 E1A protein could only be detected in hepatocellular cancer cells but not in normal cells under normoxia. E1B protein could only be detected under hypoxia condition at a MOI of 1. Conclusion: CNHK500 can efficiently replicate in and kill liver cancer cells as well as wtAd5 do while it is severely attenuated in proliferation and cytolysis among normal cells. It would be a prominsing strategy for liver cancer tratment.

基于小波包变换和Replicator Neural Network的单位置结构损伤检测

为了实现对结构的损伤检测,提出一种基于小波包变换和Replicator Neural Network(RNN)的单位置结构损伤检测方法。首先采用小波包变换对原始振动响应信号进行分解,计算分解得到的各频带的相对频带能量,这些相对频带能量的分布反映了结构特性。然后,将健康结构的相对频带能量作为输入训练RNN。最后,利用训练后的网络即可对结构进行实时损伤检测。实验表明,即使在有噪声干扰下,该方法仍然能够检测出结构是否存在损伤。

SQL Server CE中RDA与Replication的研究

介绍移动数据库SQL Server CE及其特点,详细分析RDA(远程数据访问)和Replica-tion(合并复制)数据同步技术,探讨两种技术的各自特点和应用环境,描述两种数据同步技术的实现过程,比较这两种技术适合的环境。

农村劳动力转移的进化博弈论分析

费景汉(J.Fei)和拉尼斯(G.Ranis)模型以及托达罗(M.P.Todaro)模型虽都较适用于我国的实情,但忽视了农民心理、城乡文化差异、迁移风险和制度因素等对农村劳动力转移的制约和影响,没有从农民的决策行为去考察农村劳动力的转移问题.根据有限理性“新经济人”假说和行为决策理论,用Taylor and Jonker(1978)的模仿者动态(Replicator Dynamics)模型从理论上能够较好地分析农民进城的决策选择.

Replication-selective Oncolytic Adenovirus CNHK300 in the Treatment of Breast Cancer Cell Lines in vitro

Objective： To evaluate the tumor selectivity and therapeutic efficiency of replication-competent adenovirus CNHK300 on human breast cancer cells. Methods： RT-PCR was used to detect the hTERT mRNA activity in various breast cancer and normal fibroblast cell lines. Virus proliferation assay, cell viability assay and Western blot were applied to evaluate the proliferation and cytolysis selectivity of CNHK300. Results： The telomerase activity of MCF-7, BT-549 and SK-BR-3 was positive, while telomerase in MRC-5 and BJ was negative. The progeny virus titers in MCF-7, BT-549 and SK-BR-3 after 48 h of CNHK300 exposure was 40 625, 1 265 and 20 000 fold higher than those of 0 h, even slightly higher than those of wtAd5 （except in SK-BR-3）. ONYX-015 virus proliferation ability was weaker than that of CNHK300 in cancer cells. However, CNHK300 exhibited attenuated replicative ability as compared with wtAd5 in MRC-5 and BJ. The CNHK300 replicatative multiple was 63 and 192 fold at 48 h respectively, while the wtAd5 still multiplied 3 160-4 846 fold. CNHK300 could cause about half of breast cancer cells to die within 7 days at MOI 10 pfu/cell and below, whereas the IC50 in BJ and MRC-5 was as high as MOI 100 pfu/cell. CNHK300 E1A protein could be detected in breast cancer cells and 293 cells but not in normal fibroblast cells. Conclusion： hTERT promoter can successfully modulate the CNHK300 to be selectively replicated in breast cancer cells positive for telomerase, which may be a potential treatment strategy in breast cancer.

一种基于Active Replication的TCP连接容错技术

本文提出一种基于ActiveReplication的TCP连接容错技术(ARTCP),采用两层的Cluster结构,并通过前端的分发器和聚合网关机维持多个同步的TCP连接副本,达到了相互容错的效果。测试结果表明,该技术不仅保证网络服务连接级的高可用性,而且具有恢复时间短、开销小的优势。

Replication Server数据复制技术及实例

介绍Replication Server的复制模型和应用程序体系结构,并举例如何利用Sybase Workspace构建一个完整的Replication Server系统应用,希望能给开发和管理Replication Server系统的管理员一些借鉴。

移动计算环境中的Sybase同步技术

介绍了Sybase数据库系统提供的SQLRemote、MobiLink和ReplicationServer三种同步技术的特点和体系结构,讨论了同步系统对它们的不同需求,并且对三种同步技术的综合应用提出了建议.

Replication Server数据复制技术及实例

3实例下面介绍在Sybase Workspace 1.5开发平台上,如何开发一个完整的Replication Server系统应用。实例是大型超市的POS系统数据库到经理办公室的销售数据分析数据库的复制。超市的销售数据在数据库（server_1.source）中,进行数据分析的是数据仓库（server_2.IQ）。各个超市的销售数据在数据库中是相当繁多的,但对于提供决策支持来说,只需要分析部分数据就够了。

分布式Byzantine容错系统研究进展

由于网络攻击的经济利益驱动和信息系统复杂性的不断增加,网络安全事件和代码缺陷也日益增多,导致信息系统出现各种错误、甚至被攻击者完全控制。Byzantine错误,又称为任意错误,是所有错误中最为严重的一种。分布式Byzantine容错系统由多台独立运行的服务器组成,能够容忍一定数量部件的Byzantine错误,在错误情况下仍然能提供正确服务。本文对现有代表性的Byzantine容错系统进行介绍和总结,讨论了Byzantine容错系统的技术发展。

果树试验设计与分析的PC—1500A应用系统

随着电子计算机应用的普及,特别是微型电子计算机价格比下降,电子计算机已广泛应用于果树试验设计、结果分析和科研决策中。但是,长期从事果树科研工作者,常因年龄、工作条件和机遇等原因,对计算机高级语言并不一定熟悉或运用自如。为此,笔者编辑了这套PC—1500A应用系统软件。在应用过程中勿需精通计算机高级语言。

基于MySQL Replication的数据库集群解决方案

随着电子商务的快速发展,人们对商务系统数据库的稳定性、可用性、可拓展性等提出了更高的要求,而单一的数据库服务器往往达不到这些要求。数据库集群技术的出现,为我们解决这个问题提供了很好的方法。比较了MySQL簇和MySQL Replication两种MySQL的数据库集群技术,并设计了一种基于MySQL Replication的商务系统数据库集群的解决方案。

Homologous recombination in DNA repair and DNA damage tolerance

Homologous recombination （HR） comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks （DSBs） and interstrand crosslinks （ICLs）. In addition, recombination provides critical support for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR： homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modalities of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.