Inhibitory Monoclonal Antibodies and Their Recombinant Derivatives Targeting Surface-Exposed Carbonic Anhydrase XII on Cancer Cells

Monoclonal and recombinant antibodies are widely used for the diagnostics and therapy of cancer. They are generated to interact with cell surface proteins which are usually involved in the development and progression of cancer. Carbonic anhydrase XII (CA XII) contributes to the survival of tumors under hypoxic conditions thus is considered a candidate target for antibody-based therapy. In this study, we have generated a novel collection of monoclonal antibodies (MAbs) against the recombinant extracellular domain of CA XII produced in HEK-293 cells. Eighteen out of 24 MAbs were reactive with cellular CA XII on the surface of live kidney and lung cancer cells as determined by flow cytometry. One MAb 14D6 also inhibited the enzymatic activity of recombinant CA XII as measured by the stopped-flow assay. MAb 14D6 showed the migrastatic effect on human lung carcinoma A549 and renal carcinoma A498 cell lines in a ‘wound healing’ assay. It did not reduce the growth of multicellular lung and renal cancer spheroids but reduced the cell viability by the ATP Bioluminescence assay. Epitope mapping revealed the surface-exposed amino acid sequence (35-FGPDGENS-42) close to the catalytic center of CA XII recognized by the MAb 14D6. The variable regions of the heavy and light chains of MAb 14D6 were sequenced and their complementarity-determining regions were defined. The obtained variable sequences were used to generate recombinant antibodies in two formats: single-chain fragment variable (scFv) expressed in E. coli and scFv fused to human IgG1 Fc fragment (scFv-Fc) expressed in Chinese Hamster Ovary (CHO) cells. Both recombinant antibodies maintained the same specificity for CA XII as the parental MAb 14D6. The novel antibodies may represent promising tools for CA XII-related cancer research and immunotherapy.     

钨合金圆筒爆破试验破片分布的统计分析

采用圆筒爆破试验方法研究了易碎型钨合金的破片分布特征,并与93W合金的结果进行了对比.对破片的数量和质量分布特征进行了统计分析,发现易碎型钨合金的破片率明显高于93W合金,而且破片的均匀性也明显好于93W合金,但易碎钨合金的破片回收率低于93W合金,而且受装药量的影响较大.     

Estimating and eliminating redundant data transfers over the web: a fragment based approach

Redundant data transfers over the Web, can be mainly attributed to the repeated transfers of unchanged data. Web caches and Web proxies are some of the solutions that have been proposed, to deal with the issue of redundant data transfers. In this paper we focus on the efficient estimation and reduction of redundant data transfers over the Web. We first prove that a vast amount of redundant data is transferred in Web pages that are considered to carry fresh data. We show this by following an approach based on Web page fragmentation and manipulation. Web pages are broken down to fragments, based on specific criteria. We then deal with these fragments as independent constructors of the Web page and study their change patterns independently and in the context of the whole Web page. After the fragmentation process, we propose solutions for dealing with redundant data transfers. This paper has been based on our previous work on ‘Web Components’ but also on related work by other researchers. It utilises a proxy based, client/server architecture, and imposes changes to the algorithms executed on the Proxy server and on clients. We show that our proposed solution can considerably reduce the amount of redundant data transferred on the Web. Copyright © 2004 John Wiley & Sons, Ltd.     

碎丝埋弧焊在大型立式储罐中的应用

大型储罐底板焊接及变形控制是保证储罐整体施工质量的关键环节,采用碎丝填充的焊接方法可以防止变形,同时可以有效地避免应力集中,提高施工质量。文章介绍了碎丝埋弧焊的原理、工艺参数和焊接方法。实践证明,填充碎丝不仅是一种减小底板焊接变形的手段,同时可以充分利用焊接热能,节约焊接时间和焊剂用量,经济效益好,是一种值得推广的技术。     

破片式战斗部优化设计技术研究

侧重研究了破片式战斗部装药外形的优化设计技术。提出了装药外形与破片飞散特性（如破片飞散角，分布带宽等）之间的数学描述；建立了圆弧和对数螺线装药外形母线与战斗部其他设计参数间的数学模型。在假定约束条件下，优化设计了破片了聚焦式战斗部的结构参数；静爆试验结果表明，破片分布与理论计算吻合较好。     

瞬态波存在破片群测速上的应用

破片群速度参数是壳体爆炸研究中的一项重要参数,如何准确测量破片群速度一直是国内外料研人员所追求的目标。本文介绍了一种利用高速瞬态波存所组成的破片群速度测量系统。它包括一台多通道高速瞬态波存、多通道接收靶及数据处理软件。用计算机对采集到的数据进行处理,可以直接给出破片群的速度参数。     

一种门户环境下的缓存模型和算法*

提出的门户环境下的缓存模型和算法的基本思想是把门户页面分解为I序列、布局块和内容块.用户请求页面时,门户系统只生成和传递发生改变的块,再由客户端根据这些块和I序列组装成完整的页面.实验结果表明,该算法可以提高网络带宽的利用率,缩短响应时间.     

In Vitro Characterization of Neutralizing Hen Antibodies to Coxsackievirus A16

Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Children aged <5 years are the most affected by CA16 HFMD globally. Although clinical symptoms of CA16 infections are usually mild, severe complications, such as aseptic meningitis or even death, have been recorded. Currently, no vaccine or antiviral therapy for CA16 infection exists. Single-chain variable fragment (scFv) antibodies significantly inhibit viral infection and could be a potential treatment for controlling the infection. In this study, scFv phage display libraries were constructed from splenocytes of a laying hen immunized with CA16-infected lysate. The pComb3X vector containing the scFv genes was introduced into ER2738 Escherichia coli and rescued by helper phages to express scFv molecules. After screening with five cycles of bio-panning, an effective scFv antibody showing favorable binding activity to proteins in CA16-infected lysate on ELISA plates was selected. Importantly, the selected scFv clone showed a neutralizing capability against the CA16 virus and cross-reacted with viral proteins in EV71-infected lysate. Intriguingly, polyclonal IgY antibody not only showed binding specificity against proteins in CA16-infected lysate but also showed significant neutralization activities. Nevertheless, IgY-binding protein did not cross-react with proteins in EV71-infected lysate. These results suggest that the IgY- and scFv-binding protein antibodies provide protection against CA16 viral infection in in vitro assays and may be potential candidates for treating CA16 infection in vulnerable young children.     

4-(α-吡啶甲酰基)-PMP的合成与谱学特性研究

合成了新吡唑啉酮类试剂1-苯基-3-甲基-4-(α-吡啶甲酰基)-吡唑啉-5-酮(简称4-(α-吡啶甲酰基)-PMP,下同)。在表征分子结构的同时,对其红外、紫外吸收光谱,核磁共振氢谱、碳谱,质谱等谱学特性和质谱裂解规律进行了分析与研究。     

基于像素点的碎片图像拼接技术

针对一页规则的既纵切又横切的中文文件碎片和一页规则的双面打印的英文文件碎片,分别提出了一种基于行列图像的碎片匹配算法和二维图像成片连接匹配算法。首先将碎片边缘像素点转化成灰度值,然后对各碎片的灰度值进行匹配度研究,且将匹配度作为碎片之间拼接的依据,最后使用相应的算法计算机按碎片拼接顺序输出碎片号。通过实验分析表明,该算法能够更快地获得碎片拼接结果,大大提高拼接复原效率。