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Science China(Life Sciences) 2003年第1期46卷 1-9页

作者：刘惠卢芳陈建军任红玉陈常庆 Shanghai Research Center of Biotechnology Chinese Academy of Sciences

Two tumor necrosis factor-a mutants MT1 (32Trp157Phe) and MT2 (2Lys30Ser- 32Trp157Phe) were constructed by site-directed mutagenesis. These mutants were soluble and over-expressed in E. coli. The purity of purified mutants was above 95% by serial chromatography. The results of Western blot indicated that these mutants could be cross-reactive with monoclonal antibody against native hTNF-a. Compared to parent hTNF-a, the cytotoxicity of these mutants on murine fibrosarcoma L929 cell lines reduced 4—5 orders of magnitude but was equivalent to that of native hTNF-a on human tumor cell lines. The LD50 of mutant MT1 was reduced to 0.34% of wild type and the dose of MT2 that resulted in 30% death of mice reduced to less than 1/700 that of parent hTNF-a.

关键词： human tumor necrosis factor, site-directed mutation, cytotoxicity, LD50, Western blot.

Antisense EDRF1 gene inhibited GATA-1transcription factor DNA-binding activity in K562 cells

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Science China(Life Sciences) 2002年第3期45卷 289-297页

作者：王敦成沈倍奋马淑华王升启 Beijing Institute of Basic Medical Sciences Beijing China Beijing Institute of Radiation Medicine Sciences Beijing China

Our previous studies showed that EDRF1 influenced expression of a-globin mRNA and synthesis of hemoglobin in K562 cells and modulated self-renewal of K562 cells. To illuminate the function of EDRF1 in K562 cells, sense and antisense EDRF1 constructs were prepared and transfected into K562 cells. By using microarray and dot blot assay, 60 cytokine receptors and some oncogenes sharing important functions in cell proliferation and differentiation were investigated. The results of this study demonstrated that IL-6 receptor, GM-CSF receptor, c-Jun/c-Fos, c-Myc and c-kit genes were regulated by antisense EDRF1 expression. The regulation was confirmed by RNA blot assay. GATA-1 mRNA expression was modulated by EDRF1 gene transfection. Electrophoretic mobility shift assay suggested that the DNA-binding activity of GATA-1 was remarkably inhibited in K562 cells expressing EDRF1 antisense gene. DNA binding activity of NF-E2 was at the same level as control experiment. Therefore EDRF1 may play a role in erythroid proliferation and differentiation by affecting the interaction between GATA-1 and its cis-elements.

关键词： erythroid differentiation, EMSA, transcription factor, cytokines, microarray.

Gene therapy for pathological scar with hepatocyte growth factor mediated by recombinant adenovirus vector

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Science China(Life Sciences) 2003年第3期46卷 320-327页

作者：哈小琴苑宾李元敏劳妙芬吴祖泽 Institute of Radiation Medicine Academy of Military Medical Sciences Beijing 100850 China

A complementary DNA (cDNA) encoding human hepatocyte growth factor was intro-duced into a replication-defective type 5 adenovirus (lacking E1, E3 domains) vector by homolo-gous recombination of intracellular plasmid DNA, thus a recombinant vector containing HGF (Ad-HGF) was obtained. Ad-HGF and Ad-GFP (adenovirus vector carrying green fluorescence protein gene) were expanded in 293 cells and purified by cesium chloride gradient centrifugation for large-scale preparation, then were infected to the primarily cultured scar fibroblast of rabbit ear to observe the transfer efficiency and expression level of HGF in vitro. To evaluate the effect of Ad-HGF on established scar Ad-HGF solution was injected into excessively formed scar, which bears some clinical and histologic similarities to human hypertrophic scars. The results showed that: (i) the transfer efficiency was 36.8%±14.1% on day 3 in primarily cultured scar fibroblasts treated with Ad-GFP and lasted more than 20 d; (ii) high-level expression of HGF protein was de-tected by means of ELISA in supernatant of scar fibroblasts treated with Ad-HGF, the amount of expression was 76 ng/4.0×105 cells on day 3; (iii) on day 32 after a single intradermal injection of Ad-HGF at different doses (8.6×109 pfu, 8.6×108 pfu, 8.6×107 pfu, 8.6×106 pfu) per scar, most of the scars in the former two dose groups were dramatically flattened, some were even similar to that of the normal skin. The value of HI (hypertrophic index) showed that there was a therapeutic effect of Ad-HGF on scars at the dose of 109 pfu and 108 pfu. Whereas no therapeutic effects were seen at lower dose (107 pfu and 106 pfu of Ad-HGF) groups. In addition, clusters of hair were ob-served to different extent on healed wound treated with Ad-HGF. Histopathologic examination re-vealed that in most healed wounds of Ad-HGF treated group, the dermal layer was thinner, the amount of fibrous tissue was much fewer, and hair follicles growth and sebaceous glands were observ

关键词： scar, hepatocyte growth factor, gene therapy, adenovirus vector.

Analysis of lateral stability of I-section aluminum beams

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Science China(Technological Sciences) 2006年第6期49卷 742-751页

作者： CHENG Ming SHI Yongjiu WANG Yuanqing Department of Civil Engineering Key Laboratory of Structural Engineering and Vibration of the Ministry of Education Tsinghua University Beijing 10084 China Department of Civil Engineering Key Laboratory of Structural Engineering and Vibration of the Ministry of Education Tsinghua University Beijing 10084 China Department of Civil Engineering Key Laboratory of Structural Engineering and Vibration of the Ministry of Education Tsinghua University Beijing 10084 China

This paper focuses on the lateral buckling of laterally-unrestrained aluminum beams subjected to a concentrated, uniformly loading; pure-bending action. The design methods of lateral stability of aluminum beams in the current codes are discussed. The influence of material property on the lateral buckling of aluminum beams is investigated with finite element analysis (FEA) methods. Some numerical examples are given,; the results from current codes are compared with the FEA solutions. The design method on lateral stability of steel beams specified in the Chinese standard GB 50017-2003 is modified to calibrate the stability factors of aluminum beams according to the European code, British code,; American code,; the modified method is verified by FEA results. Through comparison with the available test results, the modified design method for overall stability of aluminum bending members is proposed in this paper; proved applicable in the design of lateral stability of aluminum beams.

关键词： aluminum bending members, lateral buckling, stability factor, finite element analysis (FEA), design method.

Uniform estimate for maximum of randomly weighted sums with applications to insurance risk theory

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Science China Mathematics 2005年第10期48卷 1379-1394页

作者： WANG Dingcheng~1 SU Chun~2 & ZENG Yong~1 1. School of Management and School of Applied Mathematics,University of Electronic Science and Technology of China,Chengdu 610054,China 2. Department of Statistics and Finance,University of Science and Technology of China,Hefei 230026,China School of Management and School of Applied Mathematics University of Electronic Science and Technology of China Chengdu China Department of Statistics and Finance University of Science and Technology of China Hefei China

This paper obtains the uniform estimate for maximum of sums of independent and heavy-tailed random variables with nonnegative random weights, which can be arbitrarily dependent of each other. Then the applications to ruin probabilities in a discrete time risk model with dependent stochastic returns are considered.

关键词： dependent stochastic return, discount factor, heavy-tails, discrete time insurance risk model, maxima of randomly weighted sums, ruin probability, tail probabilities, uniformly asymptotic estimate.

Piezoelectric resonators with mechanical damping and resistance in current conduction

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Science China(Physics,Mechanics & Astronomy) 2007年第5期50卷 650-672页

作者： Yook-Kong YONG Mihir S PATEL Department of Civil and Environmental Engineering Rutgers University Piscataway NJ 08854 USA

A novel design method for high Q piezoelectric resonators was presented and proposed using the 3-D equations of linear piezoelectricity with quasi-electrostatic approximation which include losses attributed to mechanical damping in solid and resistance in current conduction. There is currently no finite element software for estimating the Q of a resonator without apriori assumptions of the resonator im- pedance or damping. There is a necessity for better and more realistic modeling of resonators and filters due to miniaturization and the rapid advances in frequency ranges in telecommunication. We presented new three-dimensional finite element models of quartz and barium titanate resonators with mechanical damping and resistance in current conduction. Lee, Liu and Ballato’s 3-D equations of linear piezoelectricity with quasi-electro- static approximation which include losses attributed to mechanical damping in solid and resistance in current conduction were formulated in a weak form and implemented in COMSOL. The resulting finite element model could predict the Q and other electrical parameters for any piezoelectric resonator without apriori as- sumptions of damping or resistance. Forced and free vibration analyses were per- formed and the results for the Q and other electrical parameters were obtained. Comparisons of the Q and other electrical parameters obtained from the free vibra- tion analysis with their corresponding values from the forced vibration analysis were found to be in excellent agreement. Hence, the frequency spectra obtained from the free vibration analysis could be used for designing high Q resonators. Results for quartz thickness shear AT-cut and SC-cut resonators and thickness stretch poled barium titanate resonators were presented. An unexpected benefit of the model was the prediction of resonator Q with energy losses via the mounting supports.

关键词： quality factor, energy sink, MEMS, mechanical dissipation and viscosity, electrical conductivity, piezoelectric materials

Experimental study on visualization of the flow field in microtube

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Science China(Technological Sciences) 2005年第5期48卷 521-529页

作者： LIU Zhigang ZHAO Yaohua Institute of Engineering Thermophysics Chinese Academy of Sciences Beijing 100080 China Institute of Engineering Thermophysics Chinese Academy of Sciences Beijing 100080 China

An experimental study was conducted to visualize the flow field and confirm the transitional Reynolds number from laminar to turbulent flow, as distilled water flows through quartz glass microtubes with inner diameter 315 and 520 μm. With gentian violet as colorant, the flow field pictures in the microtube, and therefore, is shot by a CCD camera with a microscope at different Reynolds numbers. Pressure drop data were also used to characterize the friction factor for those microtubes in the Reynolds number range of 200–2300. The experimental results clearly showed that the flow in the microtube was the laminar state and the friction factors agreed well with the Poiseuille equations when the Reynolds number was low. As the Reynolds number was larger than 1200 and 1500 for the microtube with inner diameter 315 and 520 μm, respectively, the friction factor departed from the classical laminar solution due to the earlier transition from laminar to tubulent flow. The flow turned into full turbulent when the Reynolds number reached 1500–1800.

关键词： visual experiment, microtube, microscale flow, friction factor, turbulent transition.

Isokinetic correlation analysis of the series of electrophilic substitution reactions of o-substituted phenylmercurials

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Science China Chemistry 2001年第2期44卷 182-190页

作者：王玉兰吴养洁 National Key Laboratory of Biochemical Engineering Institute of Chemical Metallurgy Chinese Academy of Sciences Beijing China Chemistry Department Zhengzhou University Zhengzhou China

Isokinetic relationships of the series of electrophilic substitution reactions of o-substi- tuted phenylmercurials are studied, and the results show, for the first time, that isokinetic correlation analysis can reveal the dominant factor in the system of the reactions. The analysis of SE2 of o-substituted phenylmercuric chlorides indicates that the steric effect of o-substituents is the pre-dominant factor when I2 is used as electrophilic agent, however, the electronic effect of o-substituents would become the predominant factor when HCl is used as the electrophilic agent. In SE1 of o-substituted phenylmercuric chlorides, the results of the analysis display that the predomi-nant factor is the field effects of o-substituents. The determination of predominant factors in those reactions would provide further scientific basis for those reaction mechanisms.

关键词： isokinetic correlation, dominant factor, electrophilic substitution, arylmercurials.

Selection of trkB-binding peptides from a phage-displayed random peptide library

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Science China(Life Sciences) 2003年第1期46卷 77-86页

作者：马仲才吴晓兰曹明媚潘卫朱分禄陈景山戚中田 Department of Microbiology Second Military Medical University Department of Psychology Yale University School of Medicine

Brain-derived neurotrophic factor (BDNF) shows potential in the treatment of neurode-generative diseases, but the therapeutic application of BDNF has been greatly limited because it is too large in molecular size to permeate blood-brain barrier. To develop low-molecular-weight BDNF-like peptides, we selected a phage-displayed random peptide library using trkB expressed on NIH 3T3 cells as target in the study. With the strategy of peptide library incubation with NIH 3T3 cells and competitive elution with 1 mg/mL of BDNF in the last round of selection, the specific phages able to bind to the natural conformation of trkB and antagonize BDNF binding to trkB were enriched effectively. Five trkB-binding peptides were obtained, in which a core sequence of CRA/TXfXXfXXC (X represents the random amino acids, f represents T, L or I) was identified. The BDNF-like activity of these five peptides displayed on phages was not observed, though all of them antagonized the activity of BDNF in a dose-dependent manner. Similar results were obtained with the synthetic peptide of C1 clone, indicating that the 5 phage-derived peptides were trkB antagonists. These low-molecular-weight antagonists of trkB may be of potential application in the treatment of neuroblastoma and chronic pain. Meanwhile, the obtained core sequence also could be used as the base to construct the secondary phage-displayed peptide library for further devel-opment of small peptides mimicking BDNF activity.

关键词： phage display, random peptide library, brain-derived neurotrophic factor, trkB antagonist.

Future options of anti-angiogenic cancer therapy

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Chinese Journal of Cancer 2016年第2期35卷 88-96页

作者： Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska Institute Department of Medical and Health Sciences Linkoping University Department of Cardiovascular Sciences University of Leicester and NIHR Leicester Cardiovascular Biomedical Research UnitGlenfield Hospital

In human patients,drugs that block tumor vessel growth are widely used to treat a variety of cancer *** rigorous phase 3 clinical trials have demonstrated significant survival benefits;however,the addition of an anti-angiogenic component to conventional therapeutic modalities has generally produced modest survival benefits for cancer ***,it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human *** this article,we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.

关键词： Angiogenesis, Cancer therapy, Anti-angiogenesis, Vascular endothelial growth factor, Biomarker