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Construction of novel tumor necrosis factor-alpha mutants with reduced toxicity and higher cytotoxicity on human tumor cells

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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.

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 observed. In Sirius red-stained sections the amount of

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

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 types.Many 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 patients.Currently,it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human patients.In 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

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.

P4κ-1-factorization of bipartite multigraphs

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Science China Mathematics 2006年第7期49卷 961-970页

作者： WANG Jian & DU Beiliang Nantong Vocational College, Nantong 226007, China Department of Mathematics, Suzhou University, Suzhou 215006, China Vocational College Nantong China Department of Mathematics Suzhou University Suzhou China

LetλKm,n be a bipartite multigraph with two partite sets having m and n vertices, respectively. A Pv-factorization of λKm,n is a set of edge-disjoint Pv-factors of λKm,n which partition the set of edges of λKm,n. When v is an even number, Ushio, Wang and the second author of the paper gave a necessary and sufficient condition for the existence of a Pv-factorization of λKm,n. When v is an odd number, we proposed a conjecture. However, up to now we only know that the conjecture is true for v= 3. In this paper we will show that the conjecture is true when v= 4k- 1. That is, we shall prove that a necessary and sufficient condition for the existence of a P4k-1-factorization of λKm,n is (1) (2κ - 1)m ≤ 2kn, (2) (2k - 1)n ≤ 2km, (3) m + n ≡0 (mod 4κ - 1), (4) λ(4κ - 1)mn/[2(2κ - 1)(m + n)] is an integer.

关键词： bipartite multigraph, factor, factorization.

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 turbulent 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.

Variable universe stable adaptive fuzzy control of nonlinear system

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Science China(Technological Sciences) 2002年第3期45卷 225-240页

作者：李洪兴苗志宏王加银 Department of Mathematics Beijing Normal University Beijing China Department of Mathematics Sichuan Normal University Chengdu China Department of Automation Tsinghua University Beijing China

A kind of stable adaptive fuzzy control of nonlinear system is implemented using variable universe method. First of all, the basic structure of variable universe adaptive fuzzy controllers is briefly introduced. Then the contraction-expansion factor that is a key tool of variable universe method is defined by means of integral regulation idea, and a kind of adaptive fuzzy controllers is designed by using such a contraction-expansion factor. The simulation on first order nonlinear system is done. Secondly, it is proved that the variable universe adaptive fuzzy control is asymptotically stable by use of Lyapunov theory. The simulation on the second order nonlinear system shows that its simulation effect is also quite good. Finally a useful tool, called symbolic factor, is proposed, which may be of universal significance. It can greatly reduce the settling time and enhance the robustness of the system.

关键词： nonlinear systems, variable universe adaptive fuzzy control, contraction-expansion factor, symbolic factor, stable domain.

Control of convergence in a computational fluid dynamic simulation using fuzzy logic

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Science China(Technological Sciences) 2002年第5期45卷 485-502页

作者：刘训良陶文铨郑平何雅玲王秋旺 School of Energy & Power Engineering Xi’an Jiaotong University Xi’an China Department of Mechanical Engineering Hong Kong University of Science & Technology China

A fuzzy control method was used to accelerate iteration convergence in numerical fluid dynamic simulation using SIMPLER algorithm. The residual ratio of momentum or energy equation between two successive iterations was used as the input variable. A fuzzy logic algorithm was developed in order to obtain the relative increment of the under-relaxation factor and its new value was then used for the next iteration. The algorithm was tested by four benchmark problems. In all cases considered, when the fuzzy control logic was used, convergence was achieved with nearly the minimum number of iterations, showing the feasibility of the proposed method.

关键词： fuzzy control, relaxation factor, convergence, SIMPLER algorithm.