• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.162-174
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• 1997

Background : Metabolic cooperation via gap junctional intercellular communication (GJIC) is an important mechanism of the bystander effect in gene therapy using the Herpes Simplex Virus thymidine kinase/ganciclovir (HSVtk) "prodrug" system. Since retinoids have been reported to increase GJIC by induction of connexin 43 expression, we hyporthesized that treatment of tumor cells with retinoic acid could augment the bystander effect of the HSVtk/GCV system and result in improved tumor cell killing by enhancing GJIC. Methods : We transferred HSVtk gene to SKHep-J cell line that does not express connexin43, and also transferred the gene to human and murine mesothelioma cell lines that express connexin43. We verified that retinoic acid enhanced GJIC utilizing a functional double-dye transfer study and evaluated the effects of retinoic acid on the growth rate of tumor cells. We then tested the effects of retinoic acid on bystander-mediated cell killing. Results : Addition of all-trans retinoic acid (RA) increased GJIC in cell lines expressing connexin 43 and was asspciated with more efficient in vitro bystander killing in cells transduced with HSVtk via adenoviral and retroviral vectors. In contrast, there was no increase in the efficiency of the bystander effect after exposure to RA in a cell line which had no delectable connexin 43. Conclusion : These results provide evidence that retinoids can augment the efficiency of cell killing with the HSVtk/GCV system by enhancing bystander effect and may thus be a promising new approach to improve responses in gene therapy utilizing the HSVtk system to treat tumors.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.587-595
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• 1998

Background: Recombinant adenovirus hold promise as vectors to carry therapeutic genes for several reasons: 1) they can infect both dividing and non-dividing cells; 2) they have the ability to directly transduce tissues in vivo; 3) they can easily be produced in high titer; and 4) they have an established record of safety as vaccination material. However, one of the major limitation in the use of adenoviruses is that transgene expression is quite short because adenovirusees insert their DNA genome episomally rather than by chromosomal integration, and an immune response against the virus destroys cells expressing the therapeutic gene. Since sodium butyrate has been reported to induce adenovirus-mediated gene expression, we hypothesized that treatment of tumor cells, transduced with herpes simples virus thymidine kinase(HSVtk) gene using adenoviral vector, with butyrate could augment the effect of gene therapy. Methods: We transduced HSVtk gene, driven by the cytomegalovirus promoter, into REN cell line(human mesothelioma cell line). Before proceeding with the comparison of HSVtk/ganciclovir mediated bystander killing, we evaluated the effect of butyrate on the growth of tumor cells in order to rule out a potential antitumor effect of butyrate alone, and also on expression of HSVtk gene by Western blot analysis. Then we determined the effects of butyrate on bystander-mediated cell killing in vitro. Results: There was no inhibition of growth of cells exposed to butyrate for 24 hours at a concentration of 1.5mM/L. Toxic effects were seen when the concentration of butyrate was greater than 2.0mM/L. Gene expression was more stable and bystander effect was augmented by butyrate treatment of a concentration of 1.5mM/L. Conclusion: These results provide evidence that butyrate can augment the efficiency of cell killing with HSVtk/GCV system by inducing transgene expression and may thus by a promising new approach to improve responses in gene therapy using adenoviral vectors.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.229-240
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• 1999

Background: The impact of the immune response on cancer gene therapy using viral vectors to deliver a "suicide gene" is currently unclear. A vigrous immune response targeted at viral proteins or transgene may enhance the efficacy of tumor destruction and even augment responses to tumor antigens. These responses may involve the release of cytokines and stimulation of tumor specific cytotoxic T-lymphocytes that enhance therapeutic efficacy. On the other hand, a vigorous rapid cellular immune response may destroy cells expressing the therapeutic gene and attenuate the response to therapy. Furthermore, development of neutralizing antibody responses may prevent readministration of virus, a potentially significant limitation. Evaluating the significance of these limitations in animal models and developing solutions are therefore of obvious importance. Methods: After retroviral transduction of mouse mesothelioma cell line(AB12) with Herpes Simplex Virus thymidine kinase (HSVtk) gene in vitro, subcutaneous flank tumors were established. To study the effect of intact immune system on efficacy of tumor erradication, the ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Balb/c mice, immunodeficient Balb/c-nude and SCID mice, and Balb/c mice immunosuppressed with cyclosporin. Results: Ganciclovir treatment resulted in greater inhibition of tumor growth in Balb/c mice compared with immunodeficient Balb/c-nude mice and SCID mice(in immunodeficient mice, there were no growth inhibition by ganciclovir treatment). Ganciclovir treatment resulted in greater inhibition of tumor growth in noncyclosporin (CSA) treated Balb/c mice compared with CSA treated Balb/c mice. On day 8, mean ganciclovir-treated tumor volume were 65% of control tumor volume in Balb/c mice versus 77% control tumor volume in CSA-treated Balb/c mice. This effect was still evident during therapy (day 11 and 13). On day 13, non-CSA treated tumor volume was 35% of control tumor volume versus 60% of control tumor volume in CSA treated Balb/c mice. Duration of expression of HSVtk was not affected by the immunosuppression with CSA. Conclusion: These results indicate that the immune responses against retrovirally transduced cells enhance the efficacy of the HSVtk/ganciclovir system. These findings have important implications for clinical trials using currently available retrovirus vectors as well as for future vector design.

• Journal of Life Science
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• v.18 no.3
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• pp.374-380
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• 2008

Rapid detection of enterovirus (EVs) is important in the management of aseptic meningitis. We examined the relative efficiency and specificity of the real-time nucleic acid sequence-based amplification (NASBA) comparing with the established reverse transcription polymerase chain reaction (RT-PCR) and viral culture method which were used for the detection of enterovirus RNA in clinical specimens. Of the total 292 samples, 145 were found to be positive to enterovirus RNA by real-time NASBA, 101 were positive by viral culture, and 86 were positive by RT-PCR. 147 samples and 46 samples were determined to be negative and positive by all methods respectively, but 4 samples were positive only by real-time NASBA. To compare the specificity of each method, various clinical samples which were diagnosed for herpes simplex virus (HSV)-1, HSV-2, adenovirus, mumps, and rhinovirus were applied. Except one rhinovirus sample which was false positive to enterovirus RNA by RT-PCR, the other different samples were negative to all three methods. The real-time NASBA procedure can be completed within 5 hours in contrast with 9 hours for the RT-PCR and 3-14 days for the viral culture. From this study, it was suggested that the real-time NASBA assay could be a standardized, rapid, specific, and sensitive procedure for the detection of enterovirus RNA.

• Analytical Science and Technology
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• v.7 no.1
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• pp.25-31
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• 1994

As for analytes which did not represent the differences of the selectivity on the stationary and mobile phase, secondary chemical equilibrium theory was applied to study pH effects on the separation of alkylphenols. Mobile phase was consisted of an aqueous sodium carbonate-bicarbonate buffer and acetonitrile. The maximum selectivity for adjacent peak pairs was predicted from those values of $k^{\prime}_{HA}/k^{\prime}_{A-}$ and ${\Delta}pK$. The optimum pH determined by this method was 11.18 pH and solvent selectivity were considered at the same time to invoke the full range of selectivity effects possible for separations. Quaternary mixture composed of methanol, acetonitrile, tetrahydrofuran and water was adjusted to optimum pH 11.18. As the statistical simplex technique of an overlapping resolution map (ORM) was used to predict the optimized solvent system. The optimum solvent, which gives complete separation of alkylphenols, was determined as follws MeOH : ACN : THF = 14.4 : 81.8 : 2.8.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.8 no.8
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• pp.1810-1817
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• 2004

A diffractive optical element(DOE) for an optical pickup system is proposed in this thesis. Optimization algorithms are used to synthesise the DOE to meet a detailed specification of the two kind of cost function. The one isso called as apodization which refers to the process of suppressing the secondary maxima and the other is so called as sharpness which refers to the process of reducing the size of primary maxima. The result obtained by simplex optimization method is that the apodization and sharpness are well achieved separately. In apodization, the secondary maxima is reduced up to 39%. And in sharpness, the size of first maxima is reduced to 95.2％.

• Transactions of the Korean Society of Automotive Engineers
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• v.12 no.3
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• pp.101-108
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• 2004

A FEM-based efficient method is developed for the shape optimization of 2-D structures. The combined SLP and Simplex method are coupled with finite element analysis. Selected set of master nodes on the design boundaries are employed as design variables and assigned to move towards their normal directions. The other nodes along the design boundaries are grouped into the master node. By interpolating the repositioned master nodes, the B-spline curves are formed so that the rest mid-nodes efficiently settle down on the B-spline curves. Mesh smoothing scheme is also applied for the nodes on the design boundary to maintain most finite elements in good quality. Finally, a numerical implementation of optimum design of an automobile torque converter piston subjected to pressure and centrifugal loads is presented. The results shows additional weight up to 13% may be saved after the shape optimization.

• Journal of the Korean Society of Propulsion Engineers
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• v.4 no.2
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• pp.21-30
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• 2000

Numerical design optimization techniques are implemented for the improvement of the ram accelerator performance. The design object is to find the minimum ram tube length required to accelerate projectile from initial velocity $V_o$ to target velocity $V_e$. The premixture is composed of $H_2$, $O_2$, $N_2$ and the mole numbers of these species are selected as design variables. The objective function and the constraints are linearized during the optimization process and gradient-based Simplex method and SLP(Sequential Linear Programming) have been employed. With the assumption of two dimensional inviscid flow for internal flow field, the analyses of the nonequilibrium chemical reactions for 8 steps 7 species have been performed. To determined the tube length, ram tube internal flow field is assumed to be in a quasi-steady state and the flow velocity is divided into several subregions with equal interval. Hence the thrust coefficients and accelerations for corresponding subregions are obtained and integrated for the whole velocity region. With the proposed design optimization techniques, the total ram tube length had been reduced 19% within 7 design iterations. This optimization procedure can be directly applied to the multi-stage, multi-premixture ram accelerator design optimization problems.

• Journal of Energy Engineering
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• v.5 no.1
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• pp.72-79
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• 1996

The effect of controllers-Exciter, Power System Stabilizer, and Static Var Compensator-in one machine infinite bus system is investigated in this paper. The structure of generator state matrix with controllers is represented, while the Static Var Compensator is installed in generator terminal bus. Eigen-value analysis is performed and the effects of controllers to the dominant eigenvalue in one machine infinite bus system are represented by first order eigenvalue sensitivity coefficients while the operating conditions of the system are varied. Optimization of controller parameters using first order eigenvalue sensitivity coefficients is performed by the Simplex Method. It is proved that exciter control is the most efficient method to improve stability of the system and the effect of Static Var Compensator is small, in the case of one machine infinite bus system.

• Journal of the Korea Institute of Building Construction
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• v.2 no.4
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• pp.89-98
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• 2002

Self-leveling material(SLM) is one of the floor finishing materials which make flat surface like as water level by itself in a short time. So it is possible to increase construction speed and enhance economical efficiency In this study, author intended to develop SLM for the industrial warehouse and factory loading heavy weight machinery and vehicles. The demanded properties for this type of SLM are above 200mm of flow value and above 300kgf/$cm^2$ of 28-days compressive strength. To possess demended strength and fluidity, SLM have to be composed of many types of binders and chemical additives. So it is difficult to decide suitable mixing proportion of composition materials. In this study, author investigated the weight percentage effect of main composition materials for high-strength self-leveling material, by experimental design such as tables of orthogonal arrays and simplex design, and by statistical analysis such as analysis of variance and analysis of response surface. Variables of experiments were ordinary Portland cement(OPC), alumina cement(AC), anhydrous gypsum(AG), lime stone(LS) and sand, and properties of tests were fluidity of fresh state and strength of hardened state. Results of this study are showed that suitable mix proportions of binders for the high strength self-leveling materials are two groups. One is 78~85.5% OPC, 7.5~9.5% AC, 9~12.5% AG and the other is 72.5~78% OPC, 9~12.5% AC, 13~15% AG.