• Journal of Integrative Natural Science
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• v.8 no.4
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• pp.258-266
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• 2015

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMFA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMFA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMFA models were generated using different alignments and the best model yielded a cross-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMFA models was found to be $r^2_{pred}$0.653. The CoMFA study revealed that the $R_3$ position of the structure is important in influencing the biological activity of the inhibitors. Electro positive groups and bulkier substituents in this position enhance the biological activity.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.225-231
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• 2003

To search and development a new material with superior melanogenesis inhibitory activity, the bioactivities (obs. pl$_{50}$) of alkyl-3,4-dihydroxybenzoyl esters and N-alkyl-3,4-dihydroxybenz-oyl amides as substrate molecules were measured in mouse melanoma cells. And also, we have studied that 3-D QSARs (3 dimensional Quantitative Structure-Activity Relationships) between molecular interaction field of substrates and the bioactivities were analyzed using CoMFA (Comparative Molecular Field Analyses) method. When cross-validation value (q$^2$) is 0.68 at 3 components, the Pearson correlation coefficient ($r^2$) is 0.900. From the basis on the findings, the model was appeared by the contour map such as steric field and electrostatic field relationships between quantitative structure and the bioactivity of the various substrate derivatives. Measured bioactivities (obs. pl$_{50}$) of unknown compounds are very similar to predicted activity (pred. pl$_{50}$) according to the CoMFA model. As the results of prediction, we could conclude that the bioactivities were increased by creation of R$_1$ substitution of 5,5-dime-thylhexoxy, 6,6-dimethylheptyl, 1-amino-6,6-dimethylheptyl group etc and R$_2$ substitution of hydroxy, methyl, methoxy group etc.p etc.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2065-2071
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• 2014

${\beta}$-Secretase (beta-amyloid converting enzyme 1 [BACE1]) is involved in the first and rate-limiting step of ${\beta}$-amyloid ($A{\beta}$) peptides production, which leads to the pathogenesis of Alzheimer's disease(AD). Therefore, inhibition of BACE1 activity has become an efficient approach for the treatment of AD. Ligand-based and docking-based 3D-quantitative structure-activity relationship (3D-QSAR) studies of acyl guanidine analogues were performed with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to obtain insights for designing novel potent BACE1 inhibitors. We obtained highly reliable and predictive CoMSIA models with a cross-validated $q^2$ value of 0.725 and a predictive coefficient $r{^2}_{pred}$ value of 0.956. CoMSIA contour maps showed the structural requirements for potent activity. 3D-QSAR analysis suggested that an acyl guanidine and an amide group in the $R_6$ substituent would be important moieties for potent activity. Moreover, the introduction of small hydrophobic groups in the phenyl ring and hydrogen bond donor groups in 3,5-dichlorophenyl ring could increase biological activity.

• Journal of Integrative Natural Science
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• v.11 no.2
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• pp.93-100
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• 2018

Caspases, a family of cysteinyl aspartate-specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage because the activation of caspases-3 stimulates a signalling pathway that ultimately leads to the death of the cell. In this study, Hologram based Quantitative Structure Activity Relationship (HQSAR) models was generated on a series of Caspase-3 inhibitors named 3, 4-dihydropyrimidoindolones derivatives. The best HQSAR model was obtained using atoms, bonds, and hydrogen atoms (A/B/H) as fragment distinction parameter using hologram length 61 and 3 components with fragment size of minimum 5 and maximum 8. Significant cross-validated correlation coefficient ($q^2=0.684$) and non cross-validated correlation coefficients ($r^2=0.754$) were obtained. The model was then used to evaluate the eight external test compounds and its $r^2_{pred}$ was found to be 0.559. Contribution map show that presence of pyrrolidine sulfonamide ring and its bulkier substituent's makes big contributions for improving the biological activities of the compounds.

• Journal of Korean Society of Industrial and Systems Engineering
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• v.33 no.3
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• pp.55-62
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• 2010

Currently, cost estimation is very important to the government acquisition programs to support decisions about funding and to evaluate resource requirement as key decision points. Parametric cost estimating models have been used extensively to obtain appropriate cost estimates in early acquisition phase. However, they have many restrictions to ensure the cost estimating result in Korean defense environment because they are developed in the U.S.A. environment. In order to obtain a good R&D cost estimate, developing our own CERs (Cost Estimation Relationships) using historical R&D data is essential. Nevertheless, there has been little research to develop our own CERs. In this research, we established a CER development process and found some cost drivers in the historical movement weapon system R&D data. The R&D CER is developed using the PCR(Principle Component Regression) method to remove multicollinearity among data and to overcome the restriction of the insufficient number of sample. At least, this research is meaningful as a first attempt in terms of defining the CER development process and obtaining our own R&D CER based on the historical data in Korean weapon system R&D environment.

• Journal of the Korean Institute of Intelligent Systems
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• v.10 no.4
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• pp.330-337
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• 2000

This paper proposes a new concept of coordinating green this which controls 10 traffic intersection systems. For instance, if we have a baseballs game at 8 pm today, traffic volume toward the baseball game at 8 pm today, traffic volume toward the baseball game will be incr eased 1 hour or 1 hour 30 minutes before the baseball game. at that time we can not pred ict optimal green time Even though there have smart elctrosensitive traffic light system. Therefore, in this paper to improve average vehicle speed and reduce average vehicle waiting time, we created optimal green time using fuzzy rules and neural network. Computer simulation results proved reducing average vehicle waiting time proposed coordinating green time better than electro-sensitive traffic light system. Therefore, in this paper to improvevehicle speed and reduce average vehicle waiting time, we created optiual green time fuzzy rules and neural network. Computer simulation results proved reducing average vehicle waiting time which proposed coordinating green time better than electro-sensitive traffic light system dosen't consider coordinating green time.

• Journal of the Korea Institute of Military Science and Technology
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• v.15 no.5
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• pp.565-576
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• 2012

Cost estimates are necessary for government acquisition program to support decisions about funding, to develop annual budget requests and to validate resource requirements at key decision points. Many researches have been done about cost estimating technique recently. Parametric cost estimating models based on CERs(Cost Estimating Relationships) have been mainly used using regression method with historical data. However, there are many restrictions in developing Korean version CERs because the number of data points are too small. Specially, data collection and data management system are unstable in Korean defense environment, when developing CERs. In this research, we analyzed the historical data, and found some cost drivers in guided weapon system area. We developed the Acquisition Unit Cost CER using the regression to remove multicollinearity in the historical data. So we could overcome the restriction of the insufficient sample number. This research as a first attempt is meaningful in terms of obtaining our own Acquisition Unit Cost CER using historical cost and physical characteristic in Korean development environment.

• Journal of Integrative Natural Science
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• v.9 no.3
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• pp.190-198
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• 2016

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organsincluding the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMSIA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMSIA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMSIA models were generated using different alignments and the best model yielded across-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMSIA models was found to be $r{^2}_{pred}$ 0.653. The study revealed the important structural features required for the biological activity of the inhibitors and could provide useful for the designing of novel and potent drugs for the inhibition of Xanthine oxidase.

• Steel and Composite Structures
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• v.32 no.4
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• pp.455-466
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• 2019

Despite the rapid advancement in computing resources, many real-life design and optimization problems in structural engineering involve huge computation costs. To counter such challenges, approximate models are often used as surrogates for the highly accurate but time intensive finite element models. In this paper, surrogates for first-order shear deformation based finite element models are built using a polynomial regression approach. Using statistical techniques like Box-Cox transformation and ANOVA, the effectiveness of the surrogates is enhanced. The accuracy of the surrogate models is evaluated using statistical metrics like $R^2$, $R^2{_{adj}}$, $R^2{_{pred}}$ and $Q^2{_{F3}}$. By combining these surrogates with nature-inspired multi-criteria decision-making algorithms, namely multi-objective genetic algorithm (MOGA) and multi-objective particle swarm optimization (MOPSO), the optimal combination of various design variables to simultaneously maximize fundamental frequency and frequency separation is predicted. It is seen that the proposed approach is simple, effective and good at inexpensively producing a host of optimal solutions.

• Bulletin of the Korean Chemical Society
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• v.34 no.12
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• pp.3553-3558
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• 2013

The three dimensional-quantitative structure activity relationship (3D-QSAR) studies on chemical features of pyridine-2-amines in the external region of c-Met active site (ER chemical features of pyridine-2-amines) were conducted by docking, comparative molecular field analysis (CoMFA), and topomer CoMFA methods. The CoMFA model obtained the partial least-squares (PLS) statistical results, cross-validated correlation coefficient ($q^2$) of 0.703, non cross-validated correlation coefficient ($r^2$) of 0.947 with standard error of estimate (SEE) of 0.23 and the topomer CoMFA obtained $q^2$ of 0.803, $r^2$ of 0.940, and SEE of 0.24. Further, the test set was applied to validate predictive abilities of models, where the predictive $r^2$ ($r{^2}_{pred}$) for CoMFA and topomer CoMFA models were 0.746 and 0.608, respectively. Each contribution of ER chemical features of pyridine-2-amines to the inhibitory potency showed correlation coefficients, $r^2$ of 0.670 and 0.913 for two core parts, 3-(benzo[d]oxazol-2-yl)pyridine-2-amine and 3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy) pyridine-2-amine, respectively, with corresponding experimental $pIC_{50}$.