• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.107-115
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• 2017

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.491-497
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• 2015

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3- gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-$1{\beta}$ and TNF-${\alpha}$ mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of $p47^{phox}$ translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress.

• Interaction and multiscale mechanics
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• v.2 no.1
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• pp.45-68
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• 2009

An aim of the study is to develop an efficient numerical simulation technique that can handle the two-scale analysis of fluid permeation filters fabricated by the partial sintering technique of small spherical ceramics. A solid-fluid mixture homogenization method is introduced to predict the mechanical characters such as rigidity and permeability of the porous ceramic filters from the micro-scale geometry and configuration of partially-sintered particles. An extended finite element (X-FE) discretization technique based on the enriched interpolations of respective characteristic functions at fluid-solid interfaces is proposed for the non-interface-fitted mesh solution of the micro-scale analysis that needs non-slip condition at the interface between solid and fluid phases of the unit cell. The homogenization and localization performances of the proposed method are shown in a typical two-dimensional benchmark problem whose model has a hole in center. Three-dimensional applications to the body-centered cubic (BCC) and face-centered cubic (FCC) unit cell models are also shown in the paper. The 3D application is prepared toward the computer-aided optimal design of ceramic filters. The accuracy and stability of the X-FEM based method are comparable to those of the standard interface-fitted FEM, and are superior to those of the voxel type FEM that is often used in such complex micro geometry cases.

• Journal of the Korean Chemical Society
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• v.22 no.5
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• pp.304-310
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• 1978

The relative permeabilities, distribution coefficients and diffusion coefficient of some salts which are important components in blood plasma through a poly(HEMA) membrane were measured. The crosslinker which was used for preparing the membrane was tetraethylene glycol dimethacrylate(TEGDMA), the weight percentage of the latter was about 2.8. We found that the diffusion coefficients ($D_m$) of the solutes decrease exponentially with increasing molecular weight, and also that $D_m$'s decrease linearly (except urea) with cylindrical radius (a). These facts were explained by a sieve pore flow model. The relative permeability and diffusion coefficient of urea at various temperature were larger than those of other solutes such as glycine, ${\beta}$-alanine, D-glucose, saccharose and maleic acid. The result indicates that the poly(HEMA) membrane might be suitable for hemodialysis application.

• Tunnel and Underground Space
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• v.8 no.3
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• pp.184-193
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• 1998

In order to dispose radioactive wastes safely, it is needed to understand the mechanical, thermal, fluid behavior of rockmass and physico-chemical interactions between rockmass and water. Also, the knowledge about mechanical and hydraulic properties of rocks is required to predict and to model many conditions of geological structure, underground in-situ stress, folding, hot water interaction, intrusion of magma, plate tectonics etc. This study is based on researches about rock mechanics issues associated with a waste disposal in deep rockmass. This paper includes the mechanical and hydraulic behavior of rocks in varying temperature conditions, thermo-hydro-mechanical coupling analysis in rock mass and deformation behavior of discontinuous rocks. The mechanical properties were measured with Interaken rock mechanics testing systems and hydraulic properties were measured with transient pulse permeability measuring systems. In all results, rock properties were sensitive to temperature variation.

• Geotechnical Engineering
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• v.13 no.5
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• pp.45-58
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• 1997

In this paper the factors developing ground disturbance with the penetration of PDB mandrels are analysed by using field reconnaissance and laboratory test. In the laboratory tests, the amount of smear zones around the PDB mandrels is compared with respect to the shape and the size of mandrels by penetrating model mandrels of various shapes into the reconstituted clay. The shapes of mandrels selected are circular, oval and rectangular. It was recognized from the field reconnaissance that the size and shape, driving techniques of mandrels, as well as the size and shape of anchor shoe could develop ground disturbance. The mandrels that would reduce the smear effect of clay is oval and rectangular shapes rat her than circular one. It was found that the smear effect becomes smaller as the ratio of the long and short edge of the rectangular shape mandrel becomes larger.

• Journal of Korean Tunnelling and Underground Space Association
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• v.18 no.1
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• pp.31-40
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• 2016

A new testing equipment is designed to investigate the characteristics of the drainage fabric which is used in the tunnel drain system. The equipment is possible to model the loading as well as boundary conditions of the shotcrete precisely and it follows the general guideline of ASTM D4716 so that the interface between shotcrete and concrete lining retains the real situation in the tunnel site. Using the real loading conditions and surface irregularities, the flow rate and its capacity of the regular fabric has been estimated. A composite drainage fabric having geogrid inside was also used to investigate the flow rate and its efficiency. The advantages of the composite fabric compared with the regular one have been demonstrated using the experimental data and brief outline of the future work is finally proposed.

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.37-42
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• 2002

Brain drug targeting through the blood-brain barrier (BBB) in vivo is possible with peptidornirnetic monoclonal antibodies that undergo receptor-mediated transcytosis through the BBB. Monoclonal antibody to the rat transferrin receptor, such as the OX26 was studied in rats as a transport vector through BBB on the transferrin receptor. But, OX26 is not an effective brain delivery vector in mouse. In the present studies, rat monoclonal antibody, 8D3 to the mouse transferrin receptor were evaluated for brain drug targeting vector intransgenic mouse model. Pharrnacokinetic parameters in plasma and organ uptakes were determined at varioustimes after i.v. bolus injection of [$^{}125}I$] 8D3 in Balb/c mice. Brain uptake of [$^{}125}I$] 8D3 was also studied with an internal carotid artery perfusioncapillary depletion method. After i.v. injection of [$^{}125}I$] 8D3, plasma concentrations declined biexponentially with elimination half lift of approximately 2.2 hours. Brain uptake of [$^{}125}I$] 8D3 was $0.50{\pm}0.09$ persent of injected dose per g brain after 2 hours i.v. injection. After perfusion 5 min the apparent volume of distibution of [$^{}125}I$] 8D3 in brain was $22.3 {\mu}l/g,$ which was 4.8 fold higher than the intravascular volume. These studies indicate rat monoclonal antibody to the mouse transferrin receptor, 8D3 may be used for brain drug targeting vector in mice.

• Journal of the Korean Geotechnical Society
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• v.18 no.3
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• pp.5-12
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• 2002

Hydraulic conductivity k is one of the most important engineering properties of soil. However, both field and laboratory procedures fur the determination of k are often tedious and expensive. This paper presents new models to predict k using statistical parameters from grain size distribution. A number of permeability tests far 36 types of sands mixed based on statistics were conducted to develop the regression-based models. Parameters used to estimate k are both the geometric mean and geometric standard deviation of the soil samples, or the particle-size distribution curve parameters such as D_{10},D_{50},D_{60}. Hydraulic conductivity predicted by this model is in good agreement with the laboratory measurements fir the soil samples obtained at 20 locations within the Korean Peninsula. The performances of the proposed models were also compared with those of existing models including Hazen's.

• The Journal of Korean Institute of Electromagnetic Engineering and Science
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• v.14 no.8
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• pp.884-890
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• 2003

In order to reduce the specific absorption rate(SAR) in a human head exposed to electromagnetic fields radiated by a cellular phone, we have analyzed an electromagnetic wave absorber attached to the handset. A manufactured electromagnetic wave absorber was composed of Mn - Zn, which had complex relative permittivity of 7.30-j0.05 and permeability of 2.20-i1.55. The SAR value from the electromagnetic wave absorber attachment was calculated by using the nonuniform finite difference time domain(FDTD) algorithm and measured by phantom model at 835 MHz. The SAR reduction due to the electromagnetic wave absorber are about 18 % at 835 MHz. The V.S.W.R and radiation pattern of antenna are good agreement with the normal antenna. The gain reduction due to the electromagnetic wave absorber are only 0.3 dB at 835 MHz. But the sensitivity of cellular phone generally improves about 1 dB.