• Archives of Pharmacal Research
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• v.29 no.4
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• pp.318-322
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• 2006

Many quaternary ammonium salts are incompletely absorbed after their oral administration and may also be actively secreted into the intestine. However, the underlying mechanism(s) that control the transport of these cations across the intestinal epithelium is not well understood. In this study, the mechanism of absorption of quaternary ammonium salts was investigated using Caco-2 cell monolayers, a human colon carcinoma cell line. Tributylmethylammonium (TBuMA) was used as a model quaternary ammonium salts. When TBuMA was administrated at a dose of 13.3 imole/kg via iv and oral routes, the AUC values were $783.7{\pm}43.6\;and\;249.1{\pm}28.0{\mu}mole\;min/L$ for iv and oral administration, indicating a lower oral bioavailability of TBuMA $(35.6\%)$. The apparent permeability across Caco-2 monolayers from the basal to the apical side was 1.3 times (p<0.05) greater than that from the apical to the basal side, indicating a net secretion of TBuMA in the intestine. This secretion appeared to be responsible for the low oral bioavailability of the compound, probably mediated by p-gp (p-glycoprotein) located in the apical membrane. In addition, the uptake of TBuMA by the apical membrane showed a $Na^+$ dependency. Thus, TBuMA appears to absorbed via a $Na^+$ dependent carrier and is then secreted via p-gp related carriers.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.768-772
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• 2003

Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e.g., pharmacokinetic studies, etc.). Tween 80 increased apical to basolateral permeability of digoxin in Caco-2 cells suggesting that Tween 80 is an in vitro inhibitor of P-gp. The overall objective of the present study was to investigate whether an inhibition of P-gp by Tween 80 can potentially influence in vivo absorption of P-gp substrates by evaluating the effect of Tween 80 on the disposition of digoxin (a model P-gp substrate with minimum metabolism) after oral administration in rats. Rats were dosed orally with digoxin (0.2 mg/kg) formulated in ethanol (40％, v/v) and saline mixture with and without Tween 80 (1 or 10％, v/v). Digoxin oral AUC increased 30 and 61％ when dosed in 1 ％ and 10％ Tween 80, respectively, compared to control (P＜0.05). To further examine whether the increase in digoxin AUC after oral administration of Tween 80 is due, in part, to a systemic inhibition of digoxin excretion in addition to an inhibition of P-gp in the GI tract, a separate group of rats received digoxin intravenously (0.2 mg/kg) and Tween 80 (10％ v/v) orally. No significant changes in digoxin IV AUC was noted when Tween 80 was administered orally. In conclusion, Tween 80 significantly increased digoxin AUC and Cmax after oral administration, and the increased AUC is likely to be due to an inhibition of P-gp in the gut (i.e., improved absorption). Therefore, Tween 80 is likely to improve systemic exposure of P-gp substrates after oral administration. Comparing AUC after oral administration with and without Tween 80 may be a viable strategy in evaluating whether oral absorption of P-gp substrates is potentially limited by P-gp in the gut.

• Geomechanics and Engineering
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• v.17 no.6
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• pp.535-541
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• 2019

Combining the radial well drilling and hydraulic fracturing technique, the production capacity of the reservoirs with low-permeability can be improved effectively. Due to the existence of radial holes, the stress around the well is redistributed, and the initiation and propagation of hydraulic fractures are different with those in traditional hydraulic fracturing. Therefore, it is necessary to study the influences of radial horizontal wells on hydraulic fracturing. The laboratory experiment was conducted to simulate the hydraulic fracturing on the physical model with radial holes. The experimental results showed that, compared with the borehole without radial holes, the sample with radial hole in the direction of maximum horizontal stress was fractured with significantly lower pressure. As the angle between direction of the horizontal hole and the maximum horizontal stress increased, the breakdown pressure grew. While when the radial hole was drilled towards the direction of the minimum horizontal stress, the breakdown pressure increased to that needed in the borehole without radial holes. When the angle between the radial hole and the maximum horizontal stress increase, the pressure required to propagate the fractures grew apparently, and the fracture become complex. Meanwhile, the deeper the radial hole drilled, the less the pressure was needed for fracturing.

• Journal of the Korean Geotechnical Society
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• v.34 no.11
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• pp.33-41
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• 2018

Soil internal erosion is a phenomenon in which fines attached to the solid skeleton are detached by fluid flow, and this continuous fine migration weakens the hydro-mechanical characteristics of the ground structure. This paper proposed governing equations for fine migration in pore spaces and its related scheme for the numerical analysis. Phase diagram for fine particles includes three different states: detached fines in the liquid phase ($c_e$), attached fines in the solid phase (${\sigma}_a$), and pore-clogged fines in the solid phase (${\sigma}_s$). Numerical formulations for finite element method are developed based on the hydraulic governing equations of pore fluid and fine migration. This study proposed a method of estimating model parameters for fine detachment, attachment, and clogging from 1D erosion experiments. And it proposed an analytical formula for hydraulic permeability function considering fine clogging. Numerical analysis of the previous erosion test developed the numerical scheme and verified the adequacy of fine migration models.

• Geomechanics and Engineering
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• v.17 no.5
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• pp.485-496
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• 2019

Sealing of leakage in waterfront or water-retaining structures is one of the major issues in geotechnical engineering practices. With demands for biological methods as sustainable ground improvement techniques, bioclogging, defined as the reduction in hydraulic conductivity of soils caused by microbial activities, has been considered as an alternative to the chemical grout techniques for its economic advantages and eco-friendliness of microbial by-products. This study investigated the feasibility of bioaugmentation and biostimulation methods to induce fermentation-based bioclogging effect in coarse sands. In the bioaugmentation experiments, effects of various parameters and conditions, including grain size, pH, and biogenic gas generation, on hydraulic conductivity reduction were examined through a series of column experiments while Leuconostoc mesenteroides, which produce an insoluble biopolymer called dextran, was used as the model bacteria. The column test results demonstrate that the accumulation of bacterial biopolymer can readily reduce the hydraulic conductivity by three-to-four orders of magnitudes or by 99.9-99.99% in well-controlled environments. In the biostimulation experiments, two inoculums of indigenous soil bacteria sampled from waterfront embankments were prepared and their bioclogging efficiency was examined. With one inoculum containing species capable of fermentation and biopolymer production, the hydraulic conductivity reduction by two orders of magnitude was achieved, however, no clogging was found with the other inoculum. This implies that presence of indigenous species capable of biopolymer production and their population, if any, play a key role in causing bioclogging, because of competition with other indigenous bacteria. The presented results provide fundamental insights into the bacterial biopolymer formation mechanism, its effect on soil permeability, and potential of engineering bacterial clogging in subsurface.

• Journal of the Korean Geotechnical Society
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• v.37 no.6
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• pp.21-28
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• 2021

The factors of landslides depend on rainfall intensity, duration, and the characteristics of the soil slope. The conventional slope stability analysis has been carried out by assuming that the slope is saturated. But, a site slope consisting of unsaturated ground must be imitated and interpreted in order to explain a proper behavior of the slope due to rainfall. In this study, by using two major categories of soils in Korea, such as granite and gneiss weathered soils, landslide model test and numerical analysis have been compared with the difference of seepage and volumetric water content. In general, the permeability of gneiss weathered soil, which contains a lot of fines content, is slower than that of granite weathered soil. As a result, in extreme rainfall, numerical analysis can show results that can penetrate quickly, resulting in saturation or more dangerous collapse.

• Herbal Formula Science
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• v.30 no.4
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• pp.293-304
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• 2022

Objectives : Sagunja-Tang is a famous prescription used in Korean medicine for the purpose of promoting vital energy, and there are few studies using Sagunja-Tang on cerebrovascular diseases yet. As previous studies confirmed that Sagunja-tang is highly likely to be used effectively for stroke, this study was intended to predict the mechanism through which Sagunja-tang would act effectively on stroke. Methods : In this study, a network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 30%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ 0.3 were applied. Using the above variables, the relations between target genes and diseases that are presumed to be involved in the selected bioavailable compounds were constructed in a network format, and proteins thought to play a major role were identified. Results : Among the compounds included in Sagunja-Tang, 26 bioavailable compounds were selected and it was confirmed that these compounds can be effectively used in cerebrovascular diseases such as Alzheimer's disease and stroke. These compounds are considered to act on proteins related in cell death and growth. The most important mechanism of action was predicted to be apoptosis, and the protein that is thought to play the most key action in this mechanism was caspase-3. Conclusions : In our future study, Sagunja-Tang will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

• KIPS Transactions on Software and Data Engineering
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• v.12 no.6
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• pp.243-250
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• 2023

Chest X-ray is radiological examination for xeamining the lungs and haert, and is particularly widely used for diagnosing lung disease. Since the quality of these chest X-rays can affect the doctor's diagnosis, the process of evaluating the quality must necessarily go through. This process can involve the subjectivity of radiologists and is manual, so it takes a lot of time and csot. Therefore, in this paper, based on the chest X-ray quality assessment guidelines used in clinical settings, we propose a tool that automates the five quality assessments of artificial shadow, coverage, patient posture, inspiratory level, and permeability. The proposed tool reduces the time and cost required for quality judgment, and can be further utilized in the pre-processing process of selecting high-quality learning data for the development of a learning model for diagnosing chest lesions.

• Journal of the Computational Structural Engineering Institute of Korea
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• v.36 no.4
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• pp.259-264
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• 2023

In this study, we devised a parametric analysis workflow for efficiently analyzing the material properties of 3D woven materials. The parametric model uses wire spacing in the woven materials as a design parameter; we generated 2,500 numerical models with various combinations of these design parameters. Using MATLAB and ANSYS software, we obtained various material properties, such as bulk modulus, thermal conductivity, and fluid permeability of the woven materials, through a parametric batch analysis. We then used this large dataset of material properties to perform a regression analysis to validate the relationship between design variables and material properties, as well as the accuracy of numerical analysis. Furthermore, we constructed an artificial neural network capable of predicting the material properties of 3D woven materials on the basis of the obtained material database. The trained network can accurately estimate the material properties of the woven materials with arbitrary design parameters, without the need for numerical analyses.

• Herbal Formula Science
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• v.31 no.3
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• pp.171-182
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• 2023

Objectives : Saposhnikoviae Radix (SR) and Glehniae Radix (GR) have been frequently used in traditional medicine to treat diseases related to 'wind' syndrome, but there have been cases where it has been mixed in a state where the plant of origin is not clear. In this study, to select materials for conducting preclinical cerebral infarction research, the network pharmacology analysis method was used to select suitable medicinal materials for the study. Methods : In this study, a Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) based network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 20%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ -0.3 were applied, then networks of bioactive compounds, target proteins, and target diseases was constructed. STRING database was used to construct a protein-protein interaction network. Results : It was confirmed that SR rather than GR has various target proteins and target diseases based on network pharmacological analysis using TCMSP database. And it was analyzed that the bioactive compounds only in SR act more on neurovascular diseases, and both drugs are expected to be effectively used for cardiovascular diseases. Conclusions : In our future study, SR will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.