• Journal of Ginseng Research
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• 제32권2호
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• pp.99-106
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• 2008

A ligand - whether an endogenous hormone, neurotransmitter, exogenous toxin or synthetic drug - binds to plasma membrane proteins (e.g., ion channels, receptors or other functional proteins) to exert its physiological or pharmacological effects. Ligands can also have functional groups, showing stereospecificity for interaction sites on their counterpart plasma membrane proteins. Previous reports have shown that the ginsenoside Rg$_3$, a bioactive ginsenoside, meets these criteria in that: 1) an aliphatic side chain of $Rg_3$ plays a role as a functional group, 2) Rg$_3$ regulates voltage- and ligand-gated ion channels in a stereospecific manner with respect to carbon-20, and 3) $Rg_3$ regulates subsets of ligand-gated and voltage-gated ion channels through specific interactions with identified amino acid residues inside the channel pore, in the outer pore entryway, or in toxin binding sites. Rg$_3$, therefore, could be a candidate for a novel ginseng-derived glycosidic ligand regulating ion channels and receptors. This review will examine how Rg$_3$ regulates voltage-gated and ligand-gated ion channels through interactions with its target proteins in the plasma membrane. Hopefully, this review will advance understanding of ginseng pharmacology at the cellular and molecular levels.

• Molecules and Cells
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• 제27권5호
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• pp.591-599
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• 2009

Nicotinic acetylcholine receptors (nAChRs) play important roles in nervous system functions and are involved in a variety of diseases. We previously demonstrated that ginsenosides, the active ingredients of Panax ginseng, inhibit subsets of nAChR channel currents, but not ${\alpha}7$, expressed in Xenopus laevis oocytes. Mutation of the highly conserved Leu247 to Thr247 in the transmembrane domain 2 (TM2) channel pore region of ${\alpha}7$ nAChR induces alterations in channel gating properties and converts ${\alpha}7$ nAChR antagonists into agonists. In the present study, we assessed how point mutations in the Leu247 residue leading to various amino acids affect 20(S)-ginsenoside $Rg_3$ ($Rg_3$) activity against the ${\alpha}7$ nAChR. Mutation of L247 to L247A, L247D, L247E, L247I, L247S, and L247T, but not L247K, rendered mutant receptors sensitive to $Rg_3$. We further characterized $Rg_3$ regulation of L247T receptors. We found that $Rg_3$ inhibition of mutant ${\alpha}7$ nAChR channel currents was reversible and concentration-dependent. $Rg_3$ inhibition was strongly voltage-dependent and noncompetitive manner. These results indicate that the interaction between $Rg_3$ and mutant receptors might differ from its interaction with the wild-type receptor. To identify differences in $Rg_3$ interactions between wild-type and L247T receptors, we utilized docked modeling. This modeling revealed that $Rg_3$ forms hydrogen bonds with amino acids, such as Ser240 of subunit I and Thr244 of subunit II and V at the channel pore, whereas $Rg_3$ localizes at the interface of the two wild-type receptor subunits. These results indicate that mutation of Leu247 to Thr247 induces conformational changes in the wild-type receptor and provides a binding pocket for $Rg_3$ at the channel pore.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.367-371
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• 2001

The chromosome 7-linked long QT syndrome (LQT2) is caused by mutations in the human ether-a- go-go-related gene (HERG) that encodes the rapidly activating delayed rectifier $K^+$ current, $I_{Kr},$ in cardiac myocytes. Different types of mutations have been identified in various locations of HERG channel. One of the mechanisms for the loss of normal channel function is due to membrane trafficking of channel protein. The decreased channel function in some deletion mutants appears to be due to loss of coupling with wild type HERG to form the functional channel as the tetramer. Most of missense mutants with few exceptions could interact with wild type HERG to form functional tetramer and caused dominant negative suppression with co-injection with wild type HERG showing variable effects on current amplitude, voltage dependence, and kinetics of activation and inactivation. Two missense mutants at pore regions of HERG found in Japanese LQT2 (A614V and V630L) showed accentuated inward rectification due to a negative shift in steady-state inactivation and fast inactivation. One mutation in S4 region (R534C) produced a negative shift in current activation, indicating the S4 serving as the voltage sensor and accelerated deactivation. The C-terminus mutation, S818L, could not express the current by mutant alone and did not show dominant negative suppression with co-injection of equal amount of wild type cRNA. Co-injection of excess amount of mutant with wild type produced dominant negative suppression with a shift in voltage dependent activation. Therefore, multiple mechanisms are involved in different mutations and functional abnormality in LQT2. Further characterization with the interactions between various mutants in HERG and the regulatory subunits of the channels (MiRP1 and minK) is to be clarified.

• Journal of Pharmaceutical Investigation
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• 제34권5호
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• pp.363-368
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• 2004

In order to investigate the effect of bovine serum albumin (BSA), as a pore former, on the controlled release of an antibiotic from a biodegradable polymeric device, polycaprolactone (PCL)-cefadroxil matrices were prepared by the solvent casting method. The amount of cefadroxil released from various formulations at $37^{\circ}C$ was measured by HPLC. The duration of antimicrobial activity of matrices against S. aureus was evaluated by measuring the diameters of the inhibition zone. The morphology of the matrices was investigated by scanning electron microscopy (SEM). The release rate and extent of cefadroxil from PCL matrix increased as the loading dose and particle size of BSA/cefadroxil mixture powder increased. Cefadroxil released from the matrix exhibited antibacterial activity for up to 4 days. SEM of the cross-section of matrix showed the typical channel formation after 3 days of release study. Thus, a biodegradable polymeric matrix loaded with antibiotic/BSA mixture can effectively prevent bacterial infection on its surface, thereby bringing about an enhancement of biocompatibility of biomaterials.

• Geomechanics and Engineering
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• 제19권5호
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• pp.447-462
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• 2019

The vacuum preloading method has been used in many countries for ground improvement and land reclamation works. A sand cushion is required as a horizontal drainage channel for conventional vacuum preloading. In terms of the dredged-fill foundation soil, the treatment effect of the conventional vacuum preloading method is poor, particularly in Tianjin, China, where a shortage of sand exists. To solve this problem, straight-line vacuum preloading without sand is widely adopted in engineering practice to improve the foundation soil. Based on the engineering properties of dredged fill in Lingang City, Tianjin, this paper presents field instrumentation in five sections and analyzes the effect of a prefabricated vertical drain (PVD) layout and a vacuum pumping method on the soft soil ground treatment. Through the arrangement of pore water pressure gauges, settlement marks and vane shear tests, the settlement, pore water pressure and subsoil bearing capacity are analyzed to evaluate the effect of the ground treatment. This study demonstrates that straight-line vacuum preloading without sand can be suitable for areas with a high water content. Furthermore, the consolidation settlement and consolidation degree system is developed based on the grey model to predict the consolidation settlement and consolidation degree under vacuum preloading; the validity of the system is also verified.

• Geomechanics and Engineering
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• 제25권1호
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• pp.31-40
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• 2021

Injection grouting is one of the most common ground improvement practice to increase the strength and reduce the hydraulic conductivity of soils. Owing to the environmental concerns of conventional grout materials, such as cement-based or silicate-based materials, bio-inspired biogeotechnical approaches are considered to be new sustainable and environmentally friendly ground improvement methods. Biopolymers, which are excretory products from living organisms, have been shown to significantly reduce the hydraulic conductivity via pore-clogging and increase the strength of soils. To study the practical application of biopolymers for seepage and ground water control, in this study, we explored the injection capabilities of biopolymer-based grout materials in both linear aperture and particulate media (i.e., sand and glassbeads) considering different injection pressures, biopolymer concentrations, and flow channel geometries. The hydraulic conductivity control of a biopolymer-based grout material was evaluated after injection into sandy soil under confined boundary conditions. The results showed that the performance of xanthan gum injection was mainly affected by the injection pressure and pore geometry (e.g., porosity) inside the soil. Additionally, with an increase in the xanthan gum concentration, the injection efficiency diminished while the hydraulic conductivity reduction efficiency enhanced significantly. The results of this study provide the potential capabilities of injection grouting to be performed with biopolymer-based materials for field application.

• 한국자기학회지
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• 제22권1호
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• pp.6-10
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• 2012

본 연구에서는 인산 용액 하에서 2차 양극 산화 기법에 의해 제작된 양극 산화 알루미나 기판 상에 최대 13 nm 두께의 얇은 니켈 박막을 증착하며 증착 시 박막 두께에 따라 감소하는 박막의 저항 변화를 살펴보았다. 양극 산화 알루미나 막 표면에 존재하는 미세 기공 구조를 따라 증착된 니켈 박막 역시 다공 구조의 박막으로 성장하게 되며 증착된 박막의 두께 범위 내에서 박막의 저항은 $150k{\Omega}$ 이상의 값을 보이면서 박막 두께에 따른 저항의 감소가 매우 천천히 일어나는 것을 확인할 수 있었다. 측정된 저항 값은 기존에 보고된 균일한 기판 상에 증착된 동일 두께의 니켈 박막에 비해 매우 큼을 볼 수 있었으며 기판 표면에 존재하는 기공 구조에 의해 핵자가 형성될 수 있는 표면 면적 비가 박막 성장을 설명하는 스미기(percolation) 현상이론에서 예측하는 임계 값보다 매우 적어 미세 기공에 의해 박막의 성장과 함께 나타나는 전자 전도 채널의 형성이 저해됨으로 이해될 수 있다. 이와 함께 기존의 박막 두께에 따른 비저항 모델과 비교해 보았을 때 미세 기공의 경계에서 나타나는 전자 산란 현상 역시 박막저항의 증가에 기여함을 알 수 있다.

• 청정기술
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• 제14권2호
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• pp.87-94
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• 2008

12-고리를 갖는 큰 기공 제올라이트인 H-모더나이트, H-베타, H-Y상에서 에탄올 아민화반응에 의한 디에틸아민합성반응을 수행하였다. 사용된 큰 기공 제올라이트의 Si/Al 비 증가는 강산점의 감소를 가져왔으며 이 강산점의 세기는 아민으로의 생성 증가와 관련지을 수 있었다. 다차원 채널 형태를 갖는 H-베타, H-Y 제올라이트는 큰 둥지 부피와 낮은 산점세기로 인해 에탄올의 이량화반응에 의한 디에틸에테르의 생성을 촉진하였다. 직선 기공 채널 형태를 갖고 있는 H-모더나이트 제올라이트는 정밀화학 중간체로 널리 쓰이는 모노, 디에틸아민 합성에 적합하였다.

• Nuclear Engineering and Technology
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• 제53권7호
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• pp.2364-2370
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• 2021

The ⁿMCP (Neutron sensitive microchannel plate) combined with advanced readout electronics is widely used in energy selective neutron imaging because of its good spatial and timing resolution. Neutron detection efficiency is a crucial parameter for the ⁿMCP. In this paper, a mathematical model based on the oblique cylindrical channel and elliptical pore was established to calculate the neutron absorption probability, the escape probability of charged particles and overall detection efficiency of ⁿMCP and analyze the effects of neutron incident position, pore diameter, wall thickness and bias angle. It was shown that when the doping concentration of the ⁿMCP was 10 mol%, the thickness of ⁿMCP was 0.6 mm, the detection efficiency could reach maximum value, about 24% for thermal neutrons if the pore diameter was 6 ㎛, the wall thickness was 2 ㎛ and the bias angle was 3 or 6°. The calculated results are of great significance for evaluating the detection efficiency of the ⁿMCP. In a subsequent companion paper, the mathematical model would be extended to the case of the spatial resolution and detection efficiency optimization of the coating ⁿMCP.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.267-273
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• 2003

We have investigated the effect on inducing substate(s) of positively charged residues replaced in position 172 of the second transmembrane domain in murine inward rectifier potassium channels, formed by stable or transient transfection of Kir2.1 gene in MEL or CHO cells. Single channel recordings were obtained from either cell-attached patches or inside-out patches excised into solution containing 10 mM EDTA to rule out the effect of $Mg^{2+}$ on the channel gating. The substate(s) could be recorded with all mutants D172H, D172K and D172R. The unitary current-voltage (I-V) relation was not linear with D172H at $pH_i$ 6.3, whereas the unitary I-V relation was linear at $pH_i$ 8.0. The relative occupancy at $S_{LC}$ was increased from 0.018 at $pH_i$ 8.0 to 0.45 at $pH_i$ 5.5. In H-N dimer, that was increased from 0.016 at $pH_i$ 8.0 to 0.23 at $pH_i$ 5.5. The larger the size of the side chain or $pK_a$ with mutants (D172H, D172K and D172R), the more frequent the transitions between the fully open state and substate within an opening. The conductance of the substate also depended upon the pKa or the size of the side chain. The relative occupancy at substate $S_{LC}$ with monomer D172K (0.50) was less than that in K-H dimer (0.83). However, the relative occupancy at substate with D172R (0.79) was similar to that with R-N dimer (0.82). In the contrary to ROMK1, positive charge as well as negative charge in position 172 can induce the substate rather than block the pore in murine Kir2.1. The single channel properties of the mutant, that is, unitary I-V relation, the voltage dependence of the mean open time and relative occupancy of the substates and the increased latency to the first opening, explain the intrinsic gating observed in whole cell recordings.