• Journal of Ginseng Research
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• v.39 no.2
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• pp.169-177
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• 2015

Background: Ginsenoside Rd (GSRd), one of the most abundant ingredients of Panax ginseng, protects the heart via multiple mechanisms including the inhibition of $Ca^{2+}$ influx.We intended to explore the effects of GSRd on L-type $Ca^{2+}$ current ($I_{Ca,L}$) and define the mechanism of the suppression of $I_{Ca,L}$ by GSRd. Methods: Perforated-patch recording and whole-cell voltage clamp techniques were applied in isolated rat ventricular myocytes. Results: (1) GSRd reduced $I_{Ca,L}$ peak amplitude in a concentration-dependent manner [half-maximal inhibitory concentration $(IC_{50})=32.4{\pm}7.1{\mu}mol/L$] and up-shifted the current-voltage (I-V) curve. (2) GSRd ($30{\mu}mol/L$) significantly changed the steady-state activation curve of $I_{Ca,L}$ ($V_{0.5}:-19.12{\pm}0.68$ vs. $-6.26{\pm}0.38mV$; n = 5, p < 0.05) and slowed down the recovery of $I_{Ca,L}$ from inactivation [the time content (${\zeta}$) from 91 ms to 136 ms, n = 5, p < 0.01]. (3) A more significant inhibitive effect of GSRd ($100{\mu}mol/L$) was identified in perforated-patch recording when compared with whole-cell recording [$65.7{\pm}3.2%$ (n = 10) vs. $31.4{\pm}5.2%$ (n = 5), p < 0.01]. (4) Pertussis toxin ($G_i$ protein inhibitor) completely abolished the $I_{Ca,L}$ inhibition induced by GSRd. There was a significant difference in inhibition potency between the two cyclic adenosine monophosphate elevating agents (isoprenaline and forskolin) prestimulation [$55{\pm}7.8%$ (n = 5) vs. $17.2{\pm}3.5%$ (n = 5), p < 0.01]. (5) 1H-[1,2,4]Oxadiazolo[4,3-a]-quinoxalin-1-one (a guanylate cyclase inhibitor) and N-acetyl-$\small{L}$-cysteine (a nitric oxide scavenger) partly recovered the $I_{Ca,L}$ inhibition induced by GSRd. (6) Phorbol-12-myristate-13-acetate (a protein kinase C activator) and GF109203X (a protein kinase C inhibitor) did not contribute to the inhibition of GSRd. Conclusion: These findings suggest that GSRd could inhibit $I_{Ca,L}$ through pertussis toxin-sensitive G protein ($G_i$) and a nitric oxide-cyclic guanosine monophosphate-dependent mechanism.

• Journal of Pharmaceutical Investigation
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• v.20 no.4
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• pp.223-228
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• 1990

The contribution of endogenous transport systems to the blood-brain barrier (BBB) transport of basic and acidic drugs was studied by using a carotid injection technique in rats and an isolated bovine cerebrovascular disease state were compared between the normotensive rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) which have been well established as an animal model with pathogenic similarities to humans. Basic drugs such as eperisone, thiamine and scopolamine inhibited, in a concentration dependent manner the in vivo uptake of $[{^3}H]choline$ through BBB, whereas amino acids and acidic drugs such as salicylic acid and valproic acid did not inhibit the uptake. The uptake of $[^3H]choline$ by B-CAP increased with time and showed a remarkable temperature dependency. The uptake of $[^3H]choline$ by B-CAP showed the very similar inhibitory effects as observed in the in vivo brain uptake, and was competitively inhibited by a basic drug, eperisone. The in vivo BBB uptakes of $[^3H]acetic$ acid and $[^{14}C]salicylic$ acid were dependent on pH of the injectate and the concentration of drugs. Several acidic drugs such such as salicylic acid, benzoic acid and valproic acid inhibited the in vivo uptake of $[^3H]acetic$ acid, whereas amino acid, choline and a basic drug such as eperisone did not inhibit the uptake. The uptake of acetic acid by B-CAP was competitively inhibited by salicylic acid. The permeability surface area product (PS) through BBB for $[^3H]choline$ in SHRSP was significantly lower than that in WKY. The concentration of choline in the brain dialysate in SHRSP was about half of that in WKY, while no significant difference was observed in the plasma concentration of choline between SHRSP and WKY. No significant difference was observed in the transport of monocarboxylic acids, glucose and neutral amino acid through BBB between SHRSP and WKY. From these results, it was concluded that BBB transport system of choline contributes to the transport of basic drugs through BBB, that acidic drugs can be transported via a moncarboxylic acid BBB transport system and that the specific dysfuntion of the BBB choline transport in SHRSP was ascribed to the reduction of the maximum velocity of choline concentration in the brain interstitial fluids.

• Journal of Intelligence and Information Systems
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• v.29 no.1
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• pp.107-119
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• 2023

The technology that recognizes a soldier's motion and movement status has recently attracted large attention as a combination of wearable technology and artificial intelligence, which is expected to upend the paradigm of troop management. The accuracy of state determination should be maintained at a high-end level to make sure of the expected vital functions both in a training situation; an evaluation and solution provision for each individual's motion, and in a combat situation; overall enhancement in managing troops. However, when input data is given as a timer series or sequence, existing feedforward networks would show overt limitations in maximizing classification performance. Since human behavior data (3-axis accelerations and 3-axis angular velocities) handled for military motion recognition requires the process of analyzing its time-dependent characteristics, this study proposes a high-performance data-driven classifier which utilizes the long-short term memory to identify the order dependence of acquired data, learning to classify eight representative military operations (Sitting, Standing, Walking, Running, Ascending, Descending, Low Crawl, and High Crawl). Since the accuracy is highly dependent on a network's learning conditions and variables, manual adjustment may neither be cost-effective nor guarantee optimal results during learning. Therefore, in this study, we optimized hyperparameters using Bayesian optimization for maximized generalization performance. As a result, the final architecture could reduce the error rate by 62.56% compared to the existing network with a similar number of learnable parameters, with the final accuracy of 98.39% for various military operations.

• KSBB Journal
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• v.13 no.2
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• pp.181-186
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• 1998

In order to obtain high-level production of recombinant human thrombopoietin (rhTPO) in insect cell line, HTI-TN-5B1-4 (TN5), conditions for optimal rhTPO expression such as multiplicity of infection (MOI), the cell density at infection, harvesting time and type of culture method as well as growth media were determined. When TN5 cells were cultured as anchorage-dependent state in 60-mm dish, cell density $2\times^6$ cells,MOI of 10 and Garvesting the culture media at 72 hr post-infection wrere the cinditions for highest rh TPO production. High production of rhTPO was also achieved by using EXPRESS FIVE serum free media rather than SF900II serum free media-1. Anchorage-dependent TN5 cells were adapted as a suspension culture when they were grown in the presence of heparin. TN5 cells were successfully cultured at 0.2 L scale in suspension culture without having aggregation. When TN5 cells were cultured as suspension state, cell density of $0.6\times10^6$ cells/mL, MOI of 1 and harvesting the culture media at 72 hr post-infection, gave the highest yield of rhTPO.

• Journal of Korean Neurosurgical Society
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• v.37 no.6
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• pp.443-448
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• 2005

Objective: A variety of genetic alterations in human glioblastoma comprises signal transduction and cell cycle arrest control of cellular processes. Subtractive hybridization is potentially a faster method for identifying differentially expressed genes associated with a particular disease state. Using the technique of subtraction, we isolated novel genes that are overexpressed in glioblastoma tissue as compared to normal brain tissue. Methods: We evaluated the differential expression of genes in each of hybridizing tester and driver cDNAs to digested 130 clones. After sequencing of 130 clones and homology search, this study performed to determine mRNA expression of the unknown gene, "clone 47", in brain tissue, glioblasoma, and several cancer cell lines by reverse transcription-polymerase chain reaction (RT-PCR). To test the time course for Go-phase arrest, serum stimulation and expression at various times for RT-PCR performed. Results: We identified 23 novel genes by BLAST of the digested 130 clones. The expressions of "clone 47" mRNA of glioblastoma and several cancer lines were significantly higher than normal brain tissues and several normal cell lines. We confirmed the mRNA expression of "clone 47" was up-regulation for $0.5{\sim}1hr$ of WI-38 cell differentiation. Conclusion: The novel gene, "Clone 47" is upregulated in glioblastoma tissue and several cancer cell lines. This gene is time dependent activation during time course of serum stimulation. This result suggests that "clone 47" playa role in brain tumorigenesis and the activation of this "clone 47" may be necessary for the development of cancer.

• Korean Journal of Plant Resources
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• v.26 no.1
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• pp.44-51
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• 2013

Morinda officinalis (MO) is a oriental medicinal herb which has been used traditionally for the treatment of impotence, anti-inflammatory, menstrual irregularity action and various brain diseases including antidepressant and anti-stress. In order to examine the mechanism of anticonvulsive effect, we treated the methanol extract of MO (100, 200 mg/kg, P.0) to the sleeping time and pentylenetetrazol (PTZ)-induced convulsive mice. The methanol extract of MO prolonged sleep time by pentobarbital. Dose-dependent of methanol extracts of MO were effected the concentration of GABA and GABA-T activity in the brain of PTZ-induced mice. Methanol extracts of MO significantly inhibited the convulsion state as well as the level of lipid peroxidation in the brain. The butanol and dichloromethane fraction of methanol extracts among the others effectively inhibited in vitro lipid peroxidation dose dependently ($5.0{\times}10^{-2}{\sim}20.0{\times}10^{-2}g/ml$).

• YAKHAK HOEJI
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• v.34 no.6
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• pp.375-383
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• 1990

The pharmacokinetics of haloperidol were determined after single oral and intravenous doses in 13 male schizophrenic patients. Plasma concentrations of haloperidol(HP) and reduced haloperidol(RH) were measured by high performance liquid chromatography. Plasma concentration data obtained were analyzed by obth model dependent (one-or two exponential decay models using nonlinear regression) and model independent (AUC and first moment curve) approaches. The two methods were found to be in close results. After intravenous injections of HP in 8 patients (10 mg/man), the mean central and peripheral volume of distributions were $2.85\;{\pm}\;1.70$ and $8.09\;{\pm}\;2.10\;l/kg$, respectively, and mean steady state volume of distribution was $11.87\;{\pm}\;3.21\;l/kg$. Mean clearance, MRT and elimination half life were $12.39\;{\pm}\;3.25\;ml/min/kg$, $925.10\;{\pm}\;166.79\;min$ and $676.35\;{\pm}\;126.45\;min$, respectively. After oral administrations of HP in 5 patients, mean peak time and peak concentration were $217.63\;{\pm}\;61.60\;min$ and $9.77\;{\pm}\;2.92\;ng/ml$, respectively. Mean MRT and elimination half life were $1112.23\;{\pm}\;131.73\;min$ and $724.02\;{\pm}\;120.03\;min$, respectively, and these parameters were not significantly different from those of intravenous injection of HP. Absolute bioavailability of HP oral product was found to be about 44%. The profiles of plasma RH concentration-time curves after oral or intravenous doses of HP were similar. Also it was found that the elimination rate of RH was solwer than that of HP by comparing the slopes of plasma concentration-time curves of HP and RH.

• Journal of Korean Society of Coastal and Ocean Engineers
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• v.25 no.5
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• pp.317-326
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• 2013

Probabilistic design methods can consider uncertainties of design variables and are widely used in the design of vertical breakwaters. The probabilistic design methods include a partial safety factor method, reliabilitybased design method, and performance-based design method. Especially the performance-based design method calculates the accumulated sliding distance during the lifetime of the breakwater or during a design storm. Recently a time-dependent performance-based design method has been developed based on the first-passage probability of individual sliding distance during a design storm. However, because the allowable criteria in the first-passage probability method are not established, the stability of structures cannot be quantitatively evaluated. In this study, the allowable first-passage probabilities for two limit states are proposed by calculating the first-passage probabilities for the cross-sections designed with various water depths and characteristics of extreme wave height distributions. The allowable first-passage probabilities are proposed as 5% and 1%, respectively, for the repairable limit state (allowable individual sliding distance of 0.03 m) and ultimate limit state (allowable individual sliding distance of 0.1 m). The proposed criteria are applied to the evaluation of the effect of wave-height increase due to climate change on the stability of the breakwater.

• The Korean Journal of Physiology
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• v.26 no.2
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• pp.99-111
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• 1992

Permissive action of thyroid hormone at the level of Ca channel and responsible mechanisms underlying thyroid hormone-induced change in myocardial contractile state and $T_3-induced$ arrhythmias were investigated in rabbit ventricular or atrial myocytes using whole cell patch clamp technique. Single cells were isolated by Langendorff perfusion with collagenase. Cardiac myocytes were incubated in $low-Cl^-,$, $high-K^+$ medium containing $1_{\mu}M\;L-triiodothyronine\;(T_3)$ at $4^{\circ}C$ for 2.10 hours. The calcium currrent $(I_{Ca})$ was increased in $T_3$ loaded cells, however, the shape of current voltage curve and reverse potential did not altered. Cyclic AMP, cyclic GMP, isoprenaline and 3-isobutyl-1-methyl-xanthine increased $I_{Ca}$ in euthyroid and hyperthyroid conditions, and acetylcholine blocked the increase of $I_{Ca}\;in\;T_3$ loaded cells. The amplitude of $I_{Ca}$ was much larger after perfusing cGMP than cGMP in both conditions, whereas the degree of increase of $I_{Ca}$ was greater after perfusing cAMP than cGMP in $T_3$ loaded cells. The degree of increase of $I_{Ca}$ after perfusing isoprenaline or IBMX also was greater in $T_3$ loaded cells than in control cells. Background current induced by isoprenaline also increased in $T_3$ loaded cells. The Ca release dependent inward current was increased in amplitude but its activation and inactivation time course was not changed in $T_3$ loaded cells. Activation of Na pump current was not changed in $T_3$ loaded cells. From the above results it is suggested that thyroid hormone induced increase in the contractile state of cardiac myocytes are accompanied by augmented $I_{Ca}$ and the increase of Ca release from sarcoplasmic reticulum and the permissive action of thyroid hormone to catecholamines could induce arrhythmias through the increase of $I_{Ca}$ and background current.

• Tunnel and Underground Space
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• v.11 no.3
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• pp.257-269
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• 2001

Numerical simulation is performed to understand the structural behavior of an underground radwaste repository, assumed to be located at the depth of 500 m, in a granitic rock mats, in which a fault intersects the roof of the repository cavern. Two dimensional universal distinct element code, UDEC is used in the analysis. The numerical model includes a granitic rock mass, a canister with PWR spent fuels surrounded by the compacted bentonite inside the deposition hole, and the mixed bentonite backfilled in the rest of the space within the repository cavern. The structural behavior of three different cases, each case with a fault of an angle of $33^{\circ},\;45^{\circ},\;and\;58^{\circ}$ passing through the cavern roof-wall intersection, has been compared. And then fro the case with the $45^{\circ}$ fault, the hydro-mechanical, thermo-mechanical, and thermo-hydro-mechanical interaction behavior have been studied. The effect of the time-dependent decaying heat, from the radioactive materials in PWR spent fuels, on the repository and its surroundings has been studied. The groundwater table is assumed to be located 10m below the ground surface, and a steady state flow algorithm is used.