• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.225-232
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• 2017

We demonstrated the effect of nortriptyline, a tricyclic antidepressant drug and serotonin reuptake inhibitor, on voltage-dependent $K^+$ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Nortriptyline inhibited Kv currents in a concentration-dependent manner, with an apparent $IC_{50}$ value of $2.86{\pm}0.52{\mu}M$ and a Hill coefficient of $0.77{\pm}0.1$. Although application of nortriptyline did not change the activation curve, nortriptyline shifted the inactivation current toward a more negative potential. Application of train pulses (1 or 2 Hz) did not change the nortriptyline-induced Kv channel inhibition, suggesting that the effects of nortiprtyline were not use-dependent. Preincubation with the Kv1.5 and Kv2.1/2.2 inhibitors, DPO-1 and guangxitoxin did not affect nortriptyline inhibition of Kv channels. From these results, we concluded that nortriptyline inhibited Kv channels in a concentration-dependent and state-independent manner independently of serotonin reuptake.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.745-755
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• 2002

To examine the effects of Yunpyesan on the cell proliferation of A549 human lung carcinoma cell line, we performed various experiments such as dose-dependent effect of Yunpyesan on cell proliferation and viability, morphological changes, quantification of apoptotic cell death and alterations of apoptosis/cell cycle-regulatory gene products. Yunpyesan declined cell viability and proliferation in both a dose- and a time-dependent manner. The anti-proliferative effect by Yunpyesan treatment in A459 cells was associated with morphological changes such as membrane shrinking and cell rounding up. Yunpyesan Induced apoptotic cell death in a time-dependent manner, which was associated with degradation of poly-(ADP-ribose) polymerase (PARP), an apoptotic target protein, without alterations of the balance between Bcl-2 and Bax expressions. DNA flow cytometric histograms showed that population of G1 phase of the cell cycle was increased by Yunpyesan treatment in a dose-dependent manner. Western blot analysis revealed that cyclin D1 and A were reduced by Yunpyesan treatment, whereas cyclin dependent kinase (Cdk) inhibitor p27 was markedly increased in a time-dependent fashion. The level of tumor suppressor p53 proteins was also increased by Yunpyesan treatment and its increase might be linked to increase of Cdk inhibitor p27. In addition, Mdm2, negative regulator of p53, was down-regulated by Yunpyesan treatment. Since the expression of retinoblastome protein (pRB), a key regulator of G1/S progression, was reduced by Yunpyesan treatment, we supposed that phosphorylation of pRB might be also blocked. The present results indicated that Yunpyesan-induced inhibition of lung cancer cell proliferation is associated with the induction of apoptosis and the blockage of G1/S progression.

• Journal of Nutrition and Health
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• v.36 no.8
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• pp.785-792
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• 2003

This study is conducted to determine the effects of dietary source of $\omega$3 fatty acids on preneoplastic foci and the glutathione dependent enzymes in rat hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats were fed one of three diets containing 10% (w/w) fats fixed p/s = -1.0 and $\omega$6/$\omega$3 ratio = -0.4 or 4.0 ; fish oil-com oil blended (FC), com oil-beef tallow-fish oil blended (CF), com oil-beef tallow-perilla oil blended (CP), from gestation period. At 10 weeks, animals of experimental groups were injected intraperitoneally with DEN (200 mg/kg body weight) and two-thirds partial hepatectomy was carried out 3 weeks later and were sacrificed 8 weeks after DEN initiation. The area and number of glutathione S-transferase placenta (GST-P) positive foci were significantly decreased in rats fed diets containing fish oil (FC and CF) than those fed perilla oil diet (CP). Fish oil feeding significantly increased the activities of glutathione dependent enzymes. Rats fed diets containing fish oil (FC and CF) significantly increased the glutathione (GSH) content and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST). Glutathione dependent enzymes had significantly negative correlation with GST-P positive foci. Glucose 6-phosphatase (G6Pase) was increased in rats feeding fish oil. Thiobarbituric acid reactive substances were not different among groups. Therefore, the preventive effect against hepatocarcinogenesis might be explained by induction of the glutathione dependent enzymes and G6Pase. (Korean J Nutrition 36(8): 785∼792, 2003)

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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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 Korea Game Society
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• v.17 no.6
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• pp.189-198
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• 2017

The purpose of this study is to investigate the relationship between smoking attitudes and psychophysiological variables and to find out whether smoking cessation activities can be helpful for smoking cessation. We set up Negative Attitudes experience as a dependent variable. Several factors including Psychological Resistance, Psychological Distress and brainwave(Left brain ${\theta}$, Right Brain ${\theta}$) as a physiological indicator, which was expected to affect flow, were set up as independent variables to perform regression analysis. As a result, psychological resistance had negative influences on negative attitudes toward smoking in smoking simulation game and psychological distress had positive effect. And left brain ${\theta}$ had negative influences on negative attitudes toward smoking in smoking simulation game and right brain ${\theta}$ had positive effect.

• Smart Structures and Systems
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• v.15 no.3
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• pp.627-643
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• 2015

Negative stiffness, previously emulated by active or semi-active control for cable vibration mitigation, is realized passively using a self-contained highly compressed spring, the negative stiffness device (NSD).The NSD installed in parallel with a viscous damper (VD) in the vicinity of cable anchorage, enables increment of damper deformation during cable vibrations and hence increases the attainable cable damping. Considering the small cable displacement at the damper location, even with the weakening device, the force provided by the NSD-VD assembly is approximately linear. Complex frequency analysis has thus been conducted to evaluate the damping effect of the assembly on the cable; the displacement-dependent negative stiffness is further accounted by numerical analysis, validating the accuracy of the linear approximation for practical ranges of cable and NSD configurations. The NSD is confirmed to be a practical and cost-effective solution to improve the modal damping of a cable provided by an external damper, especially for super-long cables where the damper location is particularly limited. Moreover, mathematically, a linear negative stiffness and viscous damping assembly has proven capability to represent active or semi-active control for simplified cable vibration analysis as reported in the literature, while in these studies only the assembly located near cable anchorage has been addressed. It is of considerable interest to understand the general characteristics of a cable with the assembly relieving the location restriction, since it is quite practical to have an active controller installed at arbitrary location along the cable span such as by hanging an active tuned mass damper. In this paper the cable frequency variations and damping evolutions with respect to the arbitrary assembly location are then evaluated and compared to those of a taut cable with a viscous damper at arbitrary location, and novel frequency shifts are observed. The characterized complex frequencies presented in this paper can be used for preliminary damping effect evaluation of an adaptive passive or semi-active or active device for cable vibration control.

• Journal of the Korean Operations Research and Management Science Society
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• v.12 no.1
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• pp.27-33
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• 1987

A stochastic model for an inventory system in which depletion of stock takes place due to random demand as well as random loss of items is studied under the assumption that the intervals between cussessive unit demands as well as those between cussessive unit losses, are independently and identically distributed random variables having negative exponential distributions with respective parameters .mu. and .lambda. It is further assumed that leadtime for each order is an outstanding-order-dependent random variable. The steady state probability distribution of the net inventory level is derived under the continuous review (S -1, S) inventory policy, from which the total expected coast expression is formulated.

• Toxicological Research
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• v.23 no.4
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• pp.289-299
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• 2007

Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane of Gram-negative bacteria. LPS is usually used as an inflammatory animal model. During the inflammation, diarrhea and changes in plasma proteins, in hepatic and/or intestinal microsomal cytochrome P450 (CYP) isozymes, and in the renal and/or biliary excretion of drugs have been reported. Thus, in rats pretreated with lipopolysaccharide endotoxin isolated from Klebsiella pneumoniae (KPLPS rats), the absorption, distribution, metabolism, and excretion of drugs could be expected to be altered. Interestingly time-dependent effects on the hepatic CYP isozymes have been reported in KPLPS rats. Thus, in KPLPS rats, the pharmacokinetics of drugs which are mainly metabolized via CYP isozymes could be expected to be time-dependent. In this review, an attempt to explain changes in pharmacokinetics of drug reported in the literature was made in terms of CYP isozyme changes or urinary and/or biliary excretion changes in KPLPS rats.

• Proceedings of the Korea Concrete Institute Conference
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• 2003.05a
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• pp.463-468
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• 2003

A finite element formulation to predict the flexural behavior of composite girder is presented in which the early-age properties of concrete are specified including maturing of elastic modulus, creep and shrinkage. The time dependent constitutive relation accounting for the early-age concrete properties is derived in an incremental format by expanding the total form of stress-strain relation by the first order Taylor series with respect to the reference time. The total potential energy of the flexural composite member is minimized to derive the time dependent finite element equilibrium equation. Numerical applications are made for the 3-span double composite steel box girders which is a composite bridge girder filled with concrete at the bottom of the steel box in the negative moment region. The numerical analysis with considering the variation of concrete elastic modulus are performed to investigate the effect of it on the early-age behavior of composite structures. The one dimensional finite element analysis results are compared with the analytical method based on the sectional analysis. Close agreement is observed among the two methods.

• Fisheries and Aquatic Sciences
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• v.14 no.4
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• pp.429-433
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• 2011

Eggs of Korean rose bitterling Rhodeus uyekii were collected and fertilized to observe temperature-related cleavage rates and mitotic intervals (${\tau}_0$). As the water temperature was increased, the slope of first cleavage frequency with elapsed time after fertilization increased, and approximately 30% of fertilized eggs reached first cleavage frequency at every 15 min. At higher temperatures, eggs developed faster and underwent further identical developmental processes. There were strong, negative correlations between ${\tau}_0$ and water temperatures at all temperatures studied (Y = -1.225X + 70.05, $r^2=0.988$, where Y is ${\tau}_0$ and X is temperature).