• The Korean Journal of Physiology and Pharmacology
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• 제6권4호
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• pp.187-191
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• 2002

Tamoxifen, an antiestrogen, has previously been shown to induce apoptosis in HepG2 human hepatoblastoma cells through activation of the pathways independent of estrogen receptors, i.e., intracellular $Ca^{2+}$ increase and generation of reactive oxygen species (ROS). However, the mechanism of tamoxifen to link increased intracellular $Ca^{2+}$ to ROS generation is currently unknown. Thus, in this study we investigated the possible involvement of calmodulin, a $Ca^{2+}$ activated protein, and $Ca^{2+}$/calmodulin-dependent protein kinase II in the above tamoxifen-induced events. Treatment with calmodulin antagonists (calmidazolium and trifluoroperazine) or specific inhibitors of $Ca^{2+}$/calmodulin-dependent protein kinase II (KN-93 and KN-62) inhibited the tamoxifen-induced apoptosis in a dose-dependent manner. In addition, these agents blocked the tamoxifen-induced ROS generation in a concentration-dependent fashion, which was completely suppressed by intracellular $Ca^{2+}$ chelation. These results demonstrate for the first time that, despite of its well-known direct calmodulin-inhibitory activity, tamoxifen may generate ROS and induce apoptosis through indirect activation of calmodulin and $Ca^{2+}$/calmodulin-dependent protein kinase II in HepG2 cells.

• 동의생리병리학회지
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• 제29권5호
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• pp.353-360
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• 2015

In a essay that was published on 'Science' in December 2014 as a part of the supplement "The Art and Science of Traditional Medicine," the eastern and western medical theories are discussed with reference to the model-dependent realism suggested by Stephen Hawking and Leonard Mlodinow. This paper examines what the model-dependent realism is, and how it affects the future direction of researches in traditional Korean medical theories. The model-dependent realism holds a meaning in that it puts traditional medical theories in a perspective of models, and allows for application of recent studies in scientific philosophy for researches in traditional medical theories. Especially, the model studies by R. Giere et al. will help elaborate the traditional medical theories from a model perspective. From a model perspective, the 'visceral manifestation', 'meridian and collateral', 'qi-blood', 'eight principles' and 'constitution' theories of traditional medicine have the potentials to develop into valid models, and the traditional medical theory's phenomenological and holistic perspective distinguishes it from western medicine, giving it a competitive edge. In addition, the epistemological pluralism of model-dependent realism can serve as an alternative to relativism or rationalism perspective which put eastern and western medicine in opposition until now.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.191-198
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• 1999

This study was undertaken to examine the effect of ethanol on $Na^+-dependent$ transport systems (glucose, phosphate, and dicarboxylate) in renal brush-border membrane vesicles (BBMV). Ethanol inhibited $Na^+-dependent$ uptakes of glucose, phosphate, and succinate in a dose-dependent manner, but not the uptakes of $Na^+-dependent.$ The $H^+/TEA$ antiport was reduced by 8% ethanol. Kinetic analysis showed that ethanol caused a decrease in $V_{max}$ of three transport systems, leaving $K_m$ values unchanged. Ethanol decreased phlorizin binding, which was closely correlated with the decrease in $V_{max}$ of $Na^+-glucose$ uptake. These results indicate that ethanol inhibits $Na^+-dependent$ uptakes of glucose, phosphate, and dicaboxylate and that the reduction in $V_{max}$ of $Na^+-glucose$ uptake is caused by a decrease in the number of active carrier proteins in the membrane.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.597-605
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• 2018

In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent $K^+$ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent $IC_{50}$ value of $5.04{\pm}1.05{\mu}M$ and a Hill coefficient of $0.78{\pm}0.06$. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of $Na^+$ channel inhibition.

• Molecules and Cells
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• 제28권4호
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• pp.365-368
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-${\beta}$ (TRIF)-dependent downstream signaling pathways. Isoliquiritigenin (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-${\kappa}B$ and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.

• 한국산학기술학회논문지
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• 제9권2호
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• pp.470-474
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• 2008

본 연구에서는 실제 현장에서 수행한 피에조콘관입 및 소산시험결과와 변형률 속도를 고려한 구성모델의 이론적 해석을 비교하였다. 이를 위하여 변형률 속도 의존적 구성모델의 수학적 유도과정을 전개하였다. 해석 결과 변형률속도를 무시한 구성모델보다 변형률속도-의존 구성모델을 활용한 지반의 거동 해석이 비의존적 구성모델인 경우의 해석 보다 현장의 시험결과와 잘 일치하므로 변형률속도-의존 구성모델의 적용이 바람직하다.

• Management Science and Financial Engineering
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• 제19권1호
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• pp.29-36
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• 2013

This paper considers common due-date assignment and scheduling on parallel machines. The main decisions are: (a) deter-mining the common due-date; (b) allocating jobs to machines; and (c) sequencing the jobs assigned to each machine. The objective is to minimize the sum of the penalties associated with common due-date assignment, earliness and tardiness. As an extension of the existing studies on the problem, we consider sequence-dependent setup times that depend on the type of job just completed and on the job to be processed. The sequence-dependent setups, commonly found in various manufacturing systems, make the problem much more complicated. To represent the problem more clearly, a mixed integer programming model is suggested, and due to the complexity of the problem, two heuristics, one with individual sequence-dependent setup times and the other with aggregated sequence-dependent setup times, are suggested after analyzing the characteristics of the problem. Computational experiments were done on a number of test instances and the results are reported.

• 한국미생물·생명공학회지
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• 제21권1호
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• pp.30-35
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• 1993

E.coli에서 발견된 ATP-dependent 효소인 Clp효소 중에서 Clp A의 ATPase 활성에 대한 영향을 검토하였다. Clp효소의 limiting amount으로 나타난 specific 활성은 일정하게 증가하는 효소의존성을 보였다. ATPase 활성을 나타내고 있는 ClP A는 casein에 의하여 활성화되어지며 2분자의 ATP가 결합하고 ATPase 활성을 나타내기 위한 ATP의 분해는 Clp효소의 단백질 분해 활성에 필요하다.

• Journal of the Korean Data and Information Science Society
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• 제24권4호
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• pp.877-883
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• 2013

The quadratic inference functions (QIF) method proposed by Qu et al. (2000) and the generalized method of moments (GMM) for marginal regression analysis of longitudinal data with time-dependent covariates proposed by Lai and Small (2007) both are the methods based on generalized method of moment (GMM) introduced by Hansen (1982) and both use generalized estimating equations (GEE). Lai and Small (2007) divided time-dependent covariates into three types such as: Type I, Type II and Type III. In this paper, we compared these methods in the case of Type II and Type III in which full covariates conditional mean assumption (FCCM) is violated and interested in whether they can improve the results of GEE with independence working correlation. We show that in the marginal regression model with Type II time-dependent covariates, GMM Type II of Lai and Small (2007) provides more ecient result than QIF and for the Type III time-dependent covariates, QIF with independence working correlation and GMM Type III methods provide the same results. Our simulation study showed the same results.

• 대한전기학회논문지:전력기술부문A
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• 제52권11호
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• pp.632-638
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• 2003

Modern power systems are very complex and to model them completely is impractical for electromagnetic transient studies. Therefore areas outside the immediate area of interest must be represented by some form of frequency dependent equivalent. The s-domain rational function form of frequency dependent equivalent does not need refitting if the simulation time-step is changed in the electromagnetic transient program. This is because the s-domain rational function coefficients are independent of the simulation time-step, unlike the z-domain rational function coefficients. S-domain rational function fitting techniques for representing frequency dependent equivalents have been developed using Least Squares Fitting(LSF). However it does not suffer the implementation error that exited in this work as it ignored the instantaneous term. This paper Presents the formulation for developing 1 Port Frequency Dependent Network Equivalent(FDNE) with the instantaneous term in S-domain and illustrates its use. This 1 port FDNE have been applied to the CIGRE Benchmark Rectifier test AC system. The electromagnetic transient package PSCAD/EMTDC is used to assess the transient response of the 1 port (FDNE) developed with Thevenin and Norton Equivalent network. The study results have indicated the robustness and accuracy of 1 port FDNE for electromagnetic transient studies.