• Korean Journal of Psychosomatic Medicine
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• v.30 no.2
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• pp.66-72
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• 2022

Clozapine is accepted as the "gold standard" antipsychotics for treatment-resistant schizophrenia. Clozapine rarely causes extrapyramidal syndrome and tardive dyskinesia, which are common with other antipsychotics, and only a transient elevation of hyperprolactinemia has been reported. Despite such clinical usefulness, there are limitations to the use of clozapine due to adverse drug reactions (ADR). Fever is a common in adverse drug reactions associated with clozapine. At initiation of clozapine most fatal ADR such as agranulocytosis and neuroleptic malignant syndrome associated with fever, in which case clozapine should be discontinued immediately. However, as benign causes of fever are much more frequent than life-threatening ADR, clozapine should not be discontinued unconditionally in the event of fever during clozapine initiation. In addition, fever may occur at any time during the maintenance of clozapine treatment. In particular, since the risk of pneumonia does not decrease over time, and clozapine has a higher risk of pneumonia than other antipsychotic drugs, it is recommended to adjust clozapine dosage through therapeutic drug monitoring.

• Journal of Life Science
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• v.32 no.11
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• pp.882-889
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• 2022

Breast cancer anti-estrogen resistance 3 (BCAR3) has been identified as one of the genes that induces anti-estrogen resistance in breast cancer. We have previously reported that BCAR3 activates promoters of c-Jun, activator protein-1, and the serum response element. In this study, we investigated the functional role of BCAR3 in the activation of the estrogen response element (ERE) in normal human breast MCF-12A cells. Transient expression of BCAR3 induced ERE activation, which was further increased by 17β-estradiol treatment but was not blocked by the anti-estrogen tamoxifen. Next, we studied the signaling pathway of BCAR3 leading to ERE activation. BCAR3-mediated ERE activation was inhibited by LY294002 and AZD5363, inhibitors of the phosphatidylinositol (PI) 3-kinase pathway, but not by PD98059 and U0126, inhibitors of the mitogen-activated protein kinase pathway. ERE activation was induced by the catalytic subunit p110α. of PI3-kinase or the active mutant of Akt, and this activation was not further increased by additional BCAR3 transfection. Based on these results, we propose that BCAR3 plays an important role in ERE activation through the PI3-kinase/Akt pathway in human breast MCF-12A cells.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.17-24
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• 2013

Objectives : This study was to evaluate the single dose toxicity of Persicae Semen (PS) in ICR mice. Methods : Aqueous extracts of PS (Yield = 18.60%) were administered as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) guidelines (2009-116, 2009). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. Results : Amygdalin contents in PS aqueous extracts were detected as $32.50{\pm}5.96{\mu}g/ml$. We could not find any PS extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations up to 2,000 mg/kg in both female and male mice, except for transient and slight loss of locomotion detected in female and male mice treated with 2,000 mg/kg. In addition, pharmacological immunomodulatory effects related findings were also demonstrated in 2,000mg/kg treated female and male mice as hypertrophy and hyperplasia of lymphoid cells in the submandibular lymph nodes. Conclusions : Based on the results of this experiment, the approximate lethal dose (ALD) of PS extracts after single oral treatment in female and male mice were considered above 2,000 mg/kg, respectively. It should be carefully used in clinics because the possibilities of respiratory or neurological disorders were observed when administered over 2,000 mg/kg of PS extract related to amygdalin.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.348-356
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• 2022

Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin exerts its neuronal and non-neuronal in vitro and in vivo effects through LPA receptor subtypes. However, it is unknown whether gintonin can bind to the plasma membrane of cells and can transactivate the epidermal growth factor (EGF) receptor. In the present study, we examined whether gintonin-biotin conjugates directly bound to LPA receptors and transactivated the EGF receptor. Methods: We designed gintonin-biotin conjugates through gintonin biotinylation and examined whether gintonin-biotin conjugate binding sites co-localized with the LPA receptor subtype binding sites. We further examined whether gintonin-biotin transactivated the EGF receptor via LPA receptor regulation via phosphor-EGF and cell migration assays. Results: Gintonin-biotin conjugates elicit [Ca²⁺]_i transient similar to that observed with unbiotinylated gintonin in cultured PC3 cells, suggesting that biotinylation does not affect physiological activity of gintonin. We proved that gintonin-biotin conjugate binding sites co-localized with the LPA1/6 receptor binding sites. Gintonin-biotin binding to the LPA1 receptor transactivates the epidermal growth factor (EGF) receptor through phosphorylation, while the LPA1/3 receptor antagonist, Ki16425, blocked phosphorylation of the EGF receptor. Additionally, an EGF receptor inhibitor AG1478 blocked gintonin-biotin conjugate-mediated cell migration. Conclusions: We observed the binding between ginseng-derived gintonin and the plasma membrane target proteins corresponding to the LPA1/6 receptor subtypes. Moreover, gintonin transactivated EGF receptors via LPA receptor regulation. Our results suggest that gintonin directly binds to the LPA receptor subtypes and transactivates the EGF receptor. It may explain the molecular basis of ginseng physiology/pharmacology in biological systems.

• Journal of Navigation and Port Research
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• v.47 no.4
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• pp.256-270
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• 2023

In this study, a sliding mode (SM) controller for dynamic positioning (DP) was specifically designed for a turret connection operation of a ship or an offshore structure in which an arbitrary point on the structure could be controlled as the motion center instead of the center of mass. The SM controller allows control of the arbitrary point and provides capability to manage uncertainties in the dynamics of ships and offshore structures, external forces caused by unknown changing marine environments, and transient performance of DP systems. The Jacobian matrix included in kinematic equations of the controlled object was modified to design the SM controller to control based on an arbitrary point of ships or offshore structures. To ensure robustness of the controller, the Lyapunov stability theory was applied in the design of the SM controller. In general, for robustness in DP control, gain scheduling based on a proportional-derivative (PD) control algorithm is employed. However, finding appropriate gains for gain scheduling complicates the application of DP systems. Therefore, in this study, the SM control algorithm was considered to mitigate the complexity of the DP controller for ships and offshore structures. To validate the proposed SM control algorithm, time-domain simulations were conducted and utilized to evaluate the performance of the control algorithm. The effectiveness of the proposed SM controller was assessed by comparing simulation results with results of a conventional PD control algorithm applied in DP control.

• Geomechanics and Engineering
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• v.32 no.1
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• pp.111-123
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• 2023

The slope of an open cut tunnel is located above the exit of the Leijia tunnel on the Changgan high-speed railway. During the excavation of the open cut tunnel foundation pit, the slope slipped twice, a large landslide of 92500 m³ formed. The landslide body and unstable slope body not only caused the foundation pit of the open cut tunnel to be buried and the anchor piles to be damaged but also directly threatened the operational safety of the later high-speed railway. Therefore, to study the stability change in the slope of the open cut tunnel under heavy rain and excavation conditions, a 3D numerical calculation model of the slope is carried out by Midas GTS software, the deformation mechanism is analyzed, anti-sliding measures are proposed, and the effectiveness of the anti-sliding measures is analyzed according to the field monitoring results. The results show that when rainfall occurs, rainwater collects in the open cut tunnel area, resulting in a transient saturation zone on the slope on the right side of the open cut tunnel, which reduces the shear strength of the slope soil; the excavation at the slope toe reduces the anti-sliding capacity of the slope toe. Under the combined action of excavation and rainfall, when the soil above the top of the anchor pile is excavated, two potential sliding surfaces are bounded by the top of the excavation area, and the shear outlet is located at the top of the anchor pile. After the excavation of the open cut tunnel, the potential sliding surface is mainly concentrated at the lower part of the downhill area, and the shear outlet moves down to the bottom of the open cut tunnel. Based on the deformation characteristics and the failure mechanism of the landslides, comprehensive control measures, including interim emergency mitigation measures and long-term mitigation measures, are proposed. The field monitoring results further verify the accuracy of the anti-sliding mechanism analysis and the effectiveness of anti-sliding measures.

• Nuclear Engineering and Technology
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• v.25 no.4
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• pp.529-538
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• 1993

A stochastic way using continuous time Markov process is presented to model the one-dimensional nuclide transport in fractured rock matrix as an extended study for previous work ［1］. A nuclide migration model by the continuous time Markov process for single planar fractured rock matrix, which is considered as a transient system where a process by which the nuclide is diffused into the rock matrix from the fracture may be no more time homogeneous, is compared with a conventional deterministic analytical solution. The primary desired quantities from a stochastic model are the expected values and variance of the state variables as a function of time. The time-dependent probability distributions of nuclides are presented for each discretized compartment of the medium given intensities of transition. Since this model is discrete in medium space, parameters which affect nuclide transport could be easily incorporated for such heterogeneous media as the fractured rock matrix and the layered porous media. Even though the model developed in this study was shown to be sensitive to the number of discretized compartment showing numerical dispersion as the number of compartments are decreased, with small compensating of dispersion coefficient, the model agrees well to analytical solution.

• Nuclear Engineering and Technology
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• v.26 no.1
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• pp.41-53
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• 1994

A SGTR accident postulated at Kori unit 1 is simulated with Mihama unit experience, which occurred on February 1991, to evaluate the capability of plant to cope with the transient. The system design and plant conditions of Kori Unit 1 are much similar with those of Mihama Unit 2. Therefore, special concern has been given to evaluate the sequence and the resulting consequence of the postulated SGTR accident at the Kori unit 1 An analysis is peformed as realistically as possible, with following the EOP of Kori unit 1. The result indicates that the leak through tube break terminates within about forty minutes, and the Kori unit 1 may be sufficient to cope with SGTR accident with same type of sequence. However, the reconsideration may be required for the design of Kori unit 1 which disconnects non-safety AC power from off-site power on SI signal generation. It may be pointed out that the content of EOP for SGTR accident is not enough to require operator's proper judgements. An analysis of SGTR accident tested in the LSTF which simulated the SGTR accident at the Mihama Unit 2 is peformed using the RELAP5/MOD3. The results indicates that the code yields in general good agreement with the test, except the break flowrate at the early stage of the event.

• Nuclear Engineering and Technology
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• v.54 no.11
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• pp.4348-4358
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• 2022

The thermal-hydraulics phenomena in a containment during an accident will necessarily include radiative heat transfer (i) within the gas mixture due to the high radiative absorption and emission of steam and (ii) between the gas mixture and the surrounding structures. The analysis of some previous PANDA experiments (PSI, Switzerland) demonstrated the importance of the proper modelling of radiation for the benefit of numerical simulations. These results together with dedicated scoping calculations conducted for the present experiments indicated that the radiative heat transfer is considerable, even for a very low amount of steam (≈2%). The H2P2 series conducted in the large-scale PANDA facility at the Paul-Scherrer-Institut (PSI) in the framework of the OECD/NEA HYMERES-2 project is intended to enhance the understanding of thermal radiation phenomena and to provide a benchmark for corresponding numerical simulations. Thus, the test matrix was tailored around the two opposite extremes: either gas compositions with small steam content such that radiative heat transfer phenomena can be neglected. Or gas mixtures containing larger amounts of steam, so that radiative heat transfer is expected to play a dominant role. The H2P2 series consists of 5 experiments designed to isolate the radiation phenomena from convective and diffusive effects as much as possible. One vessel with a diameter of 4 m and a height of 8 m was preconditioned with different mixtures of air / steam at room and elevated temperatures. This was followed by the build-up of a stable helium stratification at constant pressure in the upper part of the vessel. After that, helium was injected from the top into the vessel which leads to an increase of the vessel pressure and a corresponding elevation-dependent and transient rise of the gas temperature. It is shown that even the addition of small amounts of steam in the initial gas atmosphere considerably impacts the radiative heat transport throughout all phases of the experiments and markedly influences i) the monitored gas peak temperature, ii) the temperature history during the compression and iii) the following relaxation phase after the compression was stopped. These PANDA experiments are the first of its kind conducted in a large scale thermal-hydraulic facility.

• Journal of Life Science
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• v.33 no.5
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• pp.436-444
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• 2023

Scientific training, diet, and ergogenic aids are widely used to overcome the limits of humans' physical abilities and to achieve excellent sports records. The adoption of nutritional strategies is important for athletes to perform at their highest level, and one of the main factors determining endurance ability is increased fat metabolism. A ketogenic diet (high fat, low carbohydrates) has thus been proposed as an alternative strategy to maximize fatty acid oxidation during prolonged periods of exercise. However, studies have shown mixed results regarding the ergogenic value of a ketogenic diet. For this reason, exogenous ketone supplements (EKS, ingestible forms of ketone bodies, ketone esters, and/or salts) have been suggested to obtain nutritional ketosis, an acute transient increase in circulating acetoacetate (AcAc) and b-hydroxybutyrate (bHB) concentrations, without limiting carbohydrate intake. Some studies have suggested the beneficial effects of EKS on the performance of endurance exercises by providing an additional fuel substrate for peripheral tissues, such as cardiac and skeletal muscles, sparing carbohydrates/increasing fat oxidation and post-exercise recovery by increasing glycogen resynthesis in the liver/muscle, attenuating protein degradation, stimulating protein synthesis in the skeletal muscle, etc. However, many studies have failed to observe the beneficial effects of EKS as an ergogenic aid. As such, this review summarizes the theoretical basis of, as well as the proposed and proven effects of EKS on exercise performance and recovery to date.