• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.180-189
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• 2004

Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.

• Applied Biological Chemistry
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• v.47 no.4
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• pp.390-395
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• 2004

In order to characterize ion channels present in tomato roots, microsomes were incorporated into an artificial lipid bilayer arranged for electrophysiological analysis. Of the five different ion channels that could be found, a channel of 450 pS conductance was found most frequently. This channel displayed subconductance states of 450, 257 and 105 pS. All subconductance states showed linear current-voltage relationships. At positive holding potentials, high frequency of transient channel openings was observed; however, at negative potentials, the open times were long and open probability high. Po was 0.83 at -40 mV. When an additional 50 mM $K^+\;or\;Na^+$ was added to the cis side of bilayer, the reversal potentials shifted in the negative direction to near -10 mV. Thus, the 450 pS cation channel selects poorly between $K^+\;and\;Na^+$. In the presence of $100\;{\mu}M$ metal ions, the channel activity was severely inhibited by $La^{3+},\;Ba^{2+},\;and\;Zn^{2+}$, and Po was decreased to 0.2 or even less. However, $Al^{3+}\;and\;Cd^{2+}$ decreased the activity by only 20%. Interestingly, each metal ion showed different kinetics of channel inhibition. While $500\;{\mu}M\;La^{3+}$ inhibited the activities of all subconductance state, 1 mM $Zn^{2+}$ inhibited all except the 105 pS state. $Cd^{2+}$ changed the gating of the channel from a long-opening state to brief transient openings even at negative holding potentials. These data represent that the metal ions may have different binding sites on the channel protein and could be useful modulators and probes to investigate structural characteristics as well as the functional roles of the 450 pS channel on the root physiology.

• Journal of Veterinary Clinics
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• v.20 no.3
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• pp.286-293
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• 2003

The cardiopulmonary and antagonistic effects of atipamezole, to medetomidine (30 ug/kg, IM)-tiletamine/zolazepam (10 mg/kg, IV) were determined. Twelve healthy mongrel dogs ,(4.00$\pm$0.53 kg, mean$\pm$SD) were randomly assigned to the four experimental groups (control, A30; atipamezole 30 ug/kg, A60; atipamezole 60 ug/kg, A150; atipamezole 150 ug/kg) with 3 dogs in each group. Atropine (0.03 mg/kg, IM), medetomidine, and tiletamine/zolazepam (TZ) were injected 10 minute intervals. Atipamezole was injected intravenously 15 minutes after TZ injection. Mean arousal time (MAT) was 52.50$\pm$4.98, 43.06$\pm$2.60, 32.83$\pm$8.13, and 14.36$\pm$1.60 minutes in control, A30, A60, and Al50 groups respectively. In Al50 group, MAT was significantly reduced (P < 0.05). but mean walking time (MWT) was similar to that in control group. In recovery period, the higher doses of atimapezole, the rougher recovery including head rocking, hypersalivation, and muscle twitching. Five of twelve dogs vomited within 5 minutes after medetomidine injection. In Control group, heart rate significantly decreased in all recording stages except 15 minutes after TZ injection, 10 minutes after medetomidine injection in all groups, and 40 minutes after atipamezole injection in A30 group (P < 0.05). In Al50 group, atipamezole reversed the respiratory depression induced by medetomidine. Arterial blood pressure was significantly decreased 10minutes after medetomidine injection and 15 minutes after TZ injection in almost dogs in this study (P < 0.05). From 10 minutes after atipamezole injection to arousal time, arterial blood pressure was progressively increased in A60 and A150 group. Any value of blood gas analysis and CBC, and serum chemistry values were not significantly changed except pH of Al50 at 10 minutes after medetomidine injection. As shown in present study, atipamezole(150 ug/kg) is considered to exert a useful reversal effect in dogs anesthetized with medetomidine-tiletamine/zolazepam combination.

• Journal of Life Science
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• v.25 no.7
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• pp.801-809
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• 2015

Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.37-37
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• 2003

We have shown the $Ca^{2+}$-activated chloride current is present in cardiac myocyte in rabbit pulmonary vein (Kim et al., 2002). This current amplitude was increased as [N $a^{+}$]$_{i}$ was increased and we suggested this chloride current may be involve in the spontaneous action potential frequency change. Since this current is activated by the increase of intracellular $Ca^{2+}$, we would like to test what is the inducer of the increase of [C $a^{2+}$]$_{i}$ between a L-type $Ca^{2+}$-current or a reverse mode of N $a^{+}$-C $a^{2+}$ exchange current. White rabbit (1.5 kg) was used and anesthetized with Ketamin (100 mg/kg). Pulmonary vein (PV) was isolated and sleeve area between left atrium and PV was dissected. Using collagenase (Worthington 0.7 mg/cc), single cardiac myocytes were isolated. In the presence of 15 mM of N $a^{＋}$, three steps of voltage pulses were applied (holding potential : -40 ㎷, -80 ㎷ for 50 msec, 30 ㎷ for 5 msec, 10 ㎷ steps from -70 ㎷ to 60 ㎷). The inward and outward tail current was activated after brief 5 msec prepulse. The outward tail current was blocked by the removal of extracellular chloride substituted by glucuronic acid or by a chloride channel blocker, 5 mM 9-AC. But the inward tail current was still remained even though the amplitude was decreased. The reversal potentials were changed to the direction of the change of chloride equilibrium potential ( $E_{Cl}$ ) but the shift of equilibrium potential was not enough to match to the theoretical equilibrium potential shift. In the presence of L-type $Ca^{2+}$ channel blocker, nifedipine 1 uM, inward tail currents were greatly reduced but the outward current tail currents were still remained. In the presence of N $a^{+}$-C $a^{2+}$ exchange current blocker, 10 uM KB-R7943, the inward and outward tail currents were blocked almost completely. We tried to test the $Ca^{2+}$sensitivity of the chloride current with various [C $a^{2+}$]$_{i}$ in pipette solution from 100 nM to 1 uM but we failed to activate $Ca^{2＋}$-activated chloride currents even though the cell became contracted in the presence of 1 uM $Ca^{2+}$. From these results, we could conclude that the increase of [C $a^{2+}$]$_{i}$ to activate the outward $Ca^{2+}$-activated chloride current was mainly induced by the activation of the reverse mode of N $a^{+}$-C $a^{2+}$ exchanger, But for the increase of [C $a^{2+}$]$_{i}$ to activate the inward tail current, L-type $Ca^{2+}$ current may be the major provoking current. Since the cytosolic increase of [C $a^{2+}$]$_{i}$ through pipette solution have failed to activate $Ca^{2+}$-activated chloride current, this chloride current may have very low $Ca^{2+}$ sensitivity or a comparmental increase $Ca^{2+}$ such as in subsarcolemmal space may activate the chloride current. Since there are several reports and models that the increase of $Ca^{2+}$ in subsarcolemmal space would be over several to tens of uM, both possibility may be valid together.uM, both possibility may be valid together.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.613-618
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• 2005

This study was carried out to examine the effects of gamma irradiation on the cytotoxicity and multidrug-resistance reversing activity of methanol extracts from Coix lachryma-jobi L. var. me-yuen Stapf seed. The seed was irradiated with doses of 1, 4, 8, 16, 32 and 64 Gy of the gamma radiation, and then extracted by methanol. The extracts were examined for cytotoxicity on the human cancer cell lines, MCF-7 (human breast adenocarcinoma pleural effusion), Calu-6 (human pulmonary carcinoma) and SNU-601 (human gastric carcinoma) cells, and investigated for multidrug-resistance reversing activity using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. The growth inhibitory activity of irradiated seed extracts on human cancer cell lines was higher than that of the control. In the case of Calu-6 cell line, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. $IC_{50}$ value in the MCF-7 cell line was measured in the only 8 Gy extract. And in the SNU-601 cell line as Calu-6, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. But the extracts of gamma-irradiated seed over 32 Gy showed little growth inhibitory effect against human cancer cell lines. In this result, 8 Gy extract had significant growth inhibitory in all human cancer cell lines $(Calu-6:\;633\;{\mu}g/mL,\;MCF-7:\;653\;{\mu}g/mL\;and\;SNU-601:\;683\;{\mu}g/mL)$. The extracts of 4, 8 and 16 Gy strongly potentiated vincristine cytotoxicity in AML-2/D100 cells. The reversal fold (RF) of 4, 8 and 16 Gy extracts was 1.7, 1.8 and 1.6, respectively. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. These results indicate that the above samples would contain some principles which have cytotoxicity and multidrug-resistance reversing activity. Irradiation technology can be applied to promote physiological activities of medicinal plant seeds.

• Archives of Pharmacal Research
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• v.27 no.10
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• pp.1065-1072
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• 2004

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

• KEPCO Journal on Electric Power and Energy
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• v.1 no.1
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• pp.39-46
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• 2015

A outdoor termination installed at the outdoor substation is required to connect undergroud cables and overhead transmission lines. The joint box for AC transmission system is already developed and widely used to interconnect overhead and undergroud systems. But the development of the joint box for DC transmission system was only introduced from China and Japan, but theire developemnt staus and core technologies were not fully reported. In order to implement HVDC systems connecting ovehead transmission lines and undergroud cables, a outdoor termination should be developed, but the detailed specifications and information of this device were not reported. It is estimated that the development of the joint box for DC environment has some technical obstacles including insulating materials, electric field mitigation, thermal temperature rise, and space charge accumuations. Among this, the most important one is the DC elctrical insualtion design. Therefore, in order to investigate the DC elctrical insualton design of outdoor termination, the design of AC slip-on type outdoor termination is reffered, and DC electric field analysis performed to verify the possiblity of application of AC joint box into DC joint box. Especially for DC electric field analysis, temperature rise of insualting materials of a joint box was considered, because the conductivity of materials could be changed due to temperature rise. Furthermore, DC electric field analysis considering transinet state, and polarity reversal state were also investigated to verify which state is the most severe condition for the DC joint box. From the simualtion resulsts, it was shown that the value and the position of maximum electric field was obtained comparing AC state, DC state without temperaure rise, and DC state with temperaure rise. And it was confimred that severe DC electric field was observed considing temperaure rise. Finally, in order to reduce DC eletric field intensifation, different configuration of the joint box was applied and it was not possible to obtain satisfactory results. It means that the slight change of configuration of AC joint box was not the suitable soluton for DC joint box. It is essential to establish novel DC insulaton design skills and method for DC joint box to commercialze this product in the near future.

• Journal of the Korean Geotechnical Society
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• v.34 no.2
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• pp.19-32
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• 2018

During the process of gas hydrate extraction in the deep seabed, fine diatom particle migration occurs, which causes the seabed slope failure and the productivity deterioration of the gas hydrate. Therefore, a study related with the changes of the ground characteristics due to the fine particle migration is required. The objective of this study is to investigate the change of hydraulic properties of sand due to the migration of fine diatom particle in sandy soils. In order to simulate the sediments of the Ulleung basin gas hydrate in the East Sea, fifteen sand-diatom mixtures that have different diatom volume fractions (DVF) are prepared. During the falling head permeability tests, the coefficients of permeability are measured according to the DVF. In addition, for the simulation of the fine diatom particle migration, constant head permeability tests are conducted by applying the hydraulic pressures of 3 kPa, 6kPa, and 9 kPa on a specimen composed of two layers: a specimen with 50% DVF in upper layer and a specimen with 0% DVF in lower layer. Furthermore, the coefficient of permeability and the electrical resistivity of the migration zone are measured during the constant head permeability test. The falling head permeability tests show that the coefficient of permeability decreases as the DVF of the specimen increases. In addition, the gradient of the coefficient of permeability curve decreases in the DVF range of 10%~50% compared with that of 0%~10%, and increases above 50% in DVF. The result of constant head permeability tests shows that the coefficient of permeability decreases and electrical resistivity increases in the migration zone due to the fine diatom particle migration. This study demonstrates that fine diatom particle migration reduces the permeability of the soils and the behavior of the migration zone due to the fine diatom particle migration may be estimated based on the reversal relationship between the coefficient of permeability and the electrical resistivity.

• Journal of Korea Entertainment Industry Association
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• v.15 no.2
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• pp.169-178
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• 2021

The Korean girl group "Kara" has suffered the trilemma of its de facto failure to debut, the crisis of team breakup, and the CEO crisis of the agency. But the group has made an outstanding achievement in the history of Korean pop music after overcoming all odds. Their success strategy has never been disclosed by insiders involved in Kara's total music projects. This study has been carried out in the analysis of the strategy to provide academic implications and to honor the contribution of the late CEO Ho-yeon Lee and Kara's key member Ha-ra Gu. Therefore, between Nov. and Dec. 2020, we conducted in-depth interviews with managers, composers, stylists and Ha-ra Gu(Only in 2019, before her death) who took part in the project. The research model is set up by combining Porter's Competitive Advantage Strategy and the music value chain model into categories of "Product Innovation Differentiation (PD)" (producing, album production, performance activities) and "Marketing Differentiation (MD)" (market targeting, image specialization, promotion and communication). The analysis showed that the PD focused on complete rediscovered harmonization and revalued members' personality and sincerity with peppy songs and dainty dances as well as emission of "bright energy" which caused healing effects instead of mimicking other star singers recklessly. In terms of MD, they selected Japan's 10-20s as their main market, increasing intimacy with fans and media with the image of cute+pretty+classy+sexy. The result suggests that Poter's differentiation can function as a meaningful strategy frame in the fostering, hit, and revival of idol groups. In addition, it reaffirmed that spontaneous and passionate activities of early-stage or celebrity fan may serve as a valid catalyst for realizing differentiation, as Kara's caller of Japanese actor Gekidan Hitori caused a strong "priming effect" that drove Kara's unexpected wonderful success in Japan.