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Antitumor Activity of 7-[2-(N-Isopropylamino)ethyl]-(20s)-camptothecin, CKD602, as a Potent DNA Topoisomerase I Inhibitor

  • Lee, Jun-Hee;Lee, Ju-Mong;Kim, Joon-Kyum;Ahn, Soon-Kil;Lee, Sang-Joon;Kim, Mie-Young;Jew, Sang-Sup;Park, Jae-Gab;Hong, Chung-Il
    • Archives of Pharmacal Research
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    • v.21 no.5
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    • pp.581-590
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    • 1998
  • We developed a novel water-soluble camptothecin analobue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respecitively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to imduce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/$ED-{58}$) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in <5% tumor bearing mouse. this schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.

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A Study on the Effects of the Stress Coping Method on the Periodontal Disease (스트레스 대처방법이 치주질환에 미치는 영향)

  • Ryu, Hae-Gyum;Kim, Han-Gon
    • Journal of dental hygiene science
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    • v.12 no.5
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    • pp.469-476
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    • 2012
  • The purpose of this study to grasp the effects of the stress coping method on the periodontal disease in order to provide raw data for the studies on the development of the training for effective stress copying method resulting in improvement in prevention, occurrence, and progression of periodontal disease. Data were collected from total of 326 subjects in their forties and fifties, during the period from March to October 2011. Using questionnaire and examination of periodontal health, and were analyzed using frequency, t-test, multivariate analysis of variance, multiple regression by SPSS ver. 19.0 (IBM Co., USA). The higher emotion-focused stress coping ($\beta$=0.341), the higher the gingival index, the higher the emotion-focused stress coping ($\beta$=0.239) the deeper the pocket depth, the higher the emotion-focused stress coping ($\beta$=0.158) the higher clinical attachment loss, showed statistically significant positive association. This study suggests that the dental clinic institute needs to implement education program including stress management and coping method improvement in order to prevent periodontal disease and make the occurrence and progression to be managed by professionals.

Characterization of Schottky Diodes and Design of Voltage Multiplier for UHF-band Passive RFID Transponder (UHF 대역 수동형 RFID 태그 쇼트키 다이오드 특성 분석 및 전압체배기 설계)

  • Lee, Jong-Wook;Tran, Nham
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.44 no.7 s.361
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    • pp.9-15
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    • 2007
  • In this paper, we present the design of Schottky diodes and voltage multiplier for UHF-band passive RFID applications. The Schottky diodes were fabricated using Titanium (Ti/Al/Ta/Al)-Silicon (n-type) junction in $0.35\;{\mu}m$ CMOS process. The Schottky diode having $4{\times}10{\times}10\;{\mu}m^{2}$ contact area showed a turn-on voltage of about 150 mV for the forward diode current of $20\;{\mu}A$. The breakdown voltage is about -9 V, which provides sufficient peak inverse voltage necessary for the voltage multiplier in the RFID tag chip. The effect of the size of Schottky diode on the turn-on voltage and the input impedance at 900 MHz was investigated using small-signal equivalent model. Also, the effect or qualify factor of the diode on the input voltage to the tag chip is examined, which indicates that high qualify factor Schottky diode is desirable to minimize loss. The fabricated voltage multiplier resulted in a output voltage of more than 1.3 V for the input RF signal of 200mV, which is suitable for long-range RFID applications.

A Study of $C_9$-aldehyde Synthesis from n-Butene (노르말부텐으로부터 $C_9$-알데히드 합성에 관한 연구)

  • Jeon, Jong-Ki;Park, Seong-Ki;Park, Young-Kwon
    • Clean Technology
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    • v.14 no.3
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    • pp.176-183
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    • 2008
  • The purpose of this study is to upgrade the catalysts for synthesizing mixed octenes using normal butene and the catalysts for synthesizing $C_9$-aldehyde through hydroformylation of mixed octenes with syngas. The in-line activation method with circulating activating solution was effective for activation of the $NiO/A1_{2}O_3$ catalyst. The reason for catalyst deactivation may be ascribed to physi-sorbed materials or oligomers which block pore entrance and then prevent active sites from participating a reaction. Continuous distillation apparatus was used for separating mixed octenes from dimerization products. When reflux ratio was above 3 : 1, mixed octene fraction of which purity was above 99.57% was obtained. In $C_9$-aldehyde synthesis through hydroformylation of mixed octenes, we investigated a performance of ligand which increased catalyst stability as well as activity of Co catalyst. The results indicated that TPPO, NMP, NDMA, and succinonitrile were suitable ligand for increasing initial activity and reducing loss of Co during catalyst recovery.

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Preparation and Flame Retardancy of Poly(benzoxazole imide) Having Trifluoromethyl Group in the Main Chain (주사슬에 Trifluoromethyl 그룹을 갖는 Poly(benzoxazole imide)의 제조 및 난연 특성)

  • Yeom, Jin-Seok;Choi, Jae-Kon;Lee, Chang-Hoon
    • Elastomers and Composites
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    • v.47 no.4
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    • pp.355-363
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    • 2012
  • A series of poly(hydroxyamide)s (PHAs) having trifluoromethyl group were prepared by direct polycondensation of aromatic diimide-dicarboxylic acids with 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane by thionyl chloride and triethyl amine in N-methyl-2-pyrrolidinone (NMP). The PHAs exhibited inherent viscosity in the range of 0.54-0.96 dL/g at $35^{\circ}C$ in DMAc solution. All PHAs were readily soluble in a variety of organic solvents, whereas the polybenzoxazoles (PBOs) were quite insoluble except partially soluble in sulfuric acid. PHAs were converted to PBOs by thermal cycling reaction with heat of endotherm. The maximum weight loss temperature of the PHAs occurred in the range of $559-567^{\circ}C$. The PBOs showed relatively high char yields in the range of 47-59%. Pyrolysis Combustion Flow Calorimeter (PCFC) results of the PBOs showed 12-19 W/g heat release rate (HRR), and 2.7-3.6 kJ/g total heat release (total HR). The HRR of PBO 1 showed the lowest value of 12 W/g, which was 37% lower than that of PBO 3 (19 W/g).

Confirmation of Drought Tolerance of Ectopically Expressed AtABF3 Gene in Soybean

  • Kim, Hye Jeong;Cho, Hyun Suk;Pak, Jung Hun;Kwon, Tackmin;Lee, Jai-Heon;Kim, Doh-Hoon;Lee, Dong Hee;Kim, Chang-Gi;Chung, Young-Soo
    • Molecules and Cells
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    • v.41 no.5
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    • pp.413-422
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    • 2018
  • Soybean transgenic plants with ectopically expressed AtABF3 were produced by Agrobacterium-mediated transformation and investigated the effects of AtABF3 expression on drought and salt tolerance. Stable Agrobacterium-mediated soybean transformation was carried based on the half-seed method (Paz et al. 2006). The integration of the transgene was confirmed from the genomic DNA of transformed soybean plants using PCR and the copy number of transgene was determined by Southern blotting using leaf samples from $T_2$ seedlings. In addition to genomic integration, the expression of the transgenes was analyzed by RT-PCR and most of the transgenic lines expressed the transgenes introduced. The chosen two transgenic lines (line #2 and #9) for further experiment showed the substantial drought stress tolerance by surviving even at the end of the 20-day of drought treatment. And the positive relationship between the levels of AtABF3 gene expression and drought-tolerance was confirmed by qRT-PCR and drought tolerance test. The stronger drought tolerance of transgenic lines seemed to be resulted from physiological changes. Transgenic lines #2 and #9 showed ion leakage at a significantly lower level (P < 0.01) than ${\underline{n}}on-{\underline{t}}ransgenic$ (NT) control. In addition, the chlorophyll contents of the leaves of transgenic lines were significantly higher (P < 0.01). The results indicated that their enhanced drought tolerance was due to the prevention of cell membrane damage and maintenance of chlorophyll content. Water loss by transpiration also slowly proceeded in transgenic plants. In microscopic observation, higher stomata closure was confirmed in transgenic lines. Especially, line #9 had 56% of completely closed stomata whereas only 16% were completely open. In subsequent salt tolerance test, the apparently enhanced salt tolerance of transgenic lines was measured in ion leakage rate and chlorophyll contents. Finally, the agronomic characteristics of ectopically expressed AtABF3 transgenic plants ($T_2$) compared to NT plants under regular watering (every 4 days) or low rate of watering condition (every 10 days) was investigated. When watered regularly, the plant height of drought-tolerant line (#9) was shorter than NT plants. However, under the drought condition, total seed weight of line #9 was significantly higher than in NT plants (P < 0.01). Moreover, the pods of NT plants showed severe withering, and most of the pods failed to set normal seeds. All the evidences in the study clearly suggested that overexpression of the AtABF3 gene conferred drought and salt tolerance in major crop soybean, especially under the growth condition of low watering.

Effect of $CO_2$ Enrichment on Photosynthetic Rates, Enzyme Activity rind End Products of toro Poplar Clones, 1-214 (Populus euramericana) and Peace (P. Koreana x P. trichocarpa)

  • Shin-Young Park;Akio Furukawa
    • Journal of Environmental Science International
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    • v.1 no.1
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    • pp.51-59
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    • 1992
  • Two comparative poplar clones (I-214: Populus euramerinm, Peace: P koreana x p. trihocarpa) were exposed to two $CO_2$ concentrations (350 or 2, 000 ${\mu}L L^{-1} CO_2$) for 21 days. When both poplar clones were compared at growth conditions, the net photosynthetic rate ($P_N$) in $CO_2$-enriched ($2, 000{\mu}L L^{-1} CO_2 = C_{2, 000}$) plants become about 50-60% higher than that of 350 ${\mu}L L^{-1} CO_2 (=C_{350}$ Plants on 7 days treatment. But the enhancement of PN by high $CO_2$ was not maintained throughout all the experimental period. At 21 days, there was no difference of photosynthetic rates between $C_{350}$ and $C_{2000}$ plants. In contrast with photosynthesis, the response of leaf conductance to the elevated $CO_2$ concentration was very different between I-214 and Peace. During all experimental period, leaf conductance ($g_{s}$) of $C_{2000}$ plants is 50% lower than that of the $C_{350}$ plants for I-214, while there is no difference of gs between the plants of $C_{350}$ and $C_{2, 000}$ for Peace. The results of gs in Peace indicate that decreased photosynthetic rate after 21 days in $C_{2, 000}$ Plants for two poplar clones is possibly due to non-stomatal factors. To investigate the non-stomatal factors, starch accumulation and ribulose-1, 6-bisphosphate carboxylase (RuBPCase) were measured. We found significant accumulation of starch in two poplar clones exposed to high $CO_2$, especially starch of I-214 in $C_{2, 000}$ become 3.5 times higher than in $C_{350}$ plants at 21 days. This suggests that high proportion of photosynthates was directed into starch. After 21 days, the activity of ribulose-1, 6-bisphosphate carboxylase of $C_{2, 000}$ plants become decreased in 40-50% compared with that of the $C_{350}$ plants. Two poplar clones show the same trend to RuBPCase declines under high $CO_2$ concentration, although the decline is more significant for I-214. The results reported here suggest that starch accumulation and decreased RuBPCase activity in $C_{2, 000}$ plants can be partly ascribed to the loss of photosynthetic efficiency of high $CO_2$-grown poplar plants.

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Comparison of Nutrient Content and Retention Rate among Chuichung Cucumber, White Dadagi Cucumber, and Yellowish Overripe Cucumber according to Different Cooking Methods (취청오이, 백다다기오이, 노각의 조리방법에 따른 영양 성분 및 잔존율 연구)

  • Kim, Honggyun;Chung, Heajung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1350-1357
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    • 2017
  • General component and mineral contents according to species of Capsicum annuum were investigated. In addition, chuichung cucumber, white dadagi cucumber, and yellowish overripe cucumber were cooked by using seven different methods (boiling, steaming, pan-cooking, roasting, pan-frying, deep-frying, and microwaving), and retention rates of general components and minerals according to species were evaluated. Weight loss was observed in all cucumber species using all cooking methods. Most general component and mineral contents of C. annuum samples were significantly different according to species, and cooking method (P<0.05), whereas Fe and Cu contents were not significantly affected by species and cooking method, respectively. As a result, the highest protein, fat, ash contents were detected in deep-fried C. annuum, and high moisture contents were detected in raw, boiled, and steamed C. annuum. High mineral contents were detected in roasted and microwaved chuichung cucumber, deep-fried white dadagi cucumber and yellowish overripe cucumber. Retention rates of C. annuum by cooking method, ranged from 30~100% for protein, 10~100% for fat, 35~90% for moisture, and 30~100% for ash. High retention rates were observed for minerals in boiled, roasted, and microwaved chuichung cucumber, and deep-fried white dadagi cucumber and yellowish overripe cucumber. However, in yellowish overripe cucumber, mineral retentions rate were remarkably lowered by boiling and steaming, resulting in rates of 20~45%. These results were the data used as the basis for development of cucumbers.

Preparation of PMN-PT-BT/Ag Composite and its Mechanical and Dielectric Properties (PMN-PT-BT/Ag 복합체 제조 및 기계적, 유전적 특성)

  • Lim, Kyoung-Ran;Jeong, Soon-Yong;Kim, Chang-Sam;Nahm, Sahn
    • Journal of the Korean Ceramic Society
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    • v.39 no.9
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    • pp.846-850
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    • 2002
  • A PMN-PT-BT/Ag composite was prepared by surface modification with MgO sol with hoping to suppress silver's migration during sintering. The mixture of PbO, $N_2O_5,\;TiO_2\;with\;Mg(NO_3)_2$ instead of MgO was ball milled, the solvent was removed and then the dried powders were calcined at 950$^{\circ}C$/1h. The calcined powder were treated with 3.0 mol% $Ag_2O$ and 1.0 wt% MgO sol and calcined at 550$^{\circ}C$/1h. The dielectrics sintered at 1000$^{\circ}C$/4h under a flowing oxygen showed the density of 7.84g/$cm^3$, the room temperature dielectric constant of 18400, the dielectric loss of 2.4%, the specific resistivity of $0.24{\times}10^{12}{\Omega}{\cdot}cm$. It also showed the bending strength of $120.7{\pm}11.26$ MPa and the fracture toughness of $0.87{\pm}0.002\;MPam^{1/2}$ which were comparable to commercial PZT. The microstructure sonsisted of grains of ∼4${\mu}m$. SEM and SIMS analysis showed that Ag grew as ∼1${\mu}m$ and excess MgO as ∼0.5${\mu}m$.

A Wilcoxon signed-rank test for random walk hypothesis based on slopes (기울기를 이용한 랜덤워크 윌콕슨 부호순위검정)

  • Kim, Tae Yoon;Park, Cheolyong;Kim, Seul Gee;Kim, Min Seok;Lee, Woo Jung;Kwon, Yunji
    • Journal of the Korean Data and Information Science Society
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    • v.25 no.6
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    • pp.1499-1506
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    • 2014
  • Random walk is used for describing random phenomenon in various areas but tests for random walk developed so far are known to suffer from size distortion and low power. Kim et al. (2014) proposed a sign test for unit root (${\rho}=1$) hypothesis based on slopes. This article proposes a Wilcoxon signed rank test based on slopes for unit root hypothesis, and compares it with the augmented Dickey-Fuller test and the sign test by a simulation study. Our results confirm that the nonparametric tests are better than ADF test for small samples like n = 30. The results also show that the sign test is better than the Wilcoxon signed rank test and that for 0 < ${\rho}$ < 1 (-1 < ${\rho}$ < 0), the nonparametric tests suffer from power loss (improvement) as normal error changes to double exponential error.