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Steroid Effect on the Brain Protection During OPen Heart Surgery Using Hypothermic Circulatory Arrest in the Rabbit Cardiopulmonary bypass Model (저체온순환정지법을 이용한 개심술시 스테로이드의 뇌보호 효과 - 토끼를 이용한 심폐바이패스 실험모델에서 -)

  • Kim, Won-Gon;Lim, Cheong;Moon, Hyun-Jong;Chun, Eui-Kyung;Chi, Je-Geun;Won, Tae-Hee;Lee, Young-Tak;Chee, Hyun-Keun;Kim, Jun-Woo
    • Journal of Chest Surgery
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    • v.30 no.5
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    • pp.471-478
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    • 1997
  • Introduction: The use of rabbits as a cardiopulmonary bypass(CPB) animal model is extremely dif%cult mainly due to technical problems. On the other hand, deep hypothermic circulatory arrest(CA) is used to facilitate surgical repair in a variety of cardiac diseases. Although steroids are generally known to be effective in the treatment of cerebral edema, the protective effects of steroids on the brain during CA are not conclusively established. Objectives of this study are twofold: the establishment of CPB technique in rabbits and the evaluation of preventive effect of steroid on the development of brain edema during CA. Material '||'&'||' Methods: Fifteen New Zealan white rabbits(average body weight 3.5kg) were divided into three experimental groups; control CA group(n=5), CA with Trendelenberg position group(n=5), and CA with Trendelenberg position + steroid(methylprednisolone 30 mglkg) administration group(n=5). After anesthetic induction and tracheostomy, a median sternotomy was performed. An aortic cannula(3.3mm) and a venous ncannula(14 Fr) were inserted, respectively in the ascending aorta and the right atrium. The CPB circuit consisted of a roller pump and a bubble oxygenator. Priming volume of the circuit was approximately 450m1 with 120" 150ml of blood. CPB was initiated at a flow rate of 80~85ml/kg/min, Ten min after the start of CPB, CA was established with duration of 40min at $20^{\circ}C$ of rectal temperature. After CA, CPB was restarted with 20min period of rewarming. Ten min after weaning, the animal was sacrif;cod. One-to-2g portions of the following tissues were rapidly d:ssected and water contents were examined and compared among gr ups: brain, cervical spinal cord, kidney, duodenum, lung, heart, liver, spleen, pancreas. stomach. Statistical significances were analyzed by Kruskal-Wallis nonparametric test. Results: CPB with CA was successfully performed in all cases. Flow rate of 60-100 mlfkgfmin was able to be maintained throughout CPB. During CPB, no significant metabolic acidosis was detected and aortic pressure ranged between 35-55 mmHg. After weaning from CPB, all hearts resumed normal beating spontaneously. There were no statistically significant differences in the water contents of tissues including brain among the three experimental groups. Conclusion: These results indicate (1) CPB can be reliably administered in rabbits if proper technique is used, (2) the effect of steroid on the protection of brain edema related to Trendelenburg position during CA is not established within the scope of this experiment.

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Limno-Biological Investigation of Lake Ok-Jeong (옥정호의 육수생물학적 연구)

  • SONG Hyung-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.15 no.1
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    • pp.1-25
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    • 1982
  • Limnological study on the physico-chemical properties and biological characteristics of the Lake Ok-Jeong was made from May 1980 to August 1981. For the planktonic organisms in the lake, species composition, seasonal change and diurnal vertical distribution based on the monthly plankton samples were investigated in conjunction with the physico-chemical properties of the body of water in the lake. Analysis of temperature revealed that there were three distinctive periods in terms of vertical mixing of the water column. During the winter season (November-March) the vertical column was completely mixed, and no temperature gradient was observed. In February temperature of the whole column from the surface to the bottom was $3.5^{\circ}C$, which was the minimum value. With seasonal warming in spring, surface water forms thermoclines at the depth of 0-10 m from April to June. In summer (July-October) the surface mixing layer was deepened to form a strong thermocline at the depth of 15-25 m. At this time surface water reached up to $28.2^{\circ}C$ in August, accompanied by a significant increase in the temperature of bottom layer. Maximum bottom temperature was $r5^{\circ}C$ which occurred in September, thus showing that this lake keeps a significant turbulence Aehgh the hypolimnial layer. As autumn cooling proceeded summer stratification was destroyed from the end of October resulting in vertical mixing. In surface layer seasonal changes of pH were within the range from 6.8 in January to 9.0 in guutuost. Thighest value observed in August was mainly due to the photosynthetic activity of the phytoplankton. In the surface layer DO was always saturated throughout the year. Particularly in winter (January-April) the surface water was oversaturated (Max. 15.2 ppm in March). Vertical variation of DO was not remarkable, and bottom water was fairly well oxygenated. Transparency was closely related to the phytoplankton bloom. The highest value (4.6 m) was recorded in February when the primary production was low. During summer transparency decreased hand the lowest value (0.9 m) was recorded in August. It is mainly due to the dense blooming of gnabaena spiroides var. crassa in the surface layer. A. The amount of inorganic matters (Ca, Mg, Fe) reveals that Lake Ok-Jeong is classified as a soft-water lake. The amount of Cl, $NO_3-N$ and COD in 1981 was slightly higher than those in 1980. Heavy metals (Zn, Cu, Pb, Cd and Hg) were not detectable throughout the study period. During the study period 107 species of planktonic organisms representing 72 genera were identified. They include 12 species of Cyanophyta, 19 species of Bacillariophyta, 23 species of Chlorophyta, 14 species of Protozoa, 29 species of Rotifera, 4 species of Cladocera and 6 species of Copepoda. Bimodal blooming of phytoplankton was observed. A large blooming ($1,504\times10^3\;cells/l$ in October) was observed from July to October; a small blooming was present ($236\times10^3\;cells/l$ in February) from January to April. The dominant phytoplankton species include Melosira granulata, Anabaena spiroides, Asterionella gracillima and Microcystis aeruginota, which were classified into three seasonal groups : summer group, winter group and the whole year group. The sumner group includes Melosira granulate and Anabaena spiroides ; the winter group includes Asterionella gracillima and Synedra acus, S. ulna: the whole year group includes Microtystis aeruginosa and Ankistrodesmus falcatus. It is noted that M. granulate tends to aggregate in the bottom layer from January to August. The dominant zooplankters were Thermocpclops taihokuensis, Difflugia corona, Bosmina longirostris, Bosminopsis deitersi, Keratelle quadrata and Asplanchna priodonta. A single peak of zooplankton growth was observed and maximum zooplankton occurrence was present in July. Diurnal vertical migration was revealed by Microcystis aeruginosa, M. incerta, Anabaena spiroides, Melosira granulata, and Bosmina longirostris. Of these, M. granulata descends to the bottom and forms aggregation after sunset. B. longirostris shows fairly typical nocturnal migration. They ascends to the surface after sunset and disperse in the whole water column during night. Foully one species of fish representing 31 genera were collected. Of these 13 species including Pseudoperilnmpus uyekii and Coreoleuciscus splendidus were indigenous species of Korean inland waters. The indicator species of water quality determination include Microcystis aeruginosa, Melosira granulata, Asterionelta gracillima, Brachionus calyciflorus, Filinia longiseta, Conochiloides natans, Asplanchna priodonta, Difflugia corona, Eudorina elegans, Ceratium hirundinella, Bosmina longirostris, Bosminopsis deitersi, Heliodiaptomus kikuchii and Thermocyclops taihokuensis. These species have been known the indicator groups which are commonly found in the eutrophic lakes. Based on these planktonic indicators Lake Ok-Jeong can be classified into an eutrophic lake.

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The Effect of Nitric Oxide Donor or Nitric Oxide Synthase Inhibitor on Oxidant Injury to Cultured Rat Lung Microvascular Endothelial Cells (산화질소 공여물과 산화질소 합성효소 길항제가 백서 폐미세혈관 내피세포 산화제 손상에 미치는 영향)

  • Chang, Joon;Michael, John R.;Kim, Se-Kyu;Kim, Sung-Kyu;Lee, Won-Young;Kang, Kyung-Ho;Yoo, Se-Hwa;Chae, Yang-Seok
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.6
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    • pp.1265-1276
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    • 1998
  • Background : Nitric oxide(NO) is an endogenously produced free radical that plays an important role in regulating vascular tone, inhibition of platelet aggregation and white blood cell adhesion to endothelial cells, and host defense against infection. The highly reactive nature of NO with oxygen radicals suggests that it may either promote or reduce oxidant-induced cell injury in several biological pathways. Oxidant injury and interactions between pulmonary vascular endothelium and leukocytes are important in the pathogenesis of acute lung injury, including acute respiratory distress syndrome(ARDS). In ARDS, therapeutic administration of NO is a clinical condition providing exogenous NO in oxidant-induced endothelial injury. The role of exogenous NO from NO donor or the suppression of endogenous NO production was evaluated in oxidant-induced endothelial injury. Method : The oxidant injury in cultured rat lung microvascular endothelial cells(RLMVC) was induced by hydrogen peroxide generated from glucose oxidase(GO). Cell injury was evaluated by $^{51}$chromium($^{51}Cr$) release technique. NO donor, such as S-nitroso-N-acetylpenicillamine(SNAP) or sodium nitroprusside(SNP), was added to the endothelial cells as a source of exogenous NO. Endogenous production of NO was suppressed with N-monomethyl-L-arginine(L-NMMA) which is an NO synthase inhibitor. L-NMMA was also used in increased endogenous NO production induced by combined stimulation with interferon-$\gamma$(INF-$\gamma$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and lipopolysaccharide(LPS). NO generation from NO donor or from the endothelial cells was evaluated by measuring nitrite concentration. Result : $^{51}Cr$ release was $8.7{\pm}0.5%$ in GO 5 mU/ml, $14.4{\pm}2.9%$ in GO 10 mU/ml, $32.3{\pm}2.9%$ in GO 15 mU/ml, $55.5{\pm}0.3%$ in GO 20 mU/ml and $67.8{\pm}0.9%$ in GO 30 mU/ml ; it was significantly increased in GO 15 mU/ml or higher concentrations when compared with $9.6{\pm}0.7%$ in control(p < 0.05; n=6). L-NMMA(0.5 mM) did not affect the $^{51}Cr$ release by GO. Nitrite concentration was increased to $3.9{\pm}0.3\;{\mu}M$ in culture media of RLMVC treated with INF-$\gamma$ (500 U/ml), TNF-$\alpha$(150 U/ml) and LPS($1\;{\mu}g/ml$) for 24 hours ; it was significantly suppressed by the addition of L-NMMA. The presence of L-NMMA did not affect $^{51}Cr$ release induced by GO in RLMVC pretreated with INF-$\gamma$, TNF-$\alpha$ and LPS. The increase of $^{51}Cr$ release with GO(20 mU/ml) was prevented completely by adding 100 ${\mu}M$ SNAP. But the add of SNP, potassium ferrocyanate or potassium ferricyanate did not protect the oxidant injury. Nitrite accumulation was $23{\pm}1.0\;{\mu}M$ from 100 ${\mu}M$ SNAP at 4 hours in phenol red free Hanks' balanced salt solution. But nitrite was not detectable from SNP upto 1 mM The presence of SNAP did not affect the time dependent generation of hydrogen peroxide by GO in phenol red free Hanks' balanced salt solution. Conclusion : Hydrogen peroxide generated by GO causes oxidant injury in RLMVC. Exogenous NO from NO donor prevents oxidant injury, and the protective effect may be related to the ability to release NO. These results suggest that the exogenous NO may be protective on oxidant injury to the endothelium.

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Consideration on Shielding Effect Based on Apron Wearing During Low-dose I-131 Administration (저용량 I-131 투여시 Apron 착용여부에 따른 차폐효과에 대한 고찰)

  • Kim, Ilsu;Kim, Hosin;Ryu, Hyeonggi;Kang, Yeongjik;Park, Suyoung;Kim, Seungchan;Lee, Guiwon
    • The Korean Journal of Nuclear Medicine Technology
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    • v.20 no.1
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    • pp.32-36
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    • 2016
  • Purpose In nuclear medicine examination, $^{131}I$ is widely used in nuclear medicine examination such as diagnosis, treatment, and others of thyroid cancer and other diseases. $^{131}I$ conducts examination and treatment through emission of ${\gamma}$ ray and ${\beta}^-$ ray. Since $^{131}I$ (364 keV) contains more energy compared to $^{99m}Tc$ (140 keV) although it displays high integrated rate and enables quick discharge through kidney, the objective of this study lies in comparing the difference in exposure dose of $^{131}I$ before and after wearing apron when handling $^{131}I$ with focus on 3 elements of external exposure protection that are distance, time, and shield in order to reduce the exposure to technicians in comparison with $^{99m}Tc$ during the handling and administration process. When wearing apron (in general, Pb 0.5 mm), $^{99m}Tc$ presents shield of over 90% but shielding effect of $^{131}I$ is relatively low as it is of high energy and there may be even more exposure due to influence of scattered ray (secondary) and bremsstrahlung in case of high dose. However, there is no special report or guideline for low dose (74 MBq) high energy thus quantitative analysis on exposure dose of technicians will be conducted based on apron wearing during the handling of $^{131}I$. Materials and Methods With patients who visited Department of Nuclear Medicine of our hospital for low dose $^{131}I$ administration for thyroid cancer and diagnosis for 7 months from Jun 2014 to Dec 2014 as its subject, total 6 pieces of TLD was attached to interior and exterior of apron placed on thyroid, chest, and testicle from preparation to administration. Then, radiation exposure dose from $^{131}I$ examination to administration was measured. Total procedure time was set as within 5 min per person including 3 min of explanation, 1 min of distribution, and 1 min of administration. In regards to TLD location selection, chest at which exposure dose is generally measured and thyroid and testicle with high sensitivity were selected. For preparation, 74 MBq of $^{131}I$ shall be distributed with the use of $2m{\ell}$ syringe and then it shall be distributed after making it into dose of $2m{\ell}$ though dilution with normal saline. When distributing $^{131}I$ and administering it to the patient, $100m{\ell}$ of water shall be put into a cup, distributed $^{131}I$ shall be diluted, and then oral administration to patients shall be conducted with the distance of 1m from the patient. The process of withdrawing $2m{\ell}$ syringe and cup used for oral administration was conducted while wearing apron and TLD. Apron and TLD were stored at storage room without influence of radiation exposure and the exposure dose was measured with request to Seoul Radiology Services. Results With the result of monthly accumulated exposure dose of TLD worn inside and outside of apron placed on thyroid, chest, and testicle during low dose $^{131}I$ examination during the research period divided by number of people, statistics processing was conducted with Wilcoxon Signed Rank Test using SPSS Version. 12.0K. As a result, it was revealed that there was no significant difference since all of thyroid (p = 0.345), chest (p = 0.686), and testicle (p = 0.715) were presented to be p > 0.05. Also, when converting the change in total exposure dose during research period into percentage, it was revealed to be -23.5%, -8.3%, and 19.0% for thyroid, chest, and testicle respectively. Conclusion As a result of conducting Wilcoxon Signed Rank Test, it was revealed that there is no statistically significant difference (p > 0.05). Also, in case of calculating shielding rate with accumulate exposure dose during 7 months, it was revealed that there is irregular change in exposure dose for inside and outside of apron. Although the degree of change seems to be high when it is expressed in percentage, it cannot be considered a big change since the unit of accumulated exposure dose is in decimal points. Therefore, regardless of wearing apron during high energy low dose $^{131}I$ administration, placing certain distance and terminating the administration as soon as possible would be of great assistance in reducing the exposure dose. Although this study restricted $^{131}I$ administration time to be within 5 min per person and distance for oral administration to be 1m, there was a shortcoming to acquire accurate result as there was insufficient number of N for statistics and it could be processed only through non-parametric method. Also, exposure dose per person during lose dose $^{131}I$ administration was measured with accumulated exposure dose using TLD rather than through direct-reading exposure dose thus more accurate result could be acquired when measurement is conducted using electronic dosimeter and pocket dosimeter.

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Radiosynthesis of $[^{11}C]6-OH-BTA-1$ in Different Media and Confirmation of Reaction By-products. ($[^{11}C]6-OH-BTA-1$ 조제 시 생성되는 부산물 규명과 반응용매에 따른 표지 효율 비교)

  • Lee, Hak-Jeong;Jeong, Jae-Min;Lee, Yun-Sang;Kim, Hyung-Woo;Lee, Eun-Kyoung;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.3
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    • pp.241-246
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    • 2007
  • Purpose: $[^{11}C]6-OH-BTA-1$ ([N-methyl-$^{11}C$]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, 1), a -amyloid imaging agent for the diagnosis of Alzheimer's disease in PET, can be labeled with higher yield by a simple loop method. During the synthesis of $[^{11}C]1$, we found the formation of by-products in various solvents, e.g., methylethylketone (MEK), cyclohexanone (CHO), diethylketone (DEK), and dimethylformamide (DMF). Materials and Methods: In Automated radiosynthesis module, 1 mg of 4-aminophenyl-6-hydroxybenzothiazole (4) in 100 l of each solvent was reacted with $[^{11}C]methyl$ triflate in HPLC loop at room temperature (RT). The reaction mixture was separated by semi-preparative HPLC. Aliquots eluted at 14.4, 16.3 and 17.6 min were collected and analyzed by analytical HPLC and LC/MS spectrometer. Results: The labeling efficiencies of $[^{11}C]1$ were $86.0{\pm}5.5%$, $59.7{\pm}2.4%$, $29.9{\pm}1.8%$, and $7.6{\pm}0.5%$ in MEK, CHO, DEK and DMF, respectively. The LC/MS spectra of three products eluted at 14.4, 16.3 and 17.6 mins showed m/z peaks at 257.3 (M+1), 257.3 (M+1) and 271.3 (M+1), respectively, indicating their structures as 1, 2-(4'-aminophenyl)-6-methoxybenzothiazole (2) and by-product (3), respectively. Ratios of labeling efficiencies for the three products $([^{11}C]1:[^{11}C]2:[^{11}C]3)$ were $86.0{\pm}5.5%:5.0{\pm}3.4%:1.5{\pm}1.3%$ in MEK, $59.7{\pm}2.4%:4.7{\pm}3.2%:1.3{\pm}0.5%$ in CHO, $9.9{\pm}1.8%:2.0{\pm}0.7%:0.3{\pm}0.1%$ in DEK and $7.6{\pm}0.5%:0.0%:0.0%$ in DMF, respectively. Conclusion: The labeling efficiency of $[^{11}C]1$ was the highest when MEK was used as a reaction solvent. As results of mass spectrometry, 1 and 2 were conformed. 3 was presumed.

Effects of Planting Date and Density on Yield and It’s Components of Fritillaria thungergii MIQUEL (패모(貝母)의 파종기(播種期) 및 재식밀도(栽植密度)가 수양구성(收量構成) 형질(形質) 및 수양(收量)에 미치는 영향(影響))

  • Choi, In-Sik;Cho, Jin-Tae;Son, Seok-Yong;Park, Jae-Seong;Han, Dong-Ho;Jeong, In-Myeong
    • Korean Journal of Medicinal Crop Science
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    • v.4 no.3
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    • pp.218-223
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    • 1996
  • This experiment was carried out to investigate the effect of planting date and planting density on yield and yield components of Fritillariae bulbus from 1989 to 1991. The Chungbuk local variety was used, and the experimental materials were planted six times with 10 days interval from Aug. 20 to Oct. 10. 33, 22, 17 and 13 bulbs were planted by the square meter, respectively. The compound fertilizer for garlic $(N\;-\;P_2O\;-\;K_2O_5=9\;-\;14\;-\;10)$ was applied by 80kgs to the 0.1ha before planting. The experimental design was randomized block design with 3 replications. As the planting dates were earlier, the emerging dates were earlier, too. But the delay of 50 days in the planting affected to the delay of 14 days in the em­erging dates. The plant height was 22.7cms in the Aug. 20 plot. As the planting were later, the plant heights were shorter by $2.4{\sim}5.6cms$ than that. As compared with the 829kgs by the 0.1ha of Aug. 30 plot, the others recorded 1 percent increase in the Aug. 20 plot, 4 percent decrease in the Sep. 10 plot, 26 percent decrease in the Sep. 20 plot, 35 percent decrease in the Sep 30 plot, and 38 percent decrease in the Oct. 10 plot. So, the suitable planting dates were from Aug. 20 to Aug. 30.The emerging date of 33 bulb plot by the square meter was March 7, but as the planting densities were sparse, the emerging dates delayed by one to three days. The plant height of the 33 bulb plot by the square meter was 21. 8cms, but the other plots were short by $0.7{\sim}1.8cms$. The number of shoots of the 33 bulb plot by the square meter was 6.1. but the other plots recorded 0.4 increase in the 22 bulb plot, 0.6 increase in the 17 bulb plot and 0.5 increase in the 13 bulb plot compared with that of the 33 bulb plot. Accordingly, the number of shoots in the sparse planting plot was more than that in the dense planting plot. As compared with the 854kgs by the 0.1ha of the 22 bulb plot, the other plots recored 2 percent in­crease in the 33 bulb plot, 16 percent decrease in the 17 bulb plot and 34 percent decrease in the 13 bulb plot. All things considered, for the culture of Fritillaria thungergii MIQUEL in the middle region, Aug. 25 and 22 bulbs by the square meter were suitable for the planting date and density.

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Semiweekly variation of Spring Phytoplankton Community in Relation to the Freshwater Discharges from Keum River Estuarine Weir, Korea (금강하구언 담수방류와 춘계 식물플랑크톤 군집의 단주기 변동)

  • Yih, Won-Ho;Myung, Geum-Og;Yoo, Yeong-Du;Kim, Young-Geel;Jeong, Hae-Jm
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.10 no.3
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    • pp.154-163
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    • 2005
  • Irregular discharges of freshwater through the water gates of the Keum River Estuarine Weir, Korea, whose construction had been completed in 1998 with its water gates being operated as late as August 1994, drastically modified the estuarine environment. Sharp decrease of salinity along with the altered concentrations of inorganic nutrients are accompanied with the irregular discharges of freshwater into the estuary under the influence of regular semi-diurnal tidal effect. Field sampling was carried out on the time of high tide at 2 fixed stations(St.1 near the Estuarine Weir and St.2 off Kunsan Ferry Station) every other day for 4 months from mid-February 2004 to investigate into the semi-weekly variation of spring phytoplankton community in relation to the freshwater discharges from Keum River Estuarine Weir. CV(coefficient of variation) of salinity measurements was roughly 2 times greater in St.1 than that in St.2, reflecting extreme salinity variation in St.1 Among inorganic nutrients, concentrations of N-nutrients($NO_3^-,\;NO_2^-$ and $NH_4^+$) were clearly higher in St.1, to imply the more drastic changes of the nutrient concentrations in St.1. than St.2 following the freshwater discharges. As a component of phytoplankton community, diatoms were among the top dominants in terms of species richness as well as biomass. Solitary centric diatom, Cyclotella meneghiniana, and chain-forming centric diatom, Skeletonema costatum, dominated over the phytoplankton community in order for S-6 weeks each (Succession Interval I and II), and the latter succeeded to the former from the time of <$10^{\circ}C$ of water temperature. Cyanobacterial species, Aphanizomenon Posaquae and Phormidium sp., which might be transported into the estuary along with the discharged freshwater, occupied high portion of total biomass during Succession Interval III(mid-April to late-May). During this period, freshwater species exclusively dominated over the phytoplankton community except the low concentrations of the co-occurring 2 estuarine diatoms, Cyclotella meneghiniana and Skeletonema costatum. During the 4th Succession Interval when the water temperature was over $18^{\circ}C$, the diatom, Guinardia delicatula, was predominant for a week with the highest dominance of $75\%$ in discrete samples. To summarize, during all the Succession Intervals other than Succession Interval III characterized by the extreme variation of salinity under cooler water temperature than $18^{\circ}C$, the diatoms were the most important dominants for species succession in spring. If the scale and frequency of the freshwater discharge could have been adjusted properly even during the Succession Interval III, the dominant species would quite possibly be replaced by other estuarine diatom species rather than the two freshwater cyanobacteria, Aphanizomenon flosaquae and Phormidium sp.. The scheme of field sampling every other day for the present study was concluded to be the minimal requirement in order to adequately explore the phytoplankton succession in such estuarine environment as in Keum River Estuary: which is stressed by the unpredictable and unavoidable discharges of freshwater under the regular semi-diurnal tide.

The Effects of Isopropyl 2-(1,3-dithioetane-2-ylidene)-2-[N-(4-methyl-thiazol-2-yl)carbamoyl]acetate (YH439) on Potentiated Carbon Tetrachloride Hepatotoxicity (상승적 화학적 간독성에 미치는 YH439의 영향)

  • Kim, Sang-Geon;Cho, Joo-Youn
    • The Korean Journal of Pharmacology
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    • v.32 no.3
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    • pp.407-416
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    • 1996
  • The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

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Korean Sentence Generation Using Phoneme-Level LSTM Language Model (한국어 음소 단위 LSTM 언어모델을 이용한 문장 생성)

  • Ahn, SungMahn;Chung, Yeojin;Lee, Jaejoon;Yang, Jiheon
    • Journal of Intelligence and Information Systems
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    • v.23 no.2
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    • pp.71-88
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    • 2017
  • Language models were originally developed for speech recognition and language processing. Using a set of example sentences, a language model predicts the next word or character based on sequential input data. N-gram models have been widely used but this model cannot model the correlation between the input units efficiently since it is a probabilistic model which are based on the frequency of each unit in the training set. Recently, as the deep learning algorithm has been developed, a recurrent neural network (RNN) model and a long short-term memory (LSTM) model have been widely used for the neural language model (Ahn, 2016; Kim et al., 2016; Lee et al., 2016). These models can reflect dependency between the objects that are entered sequentially into the model (Gers and Schmidhuber, 2001; Mikolov et al., 2010; Sundermeyer et al., 2012). In order to learning the neural language model, texts need to be decomposed into words or morphemes. Since, however, a training set of sentences includes a huge number of words or morphemes in general, the size of dictionary is very large and so it increases model complexity. In addition, word-level or morpheme-level models are able to generate vocabularies only which are contained in the training set. Furthermore, with highly morphological languages such as Turkish, Hungarian, Russian, Finnish or Korean, morpheme analyzers have more chance to cause errors in decomposition process (Lankinen et al., 2016). Therefore, this paper proposes a phoneme-level language model for Korean language based on LSTM models. A phoneme such as a vowel or a consonant is the smallest unit that comprises Korean texts. We construct the language model using three or four LSTM layers. Each model was trained using Stochastic Gradient Algorithm and more advanced optimization algorithms such as Adagrad, RMSprop, Adadelta, Adam, Adamax, and Nadam. Simulation study was done with Old Testament texts using a deep learning package Keras based the Theano. After pre-processing the texts, the dataset included 74 of unique characters including vowels, consonants, and punctuation marks. Then we constructed an input vector with 20 consecutive characters and an output with a following 21st character. Finally, total 1,023,411 sets of input-output vectors were included in the dataset and we divided them into training, validation, testsets with proportion 70:15:15. All the simulation were conducted on a system equipped with an Intel Xeon CPU (16 cores) and a NVIDIA GeForce GTX 1080 GPU. We compared the loss function evaluated for the validation set, the perplexity evaluated for the test set, and the time to be taken for training each model. As a result, all the optimization algorithms but the stochastic gradient algorithm showed similar validation loss and perplexity, which are clearly superior to those of the stochastic gradient algorithm. The stochastic gradient algorithm took the longest time to be trained for both 3- and 4-LSTM models. On average, the 4-LSTM layer model took 69% longer training time than the 3-LSTM layer model. However, the validation loss and perplexity were not improved significantly or became even worse for specific conditions. On the other hand, when comparing the automatically generated sentences, the 4-LSTM layer model tended to generate the sentences which are closer to the natural language than the 3-LSTM model. Although there were slight differences in the completeness of the generated sentences between the models, the sentence generation performance was quite satisfactory in any simulation conditions: they generated only legitimate Korean letters and the use of postposition and the conjugation of verbs were almost perfect in the sense of grammar. The results of this study are expected to be widely used for the processing of Korean language in the field of language processing and speech recognition, which are the basis of artificial intelligence systems.

Dual Inoculation Response of Soybean with Rhizobium And Mycorrhiza (콩에 대한 근류균과 균근균의 혼합 접종효과)

  • Kang, Ui-Gum;Park, Hyang-Mee;Lee, Jae-Saeng;Ko, Jee-Yeon;Lee, Yong-Hwan;Jeon, Weon-Tae;Kim, Min-Tae;Joa, Jae-Ho
    • Korean Journal of Soil Science and Fertilizer
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    • v.45 no.3
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    • pp.325-331
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    • 2012
  • The dual inoculation response of soybean with rhizobium and mycorrhiza was examined in pot vermiculite and field soils. In order to select a symbiotically compatible mycorrhiza with Bradyrhizobium japonicum, a highly germinating spore among 60 strains from 32 upland soils in southern part of Korea was obtained in Acaulospora sp., Gigaspora sp. and Glomus sp., respectively. As a result of dual inoculation of Glycin max cv. Dajangkong and Eunhakong both with $1{\times}10^8$cells of B. japonicum YCK 213 and 10 spores of each mycorrhiza in vermiculite pot, only Glomus sp. treatment together with the rhizobium showed significant increase ($P{\leqq}0.05$) both in shoot dry wt and nodule mass of not Eunhakong but Dajangkong. In red-yellow soils with pH 5.2($1:5H_2O$) and 203 mg of Lancaster P per kg of soil, in which $10^3$ cells of B. japonicum and $10{\pm}0.2$ spores of mycorrhizae per gram of soil were naturalized, grain yield of G. max cv. Dajangkong was increased to 3.9% by dual inoculation both of $4.8{\times}10^6$cells of B. japonicum and 10 spores of mycorrhizae per two seeds under condition applied with 30 kg $P_2O_5$ and 34 kg $K_2O$ per hectare compared to conventionally fertilized plot (2.75 MT $ha^{-1}$) added with 30 kg N $ha^{-1}$. However, there was not significant.