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Pharmacological Studies of Cefoperazone(T-1551) (Cefoperazone(T-1551)의 약리학적 연구)

  • Lim J.K.;Hong S.A.;Park C.W.;Kim M.S.;Suh Y.H.;Shin S.G.;Kim Y.S.;Kim H.W.;Lee J.S.;Chang K.C.;Lee S.K.;Chang K.C.;Kim I.S.
    • The Korean Journal of Pharmacology
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    • v.16 no.2 s.27
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    • pp.55-70
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    • 1980
  • The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

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Life Cycle Assessment and Improvement Assessment for Manufacturing Process of Corrugated Package (골판지 포장재의 생산공정에 대한 LCA 수행 및 친환경 공정개선)

  • Jo, Hyun Jung;Hwang, Yong Woo;Park, Kwang Ho;Jo, Byoung Muk;Kim, Hyoung Jin
    • Applied Chemistry for Engineering
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    • v.16 no.5
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    • pp.620-627
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    • 2005
  • In this study, life cycle assessment (LCA) on one of corrugated cardboard box as functional unit was carried out. System boundary of this study divided according to raw material acquisition, corrugated cardboard manufacture and corrugated cardboard box manufacture stage. And environmental impacts are evaluated on each stage and sub-process. The impact categories are classified into eight categories of abiotic resource depletion, global warming stratospheric ozone depletion, photochemical oxidant creation, air acidification, eutrophication, ecotoxicity and human toxicity. From the results, it is found that environment impacts at raw material acquisition stage is the highest as about 92% of whole stage due to liner board manufacture stage. The highest environmental impacts at sub-process of corrugated cardboard and box manufacture stage is a single facer and D/W backer process that included as main process in corrugated cardboard manufacture, and is caused by used energies like electricity, B-C oil, and etc. And then diagnosis for clean production process system of package is carried out. Through diagnosis, on loss rate is reduced and inner pressure intensity of box is improved. After improvement, environmental impact was decreased about 3.8% compared with before improvement.

Effect of Pronase Treatment on Mouse Embryos: Improving Hatching and Hatched Rates (생쥐배아의 부화와 탈각에 미치는 Pronase의 영향)

  • Moon, Shin-Yong;Choi, Sung-Mi;Kim, Hee-Sun;Ryu, Buom-Yong;Oh, Sun-Kyung;Suh, Chang-Suk;Kim, Seok-Hyun;Choi, Young-Min;Kim, Jung-Gu;Choi, Kyu-Hong;Lee, Jin-Yong
    • Clinical and Experimental Reproductive Medicine
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    • v.27 no.4
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    • pp.345-351
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    • 2000
  • Objective: Hatching of the blastocyst from the zona pellucida (ZP) is a key event in mammalian implantation. In vivo, two factors have been identified as possible mediators of hatching: lysis of the ZP by substances elaborated either from the embryo or female reproductive tract and pressure exerted on the zona by expansion of the blastocyst. Two methods of zona manipulation were already in use to enhance the ability of embryos to hatch: mechanical PZD and chemical ZD by acidic Tyrode's solution. But several controversies of each method have been reported. The purpose of this study was to investigate the effect of pronase for mouse embryo hatching. Methods: Mouse embryos were obtained following ovulation induction of $F_1$ animals. Fresh and cryo-thawed morula embryos were exposed to 0.5, 1.0, 2.0, 5.0 ${\mu}g/ml$ pronase in Ham's F10 for 72 hrs. Main outcome measures were the rates of partial hatching and completely hatched blastocysts, and cell number of it. Results: In fresh and cryo-thawed group, the rates of completely hatched blastocyst were significantly higher in 5 ${\mu}g/ml$ pronase treatment group than control group. There was no difference in completely hatched blastocyst total cell number between pronase treatment group and control group. This suggest that pronase treatment did not harmful in mouse embryo development. In pronase treatment group, zona pellucida were thinner than control group. Conclusion: The addition of pronase to culture media may accelerate the hatching of embryo. So, enzymatic treatment of the zona may provide a valuable and effective assisted hatching technique for human in-vitro fertilization-embryo transfer.

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An Analysis of the Healing Effects of Forest Therapy and Horticultural Therapy (숲치유와 원예치료의 치유효과 분석)

  • Park, Sun-A;Jeong, Moon-Sun;Lee, Myungwoo
    • Journal of the Korean Institute of Landscape Architecture
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    • v.43 no.3
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    • pp.43-51
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    • 2015
  • Stresses from desolate urban environments cause illnesses and worsen health conditions of urban residents, while natural environments have a positive influence on human. Natural healing programs such as forest therapy and horticultural therapy can be differentiated by the characteristic of activity space. However, previous studies of healing programs have focused on either forest therapy or horticulture therapy and there is a limit to comprehending the effects of adopting and connecting various healing programs. This study compares and analyzes the physiological and psychological effects of forest therapy and horticultural therapy to identify the effects and differences by types of healing programs. The before and after effects of horticultural therapy and forest therapy are measured by experiment and survey for 5 days with 5 subjects in each program. For physiological reaction, blood pressure, pulse, and cortisol levels are measured and the profile of moods states(POMS) is used to measure psychological reaction. Collected data are analyzed with the analysis of variance(ANOVA) and Paired-Sample T-test in SPSS 18.0. The results of this study are as follows: 1) forest therapy and horticultural therapy show positive effects in physiological and physiological aspects, 2) forest therapy is more effective than horticultural therapy in physiological relaxation and stress mitigation, 3) horticultural therapy has a tendency to alleviate depression more effectively than forest therapy. In conclusion, this study contributes to providing fundamental information for the development of healing programs and design guidelines for healing spaces through identifying the characteristics of each healing program.

Effect of Thermal Treatments on Flavonoid Contents in Domestic Soybeans (국내산 대두(Glycine max. Merr)자원의 플라보노이드 대사체 동정 및 열처리 효과)

  • Shin, Jae-Hyeong;Kim, Heon-Woong;Lee, Min-Ki;Jang, Ga-Hee;Lee, Sung-Hyen;Jang, Hwan-Hee;Hwang, Yu-Jin;Park, Keum-Yong;Song, Beom-Heon;Kim, Jung-Bong
    • Korean Journal of Environmental Agriculture
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    • v.34 no.2
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    • pp.105-110
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    • 2015
  • BACKGROUND: Soy isoflavones, structurally similar to endogenous estrogens, may affect human body through both hormonally mediated and non-hormonally related mechanisms. Heat processing could change chemical compositions. The effects of different thermal processes, boiling and HTHP(high temperature and high pressure) on the composition of isoflavone compounds and total amount of domestic soybeans were investigated in this study. METHOD AND RESULTS: Three different kinds of soybean samples were collected from RDA-Genebank. The samples were extracted using methanol, distilled water, and formic acid based solvent. Also the same solvents were used for mobile phase in UPLC/ToF/MS. All of the isoflavone compounds were analyzed based on the aglycone type of external standard for quantification. The standard calibration curve presented linearity with the correlation coefficient R2 > 0.98, analysed from 1 to 50 ppm concentration. The total isoflavone contents does not change by treatment within the same breed. While "boiling" and "HTHP" processes tend to increase the contents of aglycone and ${beta}$-glucosides, "fresh" soybeans retained the high concentration of malonylglucosides. CONCLUSION: These results have to be considered while developing an effective functional food, from the health while point of view using soybeans.

Research for Crack Generation and Propagation of Daejeon Granite under Stress Conditions (대전 화강암에 대한 가압 조건하에서의 암석 균열 발생과 성장에 관한 연구)

  • Choi, Junghae;Kim, Hye-jin;Chae, Byung-gon
    • Economic and Environmental Geology
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    • v.52 no.6
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    • pp.587-593
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    • 2019
  • This study were subjected to accelerated weathering test under freeze-thaw and pressure conditions to observe initiation and propagation of cracks using CLSM. Applied stress was set at 50 MPa, 55 MPa, 70 MPa for 3 samples each by using compressor and freeze-thaw experiment was conducted while samples maintained that condition. In freeze-thaw experiments, a temperature range was set to -20~40℃ which was 1 cycle for 6 hours. The freeze-thaw cycle was composed of time which reached to set temperature for 1 hour and holding time for 2 hours. On the basis of this cycle, surface of samples was observed by CLSM after each 20 freeze-thaw cycle. From this research, according to increase freeze-thaw cycle, there were 7, 10, 19 each cracks and High pressured sample's accumulate length was longer than low pressured sample's. High pressured sample's crack velocities were also faster than low pressured sample's which were calculated by accumulate length and freeze-thaw cycle.

Indicators for the Quantitative Assessment of Tree Vigor Condition and Its Theoretical Implications : A Case Study of Japanese Flowering-cherry Trees in Urban Park (도시공원에 식재된 왕벚나무 수종을 중심으로 한 수목활력도의 정량평가지표 개발 및 이론적 고찰에 관한 연구)

  • Song, Youngkeun
    • Journal of the Korean Society of Environmental Restoration Technology
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    • v.17 no.4
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    • pp.57-67
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    • 2014
  • The vigor condition of trees is an important indicator for the management of urban forested area. But difficulties in how to assess the tree vigor condition still remain. Previous efforts were limited in the 1) measurement of single indicator rather than using multiple indices, 2) purpose-oriented measurement such as for air-pollution effect or specific pathological symptom, and 3) ordinal-scale evaluations by field crews 4) despite human errors based on his/her experiences or prior knowledge. Therefore, this study attempted to develop a quantitative and objective methodology for assessing tree vigor condition, by measuring multiple modules and building the profile inventory. Furthermore, the possibility and limitations were discussed in terms of schematic frames describing tree vigor condition. The vigor condition of 56 flowering cherry plants in urban park were assessed by in-situ measurements of following eight items; growth of crown(Gc), growth of shoots, individual tree volume(Vol), plant area index, woody area index, leaf area index, leaf chlorophyll content(Lc) and leaf water content(Lw). For validation, these measurements were compared with the ranks of holistic tree vigor condition, which were visually assessed using a 4-point grading scale based on the expert's knowledge. As a result, the measures of each evaluation item successfully highlighted a variety of aspects in tree vigor condition, including the states of both photosynthetic and non-photosynthetic parts. The variation in the results depending on evaluated parts was shown within an individual tree, even though the broad agreement among the results was found. The result of correlation analysis between the tested measurements and 4-point visual assessment, demonstrated that the state of water-stressed foliage of the season (Lw) or the development of plant materials since sapling phase (Vol) could be better viewed from the outer appearance of trees than other symptoms. But only based on the visual assessment, it may be difficult to detect the quality of photosynthesis (Lc) or the recent trend in growth of trees (Gc). To make this methodology simplified for the broad-scale application, the tested eight measurements could be integrated into two components by principal component analysis, which was labelled with 'the amount of plant materials' and 'vigor trend', respectively. In addition, the use of these quantitative and multi-scale indicators underlies the importance of assessing various aspects of tree vigor condition, taking into account the response(s) on different time and spatial scale of pressure(s) shown in each evaluated module. Future study should be advanced for various species at diverse developing stages and environment, and the application to wide areas at a periodic manner.

Effect of human biosignal according as foot was heating with hot water (발 부분 온수 열자극시 인체 현상에 미치는 영향)

  • Lee, Woo-Cheol;Min, Kyeug-Kee;SaKong, Sug-Chin
    • 전자공학회논문지 IE
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    • v.43 no.1
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    • pp.5-15
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    • 2006
  • In this paper, we measured the biosignal using hot-water system(STYX ford202) on foot. The biosignal transition data is observed from hot-water thermotherapy on foot. pre and post demonstration conditions under 43$^{\circ}C$ and 45$^{\circ}C$ are checked about 9 physiological factors for 10 persons and 10 days. (Checking Time: pre-test, post-test(5, 10, 15, 20 minutes)). The biosignal transition of demonstration's results showed as belows; Forehead Temperature($^{\circ}C$): -0.69 $\pm$ 0.01 dec, Leg Temperature($^{\circ}C$): 1.51 $\pm$ 0.22 inc, Blood Flow($m\ell/min$): 1.18 $\pm$ 0.50 inc, Blood Pressure(mmHg): (max) -1.49$\pm$ 2.81, (min) -0.06 $\pm$ 0.13 dec, Heart Rate(bpm): 6.97 $\pm$ 0.72 inc, Blood Sugar($mg/d\ell$) : -2.41 $\pm$ 1.55 dec, Oxygen Saturation(%): 1.34 $\pm$ 0.28 inc, Body Fat(%) -1.75 $\pm$ 0.15 dec, Weight(kg): -0.10 $\pm$ 0.04 dec. (dec: decrease, inc: increase)

A Study on the Noises of Fishes (어류가 내는 소리에 관하여)

  • CHO, AM;CHANG, Jee-won
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.8 no.1
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    • pp.14-22
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    • 1972
  • For the development of acoustic fishing method, the noises of fishes have been recorded and analy/'ed by many scientists. Some specimens of fishes were selected as such Cyprinus carpio, Ctenopharyngodon idellus Carassius carassius, and pagrosol1ms major in this experiment. The noises such as feeding noise, driving away noise, jumping noise and fi llip noise were recorded by the tape recorder, Sony Model 262, through the underwa te r microph I one, Oki ST 6582, and analyzed in frequencies bv octave band analyzer, Rion SA-55, and sound pressure level of source by sound level meter, Rion NA-opNN The supplied feed was placed within 5em apart from the hydrophone. The result of analyzed noises were as follow. Cyprinus carjJio; Feeding noise 250- 500 cps, 92- 99 dB Driving away noise 125-2, 000 eps, 101-112 dB Jumping noise 125-2, 000 eps, 99-116.5 dB Ctenopharyngodon idcllus; Driving away noise 125-1, 000 cps, 96-109 dB Carassius carassius; Feeding noise 250- 500 cps, 91. 5- 99.5 dB Driving away noise 125-1, 000 eps, 99-108 dB Carassius auratus Feeding noise 250 eps, 94-101 dB Driving away noise 125-1, 000 cps, 98-110 dB Pagrosomus major Feeding noise 230-500 cps, 90-101 dB Fillip noise 500 cps, 98-108 dB (1) Feeding noise was produced as like as snap noise of twig and gulping down saliva noise in human and dominant frequency range of the noise is 250-500 cps and noise level 90-101 dB. (2) It was found that feeding noise were not a monotonic but a complex tones though fish took the same food. (3) Driving away noise was produced not so keen and the wave form of the noise is rising very sharp and big amplitude in the oscillograph. Dominant frequency range of this noise was about 150-1, 000 cps and noise level 96-112 dB except thut of carp. (4) The frequency of snapper's fillip noise, when it produced by caudal fin in swimming at the surface of water, was 500 cps and noise level 93-108 dB snd that of jumping noise of carp about 150-2, 000 cps and noise level 99-116.5 dB.

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Numerical Analysis for Fault Reactivation during Gas Hydrate Production (가스하이드레이트 개발과정에서의 단층 재활성화 해석)

  • Kim, Hyung-Mok;Kim, A-Ram
    • Tunnel and Underground Space
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    • v.26 no.2
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    • pp.59-67
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    • 2016
  • In this paper, we perform a numerical analysis to evaluate the potential of fault reactivation during gas production from hydrate bearing sediments and the moment magnitude of induced seismicity. For the numerical analysis, sequential coupling of TOUGH+Hydrate and FLAC3D was used and the change in effective stress and consequent geomechanical deformation including fault reactivation was simulated by assuming that Mohr-Coulomb shear resistance criterion is valid. From the test production simulation of 30 days, we showed that pore pressure reduction as well as effective stress change hardly induces the fault reactivation in the vicinity of a production well. We also investigated the influence of stress state conditions to a fault reactivation, and showed that normal fault stress regime, where vertical stress is relatively greater than horizontal, may have the largest potential for the reactivation. We tested one simulation that earthquake can be induced during gas production and calculated the moment magnitude of the seismicity. Our calculation presented that all the magnitudes from the calculation were negative values, which indicates that induced earthquakes can be grouped into micro-seismic and as small as hardly perceived by human beings. However, it should be noted that the current simulation was carried out using the highly simplified geometric model and assumptions such that the further simulations for a scheduled test production and commercial scale production considering complex geometric conditions may produce different results.