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Sang-Heon Cho,Jung-Hee Lee,Hyeong-Seok Lim,Kyoo-Hyung Lee,Dae-Young Kim,Sangmin Choe,Kyun-Seop Bae,Je-Hwan Lee 대한생리학회-대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.3
The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) (23×ABW<sup>0.5</sup> mg daily) targeting an area under the concentration-time curve (AUC) of 5924 μM∙min. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a <i>posteriori</i> Bayesian estimators were estimated to calculate the predicted AUC (AUC<sub>PRED</sub>). The accuracy and precision of the AUC<sub>PRED</sub> values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of 5924 μM∙min. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of AUC<sub>PRED</sub> were -5.8% and 20.6%, respectively, in the conventional dosing group and –2.1% and 14.0%, respectively, in the new dosing scheme group. These findings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.
( Dae Hun Kwon ),( In Hee Kim ),( Bum Su Choung ),( Dae Seon Ahn ),( Sun Ho Yoo ),( Sang Bae Park ),( Seok Lee ),( Seong Hun Kim ),( Sang Wook Kim ),( Yong Jin Im ) The Editorial Office of Gut and Liver 2013 Gut and Liver Vol.7 No.6
Background/Aims: We investigated the efficacy of continu-ous long-term entecavir 0.5 mg treatment in naive chronic hepatitis B patients showing a partial virologic response (PVR). Methods: A total of 227 patients were included. PVR was defined as a more than 1 log10 IU/mL decline in detect-able serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR; ≥20 IU/mL) at week 48. A complete virologic response (CVR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL) at week 48. Results: At week 48, the rate of the PVR was 64/227 (28.2%). Among patients with PVR, the cumulative rates of virologic response (serum HBV DNA <20 IU/mL) at weeks 96 and 144 were 45.2% and 73.8%, respectively. The cumulative rates of genotypic resistance were not significantly different between patients with a PVR and patients with a CVR (p=0.057). However, the cumulative rates of virologic breakthrough were higher in patients with PVR than in patients with CVR (4% vs 0% and 11.2% vs 0% at weeks 96 and 144, respectively; p<0.001). Conclusions: Long-term continuous entecavir 0.5 mg treat-ment in patients with a PVR resulted in an additional virologic response without a significant increase in genotypic resis-tance. However, the rate of virologic breakthrough was higher in the partial responders. (Gut Liver 2013;7:712-718)
( Dae Hoe Gu ),( Min Seon Park ),( Tae Jung Yun ),( Seok Bae Yoon ),( Sun Young Yim ),( Jin Yong Jung ),( Jin Dong Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Soon Ho Um ),( Ho Sang Ryu ),( Yun Ji Pa 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: The use of antiviral agent has changed the prognosis of patients with hepatitis B virus (HBV)-related end stage liver disease. In these patients, therefore, a more efficient prognostic model for determining early mortality is necessary to properly select those who require liver transplantation. In this study, we aimed to develop a new prognostic model. Methods: We retrospectively analyzed a total of consecutive 194 patients with decompensated HBV-related liver cirrhosis (≥CTP score 7, ascites, or jaundice) who had initially started antiviral treatment in Korea university Anam hospital. Univariate and multivariate cox-regression modeling was used to develop a model for predicting 6-month mortality Results: The study population was predominantly male (128/194) and median age was 51 years. Antiviral agents were administered for a median of 41 months (lamivudine in 157 patients, entecavir in 37). At baseline 147 and 12 patients had ascites and encephalopathy, respectively, with a mean CTP score of 9. Twenty-one (10.8%) patients died within the first 6 months of treatment. Univariate analysis revealed that baseline variables such as age, the presence of ascites or encephalopathy, serum bilirubin, prothrombin time, albumin, Na, BUN, alkaline phosphatase, and HBV DNA levels were associated with the deaths within 6-months (all P<0.05). Among them serum bilirubin, prothrombin time, HBV DNA levels and age were found to be independent risk factors in multivariate analysis. Using these four risk factors, we developed new scoring system to predict 6-months mortality. This new prediction model showed AUROC of 0.941, higher than those of CTP score and MELD score which were 0.893 and 0.862, respectively. Conclusions: This newly developed prediction model for early mortality will be useful in selecting the candidates of urgent liver transplantation in patients with decompensated HBV-related liver cirrhosis.
Dae-Seok Bae,Yong-Kwon Koh,Sang-Jin Lee,Hyunjoo-Kim,Byong-Il Choi 한국방사성폐기물학회 2013 방사성폐기물학회지 Vol.11 No.2
사용후핵연료 최종처분을 위해 심층처분은 세계적으로 가장 선호되는 방법이다. 이를 위해 선진국들은 자국 여건에 가장 잘 부합되는 고유의 처분시스템 개발에 주력하고 있거나, 일부 확보하여 상용처분사업에 적용하 고 있다. 현재까지 알려진 대부분의 심층처분시스템은 공학적 및 천연방벽으로 구성된 다중방벽시스템이다. 이들 처분시스템은 수 천 년 ~ 수 십만 년 이상의 성능기간이 대하여 성능·안전성의 입증이 확인되어야 후속 상용처분사업에 적용 가능하다. 입증 현안과제들은 처분시스템의 상능·안전성 확보를 위해 수행되는 모든 행 위 즉, 조사, 분석, 해석, 평가, 설계, 건설, 운영 및 폐쇄에 이르는 전 과정에 있어서 추진 과정과 결과에 대한 실현 가능성과 실증에 필요한 내용들이 해당된다. 이를 위해 대부분의 선진국들은 자국내 분포하는 대표적인 선호암종 지역에서 지하연구시설(URL)을 건설하여 실증·시연프로그램을 수행하거나 완성단계에 있다. 이 과 정과 결과들은 후속되는 최종처분장 부지선정 과정에 평가기준으로 활용될 것이며, 최종처분시설의 성능·안 전성평가에 필수적으로 적용하게 된다. 지하연구시설은 또한 규제-일반대중-전문가 등 다양한 이해당사자들 로 하여금 심층처분의 안전성 수준에 대한 이해제고와 토론의 마당으로서 핵심적인 역할과 기능을 할 것으로 기대된다.
Bae, Dong Won,Kawk, Yeong Sik,Lee, Joon Taek,Son, Dae Young,Chun, Sung Sik,Kim, Hee Kyu 한국미생물 · 생명공학회 2000 Journal of microbiology and biotechnology Vol.10 No.6
An antifungal protein antagonistic to the rice blast fungus, Pyricularia oryzae was purified from Paenibacillus macerans PM-1 by ammonium sulfate fractionation, Q Sepharose Fast Flow column chromatography, Phenyl Sepharose CL-4B column chromatography and Superose 12gel filtration. An apparent molecular mass of the purified antifungal protein was determined as 8kDa by SDS-PAGE and 9kDa by analytical gel filtration, respectively, suggesting that the purified protein is a monomer. The antifungal protein was stable at pH range from 7-12 and up to 100℃. The protein was also stable at 0.1-1% Tween 20 and Triton X-100. The N-terminal amino acid sequence of the antifungal protein was Thr-Glu-Leu-Pro-Leu-Gly-Ile-Val-Met-Asp-Lys-Tyr-Thr-Asp-Ala-Phe-Lys-Phe-Asp-Met-Phe. Comparison of the determined sequence with other peptide and DNA sequences did not reveal homology at all. Therefore, the purified antifungal protein was speculated to be a novel protein. The conidial germination in vitro of P oryzae KJ 301: 93-39 by the purified protein (5.9㎍/㎖) was limited to 9±3.2% only, compared with 69±2.4% of the control. Ungerminated conidia were swollen at basal and mid cell by the purified protein. In vivo bioassay for inhibition of conidial germination of P oryzae KJ 301, one of the most predominating races in Korea, the purified protein (5.9㎍/㎖) strongly inhibited the conidial germination. The conidia, even though germinated, could not develop any further to produce appressoria efficiently.
Configuration sensitivity analysis of mechanical dynamics
Bae, Dae sung 한국공작기계학회 2001 한국생산제조학회지 Vol.10 No.1
Design sensitivity is an important device in improving a mechanical system design. A continuum design consists of the shape and orientation design. This research develops the shape and orientation design sensitivity method. The configuration design variables of multibody systems define the shape and orientation changes. The equations of motion are directly differentiated to obtain the governing equations for the design sensitivity. The governing equation of the design sensitivity is formulated as an overdetermined differential algebraic equation and treated as ordinary differential equations on manifolds. The material derivative of a domain functional is performed to obtain the sensitivity due to shape and orientation changes. The configuration design sensitivities of a fly-ball governor system and a spatial four bar mechanism are obtained using the proposed method and arc validated against those obtained from the finite difference method.