• 제목/요약/키워드: PK method

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럼핑법을 이용한 생리학 기반 약물동태모델 및 구획화 약물동태모델 상호 호환 연구: 보리코나졸 적용 연구 (Compatibility Study between Physiologically Based Pharmacokinetic (PBPK) and Compartmental PK Model Using Lumping Method: Application to the Voriconazole Case)

  • 류효정;강원호;채정우;윤휘열
    • 한국임상약학회지
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    • 제31권2호
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    • pp.125-135
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    • 2021
  • Background: Generally, pharmacokinetics (PK) models could be stratified into two models. The compartment PK model uses the concept of simple compartmentalization to describe complex bodies, and the physiologically based pharmacokinetic (PBPK) model describes the body using multi-compartment networking. Notwithstanding sharing a theoretical background in both models, there was still a lack of knowledge to enhance compatibility in both models. Objective: This study aimed to evaluate the compatibility among PBPK, lumping model and compartment PK model with voriconazole PK case study. Methods: The number of compartments and blood flow on each tissue in the PBPK model were modified using the lumping method, considering physiological similarities. The concentration-time profiles and area under the concentration-time curve (AUC) parameters were simulated at each model, assuming taken voriconazole oral 400 mg single dose. After that, those mentioned PK parameters were compared. Results: The PK profiles and parameters of voriconazole in the three models were similar that proves their compatibility. The AUC of central compartment in the PBPK and lumping model was within a 2-fold range compared to those in the 2- compartment model. The AUC of non-eliminating tissues compartment in the PBPK model was similar to those in the lumping model. Conclusion: Regarding the compatibility of the three PK models, the utilization of the lumping method was confirmed by suggesting its reliable PK parameters with PBPK and compartment PK models. Further case studies are recommended to confirm our findings.

인공신경망을 적용한 직사화기 무기체계의 살상확률(Pk) 산출방법론 연구 (A Study on Pk(Probability of Kill) Calculation Method of the Direct Fire Weapon System using ANN)

  • 장영천;한현진;이기택;송미진;이휘영;김종헌
    • 한국시뮬레이션학회논문지
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    • 제28권1호
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    • pp.99-107
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    • 2019
  • 기존 본 연구팀에서 연구한 직사화기 무기효과 산출방법론은 JMEM(Joint Munitions Effectiveness Manuals : 합동탄약효과편람)내(內) 표적에 대해서만 무기효과자료를 산출 가능하다는 제한 사항을 가지고 있었다. 따라서 본 연구에서는 JMEM 이외의 현실적 표적을 추가하여 무기효과자료를 산출하는 방법을 인공신경망(ANN : Artificial Neural Network)을 적용하여 도출하는 데 중점을 두었다. 즉, 미국 JMEM내(內) 표적의 제원과 효과지수인 취약면적(Av : vulnerable area)을 이용하여 인공신경망의 예측모델을 학습시키고, 학습된 예측모델에 현실적 표적의 제원을 적용하여 취약면적을 계산한다. 최종적으로 본 연구팀이 연구한 기존 직사화기 무기효과 산출방법론에 계산된 취약면적을 적용하여 살상확률(Pk)을 계산하는 방법론을 제시하였다.

HPLC-DAD를 이용한 차조기 잎의 Isoegomaketone 및 Perillaketone의 동시분석법 확립 (Simultaneous Determination of Isoegomaketone and Perillaketone in Perilla frutescens (L.) Britton Leaves by HPLC-DAD)

  • 남보미;이승영;김진백;강시용;진창현
    • 생약학회지
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    • 제47권1호
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    • pp.79-83
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    • 2016
  • This study developed an HPLC analysis method for the determination of isoegomaketone (IK) and perillaketone (PK) in Perilla frutescens (L.) Britton leaves. P. frutescens ethanol extract was optimized through an HPLC analysis using a C18 column ($250{\times}4.6mml$, D, $S-5{\mu}m$, 12 nm) with gradient elution of water and acetonitrile as the mobile phase at a flow rate of 1 mL/min and a UV detection wavelength of 254 nm. The results of this method showed linearity in the calibration curve at a coefficient of correlation ($R^2$) of IK 0.9995, PK 0.9998. The limits of detection (LOD) for IK and PK were $0.234{\mu}g/mL$ and $0.952{\mu}g/mL$. The limits of quantification (LOQ) for IK and PK were $0.017{\mu}g/mL$ and $0.043{\mu}g/mL$. The inter-day precision RSDs of IK and PK in the P. frutescens were 1.25 to 2.69% and 0.36 to 1.10%, respectively, and the intra-day precision RSDs of IK and PK were 0.96 to 2.51% and 0.90 to 1.93%, respectively. The accuracies of IK and PK were 96.31 to 97.92% and 101.26 to 105.14%. In conclusion, this method was applied successfully to the detection of IK and PK in P. frutescens.

$^{11}$C 표지 자동합성장치에서 루프법을 이용한 ($^{11}$C)(R)-PK11195의 간편한 합성법 (A Convenient Radiolabeling of [$^{11}$C](R)-PK11195 Using Loop Method in Automatic Synthesis Module)

  • 이학정;정재민;이윤상;김형우;최재연;이동수;정준기;이명철
    • Nuclear Medicine and Molecular Imaging
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    • 제43권4호
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    • pp.337-343
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    • 2009
  • 목적: (R)-1-(2-Chlorophenyl)-N-methyl-N-1-(1-methyl-propyl)-3-isoquinoline carboxamide ((R)-PK11195)는 말초형 벤조디아제핀 수용체 (PBR)의 친화성이 높으며, 활성화된 소교세포(microglia)의 PBR에 선택적으로 결합하는 것으로 알려져 있다. 본 연구에서는 말초형 벤조디아제핀 수용체 (PBR)의 FET용 리간드인[$^{11}$C](R)-PK11195를, 절차가 빠르고 간단한 [$^{11}$C]CH$_3$I 자동합성장치 및 루프법을 도입해서 합성하였다. 대상 및 방법: 사이클로트론에서 $^{14}$N(p,a)$^{11}$C핵반응에 의하여 생산된 [$^{11}$C]Co$_2$를 0.2 M LiAlH$_4$/THF (0.2 mL)로 환원한 다음 HI (1 mL)과 반응하여 [$^{11}$C]CH$_3$I를 생산하였다. 반응용매인 NaH DMF complex (0.1 mL)와 녹인 전구물질 (R)-N-desmethyl-PK11195 (1 mg)을 녹인 DMSO (0.1mL)를 섞은 혼합액을 HPLC의 루프에 미리 주입하고 [$^{11}$C]CH$_3$I를 상온에서 5분 동안 질소가스로 불어준 뒤에 semi-preparative HPLC로 [$^{11}$C](R)-PK11195를 분리하였다. 결과: 전구물질과 [$^{11}$C]CH$_3$I의 [$^{11}$C]메틸화 반응에서의 표지효율은 71.8$\pm$8.5% 이었다. 분리 후 얻은 [$^{11}$C](R)-PK11195의 비방사능은 11.8$\pm$6.4 GBq/$\mu$mol이었으며, 방사화학적 순도는 99.2% 이상이었다. C-11 표지 후 얻어진 (R)-PK11195의 물질의 질량 분석은 m/z 353.1 (M+1)으로 물질구조를 확인 할 수 이었다. 결론: 뇌염증에 의한 활성화 소교세포의 영상화를 위한 PET용 방사성의약품인 [$^{11}$C](R)-PK11195를 반복적으로 생산해야 하는 임상 적용을 위해, 합성절차가 빠르고 간단한 [$^{11}$C]CH$_3$I 자동화 합성장치를 1차 루프 방법을 이용하여 $^{11}$C을 표지 할 수 있었다. 이 연구를 통해서 [$^{11}$C](R)PK11195 표지 할 때 반응 단계를 줄이고 반응을 실온에서 할 수 있어서 표지과정을 보다 단순화할 수 있었으며, NaH의 DMF현탁액을 사용함으로써 보다 안전하게 생산할 수 있게 되었다.

Increase of L-type Calcium Current by cGMP-dependent Protein Kinase Regulates in Rabbit Ventricular Myocytes

  • Han, Jin;Kim, Na-Ri;Kim, Eui-Yong;Ho, Won-Kyung;Earm, Yung-E;Kim, Han-Kyoun
    • The Korean Journal of Physiology and Pharmacology
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    • 제2권6호
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    • pp.733-742
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    • 1998
  • Background: We have previously reported that not only cGMP but also 8-Br-cGMP or 8-pCPT-cGMP, specific and potent stimulators of cGMP-dependent protein kinase (cGMP-PK), increased basal L-type calcium current $(I_{Ca})$ in rabbit ventricular myocytes. Our findings in rabbit ventricular myocytes were entirely different from the earlier findings in different species, suggesting that the activation of cGMP-PK is involved in the facilitation of $I_{Ca}}$ by cGMP. However, there is no direct evidence that cGMP-PK can stimulate $I_{Ca}}$ in rabbit ventricular myocytes. In this report, we focused on the direct effect of cGMP-PK on $I_{Ca}}$ in rabbit ventricular myocytes. Methods and Results: We isolated single ventricular myocytes of rabbit hearts by using enzymatic dissociation. Regulation of $I_{Ca}}$ by cGMP-PK was investigated in rabbit ventricular myocytes using whole-cell voltage clamp method. $I_{Ca}}$ was elicited by a depolarizing pulse to +10 mV from a holding potential of -40 mV. Extracellular 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP), potent stimulator of cGMP-dependent protein kinase (cGMP-PK), increased basal $I_{Ca}}$. cGMP-PK also increased basal $I_{Ca}}$. The stimulation of basal $I_{Ca}}$ by cGMP-PK required both 8-Br-cGMP in low concentration and intracellular ATP to be present. The stimulation of basal $I_{Ca}}$ by cGMP-PK was blocked by heat inactivation of the cGMP-PK and by bath application of 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP), a phosphodiesterase-resistant cGMP-PK inhibitor. When $I_{Ca}}$ was increased by internal application of cGMP-PK, IBMX resulted in an additional stimulation of $I_{Ca}}$. In the presence of cGMP-PK, already increased $I_{Ca}}$ was potentiated by bath application of isoprenaline or forskolin or intracellular application of cAMP. Conclusions: We present evidence that cGMP-PK stimulated basal $I_{Ca}}$ by a direct phosphorylation of L-type calcium channel or associated regulatory protein in rabbit ventricular myocytes.

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Using Highly Secure Data Encryption Method for Text File Cryptography

  • Abu-Faraj, Mua'ad M.;Alqadi, Ziad A.
    • International Journal of Computer Science & Network Security
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    • 제21권12호
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    • pp.53-60
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    • 2021
  • Many standard methods are used for secret text files and secrete short messages cryptography, these methods are efficient when the text to be encrypted is small, and the efficiency will rapidly decrease when increasing the text size, also these methods sometimes have a low level of security, this level will depend on the PK length and sometimes it may be hacked. In this paper, a new method will be introduced to improve the data protection level by using a changeable secrete speech file to generate PK. Highly Secure Data Encryption (HSDE) method will be implemented and tested for data quality levels to ensure that the HSDE destroys the data in the encryption phase, and recover the original data in the decryption phase. Some standard methods of data cryptography will be implemented; comparisons will be done to justify the enhancements provided by the proposed method.

Aspergillus nidulans 온도감수성 돌연변이주의 분리 및 분석 (Isolation and Analysis of Temperature Sensitive Mutants in Aspergillus nidulans)

  • 박찬규;강현삼
    • 미생물학회지
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    • 제16권3호
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    • pp.111-121
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    • 1978
  • About 40 temperature-sensitive mutants have been isolated as a preliminary step to study the spore germination, the cell cycle, and the control of macromolecular synthesis in Aspergillus nidulans. To obtain temperature-sensitive mutants rapidly and effectively, the selective enrichment method using antifungal antibiotic nystatin was developed. Based on the data which had applied to the concentration of auxotrophic mutants by the earlier investigators, the optimal concentration and the time of treatment at the nonpermissive temeprature were determined as 50 to 100 units per ml and 4.5 hr., respectively. Out of 41 ts mutants assigned to the strain symbol PK, thirteen that seemed to be arrested at the earlystage of spore germination were subjected to the further cytological and genetic analysis. Elght of these mutants are able to form germ tube and five not. Staining with acid fuchsin for the 5PK strains shows that one irreversible mutant, PK6 strain able to form germ tube, accumulate mitotic spindle, being arrested in mitosis. Another PK15 and PK23 strain have more than one intact nucleolus without germ tube formation at the restrictive temperature. the temperature-senstive mutation in PK12 strain, the onlystrain which is able occurred in certain gene specific for the germination of spore. All of the ts markers are recessive and complement each other in heterokaryon between two different ts markers at the restrictive temperature.

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돼지의 백혈구 인터폐론 생산에 관한 비교연구 (Comparative Study on the Production of Interferons from Porcine Blood Leukocytes)

  • 한수남;이장락;이창업
    • 대한수의학회지
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    • 제27권2호
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    • pp.191-200
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    • 1987
  • Attempts were to produce porcine leukocyte interferon(PorLeIF) and porcine immune interferon (PorIIF) in the culture of porcine leukocytes. The interferons produced were tested for antiviral activity against vesicular stomatitis virus on poreine-derived PK(15) cells, human-derived FL cells, and Korean native black goat-derived BGK cells. The results were summarized as follws: 1. In the isolation of porcine leukocytes, the mean isolation rate by the buffy coat separation method (28.7%) was higher than that by the hydroxyethyl starch-RBC sedimentation method (9.2%). 2. When NDV(BI)-induced PorLeIFs were assyed on PK(15) cells and FL cells, the mean titers were 129 IU/ml and 72 IU/ml respectively, being 55.8% of the activity in homologous species system expressed in heterologous system. 3. The activities of PHA P-induced PorIIFs were 197 IU/ml on PK (15) cells and no activity on human FL cells. The mean antiviral activity of PorIIF was 1.5 times that of PorLeIF in PK (15) cells. 4. The cytopathic effect of vesicular stomatitis virus was observed in BGK cells derived from Korean native black goat kidney permitting interferon assay on the cells. While the cross-species antiviral activity of reference human ${\alpha},\;{\beta}-interferon$ was observed on the cells, PorLeIF and PorIIF did not show any activity.

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Cpk Index Estimation under Tw (the weakest t-norm)-based Fuzzy Arithmetic Operations

  • Hong, Dug-Hun
    • International Journal of Fuzzy Logic and Intelligent Systems
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    • 제8권3호
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    • pp.170-174
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    • 2008
  • The measurement of performance of a process considering both the location and the dispersion of information about the process is referred to as the process capacity indices (PCIs) of interest, $C_{pk}$. This information is presented by the mean and standard deviation of the producing process. Linguistic variables are used to express the evaluation of the quality of a product. Consequently, $C_{pk}$ is defined with fuzzy numbers. Lee [Eur. J. Oper. Res. 129(2001) 683-688] constructed the definition of the $C_{pk}$ index estimation presented by fuzzy numbers and approximated its membership function using the "min" - norm based Zadeh's extension principle of fuzzy sets. However, Lee's result was shown to be invalid by Hong [Eur. J. Oper. Res. 158(2004) 529-532]. It is well known that $T_w$ (the weakest t-norm)-based addition and multiplication preserve the shape of L-R fuzzy numbers. In this paper, we allow that the fuzzy numbers are of L-R type. The object of the present study is to propose a new method to calculate the $C_{pk}$ index under $T_w-based$ fuzzy arithmetic operations.

전기방사법의 제조 조건에 따른 폴리케톤 마이크로/나노섬유 분리막 제조 및 유수 분리 적용 (Preparation of Polyketone Micro/nanofiber Membrane based on Electrospinning Condition and Its Application in Oil-Water Separation)

  • 후건;윤재한;박찬주;최진원;전성일;이창현;변홍식
    • 멤브레인
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    • 제31권6호
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    • pp.426-433
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    • 2021
  • 본 연구에서는 polyketone (PK)을 이용하여 전기방사 조건에 따른 섬유 형상의 특성 변화와 유수분리 가능성을 확인해 보았다. 고습과 저습 조건에서는 마이크론 직경의 섬유가 형성되었으며, 특히 고습에서는 섬유의 표면이 거칠게 변한 것이 확인되었다. 섬유 직경을 micro에서 nano로 변경하기 위하여 방사용액에 염을 추가하였으며, 그 결과 섬유 직경이 약 90% 감소하는 것을 확인할 수 있었다. 제조된 rPK-LNC와 PK-H로 유수분리 특성을 확인하기 위해 oil/water 에멀션으로 중력 조건에서 유수분리를 진행하였으며 total organic carbon (TOC)와 탁도를 측정하여 특성을 분석하였다. 제거율 확인결과 탁도가 TOC와 동일한 경향성을 나타내는 것이 확인되었다. 따라서 본 연구에서는 고분자의 방사조건과 염의 유무에 따른 분리막의 섬유 형상과 물리적 특성변화와 이를 이용한 유수분리 특성에 대해 연구하였다.