• Biotechnology and Bioprocess Engineering:BBE
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• 제7권6호
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• pp.340-346
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• 2002

The purpose of the present study was to examine the efficacy and mechanism of the PAB (para-amino benzamidine) affinity column chromatography, Viresolve NFP virus filtration, pasteurization (60$\^{C}$ heat treatment for 10 h), and lyophilization steps employed in the manufacture of urokinase from human urine as regards the removal and/or inactivation of the hepatitis A virus (HAV). Samples from the relevant stages of the production process were spiked with HAV and subjected to scale-down processes mimicking the manufacture of urokinase Samples were collected at each step, immediately titrated using a 50% tissue culture infectious dose (TCID$\_$50/), and the virus reduction factors evaluated. PAB chromatography was found to be an effective step for removing HAV with a log reduction factor of 3.24. HAV infectivity was rarely detected in the urokinase fraction, while most of the HAV infectivity was recovered in the unbound and wash fractions. HAV was completely removed during the Viresolve NFP filtration with a log reduction factor of $\geq$ 4.60. Pasteurization was also found to be an effective step in inactivating HAV where the titers were reduced from an initial titer of 7.18 log$\_$10/ TCID$\_$50/ to undetectable levels within 10 h of treatment. The log reduction factor achieved during pasteurization was $\geq$ 4.76. Lyophilization revealed the lowest efficacy for inactivating HAV with a log reduction factor of 1.48. The cumulative log reduction factor was $\geq$ 14.08. Accordingly, these results indicate that the production process for urokinase exhibited a sufficient HAV reducing capacity to achieve a high margin of virus safety.

• Journal of Microbiology
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• 제39권1호
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• pp.67-73
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• 2001

A validation study was conducted to evaluate the efficacy and mechanism of the cryo-precipitation, monoclonal anti-FVIIIc antibody (mAb) chromatography, Q-Sepharose chromatography, and lyophilization steps involved in the manufacture of high purity factor VIII (GreenMono) from human plasma, in the removal and/or inactivation of hepatitis A virus (HAV). Samples from the relevant stages of the production process were spiked with HAV and subjected to scale-down processes mimicking the manufacture of the high purity factor VIII concentrate. Samples were collected at each step and immediately titrated using a 50% tissue culture infectious dose (TCID$\_$50/) and then the virus reduction factors were evaluated. HAV was effectively partitioned from factor VⅢ during cryo-precipitation with the log reduction factor of 3.2. The mAb chromatography was the most effective step far removal of HAV with the log reduction factor of $\geq$4.3. HAV infectivity was not detected in the fraction of factor VⅢ, while most of HAV infectivity was recovered in the fractions of flow through and wash during mAb chromatography. Q-Sepharose chromatography showed the lowest efficacy for partitioning HAV with the log reduction factor of 0.7. Lyophilization was an effective step in inactivating HAV with the log reduction factor of 2.3. The cumulative lag reduction factor, $\geq$10.5, achieved for tile entire manufacturing process was several magnitudes greater than the potential HAV load of current plasma pools.

• Journal of Microbiology and Biotechnology
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• 제11권3호
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• pp.497-503
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• 2001

The purpose of this study was to examine the efficacy and mechanism of the cryo-precipitation, solvent/detergent (S/D) treatment, monoclonal anti-FVIIIc antibody (mAb) column chromatography, Q-Sepharose column chromatography, and lyophilization involved in the manufacture of antithemophilic factor VII(GreenMono) from human plasma, in the removal and/or inactivation of blood-borne viruses. A variety of experimental model viruses for human pathogenic viruses, including the bovine viral diarrhoea virus (BVDV), bovine herpes virus (BHV), murine encephalomyocarditis virus (EMCV), and porcine parvovirus (PPV), were all selected for this study. BHV and EMCV were effectively partitioned from a factor VII during the cryo-precipitation with a log reduction factor of 2.83 and 3.24, respectively. S/D treatment using the organic solvent, tri(n-butyl) phosphate (TNBP), and the detergent, Triton X-100, was a robust and effective step in inactivating enveloped viruses. The titers of BHV and BVDV were reduced from the initial titer of 8.85 and $7.89{log_10} {TCID_50}$, respectively, reaching undetectable levels within 1 min of the S/D treatment. The mAb chromatography was the most effective step for removing nonenveloped viruses, EMCV and PPV, with the log reduction factors of 4.86 and 3.72, respectively. Q-Sepharose chromatography showed a significant efficacy for partitioning BHV, BVDV, EMCV, and PPV with the log reduction the log reduction factors of 2.32, 2.49, 2.60, and 1.33 respectively. Lyophilization was an effective step in inactivating g nonenveloped viruses rather than enveloped viruses, where the log reduction factors of BHV, BVDV, DMCV, and PPV were 1.41, 1.79, 4.76, and 2.05, respectively. The cumulative log reduction factors of BHV, BVDV, EMCV, and PPV were ${\geqq}$11.12, ${\geqq}$7.88, 15.46, and 7.10, respectively. These results indicate that the production process for GreenMono has a sufficient virus-reducing capacity to achieve a high margin of the virus safety.

• 한국식품과학회지
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• 제43권5호
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• pp.537-543
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• 2011

농약을 안전하게 관리하는데 사용되는 지표인 농약의 잔류허용기준의 결정요인 중 하나인 감소계수에 대한 연구는 최근에 더욱 요구도가 높아지고 있다. 그러나 기존의 연구들은 농산물별, 농약별로 이루어져 효율적인 데이터베이스 구축에는 적합하지 못하다. 이에 본 연구는 농약의 감소계수를 농약의 물리화학적 특성에 따라 산출하고자 실험을 계획하였다. 먼저 농약잔류허용기준이 설정된 288개의 농약을 대상으로 하여 이온화그룹포함여부, log P, 끓는점에 따라 propamocarb, azoxystrobin, fenarimol, dichlorvos, edifenphos, cypermethrin, fenvalerate의 농약을 선별하였다. 이 중 회수율과 농약의 전처리과정에서 실험이 어려웠던 propamocarb와 azoxystrobin은 최종 데이터 분석에서 제외하였다. 해당 농약들을 수돗물, 5% 아세트산 수용액, 20% 에탄올 수용액, 0.15% 세제액의 4가지의 세척방법과 데치기, 튀기기 2가지의 조리방법 총 6가지의 조건을 처리하여 Pearson 상관분석을 하였다. 그 결과, log P와의 상관성에 있어 5% 아세트산 수용액은 0.336(p=0.221)로 유의적인 상관성이 없었으나, 수돗물에서의 세척은 -0.835(p<0.001), 20% alcohol solution에서는 -0.659(p<0.01), 세제세척에서는 -0.939(p<0.001)의 값을 얻었다. 데치기와 끓는점은 유의적인 상관성을 보이지 않았으며, log P와는 0.620(p<0.05)로 유의적인 양의 상관관계를 보였다. 튀기기와 끓는점은 상관성이 있으나, 이보다는 log P와의 상관성이 -0.913(p<0.001)로 더 큼을 확인할 수 있었다. 이를 통해 세척과정에 있어서는 농약의 잔류에는 단순히 농약자체의 수용성 뿐 아니라 작물의 침투성도 관계가 있음을 확인할 수 있었다. 반면, 조리과정에 있어서는 농약의 잔류에는 log P와 끓는점이 보다 높은 상관관계를 가짐을 확인할 수 있었다.

• Communications for Statistical Applications and Methods
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• 제28권3호
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• pp.233-250
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• 2021

This paper studies if the accuracies of mortality models (LC model vs. 4-parametric model) are aggravated if a mortality structure changes due to the impact of COVID-19. LC model (LCM) uses dimension reduction for fitting to the log mortality matrix so that the performance of the dimension reduction method may not be good when the matrix structure changes. On the other hand, 4-parametric factor model (4-PFM) is designed to use factors for fitting to log mortality data by age groups so that it would be less affected by the change of the mortality structure. In fact, the forecast accuracies of LCM are better than those of 4-PFM when life-tables are used whereas those of 4-PFM are better when the mortality structure changes. Thus this result shows that 4-PFM is more reliable in performance to the structural changes of the mortality. To support the accuracy changes of LCM the functional aspect is explained by computing eigenvalues produced by singular vector decomposition

• Biotechnology and Bioprocess Engineering:BBE
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• 제9권1호
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• pp.65-68
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• 2004

The purpose of the present study was to examine the efficacy and mechanism of fraction IV cold ethanol fractionation and pasteurization (60$^{\circ}C$ heat treatment for 10 h), involved in the manufacture of albumin from human plasma, in the removal and/or inactivation of the hepatitis A virus (HAV). Samples from the relevant stages of the production process were spiked with HAV and the amount of virus in each fraction then quantified using a 50% tissue culture infectious dose (TCID$\_$50/). HAV was effectively partitioned from albumin during the fraction IV cold ethanol fractionation with a log reduction factor of 3.43. Pasteurization was also found to be a robust and effective step in inactivating HAV, where the titers were reduced from an initial titer of 7.60 log TCID$\_$50/ to undetectable levels within 5 h of treatment. The log reduction factor achieved during pasteurization was $\geq$4.76. Therefore, the current results indicate that the production process for albumin has sufficient HAV reducing capacity to achieve a high margin of virus safety.

• Journal of Microbiology and Biotechnology
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• 제18권7호
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• pp.1317-1325
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• 2008

Viral safety is an important prerequisite for clinical preparations of plasma-derived pharmaceuticals. One potential way to increase the safety of therapeutic biological products is the use of a virus-retentive filter. In order to increase the viral safety of human antihemophilic factor IX, particularly in regard to non-enveloped viruses, a virus removal process using a polyvinylidene fluoride membrane filter (Viresolve NFP) has been optimized. The most critical factor affecting the filtration efficiency was operating pH and the optimum pH was 6 or 7. Flow rate increased with increasing operating pressure and temperature. Recovery yield in the optimized production-scale process was 96%. No substantial changes were observed in the physical and biochemical characteristics of the filtered factor IX in comparison with those before filtration. A 47-mm disk membrane filter was used to simulate the process performance of the production-scale cartridges and to test if it could remove several experimental model viruses for human pathogenic viruses, including human hepatitis A virus (HAV), porcine parvovirus (PPV), murine encephalomyocarditis virus (EMCV), human immunodeficiency virus type 1 (HIV), bovine viral diarrhea virus (BVDV), and bovine herpes virus (BHV). Non-enveloped viruses (HAV, PPV, and EMCV) as well as enveloped viruses (HIV, BVDV, and BHV) were completely removed during filtration. The log reduction factors achieved were $\geq$6.12 for HAV, $\geq$4.28 for PPV, $\geq$5.33 for EMCV, $\geq$5.51 for HIV, $\geq$5.17 for BVDV, and $\geq$5.75 for BHV. These results indicate that the virus filtration process successfully improved the viral safety of factor IX.

• Journal of Microbiology
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• 제38권3호
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• pp.187-191
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• 2000

A validation study was conducted to determine the efficacy of solvent/Detergent (S/D) inactivation and Q-Sepharose column chromatographic removal of the human immunodeficiency virus (HIV) during the manufacturing of a high purity antihemopilic factor VIII (GreenMono) from human plasma. S/D treatment using the organic solvent, tri (n-butyl) phosphate, and the detergent, Trition X-100, was a robust and effective step in eliminating HIV-1. The HIV-1 titer was reduced from an initial titer of 8.3 log10 TCID50 to undetectable levels within one minute of S/D treatment, HIV-1 was effectively partitioned form factor VIII during Q-Sepharose column chromatography with the log reduction factor of 4.1 . These results strongly assure the safety of GreenMono From HIV.

• 한국통신학회논문지
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• 제25권3A호
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• pp.334-341
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• 2000

This paper presents an analysis of the capacity, the interference of adjacent cells of a CDMA cellular system, depending on the soft handoff region and log-normal shadowing. The optimum soft handoff region is chosen by using Erlang capacity. It is shown that when the soft handoff region increases, the Erlang capacity increase due to a reduction of the interference power of adjacent cells. But if the region is increased above a certain value, there is no improvement in the system’s capacity. Furthermore as the standard deviation of the log-normal shadowing's normal distribution factor increases, the soft handoff region has to be increased linearly to achieve the same Erlang capacity.

• 자원ㆍ환경경제연구
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• 제26권1호
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• pp.1-35
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• 2017

본 연구에서는 탄소세를 시행하고 있는 OECD 7개 국가를 대상으로 1995년부터 2013년 기간 동안 $CO_2$ 배출량 감소에 영향을 미치는 주요 요인에 대해 분해 분석을 실시하였다. 최근까지 진행된 $CO_2$ 배출량 변화에 대한 분해 분석 연구들은 기술에 기반을 둔 물리적인 요소에만 초점을 맞추고 있으나 본 연구는 경제적 감축수단인 탄소세의 효과를 반영하여 배출량 변화요인을 분석하였다. 로그 평균 디비지아 지수(Log Mean Divisia Index, LMDI)를 이용하여 분석한 결과, OECD 7개 국가의 총 $CO_2$ 배출량 감소에 가장 큰 기여요인은 에너지 집약도 효과와 탄소세 정책 효과로 나타났다. 다음으로, OECD 7개 국가별 분해분석 결과 에너지 집약도 효과가 배출량 감소에 가장 큰 영향을 주는 것으로 나타났으나, 탄소세 정책효과와 탄소세 세수효과는 국가별 정책 상황과 여건에 따라 상이하게 나타나는 결과를 보였다.