• 제목/요약/키워드: PD-1/PD-L1

검색결과 308건 처리시간 0.023초

Pharmacokinetics of PEG-Hemoglobin SB1, a Hemoglobin-Based Oxygen Carrier, after Its Intravenous Administration in Beagle Dogs

  • Kwon, Oh-Seung;Chung, Uoo-Tae;Chung, Youn-Bok
    • Archives of Pharmacal Research
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    • 제27권2호
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    • pp.259-264
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    • 2004
  • The purpose of the present study was to investigate the pharmacokinetics of PEG-hemoglobin SB 1, a modified bovine hemoglobin with polyethylene glycol, after its single and multiple administration in beagle dogs. For this purpose, the analytical method of free hemoglobin in the plasma was developed and validated. Excellent linearity ($r^2$=0.999) was observed in the calibration curve data, with the limit of quantification of 0.005 g/dL. The precision and the deviation of the theoretical values for accuracy were always within $\pm$15% in both the between-and the within-day results. The method was tested by measuring the plasma concentrations following intravenous administration to beagle dogs and was shown to be suitable for pharmacokinetic studies. In a single dose study, the plasma half-life (t$_{1}$2/) increased and the total body clearance (Cl$_{t}$) decreased with the dose (i.e., 0.017 to 0.75 gHb/kg as PEG-hemoglobin SB1) in both sexes. The volume of distribution at steady-state (Vd$_{ss}$ ) showed no difference with the dose. In contrast, the values of t$_{1}$2/, CL$_{t}$ and the area under the plasma concentration-time curve (AUC) after the multiple dose were significantly different from those of the single dose administration. The values of t$_{1}$2/ in the multiple administration were about two times higher-than that of the single dose. As a result, t$_{1}$2/ of hemoglobin after the administration of PEG-hemoglobin SB1 was about 15-30 h, indicating the PEG modification of the hemoglobin lead to a prolongation of plasma concentration of the protein. Therefore, these observations suggested that the PEG modification of hemoglobin is potentially applicable in the hemoglobin-based therapeutics.tics.

큰느타리버섯 균사체로 제조한 발효두부 추출물의 면역 활성 (Immuno-Activities of Extracts of Tofu Fermented with Pleurotus eryngii Mycelia)

  • 이상원;강종우;김재용;박경욱;박석규;주옥수;이성태;서권일
    • 한국식품영양과학회지
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    • 제39권1호
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    • pp.25-30
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    • 2010
  • 두부의 기능성 및 저장성을 향상시킬 목적으로 큰느타리버섯 균사체를 이용한 발효두부를 제조하여 물과 메탄올로 추출하여 면역세포 활성에 미치는 효과를 조사하였다. 큰느타리버섯 균사체를 배양하기 위한 최적 배지는 PD broth 배지인 것을 확인하였으며, 큰타리버섯 균사체를 이용한 두부의 최적 발효기간은 7일 정도가 적당하였다. 큰느타리버섯 균사체를 이용하여 발효한 두부의 물 및 메탄올추출물은 $0.01 {\mu}g/mL$ 농도 이상에서 비장세포의 증식을 유도하였으며, 이들 추출물은 IL-6, IFN-$\gamma$ 분비를 유도하는 것으로 나타났다. 발효두부 물 추출물은 대조군에 비해 대식세포의 일산화질소 생산을 $1 {\mu}g/mL$ 농도 이상에서 유의적으로 증가시키는 것을 알 수 있었으며, 메탄올 추출물은 $10 {\mu}g/mL$ 농도 이상에서 그 생산을 증가시켰다. 발효두부 추출물들은 대식세포가 분비하는 IL-6, TNF-$\alpha$, IL-1$\beta$ 및 GM-CSF 분비량을 유의하게 증가시켰다. 따라서 큰느타리버섯 균사체로 발효한 두부는 기능성 두부로 개발이 가능하리라 생각된다.

수소 분리를 위한 $V_{99.8}B_{0.2}$ 분리막의 제조와 수소투과특성 (Fabrication and Hydrogen Permeation Properties of $V_{99.8}B_{0.2}$ Alloy Membrane for Hydrogen Separation)

  • 정영민;전성일;박정훈
    • 멤브레인
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    • 제21권4호
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    • pp.345-350
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    • 2011
  • 보론이 도프된 바나듐 합금 분리막은 아직까지 연구된 적이 없다. 본 연구에서는 팔라듐이 코팅된 새로운 $V_{99.8}B_{0.2}$ 조성의 합금 분리막을 합성하여 수소 투과 특성 및 화학적 안정성에 대하여 연구를 수행하였다. 순수 수소, 수소와 이산화탄소의 혼합가스를 $400^{\circ}C$, 절대압력 1.0~3.0 bar에서 공급하여 수소 투과 특성을 알아보았다. 순수 수소를 공급하여 측정한 결과 0.5 mm 두께의 분리막은 최대 $48.5mL/min/cm^2$의 투과량을 보였다. 본 연구 결과는 수성가스 전이반응(WGS)에서 생성된 수소를 분리할 수 있는 비 팔라듐계 수소 분리막의 합성에 새로운 방향을 제시하고 있다.

Pd 코팅된 $Nb_{56}Ti_{23}Ni_{21}$ 합금 분리막의 수소투과 특성 (The Characteristics of Hydrogen Permeation through Pd-coated $Nb_{56}Ti_{23}Ni_{21}$ Alloy Membranes)

  • 정영민;전성일;박정훈
    • 멤브레인
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    • 제22권1호
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    • pp.1-7
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    • 2012
  • 니오븀 금속을 기반으로 하는 $Nb_{56}Ti_{23}Ni_{21}$ 합금 분리막의 수소 투과 특성 및 화학적 안정성에 관한 연구를 수행하였다. 이를 위하여 직경 10 mm, 두께 0.5 mm의 $Nb_{56}Ti_{23}Ni_{21}$ 합금 분리막을 제작하였으며, 2가지 조성($H_2$ 100%, $H_2$ 60% + $CO_2$ 40%)의 공급가스를 $450^{\circ}C$의 온도에서 투과시킬 때 압력에 따른 수소 투과 특성에 관한 실험을 진행하였다. 본 실험에서의 최대 수소 투과량은 순수한 수소를 투과시킬 경우 절대압력 3 bar에서 $5.58mL/min/cm^2$로 나타났다. 또한 공급가스 조성에 따른 각각의 경우 모두 Sievert's law에 잘 부합하였으며, 이산화탄소와의 혼합가스 사용시, 투과량은 수소 분압 감소에 비례하여 감소하였다. 투과 실험 후 XRD 분석을 통하여 $Nb_{56}Ti_{23}Ni_{21}$ 합금 분리막의 이산화탄소에 대한 화학적 안정성에 대한 실험을 수행하였다.

Oxytocin-induced endothelial nitric oxide dependent vasorelaxation and ERK1/2-mediated vasoconstriction in the rat aorta

  • Xu, Qian;Zhuo, Kunping;Zhang, Xiaotian;Zhang, Yaoxia;Xue, Jiaojiao;Zhou, Ming-Sheng
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권4호
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    • pp.255-262
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    • 2022
  • Oxytocin is a neuropeptide produced primarily in the hypothalamus and plays an important role in the regulation of mammalian birth and lactation. It has been shown that oxytocin has important cardiovascular protective effects. Here we investigated the effects of oxytocin on vascular reactivity and underlying the mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and in rat aorta ex vivo. Oxytocin increased phospho-eNOS (Ser 1177) and phospho-Akt (Ser 473) expression in HUVECs in vitro and the aorta of rat ex vivo. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited oxytocin-induced Akt and eNOS phosphorylation. In the rat aortic rings, oxytocin induced a biphasic vascular reactivity: oxytocin at low dose (10-9-10-8 M) initiated a vasorelaxation followed by a vasoconstriction at high dose (10-7 M). L-NAME (a nitric oxide synthase inhibitor), endothelium removal or wortmannin abolished oxytocin-induced vasorelaxation, and slightly enhanced oxytocin-induced vasoconstriction. Atosiban, an oxytocin/vasopressin 1a receptor inhibitor, totally blocked oxytocin-induced relaxation and vasoconstriction. PD98059 (ERK1/2 inhibitor) partially inhibited oxytocin-induced vasoconstriction. Oxytocin also increased aortic phospho-ERK1/2 expression, which was reduced by either atosiban or PD98059, suggesting that oxytocin-induced vasoconstriction was partially mediated by oxytocin/V1aR activation of ERK1/2. The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.

향부자(香附子)의 염증 억제 작용을 통한 항파킨슨 효과 (Anti-parkinsonian effect of Cyperi Rhizoma via inhibition of neuroinflammatory action)

  • 김효근;심여문;오명숙
    • 대한본초학회지
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    • 제28권5호
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    • pp.21-28
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    • 2013
  • Objectives : The aim of this study was to investigate the neuroprotective effects and mechanisms of Cyperi Rhizoma extracts (CRE) using in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the neuroprotective effect of CRE against 1-methyl-4-phenylpyridinium (MPP+) toxicity using tyrosine hydroxylase immunohistochemistry (IHC) in primary rat mesencephalic dopaminergic neurons. In addition, the effect of CRE was evaluated in mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For evaluations, C57bl/6 mice were orally treated with CRE 50 mg/kg for 5 days and were injected intraperitoneally with MPTP (20 mg/kg) at 2 h intervals on the last day. To identify the CRE affects on MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum of mice, the behavioral tests and IHC analysis were carried out. Also, we conducted nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) assay in dopaminergic neurons and IHC using glial markers in SNpc of mice to assess the anti-inflammation effects. Results : In primary mesencephalic culture system, CRE protected dopaminergic cells against $10{\mu}M$ MPP+-induced toxicity at 0.2 and $1.0{\mu}g/mL$. In the behavior tests, CRE treated group showed improved motor deteriorations than those in the MPTP only treated group. CRE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, CRE inhibited productions of NO and TNF-${\alpha}$ in dopaminergic culture system and activation of astrocyte and microglia in SNpc of the mice. Conclusion : We concluded that CRE shows anti-parkinsonian effect by protecting dopaminergic neurons against MPP+/MPTP toxicities through anti-inflammatory actions.

Matrix Modification for Graphite Furnace Atomic Absorption Spectrophotometric Determination of Volatile Elements(III) Trace Bismuth

  • Kim, Young-Sang;Choi, Jong-Moon;Kim, Young-Man
    • 분석과학
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    • 제8권4호
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    • pp.435-442
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    • 1995
  • A matrix modification was studied for the determination of trace bismuth in water samples by graphite furnace atomic absorption spectrophotometry. The type and quantity of modifiers as well as the use of auxiliary modifiers were investigated to realize the efficient modification. Palladium was chosen as a single modifier. By the addition of palladium($5{\mu}g/mL$) to 100 ng/mL bismuth solution, the temperatures could be raised from $500^{\circ}C$ to $1,300^{\circ}C$ for the charring and from $2,000^{\circ}C$ to $2,200^{\circ}C$ for the atomization as well as the sensitivity and reproducibility were improved. The absorbance of bismuth was maximum and not changed in the range of Pd $3-25{\mu}g/mL$. And several materials were examined as an auxiliary modifier. The mixed solution of $1{\mu}g/mL$ palladium and $200{\mu}g/mL$ nickel have raised the temperatures as with $5{\mu}g/mL$ palladium only. The maximum absorbance of bismuth was shown in the nickel concentration range of $100-300{\mu}g/mL$ in $1{\mu}g/mL$ palladium modified system. With such optimum conditions, the trace amount of bismuth in several water samples could be determined by a calibration curve method, and good recoveries were also obtained.

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배양림프구에서 Paraquat의 세포독성에 대한 Vitamin C와 Deferoxamine의 항산화 효과 (The Antioxidant Effect of Vitamin C and Deferoxamine on Paraquat-induced Cytotoxicity in Cultured Lymphocytes)

  • 어은경;김경희
    • 대한임상독성학회지
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    • 제4권1호
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    • pp.7-16
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    • 2006
  • Purpose: As basic information of antioxidant treatments for the patient with paraquat intoxication, in human peripheral lymphocytes, the cytotoxicity of paraquat was measured, and to evaluate the antioxidant effect of vitamin C and deferoxamine against this cytotoxicity, malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured. Methods: From 10 healthy adults, after obtaining a consent, 20ml peripheral blood was collected. Experimental groups were divided to (1) control group, the group treated with an identical amount of saline, (2) P group: the group treated with paraquat only, (3) PV group: the group treated with paraquat followed by vitamin C 30 minutes later, (4) PD group: the group treated with paraquat followed by deferoxamine 30 minutes later, (5) PVD group: the group treated with paraquat followed by vitamin C 30 minutes later and subsequently deferoxamine one hour later, and (6) PDV group: the group treated with paraquat followed by deferoxamine 30 minutes later and subsequently vitamin C 1 hour later, and thus to total 6 groups. In each group, 10 samples of peripheral blood was assigned and $100{\mu}M\;paraquat,\;100{\mu}M$ vitamin C, and $100{\mu}M$ deferoxamine were used as reagent. Lymphocytes were isolated, cultured, and cytotoxicity was measured by the Microculture Tetrazolium method (MTT assay), MDA and SOD activity, and TAS concentration were measured. Results: In regard to the cytotoxicity measured in each group, their cytotoxicity was decreased in the group treated with antioxidants, in comparison with the group treated with paraquat only. In the cases that the order of the treatment of these two antioxidants was altered, viability in the PDV group $(1.077{\pm}0.121)$ was increased more that the PVD group $(0.888{\pm}0.152)$ statistically significantly (p=0.018). Concerning the amount of MDA, in comparison with the P group $(6.78{\pm}0.93{\mu}mol/L)$, after the treatment of each antioxidant, the concentration of MDA was decreased statistically significantly (p<0.05). In the group treated with two antioxidants together, in comparison with the group treated only with one antioxidant, the amount of MDA was increased statistically significantly $(PV:\;3.96{\pm}0.98{\mu}mol/L,\;PD:\;4.92{\pm}1.50{\mu}mol/L,\;PVD:\;3.22{\pm}0.83{\mu}mol/L,\;and\;PDV:\;3.42{\pm}0.95{\mu}mol/L,\;p=0.007)$. The concentration of SOD measured in the blood in each group after the administration of paraquat, in comparison with the control group, a pattern of the elevation of SOD activity and subsequent decrease was detected, however, it was not statistically significant. In the comparison of the groups treated with antioxidants, in comparison with the P group $(1419.9{\pm}265.9{\mu}mol/L)$, SOD activity was decreased statistically significantly in only the PDV group $(1176.4{\pm}238.9{\mu}mol/L)$ (p=0.017). In regard to TAS measured in each group, in comparison with the P group $(0.87{\pm}0.05{\mu}mol/L)$, in all groups treated with the antioxidants, the PV group was $1.00{\pm}0.03{\mu}mol/L$ (p=0.005), the PD group was $9.01{\pm}0.24{\mu}mol/L$ was $4.64{\pm}3.98{\mu}mol/L$ (P=0.005), and the PDV group was $9.41{\pm}0.27{\mu}mol/La$ (p=0.005), and thus total antioxidant activity was increased statistically significantly In a multiple comparison test, the PDV group showed the highest total antioxidant activity (p<0.0001). Conclusion: The result of the assessment of the antioxidant effect of vitamin C and deferoxamine on paraquat-induced cytotoxicity showed that in regard to cytotoxicity, SOD activity and TAS measurement, the best result was observed in the PDV group. Therefore, it was found that vitamin C and deferoxamine were effective antioxidants for the paraquat-induced cytotoxicity, and it suggests that the administration of deferoxamine followed by vitamin C may improve their antioxidant effect more.

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파킨슨병환자의 호흡기능, UPDRS 및 Senior Fitness의 관련성 (Correlations among Respiratory Function, UPDRS and Senior Fitness in Parkinson's Disease Patients)

  • 강동연;천상명;성혜련;이경순;김경
    • The Journal of Korean Physical Therapy
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    • 제26권2호
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    • pp.48-55
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    • 2014
  • Purpose: The purpose of this study was to examine correlations among UPDRS, respiratory function, and senior fitness and to investigate the effects of restrictive respiratory function on these factors in Parkinson's disease patients. Methods: Subjects (n=25, Hoehn & Yahr (H&Y) stage: 2-3, $69.3{\pm}5.9$ yrs) from D Hospital Parkinson's Disease Center at Busan metropolitan area in the Republic of Korea volunteered for this study. They performed the pulmonary function test, UPDRS, and the senior fitness test. SPSS 18.0 was used for analysis of data, and the collected data were analyzed using Pearson's correlation coefficient (n=25). In addition, Independent t-test was used for determination of differences between two groups (between the normal pulmonary function group (n=10) and the restrictive pulmonary function group (n=10)). Results: Forced vital capacity (FVC (L)) showed significant negative correlation (r=-0.44, p<0.05) with H&Y stage in Parkinson's disease patients, and chair stand showed significant negative correlations (r=0.41, 0.43, 0.42, p<0.05) with FVC (L), FVC (%), and FEV1 (L). FVC (%) showed significant positive correlations (r=0.44, r=0.44, p<0.05) with right and left back scratch. In addition, the restrictive respiratory function group showed significantly lower FVC (%) (p<0.01) and was significantly slower (p<0.05) in the 8-foot up-and-go test than the normal respiratory function group. Conclusion: In conclusion, these results suggest that restrictive respiratory function in PD was related to H&Y stage. In addition, agility of PD patients was lower in the restrictive respiratory function group than in the normal function group.

어피 펩타이드 리포좀 대량생산 최적 조건 및 저장 안정성 (Optimization and Scale-up of Fish Skin Peptide Loaded Liposome Preparation and Its Storage Stability)

  • 이중규;이윤정;백정정;김수진;조영재;최미정
    • 산업식품공학
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    • 제21권4호
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    • pp.360-366
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    • 2017
  • 본 연구에서는 lab scale 용량으로 100 mL, 1 L 단위로 리포좀을 제조하였으며, prototype scale로서 10 L 단위로 blank 리포좀의 제조한 뒤 입자 크기 및 포집 효율을 측정하여 최적 제조 조건 선정하였다. 선정한 최적조건으로 어피 펩타이드를 리포좀으로 포집하여 그에 따른 저장 안정성을 평가하였다. 1차 균질 조건은 초고속균질기를 사용하여 3분간 각각 4,000 rpm, 8,000 rpm, 12,000 rpm으로 균질하였으며, 2차 균질 조건은 초음파균질기를 이용하여 각각 40 W, 60 W, 80 W로 3분간 균질하여 최적 균질 조건을 확립한 뒤 어피 펩타이드 리포좀을 농도에 따라 제조하여 $4^{\circ}C$에서 냉장 저장하였다. 최적 제조 조건 실험 결과를 two-way ANOVA로 분석한 결과 1, 2차 균질에서는 제조 용량이 입자크기와 제타 전위에 유의적으로 가장 큰 영향을 미쳤으며(p<0.001), pdI는 2차 균질 조건에서 제조용량을 제외하고는 어떤 요인도 유의적으로 영향을 미치지 못하였다(p>0.05). 1차 균질 실험 결과 lab scale에서 prototype scale로 제조 용량이 증가하였을 때, 유의적으로 입자크기가 증가하였으며(p<0.05), 가장 입자크기가 작고 제타전위의 절대값이 높은 4,000 rpm을 최적조건으로 선정하였다. 2차 균질 실험결과 40 W에서 제조 용량이 증가하였을 때 유의적으로 제타전위가 감소하였으며, 60 W 이상에서는 안정적인 결과가 나타났다. 리포좀의 산업적 적용을 고려할 때 공정비용 감소 측면에서 80 W보다 60 W가 적절하다고 사료된다. 선정된 리포좀 최적 조건으로 농도(3, 6, 12, 24%)별로 어피 펩타이드를 포집하였을 때, 24%에서 입자크기가 1 mm 이상으로 크게 나타났다. 이후 저장실험에서는 24%를 제외한 3가지 조건으로 진행하였다. 1달간 어피 펩타이드 리포좀을 냉장 저장한 결과를 two-way ANOVA로 분석한 결과, 펩타이드 농도에 따라 제조하였을 때는 입자크기와 제타 전위가 제조용량보다 펩타이드 농도에 더 큰 영향을 받았다. 또한 저장기간은 pdI에 유의적으로 영향을 미치는 것으로 나타났다(p<0.001). 입자크기는 제조용량과 펩타이드 농도가 증가함에 따라서 유의적으로 증가하였으며, 저장기간에 따라서 감소하였다. 제타전위는 10 L 용량에서 저장기간에 따라 증가하는 경향을 보였다. 이는 리포좀이 풀리면서 비표면적이 증가하여 제타전위가 증가한 것으로 사료된다. 또한 12%에서 3주차부터 침전물층이 형성되는 것이 관찰되어 6%가 가장 산업적용으로 적합한 농도로 사료된다.