• 제목/요약/키워드: FPP

검색결과 60건 처리시간 0.033초

스타틴 그리고 배아줄기세포에서의 작용 (Statins and Their Effects on Embryonic Stem Cells)

  • 이미희;한용만;조이숙
    • 한국발생생물학회지:발생과생식
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    • 제11권2호
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    • pp.59-66
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    • 2007
  • 배아줄기세포를 이용한 치료법 개발을 위해서는 배아줄기세포의 자가재생산 및 분화과정을 조절하는 분자적 기전을 이해하는 것이 매우 중요하다. 지질합성경로(Mevalonate pathway)에 작용하는 HMG-CoA 환원효소(Hydroxymethylglutaryl-coenzyme A reductase)의 억제제인 스타틴은 콜레스테롤 저하제로 잘 알려져 있으며, 콜레스테롤 이외에 단백질 isoprenylation의 기질로 작용하는 아이소프레노이드(Isoprenoids)(Farnesyl pyrophosphate(FPP), Geranylgeranyl pyrophosphate(GGPP))의 생성을 억제하는 효능을 가지고 있다. 스타틴에 의해 매개되는 표적단백질의 isoprenylation 억제는 다양한 세포내 신호전달과정에 영향을 미치게 되며, 결과적으로 세포기능을 조절하는데 핵심적인 역할을 하게 된다. 스타틴이 첨가된 배양배지에서 배양된 배아줄기세포는 자가재생산능이 억제되고 분화가 촉진되는데, 특히 지방/골세포 직계열로의 분화가 촉진된다. 배아줄기세포에서의 스타틴의 효과 및 작용기전에 대한 이해가 아직은 미비한 수준이나, 최근 우리 연구팀에서는 스타틴이 콜레스테롤 작용과는 무관하게 RhoA G-단백질의 세포내 분포 및 활성을 억제함으로써 배아 줄기세포의 자가재생산능을 억제하고 있음을 규명하였다. 스타틴 다면효과와 그 작용에 대한 이해는 배아줄기세포의 미분화 및 분화상태를 조절하는데 관여하는 분자적 조절기전을 이해하는데 중요한 모델이 될 수 있을 것으로 추정된다.

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원자력발전소 사고 사망의 통계적 생명가치와 사회적 비용 및 에너지정책 시사점 (The Value of a Statistical Life and Social Costs of Death due to Nuclear Power Plant Accidents and Energy Policy Implications)

  • 김용주
    • 한국방사선학회논문지
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    • 제17권1호
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    • pp.79-90
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    • 2023
  • 본 논문은 원자력발전소(원전) 사고에 의한 조기사망의 사회적 비용을 추정하기 위해 조건부가치측정법(Contingent Valuation Method, CVM)을 이용하여 통계적 생명가치(Value of a Statistical Life, VSL)를 추정한다. VSL 추정치는 약 35억 5천만 원이다. 이에 세계 원전 역사상 발생한 모든 사고 사망자수 약 181만 명을 곱하여 추정한 사회적 비용은 1,952조 원으로서 한국의 2022년 실질 GDP에 비견되는 수준이다. 연평균 조기사망자수와 사회적 비용은 각각 26,000명과 28조 원이다. 1987~2021년간 세계 화력발전소의 사고와 대기오염물질 배출로 인해 발생한 조기사망의 사회적 비용 추정치는 26,919조 원인데, 이는 미국의 2021년 GDP 규모에 상당하는 규모로서 9조 원을 기록한 원전의 약 3,000배에 달한다. 2021년 한 해만 보더라도, 화력발전소의 사회적 비용은 1,075조 원에 달하지만, 원전은 2,920억 원에 불과하다. 한국의 경우, 2050 탄소중립 정책의 영향으로 재생에너지 발전 비중이 증가할 것이므로, 화력발전 대비 원자력발전 비중을 증가시키는 에너지믹스를 제안한다. 본 논문은 또한 효율적인 에너지 정책을 담보하기 위해 CVM을 이용한 VSL 추정 연구를 지속적으로 축적할 필요가 있음을 강조한다.

반도체 웨이퍼 면저항 측정기의 설계제작 (A Design and Manufacture on Sheet Resistance Measure Instrument of Semiconductor Wafers)

  • 강전홍;김한준;한상옥;김종석;류제천
    • 대한전기학회:학술대회논문집
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    • 대한전기학회 2005년도 제36회 하계학술대회 논문집 C
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    • pp.2034-2036
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    • 2005
  • Four Point Probe 방법을 이용한 반도체 wafer의 면저항 측정을 위하여 single configuration 기술을 적용한 회로를 설계 제작하였으며, 제작된 FPP장치의 면저항 측정범위는 $10{\sim}3000{\Omega}/sq.$ 이고 측정의 정확도는 약 0.5%이하이다.

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Electrospray-Mass Spectrometric Analysis of Plasma Pyrophosphates Separated on a Multi-Modal Liquid Chromatographic Column

  • Lee, Su-Hyeon;Lee, Jeong-Ae;Lee, Won-Yong;Chung, Bong-Chul;Choi, Man-Ho
    • Mass Spectrometry Letters
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    • 제2권4호
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    • pp.92-95
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    • 2011
  • Pyrophosphates are the key intermediates in the biosynthesis of isoprenoids, and their concentrations could reveal the benefits of statins in cardiovascular diseases. Quantitative analysis of five pyrophosphates, including isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP), was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in negative ionization mode. After dilution with methanol, samples were separated on a 3 ${\mu}m$ particle multi-modal $C_{18}$ column ($50{\times}2$ mm) and quantified within 10 min. The gradient elution consists of 10 mM ammonium bicarbonate and 0.5% triethylamine (TEA) in water and 0.1% TEA in 80% acetonitrile was used at the flow rate of 0.4 mL/min. Overall recoveries were 51.4-106.6%, while the limit of quantification was 0.05 ${\mu}g$/mL for GPP and FPP and 0.1 ${\mu}g$/mL for IPP, DMAPP, and GGPP. The precision (% CV) and accuracy (% bias) of the assay were 1.9-12.3% and 89.6-111.8%, respectively, in 0.05-10 ${\mu}g$/mL calibration ranges ($R^2$ > 0.993). The devised LC-MS/MS technique with the multi-modal $C_{18}$ column can be used to estimate the biological activity of pyrophosphates in plasma and may be applicable to cardiovascular events with cholesterol metabolism as well as the drug efficacy of statins.

Propenone 유도체의 $NF-{\kappa}B$ 활성 억제 및 IL-8 유도에 의한 단핵구의 장 상피세포 부착 억제 효과 (Inhibitory Effects of Propenone Derivatives on $NF-{\kappa}B$ activity and IL-8-Induced Monocyte Adhesion to Colon Epithelial Cells)

  • 박수영;김경진;이종숙;이응석;김정애
    • 약학회지
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    • 제52권1호
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    • pp.62-66
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    • 2008
  • In this study, we examined the inhibitory effects of propenone derivatives, 1,3-diphenyl-propenone (DPhP), 3-phenyl-1-thiophen-2-yl-propenone (PhT2P), 3-phenyl-1-thiophen-3-yl-propenone (PhT3P) and 1-furan-2-yl-3-phenyl-propenone (FPhP), on $TNF-{\alpha}$-induced nuclear factor (NF)-${\kappa}B$ activity and interleukin (IL)-8-induced monocyte adhesion to colon epithelial cells. 1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) that is previously reported as a $NF-{\kappa}B$ inhibitor suppressed $TNF-{\alpha}$-induced monocyte-epithelial cell adhesion in a concentration-dependent manner. The propenone derivatives, DPhP, PhT2P, PhT3P, FPhP, also inhibited $TNF-{\alpha}$-induced $NF-{\kappa}B$ activation in a similar degree to FPP-3. In a DPPH radical scavenging assay, none of the compounds showed DPPH radical scavenging activity, indicating that the inhibitory actions of the propenone derivatives on redox-sensitive $NF-{\kappa}B$ activity is not due to a simple free radical scavenging activity. In addition, the propenone derivatives also suppressed the IL-8-induced monocyte adhesion to colon epithelial cells. Furthermore, the effective concentrations of the propenone derivatives on both $NF-{\kappa}B$ activation as well as IL-8 induced monocyte-epithelial cell adhesion were 1000 times lower than 5-aminosalicylic acid (5-ASA), a clinically used drug for inflammatory bowel disease. These results suggest that the propenone derivatives may be a potential lead having a strong inhibitory activity against inflammatory cytokine-induced epithelial inflammation.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 한국균학회 2016년도 춘계학술대회 및 임시총회
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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van der Pauw와 four point probe 방법에 의한 반도체 웨이퍼의 면저항 비교 (Comparison of van der Pauw method with FPP method in Sheet Resistance Measurements of Semiconductor Wafer)

  • 강전홍;김한준;유광민;한상옥;김종석;박강식;구경완
    • 대한전기학회:학술대회논문집
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    • 대한전기학회 2004년도 하계학술대회 논문집 C
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    • pp.1634-1636
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    • 2004
  • 반도체 웨이퍼의 면저항을 정밀 측정하는 대표적인 두가지 방법인 4탐침(four point probe)방법과 van der Pauw방법으로 반도체 웨이퍼의 면저항을 비교평가 하였다. 4탐침방법에 의한 측정 시스템을 사용하여 웨이퍼의 전체 면에 대하여 면저항을 측정하고, 같은 웨이퍼의 가장자리 네 지점에 탐침 전극을 구성한 후 van der Pauw 방법으로 면저항을 측정한 결과 4탐침 방법에 의한 측정결과를 기준으로 1 %이하의 일치도를 나타냈다.

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빙해선박의 선수 선형에 관한 연구 (A Study on the Bow Shape of Ice Breaking Vessel)

  • 김현수;이춘주
    • 대한조선학회논문집
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    • 제47권3호
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    • pp.469-475
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    • 2010
  • The operation scenarios, types of ice, draft and propulsion system are important design point on the beginning stage of the ice breaking vessel. The concept of hull form in ice breaking vessel has to compromise the performance according to the operation route especially if ship is operating in ice and ice free water. The several hull forms were proposed to optimize the capability of the vessel in this paper. The effect of hull form according to type of ice is also discussing and explaining the ice resistance in each ice type as like pack ice, brash ice, level ice, rubble ice and ice ridge. The draft effect was examined and propulsion system for example FPP(Fixed pitch propeller), CPP(Controllable pitch propeller) and POD system was compared focusing on the propulsion efficiency.

박막 재료의 면저항 측정기 개발 (A Development of Sheet Resistance Meter for Thin Film Materials)

  • 강전홍;유광민;김한준;한상옥
    • 한국전기전자재료학회:학술대회논문집
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    • 한국전기전자재료학회 2009년도 하계학술대회 논문집
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    • pp.233-234
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    • 2009
  • 박막 재료의 면저항 측정은 일반적으로 FPP(Four-Point Probe)원리를 적용한 측정기률 사용하고 있다. 개발된 면저항 측정기의 특징은 dual configuration 기술을 적용하여 탐침 간격에 대한 시료의 크기 및 두께에 대한 보정계수를 고려하지 않아도 되므로 누구나 업고 정확하게 사용 할 수 있다. 측정범위는 $1\;m{\Omega}{/\square}\;{\sim}\;1\;G{\Omega}{/\square}$이며, 반복성과 재현성 및 직선성은 0.1 %이하로서 우수한 특성을 나타냈다. 또한 기존의 면저항 측정기에 적용된 single configuration 기술에서 나타나는 가장자리 효과의 단점을 dual configuration 기술을 적용하여 해결하였고 정밀 정확도를 향상시켰다. 개발된 면저항 측정기의 특성평가는 국가측정표준으로부터 소급성이 유지된 표준저항, 분할저항기, 면저항 인증표준물질 등을 사용하였다.

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