• Title/Summary/Keyword: Current regulator

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Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells

  • Kim, Hyun Jong;Woo, JooHan;Nam, Yu-Ran;Seo, Yohan;Namkung, Wan;Nam, Joo Hyun;Kim, Woo Kyung
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.4
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    • pp.329-338
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    • 2020
  • Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl- and HCO3- is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calcium-activated Cl- channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Semiconductor wafer exhaust moisture displacement unit (반도체 웨이퍼 공정 배기가스 수분제어장치)

  • Chan, Danny;Kim, Jonghae
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.8
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    • pp.5541-5549
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    • 2015
  • This paper introduces a safer and more power efficient heater by using induction heating, to apply to the semiconductor wafer fabrication exhaust gas cleaning system. The exhaust gas cleaning system is currently made with filament heater that generates an endothermic reaction of N2 gas for the removal of moisture. Induction theory, through the bases of theoretical optimization and electronic implementation, is applied in the design of the induction heater specifically for the semiconductor wafer exhaust system. The new induction heating design provides a solution to the issues with the current energy inefficient, unreliable, and unsafe design. A robust and calibrated design of the induction heater is used to optimize the energy consumption. Optimization is based on the calibrated ZVS induction circuit design specified by the resonant frequency of the exhaust pipe. The fail-safe energy limiter embedded in the system uses a voltage regulator through the feedback of the MOSFET control, which allows the system performance to operate within the specification of the N2 Heater unit. A specification and performance comparison from current conventional filament heater is made with the calibrated induction heater design for numerical analysis and the proof of a better design.

A Power MOSFET Driver with Protection Circuits (보호 회로를 포함한 전력 MOSFET 구동기)

  • Han, Sang-Chan;Lee, Soon-Seop;Kim, Soo-Won;Lee, Duk-Min;Kim, Seong-Dong
    • Journal of the Korean Institute of Telematics and Electronics D
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    • v.36D no.2
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    • pp.71-80
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    • 1999
  • In this paper, a power MOSFET driver with protection circuits is designed using a 2${\mu}m$ high-voltage CMOS process. For stable operations of control circuits a power managing circuit is designed, and a voltage-detecting short-circuit protection(VDSCP) is proposed to protect a voltage regulator in the power control circuit. The proposed VDSCP scheme eliminates voltage drop caused by a series resistor, and turns off output current under short-circuit state. To protect a power MOSFET, a short-load protection, a gate-voltage limiter, and an over-voltage protection circuit are also designed A high voltage 2 ${\mu}m$ technology provides the breakdown voltage of 50 V. The driver consumes the power of 20 ~ 100 mW along its operation state excluding the power of the power MOSFET. The active area of the power MOSFET driver occupies $3.5 {\times}2..8mm^2$.

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Differential Expression and Stability of Endogenous Nuclear Factor E2-related Factor 2 (Nrf2) by Natural Chemopreventive Compounds in HepG2 Human Hepatoma Cells

  • Jeong, Woo-Sik;Keum, Young-Sam;Chen, Chi;Jain, Mohit R.;Shen, Guoxiang;Kim, Jung-Hwan;Li, Wenge;Kong, Ah-Ng Tony
    • BMB Reports
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    • v.38 no.2
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    • pp.167-176
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    • 2005
  • Nuclear factor-E2-related factor 2 (Nrf2) is known as a key regulator of ARE-mediated gene expression and the induction of Phase II detoxifying enzymes and antioxidant enzymes, which is also a common property of many chemopreventive agents. In the present study, we investigated the regulatory role of different chemopreventive agents including sulforaphane (SUL), allyl isothiocyanate (AITC), indole-3-carbinol (I3C), and parthenolide (PTL), in the expression and degradation of Nrf2 and the induction of the antioxidant enzyme HO-1. SUL strongly induced Nrf2 protein expression and ARE-mediated transcription activation, retarded degradation of Nrf2 through inhibiting Keap1, and thereby activating the transcriptional expression of HO-1. AITC was also a potent inducer of Nrf2 protein expression, ARE-reporter gene and HO-1 but had little effect on delaying the degradation of Nrf2 protein. Although PTL and I3C could induce ARE reporter gene expression and Nrf2 to some extent, they were not as potent as SUL and AITC. However, PTL dramatically induced the HO-1 expression, which was comparable to SUL, while I3C had no effect. In addition, when treated with SUL and PTL, inhibition of proteasome by MG132 did not cause additional accumulation of Nrf2, suggesting the involvement of other degradation mechanism(s) in the presence of these compounds such as SUL and PTL. In summary, the results of our current study indicated that different chemopreventive compounds have different regulatory properties on the accumulation and degradation of Nrf2 as well as the induction of cellular antioxidant enzyme HO-1.

Linkage between Trade and SPS Measure through Establishment of Reasonable-Regulator Approach to Judicial Review : Focusing on US-Hormones Suspension Case (합리적 규제자 기준의 확립을 통한 무역과 위생검역조치의 조화 - US-Hormones Suspension 사건을 중심으로 -)

  • Lee, Ju-Young;Lee, Eun-Sup
    • International Commerce and Information Review
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    • v.13 no.3
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    • pp.403-431
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    • 2011
  • The environmental issues including domestic measures to protect public life or health are generally easy to bring the tension between the WTO and its member countries. The standard of review, whether de novo review, total deference, or somewhere in between, is largely important in the WTO's adjudicating mechanism because it is closely related to the appropriate balance of power between sovereign nations and the WTO: The multilateral trading regime, through the proper standard of review, could harmoniously operated without interest conflicts among the member countries and at the same time between the WTO and the member countries. Irrespective the important function of the standard of review in the WTO judicial system, applicable standard of review has not been established in the current SPS Agreement. Furthermore, the nature of the SPS Agreement related in scientific factors, such as scientific experiment, data and assessment prevents the WTO's panel from applying consistent standard of review. Considering the judicial demand for the moderate treatment of the case under the SPS Agreement, this paper explores appropriate standard of review applicable the SPS-related environmental measures, particularly, by analysing the recent SPS-related dispute, US-Hormones Suspension.

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Histone H3 Lysine Methylation in Adipogenesis (Adipogenesis에서 히스톤 H3 lysine methylation)

  • Jang, Younghoon
    • Journal of Life Science
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    • v.30 no.8
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    • pp.713-721
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    • 2020
  • Adipogenesis as a model system is needed to understand the molecular mechanisms of human adipocyte biology and the pathogenesis of obesity, diabetes, and other metabolic syndromes. Many relevant studies have been conducted with a focus on gene expression regulation and intracellular signaling relating to Peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), which are master adipogenic transcription factors. However, epigenome regulation of adipogenesis by epigenomic modifiers or histone mutations is not fully understood. Histone methylation is one of the major epigenetic modifications on gene expression in mammals, and histone H3 lysine methylation (H3Kme) in particular implicates cell differentiation during various tissue and organ development. During adipogenesis, cell type-specific enhancers are marked by histone H3K4me1 with the active enhancer mark H3K27ac. Mixed-lineage leukemia 4 (MLL4) is a major H3K4 mono-methyltransferase on the adipogenic enhancers of PPARγ and C/EBPα loci. Thus, MLL4 is an important epigenomic modifier for adipogenesis. The repressive mark H3K27me3 is mediated by the enzymatic subunit Enhancer zeste homolog 2 (EZH2) of the polycomb repressive complex 2. EZH2-mediated H3K27 tri-methylation on the Wnt gene increases adipogenesis because WNT signaling is a negative regulator of adipogenesis. This review summarizes current knowledge about the epigenomic regulation of adipogenesis by histone H3 lysine methylation which fundamentally regulates gene expression.

Expression and Clinical Significance of mTOR in Surgically Resected Non-small Cell Lung Cancer Tissues: a Case Control Study

  • Liu, Zhe;Wang, Liang;Zhang, Li-Na;Wang, Yue;Yue, Wen-Tao;Li, Qi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6139-6144
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    • 2012
  • Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

Studies on OsABF3 Gene Isolation and ABA Signal Transduction in Rice Plants Against Abiotic Stress (비 생물학적 스트레스 시 벼에서 OsABF3 유전자 분리와 ABA 신호전달 대한 연구)

  • Ahn, Chul-Hyun;Park, Phun-Bum
    • Korean Journal of Plant Resources
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    • v.30 no.5
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    • pp.571-577
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    • 2017
  • Abscisic acid (ABA) is an important phytohormone involved in abiotic stress tolerance in plants. The group A bZIP transcription factors play important roles in the ABA signaling pathway in Arabidopsis but little is known about their functions in rice. In our current study, we have isolated and characterized a group A bZIP transcription factor in rice, OsABF3 (Oryza sativa ABA responsive element binding factor 3). We examined the expression patterns of OsABF3 in various tissues and time course analysis after abiotic stress treatments such as drought, salinity, cold, oxidative stress, and ABA in rice. Subcellular localization analysis in maize protoplasts using a GFP fusion vector further indicated that OsABF3 is a nuclear protein. Moreover, in a yeast one-hybrid experiment, OsABF3 was shown to bind to ABA responsive elements (ABREs) and its N-terminal region found to be necessary to transactivate a downstream reporter. A homozygous T-DNA insertional mutant of OsABF3 is more sensitive to salinity, drought, and oxidative stress compared with wild type plants & OsABF3OX plants. In addition, this Osabf3 mutant showed a significantly decreased sensitivity to high levels of ABA at germination and post-germination. Collectively, our present results indicate that OsABF3 functions as a transcriptional regulator that modulates the expression of abiotic stress-responsive genes through an ABA-dependent pathway.

Activation of Lysophosphatidic Acid Receptor Is Coupled to Enhancement of $Ca^{2+}$ -Activated Potassium Channel Currents

  • Choi, Sun-Hye;Lee, Byung-Hwan;Kim, Hyeon-Joong;Hwang, Sung-Hee;Lee, Sang-Mok;Nah, Seung-Yeol
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.3
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    • pp.223-228
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    • 2013
  • The calcium-activated $K^+$ ($BK_{Ca}$) channel is one of the potassium-selective ion channels that are present in the nervous and vascular systems. $Ca^{2+}$ is the main regulator of $BK_{Ca}$ channel activation. The $BK_{Ca}$ channel contains two high affinity $Ca^{2+}$ binding sites, namely, regulators of $K^+$ conductance, RCK1 and the $Ca^{2+}$ bowl. Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is one of the neurolipids. LPA affects diverse cellular functions on many cell types through G protein-coupled LPA receptor subtypes. The activation of LPA receptors induces transient elevation of intracellular $Ca^{2+}$ levels through diverse G proteins such as $G{\alpha}_{q/11}$, $G{\alpha}_i$, $G{\alpha}_{12/13}$, and $G{\alpha}s$ and the related signal transduction pathway. In the present study, we examined LPA effects on $BK_{Ca}$ channel activity expressed in Xenopus oocytes, which are known to endogenously express the LPA receptor. Treatment with LPA induced a large outward current in a reversible and concentration-dependent manner. However, repeated treatment with LPA induced a rapid desensitization, and the LPA receptor antagonist Ki16425 blocked LPA action. LPA-mediated $BK_{Ca}$ channel activation was also attenuated by the PLC inhibitor U-73122, $IP_3$ inhibitor 2-APB, $Ca^{2+}$ chelator BAPTA, or PKC inhibitor calphostin. In addition, mutations in RCK1 and RCK2 also attenuated LPA-mediated $BK_{Ca}$ channel activation. The present study indicates that LPA-mediated activation of the $BK_{Ca}$ channel is achieved through the PLC, $IP_3$, $Ca^{2+}$, and PKC pathway and that LPA-mediated activation of the $BK_{Ca}$ channel could be one of the biological effects of LPA in the nervous and vascular systems.

Current research on seed oil biosynthesis (식물 종자지방 합성대사 연구의 최근 동향)

  • Kim, Hyun Uk;Lee, Kyeong-Ryeol;Kim, Eun Ha;Jung, Su-Jin;Roh, Kyung Hee;Kang, Han Chul;Kim, Jong-Bum
    • Journal of Plant Biotechnology
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    • v.41 no.1
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    • pp.10-18
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    • 2014
  • Seed oils (triacylglycerols) of plants are used as a source of essential fatty acids and nutrition for human. In addition, triacylglycerols have been used as industrial raw materials and biofuels. Triacylglycerols are mainly accumulated in seeds by complicated biochemical pathways. Fatty acids are synthesized in the plastids and transported into the endoplasmic reticulum for synthesizing triacylglycerols. It is known for a long time that biosynthesis of triacylglycerols is performed by a de novo synthesis, the Kennedy pathway. However recent studies have revealed that phosphatidylcholine, a major component of cell membrane, plays a central role for triacylglycerols biosynthesis. Phosphatidylcholine is a key regulator determining the relative proportions of unsaturated fatty acids in seeds. It may be a major carrier for the fluxes of fatty acids from the plastid to the endoplasmic reticulum. This finding further suggests that studies of the functions of enzymes involved in the fluxes of fatty acids from phosphatidylcholine to triacylglycerols elucidate the specialized subdomains in the endoplasmic reticulum for triacylglycerols biosynthesis.