• Title/Summary/Keyword: IRF-3

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Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors by a Differential Mechanism

  • Lee, Jeong Yoon;Kim, Seong-Jun;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • v.29 no.12
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    • pp.2014-2021
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    • 2019
  • Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the genus Betacoronavirus and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such as chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-β) promoter activities. Here, we report that ORF8b seemed to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. In addition, ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, the last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/RIG-I receptor signaling pathway.

Design and Implementation on Frequency Synthesizer Qualification Model Level for SAR payload (위성 레이다용 QM급 주파수합성기 설계 및 제작)

  • Kim, Dongsik;Kim, Hyunchul;Heo, John;Kim, Wansik
    • The Journal of the Institute of Internet, Broadcasting and Communication
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    • v.20 no.3
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    • pp.9-14
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    • 2020
  • In this paper, Qualification Model of frequency synthesizer is designed for X-band SAR system and performed electrical and environment test. Designed frequency synthesizer generate 13.65 GHz with very low phase noise performance. The integrated phase noise from 10Hz to 1MHz is -37.91 dBc. IRF performances are analyzed according to phase noise and jitter. Also, thermal and structure analysis are achieved for stable operation in space environment. Designed frequency synthesizer is consist of 2 modules of 6U size and generate L-band, C-band, Ku-band. The result of this study would enhance the design ability of RF module and help the frequency synthesizer design for SAR payload system.

Apoptosis of Human Islet Cells by Cytokines

  • Kim, Sun-Shin;Kim, Kyoung-Ah;Suk, Kyoung-Ho;Kim, Yun-Hee;Oh, Seung-Hoon;Lee, Moon-Kyu;Kim, Kwang-Won;Lee, Myung-Shik
    • IMMUNE NETWORK
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    • v.12 no.3
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    • pp.113-117
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    • 2012
  • FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

Dimming Control of the LED Luminaire Emergency Exit Sign Operation using a Hybrid Super Capacitor of DC-DC Convertor (하이브리드 슈퍼커패시터 DC-DC 컨버터를 이용한 LED 비상 유도등 동작 디밍 제어)

  • Hwang, Lark-Hoon;Kim, Jin-Sun;Na, Yong-Ju
    • Journal of Advanced Navigation Technology
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    • v.21 no.3
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    • pp.220-229
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    • 2017
  • In this paper, To take advantage a variety of DC power as the boost DC-DC converter design specifications through the inductor L and capacitor C through PSPICE to calculate the best estimate of the value. Boost DC-DC converter with a switch device using IRF840 and reverse recovery time Schottky diodes with excellent with constant current controller using D10SC6M and resistance can be configured to considering the Power LED Module was driven by the production. Converter's switching frequency is 50 kHz, the first Duty Rate was made to increase gradually depending on the value of the detection were, 10 % in the output voltage. As a result, the simulated Boost Power LED driver characteristics is in comparison with the design specifications, 5% or less as the error was approximated. Finally, when input 15 V were offered, a stable output 24 V were obtained. and Dimming Control through the adjustment of brightness and current consumption were possible.

The Experience on Intake Estimation and Internal Dose Assessment by Inhalation of Iodine-131 at Korean Nuclear Power Plants (국내 원전에서 $^{131}I$ 내부 흡입 에 따른 섭취량 산정과 내부피폭 방사선량 평가 경험 몇 개선방향에 대한 연구)

  • Kim, Hee-Geun;Kong, Tae-Young
    • Journal of Radiation Protection and Research
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    • v.34 no.3
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    • pp.129-136
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    • 2009
  • During the maintenance period at Korean nuclear power plants, internal exposure of radiation workers occurred by the inhalation of $^{131}I$ released to the reactor building when primary system opened. The internal radioactivity of radiation workers contaminated by $^{131}I$ was measured using a whole body counter. Intake estimation and the calculation of committed effective dose were also conducted conforming to the guidance of internal dose assessments from publications of International Commission on Radiological Protection. Because the uptake and excretion of $^{131}I$ in a body occur quickly and $^{131}I$ is accumulated in the thyroid gland, the estimated intakes showed differences depending on the counting time after intake. In addition, since ICRP publications do not provide the intake retention fraction (IRF) for whole body of $^{131}I$, the IRF for thyroid was substitutionally used to calculate the intake and subsequently this caused more error in intake estimation. Thus, intake estimation and the calculation of committed effective dose were conducted by manual calculation. In this study, the IRF for whole body was also calculated newly and was verified. During this process, the estimated intake and committed effective dose were reviewed and compared using several computer codes for internal dosimetry.

TNF-induced genes and Proteins

  • 이태호
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.11a
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    • pp.17-20
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    • 1993
  • As a step toward a more complete understanding of the molecular actions of TNF, we prepared a cDNA library from TNF-treated human FS-4 fibroblasts and used differential hybridization to identify cDNA clones corresponding to mRNAs enriched in TNF-treated eells. In Quiescent FS-4 cells n induces an increase in the level of some mRNAs within 20 to 30 min. Some of these immediate-early response mRNAs are elevated only transiently for about 30 to 120 min, e. g., c-fos and c-myc (Lin and Vilcek,1987) or the transcription factor IRF-1 (Fujita et al.1989). Such immediate-early gene products may be important for the activation of other genes, but their transient induction suggests that they are not the actual effector molecules responsible for the phenotypic changes induced by TNF. We chose a 3-h incubation with W because we were seeking cDNAs corresponding to messages that are more stably elevated after TNF treatment. Indeed, the results shown in Figure 8 and 9 indicate that all of the mRNAs corresponding to the eight TSG cDNAs isolated remained significantly elevated after 16h of continuous treatment with TNF, and their kinetics of induction were clearly different from those of the immediate-early response mRNAs such as c-fos, c-myc or IRF-1. Nevertheless, only the induction of TSG-21 (collagenase) and TSG-27 (stromelysin) nNAs was completely inhibited by cycloheximide and the induction of TSG-37 (metallothionein-II) was reduced in the presence of this inhibitor of protein synthesis. Induction of the other five TSG mRNAs by TNF was completelyresistant to cycloheximide, suggest ins that no protein intermediate is needed for the upregulation of these mRNAs.

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Multi-channel analyzer based on a novel pulse fitting analysis method

  • Wang, Qingshan;Zhang, Xiongjie;Meng, Xiangting;Wang, Bao;Wang, Dongyang;Zhou, Pengfei;Wang, Renbo;Tang, Bin
    • Nuclear Engineering and Technology
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    • v.54 no.6
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    • pp.2023-2030
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    • 2022
  • A novel pulse fitting analysis (PFA) method is presented for the acquisition of nuclear spectra. The charging process of the feedback capacitor in the resistive feedback charge-sensitive preamplifier is equivalent to the impulsive pulse, and its impulse response function (IRF) can be obtained by non-linear fitting of the falling edge of the nuclear pulse. The integral of the IRF excluding the baseline represents the energy deposition of the particles in the detector. In addition, since the non-linear fitting process in PFA method is difficult to achieve in the conventional architecture of spectroscopy system, a new multi-channel analyzer (MCA) based on Zynq SoC is proposed, which transmits all the data of nuclear pulses from the programmable logic (PL) to the processing system (PS) by high-speed AXI-Stream in order to implement PFA method with precision. The linearity of new MCA has been tested. The spectrum of 137Cs was obtained using LaBr3(Ce) scintillator detector, and was compared with commercial MCA by ORTEC. The results of tests indicate that the MCA based on PFA method has the same performance as the commercial MCA based on pulse height analysis (PHA) method and excellent linearity for γ-rays with different energies, which infers that PFA method is an effective and promising method for the acquisition of spectra. Furthermore, it provides a new solution for nuclear pulse processing algorithms involving regression and iterative processes.

Induction of IFN-β through TLR-3- and RIG-I-Mediated Signaling Pathways in Canine Respiratory Epithelial Cells Infected with H3N2 Canine Influenza Virus

  • Park, Woo-Jung;Han, Sang-Hoon;Kim, Dong-Hwi;Song, Young-Jo;Lee, Joong-Bok;Park, Seung-Yong;Song, Chang-Seon;Lee, Sang-Won;Choi, In-Soo
    • Journal of Microbiology and Biotechnology
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    • v.31 no.7
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    • pp.942-948
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    • 2021
  • Canine influenza virus (CIV) induces acute respiratory disease in dogs. In this study, we aimed to determine the signaling pathways leading to the induction of IFN-β in a canine respiratory epithelial cell line (KU-CBE) infected with the H3N2 subtype of CIV. Small interfering RNAs (siRNAs) specific to pattern recognition receptors (PRRs) and transcription factors were used to block the IFN-β induction signals in H3N2 CIV-infected KU-CBE cells. Among the PRRs, only the TLR3 and RIG-I expression levels significantly (p < 0.001) increased in CIV-infected cells. Following transfection with siRNA specific to TLR3 (siTLR3) or RIG-I (siRIG-I), the mRNA expression levels of IFN-β significantly (p < 0.001) decreased, and the protein expression of IFN-β also decreased in infected cells. In addition, co-transfection with both siTLR3 and siRIG-I significantly reduced IRF3 (p < 0.001) and IFN-β (p < 0.001) mRNA levels. Moreover, the protein concentration of IFN-β was significantly (p < 0.01) lower in cells co-transfected with both siTLR3 and siRIG-I than in cells transfected with either siTLR3 or siRIG-I alone. Also, the antiviral protein MX1 was only expressed in KU-CBE cells infected with CIV or treated with IFN-β or IFN-α. Thus, we speculate that IFN-β further induces MX1 expression, which might suppress CIV replication. Taken together, these data indicate that TLR3 and RIG-I synergistically induce IFN-β expression via the activation of IRF3, and the produced IFN-β further induces the production of MX1, which would suppress CIV replication in CIV-infected cells.

Anti-cancer and Anti-inflammatory Effects of Curcumin by the Modulation of Toll-like Receptor 2, 3 and 4 (Toll-like receptor 2, 3, 4의 신호전달체계 조절을 통한 curcumin의 항암${\cdot}$항염증 효과)

  • Kang, Soon-Ah;Hwang, Daniel;Youn, Hyung-Sun
    • Korean Journal of Food Science and Technology
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    • v.39 no.2
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    • pp.175-180
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    • 2007
  • Toll-like receptors induce innate immune responses recognizing conserved microbial structural molecules that are known as pathogen-associated molecular patterns (PAMPs). Ligand-induced homotypic oligomerization was found to proceed in LPS-induced activation of TLR4 signaling pathways. TLR2 is known to heterodimerize with TLR1 or TLR6 and recognize diacyl- or triacyl-lipopeptide, respectively. These results suggest that ligand-induced receptor dimerization of TLR4 and TLR2 is required for the activation of downstream signaling pathways. Therefore, receptor dimerization may be one of the first lines of regulation in the activation of TLR-mediated signaling pathways and induction of subsequent innate and adaptive immune responses. Here, we report biochemical evidence that curcumin from the plant Curcuma longa inhibits activation of $NF-{\kappa}B$, expression of COX-2, and dimerization of TLRs induced by TLR2, TLR3 and TLR4 agonists. These results imply that curcumin can modulate the activation of TLRs and subsequent immune/inflammatory responses induced by microbial pathogens.

The Anti-Inflammatory Effects of Phytochemicals by the Modulation of Innate Immunity

  • Youn, Hyung-Sun
    • Biomedical Science Letters
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    • v.18 no.3
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    • pp.181-192
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    • 2012
  • Toll-like receptors (TLRs) induce innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways; myeloid differential factor 88 (MyD88) and Toll/IL-1R domain-containing adaptor inducing IFN-${\beta}$ (TRIF) leading to the activation of NF-${\kappa}B$ and IRF3. Numerous studies demonstrated that certain phytochemicals possessing anti-inflammatory effects inhibit NF-${\kappa}B$ activation induced by pro-inflammatory stimuli including lipopolysaccharide and tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$). However, the direct molecular targets for such anti-inflammatory phytochemicals are not fully identified. In this paper, we will discuss about the molecular targets of phytochemicals in TLRs signaling pathways. These results present a novel anti-inflammatory mechanism of phytochemicals in TLRs signaling.