• Title/Summary/Keyword: Gamma shift

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Inhibition of NF-kB/Rel by Paclitaxel in Mouse Macrophages

  • Lim, Jin-Soo;Lee, Seog-Ki;Jeon, Young-Jin
    • Toxicological Research
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    • v.23 no.1
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    • pp.19-24
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    • 2007
  • We demonstrate that paclitaxel, an antitumor agent derived from yew tree, inhibits LPS- and $IFN-{\gamma}$-induced NF-kB/Rel activation in RAW 264.7 cells. Previously, paclitaxel ($>10{\mu}M$) has been known to induce iNOS gene expression in macrophages. However, in the previous report we described that the pretreatment of macrophages with low concentration of paclitaxel ($0.1{\mu}M$) for 8 h inhibited LPS-induced iNOS gene expression. Pretreatment of RAW 264.7 cells with paclitaxel significantly inhibited NF-kB/Rel transcriptional activation. Electrophoretic mobility shift assay further confirmed that pretreatment of macrophages with paclitaxel inhibited NF-kB/Rel DNA binding. Taxotere, a semisynthetic analog of paclitaxel, also inhibited LPS- and $IFN-{\gamma}$-induced iNOS gene expression. Collectively, these series of experiments indicate that paclitaxel inhibits iNOS gene expression by blocking NF-kB/Rel activation.

Electrical Characteristics of IGBT for Gate Bias under $\gamma$ Irradiation (게이트바이어스에서 감마방사선의 IGBT 전기적 특성)

  • Lho, Young-Hwan
    • Journal of the Institute of Electronics Engineers of Korea SC
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    • v.46 no.2
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    • pp.1-6
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    • 2009
  • The experimental results of exposing IGBT (Insulated Gate Bipolar Transistor) samples to gamma radiation source show shifting of threshold voltages in the MOSFET and degradation of carrier mobility and current gains. At low total dose rate, the shift of threshold voltage is the major contribution of current increases, but for more than some total dose, the current is increased because of the current gain degradation occurred in the vertical PNP at the output of the IGBTs. In the paper, the collector current characteristics as a function of gate emitter voltage (VGE) curves are tested and analyzed with the model considering the radiation damage on the devices for gate bias and different dose. In addition, the model parameters between simulations and experiments are found and studied.

Gamma-radiation Effects on Fiber Bragg Gratings Written in Photo-sensitive and Commercial Single-mode Optical Fibers (광민감 광섬유와 일반 단일모드 광섬유로 제작한 브래그 격자 센서의 감마방사선 영향)

  • Kim, Jong-Yeol;Lee, Nam-Ho;Jung, Hyun-Kyu;Im, Don-Sun
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2014.05a
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    • pp.701-704
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    • 2014
  • In this study, we studied the effect of $Co^{60}$ gamma-radiation on the FBGs written in photo-sensitive and commercial Ge-doped single-mode optical fibers. The FBGs were exposed to gamma-radiation up to a dose of 17.8 kGy at the dose rate of 300 Gy/min. According to the experimental data and analysis results, the lowest Bragg wavelength shift (18 pm) was obtained by a grating written in photosensitive fiber without $H_2$-loading.

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Comparative Study of the Endotoxemia and Endotoxin Tolerance on the Production of Th Cytokines and Macrophage Interleukin-6: Differential Regulation of Indomethacin

  • Chae, Byeong-Suk
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.910-916
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    • 2002
  • Endotoxin tolerance reduces the capacity of monocytes to produce proinflammatory cytokines, results in cellular immune paralysis, and down-regulates the production of helper T (Th)1 type cytokines with a shift toward a Th2 cytokine response. Prostaglandin (PG)E$_2$ in the immune system also results in macrophage inactivation and the suppression of Th1 activation and the enhancement of Th2 activation. However, the inhibitory effects of PGE$_2$ on the altered polarization of the Th cell and macrophage interleukin (IL)-6 production characterized in part by cellular immune paralysis in a state of endotoxin tolerance is unclear. This study was undertaken, using indomethacin, to investigate the role of endogenous PGE$_2$ on the Th cytokines and macrophage IL-6 production in a state of endotoxin tolerance compared to those with endotoxemia mice, wherein, in this latter case, the increased production of proinflammatory cytokines and PGE$_2$ is exhibited. Endotoxemia was induced by injection of lipopolysaccharide (LPS; 10 mg/kg in saline) i.p. once in BALB/c mice, and endotoxin tolerance was induced by pretreatment with LPS (1 mg/kg in saline) injected i.p. daily for two consecutive days and then with LPS 10 mg/kg on day 4. Splenocytes or macrophages were obtained from endotoxemia and endotoxin tolerance models pretreated with indomethacin, and then cytokine production was induced by Con A-stimulated splenocytes for the Th cytokine assays and LPS-stimulated macrophages for the IL-6 assay. Our results showed that endotoxemia led to significantly reduced IL-2 and IL-4 production, to significantly increased IL-6 production, whereas interferon $(IFN)-{\gamma}$ production was not affected. Indomethacin in the case of endotoxemia markedly attenuated $IFN-{\gamma}$ and IL-6 production and didnt reverse IL-2 and IL-4 production. Endotoxin tolerance resulted in the significantly reduced production of IL-2 and $IFN-{\gamma}$ and the significantly increased production of IL-4 and IL-6. Indomethacin in endotoxin tolerance greatly augmented IL-2 production, significantly decreased IL-4 production, and slightly attenuated IL-6 production. These findings indicate that endogenous PGE$_2$ may mediate the suppressed Th1 type immune response, with a shift toward a Th2 cytokine response in a state of endotoxin tolerance, whereas endotoxemia may be regulated differentially. Also, endogenous PGE$_2$ may mediate macrophage IL-6 production in the case of endotoxemia to a greater extent than in the case of endotoxin tolerance.

Intracellular calcium-dependent regulation of the sperm-specific calcium-activated potassium channel, hSlo3, by the BKCa activator LDD175

  • Wijerathne, Tharaka Darshana;Kim, Jihyun;Yang, Dongki;Lee, Kyu Pil
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.2
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    • pp.241-249
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    • 2017
  • Plasma membrane hyperpolarization associated with activation of $Ca^{2+}$-activated $K^+$ channels plays an important role in sperm capacitation during fertilization. Although Slo3 (slowpoke homologue 3), together with the auxiliary ${\gamma}^2$-subunit, LRRC52 (leucine-rich-repeat-containing 52), is known to mediate the pH-sensitive, sperm-specific $K^+$ current KSper in mice, the molecular identity of this channel in human sperm remains controversial. In this study, we tested the classical $BK_{Ca}$ activators, NS1619 and LDD175, on human Slo3, heterologously expressed in HEK293 cells together with its functional interacting ${\gamma}^2$ subunit, hLRRC52. As previously reported, Slo3 $K^+$ current was unaffected by iberiotoxin or 4-aminopyridine, but was inhibited by ~50% by 20 mM TEA. Extracellular alkalinization potentiated hSlo3 $K^+$ current, and internal alkalinization and $Ca^{2+}$ elevation induced a leftward shift its activation voltage. NS1619, which acts intracellularly to modulate hSlo1 gating, attenuated hSlo3 $K^+$ currents, whereas LDD175 increased this current and induced membrane potential hyperpolarization. LDD175-induced potentiation was not associated with a change in the half-activation voltage at different intracellular pHs (pH 7.3 and pH 8.0) in the absence of intracellular $Ca^{2+}$. In contrast, elevation of intracellular $Ca^{2+}$ dramatically enhanced the LDD175-induced leftward shift in the half-activation potential of hSlo3. Therefore, the mechanism of action does not involve pH-dependent modulation of hSlo3 gating; instead, LDD175 may modulate $Ca^{2+}$-dependent activation of hSlo3. Thus, LDD175 potentially activates native KSper and may induce membrane hyperpolarization-associated hyperactivation in human sperm.

Reduction of Gamma Distortion in Oblique Viewing Directions in Polymer-stabilized Vertical Alignment Liquid Crystal Mode

  • Kim, Hyo Joong;Lim, Young Jin;Murali, G.;Kim, Min Su;Kim, Gi Heon;Kim, Yong Hae;Lee, Gi-Dong;Lee, Seung Hee
    • Current Optics and Photonics
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    • v.1 no.2
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    • pp.157-162
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    • 2017
  • In large liquid crystal displays, the image quality in an oblique viewing direction is a crucial issue. From this perspective, 8-domain polymer-stabilized vertical alignment (PS-VA) mode has been developed to suppress the color shift in oblique viewing directions, compared to that in 4-domain PS-VA mode. To realize the 8-domain PS-VA, the four domains in a pixel are each divided into two regions, such that applying different electric potentials result in different tilt angles in these two regions, while keeping four azimuthal directions in each domain. However, applying different voltages in a pixel causes drawbacks, such as requiring additional processes to construct a capacitor and a transistor, which will further reduce the aperture ratio. Here we propose a different approach to form the 8-domain, by controlling surface polar anchoring energy and the width of patterned electrodes in two regions of a pixel. As a result, the gamma-distortion index (GDI), measured at an azimuthal angle of $0^{\circ}$, is reduced by about 23% and 8%, compared to that of a conventional 4-domain at polar angles of $30^{\circ}$ and $60^{\circ}$ respectively.

Development of Radiation Dosimeter on P Channel Power MOSFET for $\gamma$-rays Real-Time Detection ($\gamma$선 실시간 검출을 위한 P채널 Power MOSFET 방사선 선량 시스템 개발)

  • Han, Sang-Hyun;Ji, Yong-Kun;Kwon, O-Sang;Min, Hong-Ki;Lee, Eung-Hyuk
    • Journal of Sensor Science and Technology
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    • v.9 no.3
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    • pp.213-223
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    • 2000
  • It is necessary that radiation dose would be detect exactly generated from facility related to nuclear, space, radiotherapy center, etc. This paper is to use of the radiation-induced threshold voltage change as an accumulated radiation dose monitoring sensor. Commercial P Channel Power MOSFET(metal oxide field effect transistor) were tested in a Co-60 gamma irradiation facility to see their capabilities as a radiation dosimeter. We found that the transistors showed good linearity in their threshold voltage shift characteristics with radiation dose. The results demonstrate the potential use of commercial P Channel Power MOSFET as inexpensive radiation sensors.

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THE MILLIMETER-RADIO EMISSION OF BL LACERTAE DURING TWO γ-RAY OUTBURSTS

  • Kim, Dae-Won;Trippe, Sascha;Lee, Sang-Sung;Park, Jong-Ho;Kim, Jae-Young;Algaba, Juan-Carlos;Hodgson, Jeffrey A.;Kino, Motoki;Zhao, Guang-Yao;Wajima, Kiyoaki;Kang, Sincheol;Oh, Junghwan;Lee, Taeseok;Byun, Do-Young;Kim, Soon-Wook;Kim, Jeong-Sook
    • Journal of The Korean Astronomical Society
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    • v.50 no.6
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    • pp.167-178
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    • 2017
  • We present a study of the inexplicit connection between radio jet activity and ${\gamma}$-ray emission of BL Lacertae (BL Lac; 2200+420). We analyze the long-term millimeter activity of BL Lac via interferometric observations with the Korean VLBI Network (KVN) obtained at 22, 43, 86, and 129 GHz simultaneously over three years (from January 2013 to March 2016); during this time, two ${\gamma}$-ray outbursts (in November 2013 and March 2015) can be seen in ${\gamma}$-ray light curves obtained from Fermi observations. The KVN radio core is optically thick at least up to 86 GHz; there is indication that it might be optically thin at higher frequencies. To first order, the radio light curves decay exponentially over the time span covered by our observations, with decay timescales of $411{\pm}85$ days, $352{\pm}79$ days, $310{\pm}57$ days, and $283{\pm}55$ days at 22, 43, 86, and 129 GHz, respectively. Assuming synchrotron cooling, a cooling time of around one year is consistent with magnetic field strengths $B{\sim}2{\mu}T$ and electron Lorentz factors ${\gamma}$ ~ 10 000. Taking into account that our formal measurement errors include intrinsic variability and thus over-estimate the statistical uncertainties, we find that the decay timescale ${\tau}$ scales with frequency ${\nu}$ like ${\tau}{\propto}{\nu}^{-0.2}$. This relation is much shallower than the one expected from opacity effects (core shift), but in agreement with the (sub-)mm radio core being a standing recollimation shock. We do not find convincing radio flux counterparts to the ${\gamma}$-ray outbursts. The spectral evolution is consistent with the 'generalized shock model' of Valtaoja et al. (1992). A temporary increase in the core opacity and the emergence of a knot around the time of the second ${\gamma}$-ray event indicate that this ${\gamma}$-ray outburst might be an 'orphan' flare powered by the 'ring of fire' mechanism.

Cloning and Expression of Human Liver UDP-Glucuronosyltransferase cDNA, UDPGTh2

  • Dong, Misook;Owens, Ida-S.;Sheen, Yhun-Yhong
    • Archives of Pharmacal Research
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    • v.20 no.5
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    • pp.459-464
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    • 1997
  • The human liver cDNA clone UDPGTh2, encoding a liver UDP-glucuronosyltransferase (UDPGT) was isolated from a .gamma. gt 11 cDNA library by hybridization to mouse transferase cDNA clone, UDPGTm1. UDPGTh2 encoded a 529 amino acid protein with an amino terminus membrane-insertion signal peptide and a carboxyl terminus membrane-spanning region. There were three potential asparagine-linked glycosylation sites at residues 67, 68, and 315. In order to obtain UDPGTh2 protein encoded from cloned human liver UDP-glucuronosyltransferase cDNA, the clone was inserted into the pSVL vector (pUDPGTh2) and expressed in COS 1 cells. The presence of a transferase with Mr-52,000 in transfected cells cultured in the presence of $[^{35}S]$ methionine was shown by immunocomplexed products with goat antimouse transferase IgG and protein A-Sepharose and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The expressed UDPGT was a glycoprotein as indicated by electrophoretic mobility shift in Mr-3,000-4,000 when expressed in the presence of tunicamycin. The extent of glycosylation was difficult to assess, although one could assume that glycosyl structures incorporated at the level of endoplasmic reticulum were always the core oligosaccharides. Thus, it is likely that at least two moieties inserted can account for the shift of Mr-3,000-4,000. This study demonstrates the cDNA and deduced amino acid sequence of human liver UDP-glucuronosyltransferase cDNA, UDPGTh2.

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Increased Expression of Phospholipase C-$\gamma1$ Activator Protein, AHNAK in Human Lung Cancer Tissues (인체 폐암조직에서 Phospholipase C-$\gamma1$의 활성화 단백, AHNAK의 발현양상)

  • Oh, Yoon-Jung;Park, Chun-Seong;Choi, So-Yeon;Cheong, Seong-Cheoll;Lee, Sun-Min;Hwang, Sung-Chul;Lee, Yi-Hyeong;Hahn, Myung-Ho;Lee, Kyi-Beom;Ryu, Han-Young;Ha, Mahn-Joon;Bae, Yoon-Su;Rhee, Seo-Goo
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.3
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    • pp.347-355
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    • 1999
  • Background: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate($PIP_2$) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate($IP_3$) and diacylglycerol. PLC-${\gamma}1$, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-yl have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by $IP_3$, phosphatidic acid, etc. Very recently, another PLC-${\gamma}1$ activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-${\gamma}1$ activator, AHNAK, in lung cancer specimens and their paired normal. Methods: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract Immunohistochemical stain was performed with primary antibody against AHNAK protein. Results: Twenty-two among twenty-eight lung cancer tissues showed overexpression of AHNAK protein (eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomas). The resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot Conclusion: The overexpression of PLC-${\gamma}1$ activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-${\gamma}1$ act in concerted manner in carcinogenesis.

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