• Title/Summary/Keyword: 3-level modulation

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Gambigyeongsinhwan(1) Improves Body Weight and Lipid Metabolism in High Fat Diet-Fed Obese Animal Model (감비경신환(1)에 의한 고지방식이 비만동물모델에서 체중감량과 지질대사의 조절)

  • Shin, Soon Shik;Yoon, Michung;Tsung, Pei Chin;Lee, Yong Tae
    • The Korea Journal of Herbology
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    • v.29 no.1
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    • pp.35-43
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    • 2014
  • Objectives : We investigated the effects of gambigyeongsinhwan(GGH)(1) on body weight and non-alcoholic fatty liver disease(NAFLD) examined whether blood total cholesterol, LDL-cholesterol, free fatty acid and triglyceride levels and hepatic lipid accumulation are inhibited by it in high fat diet-fed obese male mice. Methods : 8 weeks old, high fat diet-fed obese male mice were divided into 5 groups: C57BL/6N normal, control, GGH(1)-1, GGH(1)-2 and GGH(1)-3. After mice were treated with GGH(1) for 8 weeks, we measured body weight gain, food intake, feeding efficiency ratio, fat weight, plasma ALT, leptin and lipid levels. We also did histological analysis for liver and fat on the mice. Results : Compared with controls, GGH(1)-treated mice had lower body weight gain and adipose tissue weight, the magnitudes of which were prominent in GGH(1)-3. Compared with controls, GGH(1)-treated mice had lower feeding efficiency ratio and blood leptin level, the magnitudes of which was prominent in GGH(1)-3. Compared with controls, GGH(1)-treated mice had lower blood plasma total cholesterol, LDL-cholesterol, free fatty acid and triglyceride levels. Compared with controls, GGH(1)-3 treated mice had lower blood plasma ALT concentration. Consistent with their effects on body weight gain, the size of adipocytes were significantly decreased by GGH(1), whereas the adipocyte number per unit area was significantly increased, suggesting that GGH(1) decreased the number of large adipocytes. Hepatic lipid accumulation was decreased by GGH(1). Conclusions : In conclusion, these results suggest that GGH(1) exhibits anti-obesity effects through the modulation of feeding efficiency ratio and plasma obesity parameters. Moreover, it seems that GGH(1) also contributes to improve NAFLD through the regulation of plasma ALT and hepatic triglyceride accumulation.

Studies on Anti-aging Action of Brown Algae (Undaria pinnatifida) -2. Dose Effect of Alginic Acid as Modulator of Anti-aging Action in Liver Membranes- (해조류 성분의 노화억제작용에 관한 연구 -2. 간장 세포막속의 노화억제작용의 조절성분으로서 알긴산의 투여효과-)

  • CHOI Jin-Ho;KIM Il-Sung;KIM Jae-Il;YOON Tae-Hyun
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.25 no.3
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    • pp.181-188
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    • 1992
  • To study the effect of alginic acid on modulation of the aging process, Sprague-Dawley(SD) male rats were fed the diets containing 0, 3, 6 and $9\%$ alginic acid isolated from brown algae(Undaria pinnatifida) for 16 weeks. The effects of alginic acid on body weight, malondialdehyde(MDA) content, peroxidizability index, cholesterol and phospholipid levels, cholesterol/phospholipid(Ch/Ph) molar ratio, and fatty acid compositions in liver membranes were investigated. Increasing alginic acid level in diets did not alter food intakes but effectively decreased body weights gain(p<0.01-0.005). Malondialdehyde(MDA) contents of diets containing 6 and $9\%$ alginic acid were effectively decreased in ranges of $54.1-43.0\%$ in mitochondria, and $65.5-87.7\%$ in microsome compared with $100\%$ of control group. Cholesterol levels of all diets containing alginic acid were significantly decreased in ranges of $87.0-72.3\%$ in mitochondria, and $87.4-68.1\%$ in microsome compared with $100\%$ of control group. Phopholipid levels in microsome were significantly decreased by diets containing 3 and $ 6\%$ alginic acid but Ch/Ph molar ratios in both membranes were decreased by diets containing 3 and $6\%$ alginic acid. Increasing alginic acid level in diets significantly decreased total fatty acid but effectively increased linoleic acid in microsome except for diet containing $9\%$ alginic acid. These data on liver membranes suggest that alginic acid added to diets can modulate the physiological changes if the aging process.

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Neuroprotective Effects of Pinelliae Rhizoma Water-Extract by Suppression of Reactive Oxygen Species and Mitochondrial Membrane Potential Loss in a Hypoxic Model of Cultured Rat Cortical Cells. (배양대뇌신경세포 저산소증모델에서 유해산소생성억제 및 사립체막전위 소실방지에 의한 반하(半夏)의 신경세포사 억제 효능)

  • Kwon, Gun-Rok;Moon, Il-Soo;Lee, Won-Chul
    • Journal of Life Science
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    • v.19 no.5
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    • pp.598-606
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    • 2009
  • Oxidative stress by free radicals is a major cause of neuronal cell death. Excitotoxicity in hypoxia/ischemia causes an increase in reactive oxygen species (ROS) and a loss of mitochondrial membrane potential (MMP), resulting in dysfunction of the mitochondria and cell death. Pinelliae Rhizoma (PR) is a traditional medicine for incipient stroke. We investigated the effects of PR Water-Extract on the modulation of ROS and MMP in a hypoxic model using cultured rat cortical cells. PR Water-Extract was added to the culture medium at various concentrations (0.25${\sim}$5, 5.0 ${\mu}g/ml$) on day in vitro 12(DIV12), given a hypoxic shock (2% $O_2$/5% $CO_2$, $37^{\circ}C$, 3 hr), and cell viability was assessed on DIV15 by Lactate Dehydrogenase Assay (LDH assays). PR Water-Extract showed a statistically significant effect on neuroprotection (10${\sim}$15% increase in viability; p<0.01) at 1.0 and 2.5 ${\mu}g/ml$ in normoxia and hypoxia. Measurement of ROS production by $H_2DCF-DA$ stainings showed that PR Water-Extract efficiently reduced the number and intensity of ROS-producing neurons, especially at 1 hr post shock and DIV15. When MMP was measured by JC-1 stainings, PR Water-Extract efficiently maintained high-energy charged mitochondria. These results indicate that PR Water-Extract protects neurons in hypoxia by preventing ROS production and preserving the cellular energy level.

Effect of lactoferrin hydrolysates on inflammatory cytokine modulation in HEK-293, RBL-2H3, and HMC-1 cells

  • Son, Ji Yoon;Bae, Hyung Churl;Renchinkhand, Gereltuya;Nam, Myoung Soo;Kim, Woan-sub
    • Korean Journal of Agricultural Science
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    • v.47 no.1
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    • pp.83-93
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    • 2020
  • Lactoferrin (LF) is an iron-binding glycoprotein that is present in colostrum, milk, and other body secretions. The objective of this study was to investigate the effects of lactoferrin hydrolysates (LHs) on the production of immunomodulatory factors, including inflammatory related cytokines. The nuclear factor (NF)-κB reporter assay using human embryonic kidney 293 cells (HEK-293) revealed that NF-κB activity was significantly decreased by 1, 50, and 100 ㎍/mL of LH and the fractions above and below the 10 kDa LH. The mRNA expression of interferon (IFN)-γ in rat basophilic leukemia mast cells (RBL-2H3) treated with the fraction above the 10 kDa LH decreased in a dose-dependent manner, but the cells treated with LH and the fraction below the 10 kDa LH showed an increased expression of IFN-γ in a dose-dependent manner. The level of cyclooxygenase (COX)-2 expression decreased dose-dependently in RBL-2H3 cells treated with LH and the fraction above the 10 kDa LH, but the cells treated with the fraction below the 10 kDa LH showed an increased COX-2 expression in a dose-dependent manner. The mRNA expression of interleukin (IL)-4) was dose-dependently decreased by the fraction below the 10 kDa LH in human mast cells (HMC-1). The mRNA expressions of tumor necrosis factor (TNF)-α and IL-6 were significantly dose-dependently decreased by the fractions above and below the 10 kDa LH, but was dose-dependently increased by LH. The production of IL-4 was a little increased by the fraction above the 10 kDa LH compared to the positive control, but was decreased with LH and the fraction below the 10 kDa LH in HMC-1 cells. It was concluded that LF hydrolysates had an immunomodulating effect on anti-, pro-inflammatory and anti-allergic reactions.

Modulation of $Ca^{2+}-Activated$ Potassium Channels by cGMP-Dependent Signal Transduction Mechanism in Cerebral Arterial Smooth Muscle Cell of the Rabbit

  • Han, Jin;Kim, Na-Ri;Lee, Kwang-Bok;Kim, Eui-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.6
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    • pp.445-453
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    • 2000
  • The present investigation tested the hypothesis that the activation of protein kinase G (PKG) leads to a phosphorylation of $Ca^{2+}-activated$ potassium channel $(K_{Ca}\;channel)$ and is involved in the activation of $K_{Ca}$ channel activity in cerebral arterial smooth muscle cells of the rabbit. Single-channel currents were recorded in cell-attached and inside-out patch configurations of patch-clamp techniques. Both molsidomine derivative 3-morpholinosydnonimine-N-ethylcarbamide $(SIN-1,\;50\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate $(8-pCPT-cGMP,\;100\;{\mu}M),$ a membrane-permeable analogue of cGMP, increased the $K_{Ca}$ channel activity in the cell-attached patch configuration, and the effect was removed upon washout of the drugs. In inside-out patches, single-channel current amplitude was not changed by SIN-1 and 8-pCPT-cGMP. Application of ATP $(100\;{\mu}M),$ cGMP $(100\;{\mu}M),$ ATP+cGMP $(100\;{\mu}M\;each),$ PKG $(5\;U/{\mu}l),$ ATP $(100\;{\mu}M)+PKG\;(5\;U/{\mu}l),$ or cGMP $(100\;{\mu}M)+PKG\;(5\;U/{\mu}l)$ did not increase the channel activity. ATP $(100\;{\mu}M)+cGMP\;(100\;{\mu}M)+PKG\;(5\;U/{\mu}l)$ added directly to the intracellular phase of inside-out patches increased the channel activity with no changes in the conductance. The heat-inactivated PKG had no effect on the channel activity, and the effect of PKG was inhibited by 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer $(Rp-pCPT-cGMP,\;100\;{\mu}M),$ a potent inhibitor of PKG or protein phosphatase 2A (PP2A, 1 U/ml). In the presence of okadaic acid (OA, 5 nM), PP2A had no effect on the channel activity. The $K_{Ca}$ channel activity spontaneously decayed to the control level upon washout of ATP, cGMP and PKG, and this was prevented by OA (5 nM) in the medium. These results suggest that the PKG-mediated phosphorylations of $K_{Ca}$ channels, or some associated proteins in the membrane patch increase the activity of the $K_{Ca}$ channel, and the activation may be associated with the vasodilating action.

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Ethyl acetate fraction of GGEx18 modulates feeding efficiency ratio and blood leptin level in high fat diet-fed obese mice (GGEx18의 ethyl acetate 분획물에 의한 고지방식이 비만 마우스의 식이효율과 혈중 leptin 농도에 미치는 영향)

  • Park, Ki-Jeong;Lee, Hee-Young;Lee, Hye-Rim;Yoon, Mi-Chung;Park, Sun-Dong;Lee, Yong-Tae;Shen, Zhi-Bin;Cui, Hong-Hua;Shin, Soon-Shik
    • Herbal Formula Science
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    • v.19 no.1
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    • pp.219-231
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    • 2011
  • Objectives : This study was designed to determine the effects of the GGEx18 ethyl acetate fraction(EF) on body weight gain, feeding efficiency ratio, and obesity-related factors in plasma as well as histology of liver and adipose tissues using high fat diet-fed male C57BL/6N obese mice. Methods : 8 weeks old, high fat diet-fed obese male mice were divided into 5 groups: C57BL/6N normal, control, EF(1), EF(2) and EF(3). After mice were treated with EF for 9 weeks, we measured body weight gain, food intake, feeding efficiency ratio, fat weight, plasma leptin and lipid levels. We also analysed histology of liver and adipose tissues on high fat diet-fed male C57BL/6N obese mice. Results : Compared with control, EF-treated mice had significantly lower body weight gain and feeding efficiency ratio. Consistent with the effects on body weight gain, EF significantly decreased the adipose tissue weight compared with control. Consistent with the effects on feeding efficiency ratio, EF significantly decreased plasma leptin concentrations compared with control. EF reduced the size of adipocytes as well as hepatic lipid accumulation compared with control. EF seems to be safe since not only the plasma levels of ALT and AST are within the normal range, but also EF did not show any toxic effects on organs. EF(3) was most effective among EF(1), EF(2), and EF(3) at doses of 25, 50, and 100 mg/kg, respectively. Conclusions : These results demonstrate that EF effectively reduces body weight gain, feeding efficiency ratio in high fat diet-fed obese mice, leading to the modulation of obesity. In addition, EF decreases the size of adipocytes and improves plasma lipids and controls hepatic lipid accumulation, suggesting that EF may act as a therapeutic agent for obesity.

Inhibitory effect of water-soluble mulberry leaf extract on hepatic lipid accumulation in high-fat diet-fed rats via modulation of hepatic microRNA-221/222 expression and inflammation (고지방식이 급여 쥐에서 수용성 뽕나무 잎 추출물의 간 microRNA-221/222 발현 및 염증 조절을 통한 간 지질 축적억제 효과)

  • Lee, Mak-Soon;Kim, Cheamin;Ko, Hyunmi;Kim, Yangha
    • Journal of Nutrition and Health
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    • v.55 no.2
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    • pp.227-239
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    • 2022
  • Purpose: This study investigated the effects of water-soluble mulberry leaf extract (ME) on hepatic lipid accumulation in high-fat diet-fed rats via the regulation of hepatic microRNA (miR)-221/222 and inflammation. Methods: Male Sprague-Dawley rats (4 weeks old) were randomly divided into 3 groups (n = 7 each) and fed with 10 kcal% low-fat diet (LF), 45 kcal% high-fat diet (HF), or HF + 0.8% ME for 14 weeks. Lipid profiles and cytokine levels of the liver and serum were measured using commercial enzymatic colorimetric and enzyme-linked immunosorbent assay, respectively. The messenger RNA (mRNA) and miR levels in liver tissue were assayed by real-time quantitative reverse-transcription polymerase chain reaction. Results: Supplementation of ME reduces body weight and improves the liver and serum lipid profiles as compared to the HF group. The mRNA levels of hepatic peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, fatty acid synthase, and fatty acid translocase, which are genes involved in lipid metabolism, were significantly downregulated in the ME group compared to the HF group. In contrast, the mRNA level of hepatic carnitine palmitoyl transferase-1 (involved in fatty acid oxidation) was upregulated by ME supplementation. Furthermore, administration of ME significantly downregulated the mRNA levels of inflammatory mediators such as hepatic tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The serum levels of TNF-α, IL-6, and nitric oxide were also significantly reduced in ME group compared to the HF group. Expression of hepatic miR-221 and miR-222, which increase in the inflammatory state of the liver, were also significantly inhibited in the ME group compared to the HF group. Conclusion: These results indicate that ME has the potential to improve hepatic lipid accumulation in high-fat diet-fed rats via modulation of inflammatory mediators and hepatic miR-221/222 expressions.

Herbal medicine In-Jin-Ho-Tang as a potential anti-cancer drug by induction of apoptosis in human hepatoma HepG2 cells. (사람 간암 세포주인 HepG2에 대한 인진호탕(茵陳蒿湯)의 항암 효과)

  • Yun, Hyun-Joung;Kim, Byung-Wan;Lee, Chang-Hyun;Jung, Jae-Ha;Heo, Sook-Kyung;Park, Won-Hwan;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.22 no.3
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    • pp.27-37
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    • 2007
  • Objectives: Hepatocellular carcinoma is the most common primary malignant tumor of the liver worldwide. In-Jin-Ho-Tang(IJHT) has been used as a traditional Chinese herbal medicine since ancient time. and today it is widely applied as a medication for jaundice which is associated with inflammation in liver. In this study, I investigated whether methanol extract of IJHT induced HepG2 cancer cell death. Methods: Cytotoxic activity of IJHT on HepG2 cells was using XTT assay. Apoptosis induction by Ros A in HCT116 cells was verified by the induction of cleavage of poly ADP-ribose polymerase (PARP). and activation of caspase-3, -8 and -9. The release of cytochrome c from mitochondria to cytosol. the level of Bcl-2 and Bax and the expression of p53 and p21 were examined by western blotting analysis. Furthermore, MAPKs activation was analyzed by western blotting analysis. Results: IJHT induced apoptosis in HepG2 cells. And treatment of IJHT resulted in the release of cytochrome c into cytosol, decreased anti-apoptotic Bcl-2, and increased pri-apoptotic Bax expression. IJHT markedly inactivated extracellular signal-regulated kinase (ERK1/2), and activated p38 mitogen-activated protein (MAP) kinase. Sodium orthovanadate (SOV), a phosphatase inhibitor, to reverse IJHT-induced ERK1/2 inactivation and SB203580, a specific p38 MAP Kinase inhibitor efficiently blocked apoptosis of HepG2. Thus, IJHT induces apoptosis in HepG2 cells via MAP kinase modulation. Conclusion: These results indicated that IJHT has some potential for use as an anti-cancer agent.

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Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice

  • Cao, Zhiyun;Chen, Xuzheng;Lan, Lan;Zhang, Zhideng;Du, Jian;Liao, Lianming
    • Nutrition Research and Practice
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    • v.9 no.2
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    • pp.129-136
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    • 2015
  • BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU ($10mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.p), or AHCC ($360mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.g) plus 5-FU, respectively, for 5 d. $CD^{3+}$, $CD^{4+}$, $CD^{8+}$, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and $TNF{\alpha}$ in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of $CD^{3+}$, $CD^{4+}$, and NK cells (P < 0.01), and ratio of $CD^{4+}$/$CD^{8+}$ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and $TNF{\alpha}$ compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

A Study of Limitation of Service Area by UWB Transmission Jamming in DMB System (DMB 시스템에서 UWB 전파가 서비스에 미치는 영향에 관한 연구)

  • Kim, Dong-Ok
    • Journal of The Institute of Information and Telecommunication Facilities Engineering
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    • v.4 no.2
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    • pp.1-8
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    • 2005
  • In this paper, n system did research about effect that interference effect with neighborhood single equipment or group equipment gets in DMB service. For this, 2.6425 GHz SDMB(Satellite Digital Multimedia Broadcasting) that a special of electric wave interference is near frequency-band including interference of signal by unnecessary radiation level that is radiated in UWB system, and degree of 3.4125GHz broadcasting relay net that is In-band frequency-band and interference effect that get in service analyzed comparison ud, modulation of broadcasting relay net and interference measurement equipment used Impulse and OFDM methods. Impulse method was $BER=1{\times}10^4$ that broadcasting signal receiption is possible at 1.4m point because interference effect happens from 2m point in SDMB system, and it was $BER=1^{\times}10-4$ that OFDM method receives interference effect from 0.8m point and broadcasting signal receiption is possible at 0.5m point. Also, about gap-filler center frequency, in case of space interval more than 0.01m, there was no interference effect. Therefore, for the electric wave of W system that is small output applies to system without interference effect in DMB service, confirmed that UWB system of OFDM method is less interference effect than UWB system of impulse method.

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