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Effects of long-term tubular HIF-2α overexpression on progressive renal fibrosis in a chronic kidney disease model

  • Dal-Ah Kim;Mi-Ran Lee;Hyung Jung Oh;Myong Kim;Kyoung Hye Kong
    • BMB Reports
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    • v.56 no.3
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    • pp.196-201
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    • 2023
  • Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

Daily Travel Pattern using Public Transport Mode in Seoul:An Analysis of a Multi-Dimensional Motif Search (핵심정보배열 추출에 의한 서울시 대중교통 통행패턴 분석)

  • Joh, Chang-Hyeon
    • Journal of the Korean Geographical Society
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    • v.44 no.2
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    • pp.176-186
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    • 2009
  • Transportation policy to facilitate the public mode use is of the foremost importance to the local governments of Metropolitan Seoul, regarding the economic and environmental consequences of the increasing use of car. Understanding the travel behaviour is essential to the establishment of proper policy to guide more people to the use of public modes instead of private. The paper reports a result of sequential analysis of individual travel behaviour in Metropolitan Seoul, using a multi-dimensional motif search technique applied to Smart Card data that integrates individuals' different public mode uses. Groups of travel patterns with similar sequential information identified distinctive travel behaviour between Seoul north and south and between metro and bus uses. Travel patterns are more bounded within north Seoul and south Seoul respectively than crossing Han River between north and south. Within north and south, travel patterns visiting northern CBD and southern CBD, respectively, as well as their local neighbour in north and south, often use metro and metro-local bus combination, while travel patterns visiting only the north and south locals without CBDs more use only the local bus line and even only the areal bus line.

Supporting Policy for GeoSpatial Information Convergence Industry by Comparing Laws about Convergence Industry (융합산업 관련 법제도 비교를 통한 공간정보융합산업 지원방안)

  • Song, Ki Sung;Woo, Hee Sook;Kim, Byung Guk;Hwang, Jeong Rae
    • Spatial Information Research
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    • v.23 no.6
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    • pp.9-17
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    • 2015
  • The convergence industry is a combination of technologies or industries of the same type or various types, thereby maintaining and/or expanding the existing values or creating fresh values. As the industry is drawing greater attention over the world, each country is making huge efforts to provide support for it. GeoSpatial Information is a representative convergence industry characterized by being utilized as a basis for other industrial fields by being linked and fused with other industries and technologies. It is well recognized as being a promising industry that will likely lead the national economy in the future. GeoSpatial Information is necessary to analyze the distinctive features and obstacle factors of the convergence industry. Because it will be able to induce a smooth convergence among different industries. In this paper, we has segmented the support elements through a comparative analysis of the legal system related to (Nano Technology, Information and Communication Technology, Culture Technology, etc)the convergence industry. Based on this proposed policy support for GeoSpatial Information Convergence industry. We expect that this study will be used as basic data of the policy established to effectively support for the GeoSpatial Information convergence industry.

Heat Insulation Characteristics of Multi Layer Materials for Greenhouse (시설원예용 조합형 다겹보온자재의 보온 특성)

  • Chung, Sung-Won;Kim, Dong-Keon;Lee, Suk-Gun;Nam, Sang-Heon;Lee, Yong-Beom
    • Journal of Bio-Environment Control
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    • v.18 no.4
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    • pp.341-347
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    • 2009
  • Experiments and computations were conducted to investigate the heat insulation characteristics of multi layer materials for cultivation greenhouse. In case of the experiments, measurements of temperature were carried out with a K-type thermocouples and data logger to research the heat transfer in the experimental module generated by the heat source. A thermal conductivity meter, QTM-500 based on modified transient hot wire method was used to measure the thermal conductivity of multi layer materials. The numerical analyses were performed by commercial code CFX-11 according to the variation of multi layer materials without air layer. The experimental results showed that the heat insulation of multi layer materials was higher than single layer materials by 50~90%. It was found that the effect of heat insulation was raised by the combination of multi layer materials.

Factors Influencing Users' Intension to Play Mobile Games: A Combination of Game-Contents Traits and Mobile Handset's Capabilities into the Technology Acceptance Model (게임 콘텐츠 특성과 단말기 요인을 고려한 모바일게임 사용의도의 영향요인에 관한 연구)

  • Han, Kwang-Hyun;Kim, Tae-Ung
    • Information Systems Review
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    • v.7 no.2
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    • pp.41-59
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    • 2005
  • Mobile games have emerged as the most innovative entertainment technology adding new revenue streams, taking advantage of the potential of wireless consumer applications and service offerings. Mobile games, like any other types of computer game, offer a unique value for users in providing an exciting digital experience in virtual worlds. Players can become empowered through the development of new characters and strategies within games to achieve rewarding successes against the computers and other players. In this paper, we attempt to investigate the factors influencing the usage and acceptance of the mobile games in Korea, based on the extended version of the Technology Acceptance Model(TAM). Based on data collected from survey, we show that perceived usefulness is the major determinant for users to play mobile games. Two factors, including perceived enjoyment and self-expressiveness, are empirically shown to determine perceived usefulness. In addition, perceived ease of use, rewards, operational quality of device, and design/story have been showed to significantly and directly affect perceived enjoyment. It was also confirmed that self-efficacy and operational quality of device are the antecedents of perceived ease of use. Based upon the statistical results, some useful guidelines for game development and market penetration strategies are also provided.

Analysis of Apoptosis on the Somatic Cell Nuclear Transfer embryos in porcine (돼지 체세포 복제 수정란의 자가 사멸 분석)

  • Ryu, Ji-Eun;Yoon, Jong-Taek
    • Journal of Embryo Transfer
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    • v.33 no.3
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    • pp.119-127
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    • 2018
  • The purpose of this study is to examined the electrofusion and activation conditions for the production of porcine somatic cell nuclear transfer (SCNT) embryos. In this study, immature oocytes were cultured in TCM-199 with and without hormones for 22 hours. Skin fibroblasts cells of porcine were transferred into the perivitelline space of enucleated in vitro matured oocytes. Cell fusion was performed with two different pulses that each one pulse (DC) of 1.1 kV/cm or 1.5 kV/cm for $30{\mu}sec$. After fusion subsequent activation were divided into three groups; non-treatment (control) and treatment with 2 mM 6-DMAP or $7.5{\mu}g/ml$ cytochalasin B for 4 hours. Transferred embryos were cultured in PZM-3 (Porcine Zygote Medium-3) in $5%\;CO_2$ and 95% air at $39^{\circ}C$ for 7 day. Apoptosis-related genes (Caspase-3, BCL-2, mTOR, and MMP-2) were analyzed by immunofluorescence staining. There was no significant difference between two different electrofusion stimuli in the cleavage rate; $64.9{\pm}4.8%$ in 1.1 kV/cm and $62.7{\pm}4.0%$ in 1.5 kV/cm. However, blastocyst formation rate (%) was significantly different among three different activation groups (no treatment, 2 mM 6-DMAP or $7.5{\mu}g/ml$ cytochalasin B) combined with electrofusion of 1.1 kV/cm. The blastocyst formation rate was $12.6{\pm}2.5$, $20.0{\pm}5.0$, and $34.9{\pm}4.3%$ in control, 2 mM 6-DMAP, and $7.5{\mu}g/ml$ cytochalasin B, respectively. Immunofluorescence data showed that expression levels of caspase-3 in SCNT embryos undeveloped to blastocyst stage were higher than those in the blastocyst stage embryos. Expression levels of Bcl-2 in blastocyst stage embryos were higher than those in the arrested SCNT embryos. These results showed that the combination of an electric pulse (1.1 kV/cm for $30{\mu}sec$) and $7.5{\mu}g/ml$ cytochalasin B treatment was effective for production of the porcine SCNT embryos.

Potential Importance of Proteomics in Research of Reproductive Biology (생식생물학에세 프로테오믹스의 응용)

  • Kim Ho-Seung;Yoon Yong-Dal
    • Development and Reproduction
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    • v.8 no.1
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    • pp.1-9
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    • 2004
  • The potential importance of proteomic approaches has been clearly demonstrated in other fields of human medical research, including liver and heart disease and certain forms of cancer. However, reproductive researches have been applied to proteomics poorly. Proteomics can be defined as the systematic analysis of proteins for their identity, quantity, and function. It could increase the predictability of early drug development and identify non-invasive biomarkers of toxicity or efficacy. Proteome analysis is most commonly accomplished by the combination of two-dimensional gel electrophoresis(2DE) and MALDI-TOF(matrix-assisted laser desorption ionization-time of flight) MS(mass spectrometry) or protein chip array and SELDI-TOF(surface-enhanced laser desorption ionization-time of flight) MS. In addition understanding the possessing knowledge of the developing biomarkers used to assess reproductive biology will also be essential components relevant to the topic of reproduction. The continued integration of proteomic and genomic data will have a fundamental impact on our understanding of the normal functioning of cells and organisms and will give insights into complex cellular processes and disease and provides new opportunities for the development of diagnostics and therapeutics. The challenge to researchers in the field of reproduction is to harness this new technology as well as others that are available to a greater extent than at present as they have considerable potential to greatly improve our understanding of the molecular aspects of reproduction both in health and disease.

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Measurement of the Benefits from Safeguarding Energy Security through Building the Integrated Gasification Combined Cycle Power Plant (석탄가스화 복합발전소 건설의 에너지안보 확보편익 추정)

  • Lim, Seul-Ye;Choi, Hyo-Yeon;Yoo, Seung-Hoon
    • Journal of Energy Engineering
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    • v.24 no.3
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    • pp.40-47
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    • 2015
  • Integrated gasification combined cycle (IGCC) power plants not only emit less greenhouse gases and air pollutants than conventional coal-fired power plants, but also use low-price, low-quality, and internationally easily procurable coal. Thus we can benefit from safeguarding energy security through building the IGCC power plant. This paper attempts to value the benefits of energy security enhanced by IGCC power plant. To this end, we report here the results from a contingent valuation survey of randomly selected 600 households. A combination of a double-bounded model and a spike model is applied for the purpose of increasing statistical efficiency and dealing with zero(0) willingness to pay data, respectively. The results show that the respondents are additionally willing to pay 6.05 won for 1kWh of electricity generated from IGCC power plant. In other words, the benefits from safeguarding energy security through building the IGCC power plant are 6.05 won per kWh. Given that the expected amount of generation from the Taean IGCC power plant that is scheduled to be built in late 2015 is 2.27 TWh per year, the benefits are estimated to be 13.74 billion won per year.

Cooperation of $G{\beta}$ and $G_{\alpha}q$ Protein in Contractile Response of Cat Lower Esophageal Sphincter (LES)

  • Sohn, Uy-Dong;Lee, Tai-Sang
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.6
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    • pp.349-355
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    • 2003
  • We previously shown that LES contraction depends on $M_3$ receptors linked to PTX insensitive $G_q$ protein and activation of PLC. This results in production of $IP_3$, which mediates calcium release, and contraction through a CaM dependent pathway. In the esophagus ACh activates $M_2$ receptors linked to PTX sensitive $G_{i3}$ protein, resulting in activation of PLD, presumably, production of DAG. We investigated the role of PLC isozymes which can be activated by $G_q$ or $G{\beta}$ protein on ACh-induced contraction in LES and esophagus. Immunoblot analysis showed the presence of 3 types of PLC isozymes, $PLC-{\beta}1$, $PLC-{\beta}3$, and $PLC-{\gamma}1$, but not $PLC-{\beta}2$, $PLC-{\beta}4$, $PLC-{\gamma}2$, $PLC-{\delta}1$, and $PLC-{\delta}2$ from both LES and esophageal muscle. ACh produced contraction in a dose dependent manner in LES and esophageal muscle cells obtained by enzymatic digestion with collagenase. $PLC-{\beta}1$ or $PLC-{\beta}3$ antibody incubation reduced contraction in response to ACh in LES but not in esophageal permeabilized cells, but $PLC-{\gamma}1$ antibody incubation did not have an inhibitory effect. The inhibition by $PLC-{\beta}1$ or $PLC-{\beta}3$ antibody on Ach-induced contraction was antibody concentration dependent. The combination with $PLC-{\beta}_1$ and $PLC-{\beta}_3$ antibody completely abolished the contraction, suggesting that $PLC-{\beta}1$ and $PLC-{\beta}3$ have a synergism to inhibit the contraction in LES. $PLC-{\beta}1$, -${\beta}3$ or -${\gamma}1$ antibody did not reduce the contraction of LES cells in response to DAG ($10^{-6}$ M), suggesting that this isozyme of PLC may not activate PKC. When $G_{q/11}$ antibody was incubated, the inhibitory effect of the incubation of PLC ${\beta}3$, but not of PLC ${\beta}_1$ was additive (Fig. 6). In contrast, when $G_{\beta}$ antibody was incubated, the inhibitory effect of the incubation of PLC ${\beta}_1$, but not of PLC ${\beta}_3$ was additive. This data suggest that $G_{q/11}$/11 or $G{\beta}$ may activate cooperatively different PLC isozyme, $PLC{\beta}_1$ or $PLC{\beta}_3$ respectively.

Interaction of Pyrazole - and Chloroacetamide Herbicide Combinations in Control of Echinochloa crusgalli (Pyrazole계(系)와 Chloroacetamide계(系) 제초제(除草劑)들의 혼합처리(混合處理)가 피(Echinochloa crusgalli)의 살초효과(殺草效果)에 미치는 상호작용(相互作用))

  • Kwon, Y.W.;Seong, K.Y.;Soh, C.H.
    • Korean Journal of Weed Science
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    • v.5 no.2
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    • pp.155-163
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    • 1985
  • Three pyrazole-herbicides, pyrazolate, pyrazoxyfene and benzophenap, were evaluated for their interaction in controlling barnyardgrass (Echinochloa crusgalli) with two chloroacetamide-herbicides, butachlor and pretilachlor. Percent inhibition of barnyardgrass growth by pyrazolate, pyrazoxyfene, and benzophenap was 44%, 64%, and 0%, respectively, when each was applied at the 1.5 leaf-stage of barnyardgrass at a rate of 3㎏ ai per ㏊ as single treatment, and the benzophenap showed 60% inhibition when it was applied at the coleoptile stage. While the lowest rate controlling the 1.5 leaf-stage barnyardgrasses by 98 to 100% of the butachlor and pretilachlor was 1.5㎏ and 200g per ㏊, respectively. All of the combinations of pyrazolate with butachlor, pyrazoxyfene with pretilachlor, and benzophenap with butachlor have shown synergistic interaction in controlling barnyardgrass on the Chisaka's isobole of 90% growth inhibition as well as on the Colby`s interaction efficacy data; synergism indices were 2.44, 1.62 and 1.52 in order. The dose combinations shown the maximal synergism were 1870g of pyrazolate with 140g of butachlor (1:0.075), 33008 of pyrazoxyfene with 338 of pretilachlor (1:0.01), and 3350g of benzophenap with 520g of butachlor (1:0.15) on the ai/㏊ basis.

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