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Novel Anti-Angiogenic and Anti-Tumour Activities of the N-Terminal Domain of NOEY2 via Binding to VEGFR-2 in Ovarian Cancer

  • Rho, Seung Bae;Lee, Keun Woo;Lee, Seung-Hoon;Byun, Hyun Jung;Kim, Boh-Ram;Lee, Chang Hoon
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.506-518
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    • 2021
  • The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3'-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the three-dimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

A Study on the Form-Element of Buildings Affecting in Street Spaces (가로공간 이미지에 영향을 미치는 가로변건축물 형태구성요소에 관한 연구)

  • Choi, Im-Joo;Jo, Hyun-Duk
    • Journal of the Korean Association of Geographic Information Studies
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    • v.13 no.1
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    • pp.16-27
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    • 2010
  • A street, as a linear factor constituting the city, is an axis of urban development. The substantial function of the street is the traffic space for the passage but now it plays the important role of the place of community where contains various activities such as meeting between people and people, rest, entertainment etc. A street is basically the 3 dimensional space consisted of the sidewalk, roadway and the roadside structures surrounding the street. In this case, the roadside structures are the physical composition factors for the street space and the facade of the roadside structures acts as important variables to form the image of street space. Thus, this study is to provide the basic data to be applied in the future urban street landscape plan by extracting the superior factors in visual and perceptional aspects which affect the image of street view from the shape composition factors which constitute the facade of the roadside structures, and by searching and analyzing the satisfaction degree and preference of each factors.

Strategy of Market Spread-Commercialization in EVs Industry : Visegrad and Nordic Countries (EVs 산업의 시장파급과 상용화의 전략비교 : 비셰그라드 그룹과 북유럽 협의체와의 산업역량중심으로)

  • Seo, Dae-Sung
    • The Journal of Industrial Distribution & Business
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    • v.9 no.3
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    • pp.57-68
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    • 2018
  • Purpose - The purpose of this study is to classify that the quality factors for comparing the Visegrard Group with the Nordic Council have historical similarities against Germany and the Soviet Union. However, this is because in the integrated European market, the competitiveness possessed by the two groups of countries is invested in the priority order to grow. Research design, data, and methodology - The study was conducted on the research design, and the reason for trying to compare the competence of the automobile industry in the assessment of industrial capability is that the Visegrard Group focuses on automotive production and the Nordic Association focuses on the commercialization of the automobile(market). In this study, searching and quantifying indirect evidence was made through standards are more complementary in Europe since each country acts like the role of the European automotive industry for example, which is different from the realistic evaluation criteria, are more important than those of the United States(first in the world) or Germany(first in Europe). Results - The results of this study are as follows: In the global EV market U.S.(export: $ 2.62 billion /share: 36.7%), Germany($ 1.29 billion /18.1%), France($ 390 million /5.4%), United Kingdom($ 380 million /5.4%), and South Korea($ 320 million/ 4.4%). South Korea's share of the EV market is 4.4%, while TSI reaches at +0.9 which measures the comparative advantage of a specific commodity in the world trade market. There is great potential for evaluated as products processing in export competition. But, commercialization, standardization, and overall market expansion did not have a positive impact on global satisfaction. Conclusions - EVs put importance on various utilities. So this suggests that Korea's exports to the EU, including the Visegrard Group, should be more focused on marketability when illuminating with a sharing industrial system under the European Union. It is necessary to specialize in manufacturing and commercialization by country(region) to prepare sharing economy and blockchain in order to create a smart-sharing city linked on artificial intelligence, as the commercialization of electric vehicles, which will have a larger growth rate than that of manufacturing in the fourth revolutionary era.

Resveratrol Down-regulates Bmi-1 Expression and Inhibits Breast Cancer Cell Growth In Vitro (유방암세포 성장과 Bmi-1 발현에 대한 레스베라트롤의 억제 효과)

  • Park, Hyun-Joo;Bak, Kwang Je;Ok, Chang Youp;Jang, Hye-Ock;Bae, Moon-Kyoung;Bae, Soo-Kyung
    • KSBB Journal
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    • v.32 no.3
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    • pp.224-232
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    • 2017
  • Resveratrol has been actively investigated as an anticancer drug since it induces cell growth inhibition and apoptosis in many cancer cells. Resveratrol acts through modulation of multiple pathways and genes. In this study, we found resveratrol reduced cell growth and mammosphere formation in MDA-MB-231 triple-negative human breast cancer cells. This suppressive effect of resveratrol is accompanied by a reduction in Bmi-1 gene expression. We also observed that knock-down of Bmi-1 gene by small interfering RNA effectively sensitizes breast cancer cells to resveratrol treatment. Our data demonstrate, for the first time, that resveratrol down-regulates Bmi-1 expression in human breast cancer cells and suggest that specific molecular targeting of Bmi-1 can be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to resveratrol.

Enhanced Anti-inflammatory Effects of γ-irradiated Pig Placenta Extracts

  • Kim, Kang Chang;Heo, Jae Hyeok;Yoon, Jong Kwang;Jang, Yuyeon;Kim, Youn Kyu;Kim, Chang-Kyu;Oh, Yu-Kyung;Kim, Young Bong
    • Food Science of Animal Resources
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    • v.35 no.3
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    • pp.293-298
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    • 2015
  • Porcine placenta extract (PPE) is known to possess anti-inflammatory properties owing to its high concentration of bioactive substances. However, the need to eliminate blood-borne infectious agents while maintaining biological efficacy raises concerns about the optimal method for sterilizing PPE. Therefore, the objective of this study was to compare the effects of the standard pressurized heat (autoclaving) method of sterilization with γ-irradiation on the anti-inflammatory effects of PPE. The anti-inflammatory actions of these two preparations of PPE were evaluated by measuring their inhibitory effects on the production of NO, the expression of iNOS protein, and the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA in lipopolysaccharide-stimulated RAW 264.7 cells. Compared with autoclaved PPE, γ-irradiated PPE showed significantly greater inhibition of NO production and iNOS protein expression, and produced a greater reduction in the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA. These results provide evidence that the sterilization process is crucial in determining the biological activity of PPE, especially its anti-inflammatory activity. Collectively, our data suggest that γ-irradiated PPE acts at the transcriptional level to effectively and potently suppresses the production of NO and the expression of pro-inflammatory cytokines.

Proposal of Personalized Recommendation for Korean Food and Tour Using Beacon System (비콘을 활용한 개인 맞춤형 한식과 관광지 추천 관리 시스템 제안)

  • Sung, Kihyuk;Ryu, Gihwan;Yun, Daiyeol
    • The Journal of the Convergence on Culture Technology
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    • v.6 no.3
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    • pp.267-273
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    • 2020
  • Beacon is a wireless communication device that can automatically recognize the smart device in the short distance and transmit the necessary data, Beacon is a representative Internet of Things (IoT) facility in the era of the 4th Industrial Revolution, which is utilized in various fields such as short-distance information delivery, mobile location service, shopping, and marketing, and is constantly evolving. In this paper, it is based on tourist site-based recommendation information service. A system is proposed that recommends customized information according to the user's interest, preference, etc. by incorporating beacon technology. In other words, it acts as an information agent that informs tourists of desired information. In order to meet the needs of tourists, it is necessary to build an intelligent tourism recommendation system. The personalized Korean food and tourism recommendation management system using the beacon technology proposed in this paper is expected to provide high-quality services not only to foreigners visiting Korea but also to Korean tourists.

Sensibility Evaluation of Components of Middle and High-rise Apartment Facade in Aesthetic Old Town Districts of Kyoto - Extraction of Component Combinations Using Rough Set Theory - (쿄토시 구시가지형미관지구에서 중고층 집합주택 입면의 구성요소에 대한 감성평가 - 러프 집합을 이용한 구성요소 조합의 추출 -)

  • Shon, Dong-Hwa
    • Journal of the Korean housing association
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    • v.25 no.3
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    • pp.105-114
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    • 2014
  • Landscape zones have been designated as aesthetic old town districts across a wide range of Nakakyo-Ku and Shimokyo-Ku, city center of Kyoto, Japan. In these districts in which traditional structures and new buildings coexist, regulations of restriction on acts such as new building's heights, shapes, materials, and colors are carried out according to local governmental landscape ordinance based on Scenic Conservation Act. And yet, minimal fulfillment of the regulations according to different designer's subjective interpretation and principle of economy is rather creating abnormal shapes not harmonized with the traditional landscape. Thus, this study aims to extract combinations between form elements of middle and high rise apartment facade that affects 'harmony' and 'mismatch' in the districts by clarifying the social rules commonly implied based on intuitive judgments (sensibility evaluation) in which human experiential knowledge is involved. As research methods, the study first analyzes the form elements of the facade through a field survey, sets up a standard model through tasks of classification and segmentation and draws computer graphic images with 99 different patterns based on it. Based on these images, this study carries out sensibility evaluation and analyzes experimental data applying the rough set theory. As a result of the analysis, the combinations of form elements that affect harmony or mismatch act greatly when the colors and shapes of the pillars, positions and the patterns of the use of the first floor are combined.

Thermodynamic, Infrared, and Magnetic Studies on the Complexation of Gd(III) by Benzoate Anion (Gadolinium-benzoate 착물의 열역학적, 적외선 및 자기적 성질에 관한 연구)

  • Young-Inn Kim;Heung-Jae Park;Sung-Nak Choi;Sock-Seung Yun
    • Journal of the Korean Chemical Society
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    • v.36 no.2
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    • pp.212-217
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    • 1992
  • The thermodynamic parameters for the formation of gadolinium benzoate have been determined in the ionic medium of 0.1 M $NaClO_4$ at $25^{\circ}C$ in aqueous solution. The thermodynamic results indicate that the complex is stabilized by the excess entropy effect caused by the dehydration of reacting ions. The especially high stability of Gd(III)-benzoate compared to the monodentate ligand complexes might be ascribed to the conjugation effect of the benzene ring in the benzoate ligand. IR spectra show that benzoate anion acts as a bidentate ligand toward $Gd^{3+}$ to form a chelate ring in solid state. Magnetic susceptibility data of the compound were also obtained and well described by Curie-Weiss law in the temperature range 80${\sim}$300K.

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Assessing Unit Hydrograph Parameters and Peak Runoff Responses from Storm Rainfall Events: A Case Study in Hancheon Basin of Jeju Island

  • Kar, Kanak Kanti;Yang, Sung-Kee;Lee, Jun-Ho
    • Journal of Environmental Science International
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    • v.24 no.4
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    • pp.437-447
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    • 2015
  • Estimation of runoff peak is needed to assess water availability, in order to support the multifaceted water uses and functions, hence to underscore the modalities for efficient water utilization. The magnitude of storm rainfall acts as a primary input for basin level runoff computation. The rainfall-runoff linkage plays a pivotal role in water resource system management and feasibility level planning for resource distribution. Considering this importance, a case study has been carried out in the Hancheon basin of Jeju Island where distinctive hydrological characteristics are investigated for continuous storm rainfall and high permeable geological features. The study aims to estimate unit hydrograph parameters, peak runoff and peak time of storm rainfalls based on Clark unit hydrograph method. For analyzing observed runoff, five storm rainfall events were selected randomly from recent years' rainfall and HEC-hydrologic modeling system (HMS) model was used for rainfall-runoff data processing. The simulation results showed that the peak runoff varies from 164 to 548 m3/sec and peak time (onset) varies from 8 to 27 hours. A comprehensive relationship between Clark unit hydrograph parameters (time of concentration and storage coefficient) has also been derived in this study. The optimized values of the two parameters were verified by the analysis of variance (ANOVA) and runoff comparison performance were analyzed by root mean square error (RMSE) and Nash-Sutcliffe efficiency (NSE) estimation. After statistical analysis of the Clark parameters significance level was found in 5% and runoff performances were found as 3.97 RMSE and 0.99 NSE, respectively. The calibration and validation results indicated strong coherence of unit hydrograph model responses to the actual situation of historical storm runoff events.

Finite element modeling of corroded RC beams using cohesive surface bonding approach

  • Al-Osta, Mohammed A.;Al-Sakkaf, Hamdi A.;Sharif, Alfarabi M.;Ahmad, Shamsad;Baluch, Mohammad H.
    • Computers and Concrete
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    • v.22 no.2
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    • pp.167-182
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    • 2018
  • The modeling of loss of bond between reinforcing bars (rebars) and concrete due to corrosion is useful in studying the behavior and prediction of residual load bearing capacity of corroded reinforced concrete (RC) members. In the present work, first the possibility of using different methods to simulate the rebars-concrete bonding, which is used in three-dimensional (3D) finite element (FE) modeling of corroded RC beams, was explored. The cohesive surface interaction method was found to be most suitable for simulating the bond between rebars and concrete. Secondly, using the cohesive surface interaction approach, the 3D FE modeling of the behavior of non-corroded and corroded RC beams was carried out in an ABAQUS environment. Experimental data, reported in literature, were used to validate the models. Then using the developed models, a parametric study was conducted to examine the effects of some parameters, such as degree and location of the corrosion, on the behavior and residual capacity of the corroded beams. The results obtained from the parametric analysis using the developed model showed that corrosion in top compression rebars has very small effect on the flexural behaviors of beams with small flexural reinforcement ratio that is less than the maximum ratio specified in ACI-318-14 (singly RC beam). In addition, the reduction of steel yield strength in tension reinforcement due to corrosion is the main source of reducing the load bearing capacity of corroded RC beams. The most critical corrosion-induced damage is the complete loss of bond between rebars and the concrete as it causes sudden failure and the beam acts as un-reinforced beam.