• Title/Summary/Keyword: Docking Method

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Bad Translocation to Mitochondria with Bcl-XL Traced in-vivo by Using GFP (GFP를 이용하여 in-vivo에서 추적한 Bad와 Bcl-XL의 Mitochondria 이동)

  • Yoon, Soo Han;Kim, Jin Young;Park, Seung Woo;Ahn, Young Hwan;Ahn, Young Min;Cho, Ki Hong;Cho, Kyung Gi
    • Journal of Korean Neurosurgical Society
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    • v.29 no.10
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    • pp.1283-1288
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    • 2000
  • Objectives : The subcellular locations of Bad, Bid, Bax and Bcl-XL change during apoptosis and this change is important for the regulation of cell death. The purpose this study was to elucidate binding of Bad with Bcl-XL in vivo Methods : We mads Bad with Green Fluorescent Protein(GFP) using PCR method. We transfected and overexpressed GFP-Bad with or without Bcl-XL cotransfection in living COS-7 cell. Results : Bad and Bcl- XL bind one another in healthy living cells and this association controled mitochondrial docking. In the absence of Bad-XL, Bad was mainly cytosolic and partially bound to mitochondria. Upon coexpression of Bad and Bcl-XL, most of Bad translocated to mitochondria. These should suggest that Bad binds to the mitochondrial and cytoplasmic forms of Bcl-XL and Bad bound to cytoplasmic Bcl-XL translocates to mitochondria. These in vivo findings confirm that Bad make a complexes with Bcl- XL and cause mitochondrial translocation of Bad-Bcl-XL complex.

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Study on Spray characteristics of Dual-Manifold Injector with Various Tangential Entries (이중 매니폴드 분사기에서 접선방향 유입구의 변화에 따른 분사특성 연구)

  • Lee, Ingyu;Jeong, Seokgyu;Yoon, Jungsoo;Park, Gujeong;Yoon, Youngbin
    • Journal of the Korean Society for Aeronautical & Space Sciences
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    • v.43 no.10
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    • pp.868-874
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    • 2015
  • Thrust variation is an essential parameter in a space mission such as landing on an atmosphereless planet or docking a spacecraft. In order to achieve the thrust variation control, using throttleable injector is a representative and general method. A dual-manifold injector, one of throttleable injectors, was used to control mass flow rate. Five kinds of injectors were designed and investigated in order to compare the spray characteristics of the dual-manifold injector with various tangential entries. Spray angles and patterns were measured to determine external flow characteristics and film thicknesses were measured in order to investigate the internal flow patterns.

Pharmacophore Design for Anti-inflammatory Agent Targeting Interleukin-2 Inducible Tyrosine Kinase (Itk)

  • Chandrasekaran, Meganathan;Sakkiah, Sugunadevi;Thangapandian, Sundarapandian;Namadevan, Sundaraganesan;Kim, Hyong-Ha;Kim, Yong-Seong;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.31 no.11
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    • pp.3333-3340
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    • 2010
  • A three dimensional pharmacophore model was generated for the molecules which are responsible for anti-inflammatory activities targeting Interleukin-2 inducible tyrosine kinase (Itk). 16 structurally diverse molecules were selected as training set to generate the hypotheses using Discovery Studio v2.1. The best hypothesis, Hypo1, comprises two hydrogen bond acceptor (HBA), one hydrophobic aromatic (HA), one ring aromatic (RA) and shows high cost difference (63.71), high correlation coefficient (0.97) as well as low RMS deviation (0.81). Hypo1 has been further validated toward a test set, decoy set and Fischer's randomization method. Furthermore, Hypo1 was used to screen NCI and Maybridge databases. Finally, 2 hit molecules were identified as potential leads against Itk, which may be useful for future drug development.

Identification of the Antidepressant Vilazodone as an Inhibitor of Inositol Polyphosphate Multikinase by Structure-Based Drug Repositioning

  • Lee, Boah;Park, Seung Ju;Lee, Seulgi;Park, Seung Eun;Lee, Eunhye;Song, Ji-Joon;Byun, Youngjoo;Kim, Seyun
    • Molecules and Cells
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    • v.43 no.3
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    • pp.222-227
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    • 2020
  • Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

Evaluation of the gastroprotective effects of 20 (S)-ginsenoside Rg3 on gastric ulcer models in mice

  • Zhang, Kai;Liu, Ying;Wang, Cuizhu;Li, Jiannan;Xiong, Lingxin;Wang, Zhenzhou;Liu, Jinping;Li, Pingya
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.550-561
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    • 2019
  • Background: Gastric ulcer (GU) is a common gastrointestinal disease that can be induced by many factors. Finding an effective treatment method that contains fewer side effects is important. 20 (S)-ginsenoside Rg3 is a kind of protopanaxadiol and has shown superior antiinflammatory and antioxidant effects in many studies, especially cancer studies. In this study, we examined the treatment efficacy of 20 (S)-ginsenoside Rg3 on GU. Methods: Three kinds of GU models, including an alcohol GU model, a pylorus-ligated GU model, and an acetic acid GU model, were used. Mouse endothelin-1 (ET-1) and nitric oxide (NO) levels in blood and epidermal growth factor (EGF), superoxide dismutase, and NO levels in gastric mucosa were evaluated. Hematoxylin and eosin staining of gastric mucosa and immunohistochemical staining of ET-1, inducible nitric oxide synthase (NOS2), and epidermal growth factor receptors were studied. Ulcer index (UI) scores and UI ratios were also analyzed to demonstrate the GU conditions in different groups. Furthermore, Glide XP from $Schr{\ddot{o}}dinger$ was used for molecular docking to clarify the interactions between 20 (S)-ginsenoside Rg3 and EGF and NOS2. Results: 20 (S)-ginsenoside Rg3 significantly decreased the UI scores and UI ratios in all the three GU models, and it demonstrated antiulcer effects by decreasing the ET-1 and NOS2 levels and increasing the NO, superoxide dismutase, EGF, and epidermal growth factor receptor levels. In addition, high-dose 20 (S)-ginsenoside Rg3 showed satisfactory gastric mucosa protection effects. Conclusion: 20 (S)-ginsenoside Rg3 can inhibit the formation of GU and may be a potential therapeutic agent for GU.

Estimation of Residual Strength for an Aged Floating Dock (노후화된 플로팅도크의 잔류 구조강도 평가)

  • Seo, Kwang-Cheol;Hong, Taeho;Park, Joo-Shin
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.25 no.1
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    • pp.122-129
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    • 2019
  • Due to its nature the manufacturing industry faces a cyclical economy, and therefore there is an urgent need for a companion industry to cope with this cyclic pattern in the long run. The sector suitable for meeting this demand is the repair and shipbuilding industry. In order to operate a shipbuilding repair business, a floating dock is indispensable, and most obsolete floating docks were imported from overseas and operated through repair/maintenance. However, there is no precise guideline for floating dock safety, and most models have been in use for at least 30 years without being required to enter classification at the time of operation. In this study, structural strength analysis was carried out using measured thickness information of aged floating docks, and the residual structural strength of floating docks in operation was analyzed. The main results derived from this study can be referred to as guidelines for the review of the structural safety of similar equipment, and it is expected that an optimal solution will be found within a short time using this method for repair/maintenance.

A Study on the Determination of Minimum Welding Condition Based on Structural Strength under Launching for Tandem Blocks (선체 블록 진수 시 필요한 최소 용접 구조 강도 평가에 관한 연구)

  • Myung-Su Yi;Joo-Shin Park
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.28 no.7
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    • pp.1267-1273
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    • 2022
  • Although the Korea shipbuilding industry has recently been receiving most of the orders for ships in the world, production processes are being disrupted due to a shortage of manpower at the production site. This is because the workers quit the shipyard as both work and wages were reduced due to the long slump in the shipbuilding industry. The main reason for the increase in orders was the large-scale orders for Qatar LNG carriers, and the situation in which the technical specifications required for ships are becoming more complex is also working to an advantage. Because the contract delivery time is of utmost importance for ships, the dock launch plan is the most important management item among the shipyard's major processes. The structure to be built in the dock may be a hull that has left the design work or a finished vessel, and in some cases, it is often at the level of some blocks of the hull. When launching, the hull is affected by the hogging or sagging moment due to the fluid force, and securing the safety of the structural strength of the block connection is of utmost importance. In a normal process, the connecting member launches after welding has been completed, but in actual shipbuilders, quick decision-making is needed on the conditions for securing structural safety to comply with the docking schedule. In this study, a detailed analysis method and applicability using a bending stress evaluation method and finite element analysis modelling were analyzed to rationally judge the above-mentioned problems from an engineering point of view. The main contents mentioned in the thesis can be used as good examples when conducting similar structural strength evaluations in the future.

Orbital Transfer Process and Analysis of Small Satellite for Capturing Korean Satellite as Active Debris Removal (ADR) Mission (우리별 위성 포획 임무 수행을 위한 소형위성의 궤도 천이 방법 및 분석)

  • Junchan Lee;Kyungin Kang
    • Journal of Space Technology and Applications
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    • v.3 no.2
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    • pp.101-117
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    • 2023
  • Active debris removal, a technology that approaches and removes space debris in orbit, and the on-orbit service, a technology for extending the mission life of satellites by fuel charging or by exchanging the battery, are gaining interest with the growth of the space community. SaTReC plans to develop a satellite capable of capturing and removing Korean satellites orbiting in space after the end of their missions. In contrast to the previously launched satellites by Korea, which were mainly intended to observe Earth and the space environment, rendezvous/docking technologies, as required in the future during, for instance, space exploration missions, will be implemented and demonstrated. In this paper, an orbital transition method for next-generation small satellites that will capture and remove space debris will be introduced. It is assumed that a small satellite with a mass of approximately 200 kg will be injected into the mission orbit through Korea Space Launch Vehicle-II in 2027. Because the satellite must access the target using a minimum amount of fuel, an approaching technology using Earth's J2 perturbation force has been developed. This method is expected to enable space debris removal missions for relatively lightweight satellites and to serve as the basis for carrying out a new type of space exploration in what is termed the 'Newspace' era.

Solid Phase Synthesis of N-(3-hydroxysulfonyl)-L-homoserine Lactone Derivatives and their Inhibitory Effects on Quorum Sensing Regulation in Vibrio harveyi (고체상 합성법에 의해 합성된 N-(3-hydroxysulfonyl)-L-homoserine Lactone 유사체들의 Vibrio harveyi 쿼럼 센싱에 대한 저해 효과)

  • Kim, Cheol-Jin;Park, Hyung-Yeon;Kim, Jae-Eun;Park, Hee-Jin;Lee, Bon-Su;Choi, Yu-Sang;Lee, Joon-Hee;Yoon, Je-Yong
    • Microbiology and Biotechnology Letters
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    • v.37 no.3
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    • pp.248-257
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    • 2009
  • The inhibitors against Vibrio harveyi quorum sensing (QS) signaling were developed by modifying the molecular structure of the major signal, N-3-hydroxybutanoyl-L-homoserine lactone (3-OH-$C_4$-HSL). A series of structural derivatives, N-(3-hydroxysulfonyl)-L-homoserine lactones (HSHLs) were synthesized by the solid-phase organic synthesis method. The in vivo QS inhibition by these compounds was measured by a bioassay system using the V. harveyi bioluminescence, and all showed significant inhibitory effects. To analyze the interaction between these compounds and LuxN, a 3-OH-$C_4$-HSL receptor protein of V. harveyi, we tentatively determined the putative signal binding domain of LuxN based on the sequence homology with other acyl-HSL binding proteins, and predicted the partial 3-D structure of the putative signal binding domain of LuxN by using ORCHESTRA program, and further estimated the binding poses and energies (docking scores) of 3-OH-$C_4$-HSL and HSHLs within the domain. In comparison of the result from this modeling study with that of in vivo bioassay, we suggest that the in silica interpretation of the interaction between ligands and their receptor proteins can be a valuable way to develop better competitive inhibitors, especially in the case that the structural information of the protein is limited.