• Advances in nano research
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• v.12 no.5
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• pp.501-514
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• 2022

This study aimed to investigate the effects and potential mechanisms of Chikusetsusaponin V (CsV) on endothelial nitric oxide synthase (eNOS) and vascular endothelial cell functions. Different concentrations of CsV were added to animal models, bovine aorta endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) cultured in vitro. qPCR, Western blotting (WB), and B ultrasound were performed to explore the effects of CsV on mouse endothelial cell functions, vascular stiffness and cellular eNOS mRNA, protein expression and NO release. Bioinformatics analysis, network pharmacology, molecular docking and protein mass spectrometry analysis were conducted to jointly predict the upstream transcription factors of eNOS. Furthermore, pulldown and ChIP and dual luciferase assays were employed for subsequent verification. At the presence or absence of CsV stimulation, either overexpression or knockdown of purine rich element binding protein A (PURA) was conducted, and PCR assay was employed to detect PURA and eNOS mRNA expressions, Western blot was used to detect PURA and eNOS protein expressions, cell NO release and serum NO levels. Tube formation experiment was conducted to detect the tube forming capability of HUVECs cells. The animal vasodilation function test detected the vasodilation functions. Ultrasonic detection was performed to determine the mouse aortic arch pulse wave velocity to identify aortic stiffness. CsV stimulus on bovine aortic cells revealed that CsV could upregulate eNOS protein levels in vascular endothelial cells in a concentration and time dependent manner. The expression levels of eNOS mRNA and phosphorylation sites Ser1177, Ser633 and Thr495 increased significantly after CsV stimulation. Meanwhile, CsV could also enhance the tube forming capability of HUVECs cells. Following the mice were gavaged using CsV, the eNOS protein level of mouse aortic endothelial cells was upregulated in a concentration- and time-dependent manner, and serum NO release and vasodilation ability were simultaneously elevated whereas arterial stiffness was alleviated. The pulldown, ChIP and dual luciferase assays demonstrated that PURA could bind to the eNOS promoter and facilitate the transcription of eNOS. Under the conditions of presence or absence of CsV stimulation, overexpression or knockdown of PURA indicated that the effect of CsV on vascular endothelial function and eNOS was weakened following PURA gene silence, whereas overexpression of PURA gene could enhance the effect of CsV upregulating eNOS expression. CsV could promote NO release from endothelial cells by upregulating the expression of PURA/eNOS pathway, improve endothelial cell functions, enhance vasodilation capability, and alleviate vessel stiffness. The present study plays a role in offering a theoretical basis for the development and application of CsV in vascular function improvement, and it also provides a more comprehensive understanding of the pharmacodynamics of CsV.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.179-184
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• 2014

Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of $80{\mu}M$, $21{\mu}M$, and $82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4331-4338
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• 2014

$N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.

• Journal of the Korean Society for Aeronautical & Space Sciences
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• v.46 no.3
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• pp.219-229
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• 2018

This paper proposes Kalman Filter-based relative navigation algorithms for proximity tasks such as rendezvous/docking/cluster-operation of spacecraft using PSD Sensors and Infrared Beacon Modules. Numerical simulations are performed for comparative analysis of the performance of each relative-navigation technique. Based on the operation principle and optical modeling of the PSD Sensor and the Infrared Beacon Module used in the relative navigation algorithm, a measurement model for the Kalman filter is constructed. The Extended Kalman Filter(EKF) and the Unscented Kalman Filter(UKF) are used as probabilistic relative navigation based on measurement fusion to utilize kinematics and dynamics information on translational and rotation motions of satellites. Relative position and relative attitude estimation performance of two filters is compared. Especially, through the simulation of various scenarios, performance changes are also investigated depending on the number of PSD Sensors and IR Beacons in target and chaser satellites.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.247-257
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• 2020

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

• Journal of Korea Port Economic Association
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• v.25 no.3
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• pp.67-92
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• 2009

A tugboat (tug) is a boat that maneuvers vessels by pushing or towing them. Tugs move vessels that should not move themselves alone, such as ships in a crowded harbor or a narrow canal, or those that cannot move themselves, such as barges, disabled ships, or oil platforms. Tugboats are powerful for their size and strongly built, some are ocean-going. Historically tugboats were the first seagoing vessels to receive steam propulsion, freedom from the restraint of the wind, and capability of going in any direction. As such, they were employed in harbors to assist ships in docking and departure. Towage is in essence a service by one vessel to another vessel for a fixed remuneration. The most common reason for requiring this service is the lack of its own motive power. Conventionally, towage is defined as "the employment of one vessel to expedite the voyage of another, when nothing more is required than the accelerating of her progress". Apart from accelerating vessels, acquiring towage service is a common practice for towing barges, platform of drilling oil, floating ship yards, etc.

• BMB Reports
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• v.56 no.6
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• pp.359-364
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• 2023

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.

• 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.

• KIPS Transactions on Software and Data Engineering
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• v.2 no.2
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• pp.81-90
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• 2013

During the past decade, many changes and attempts have been tried and are continued developing new technologies in the computing area. The brick wall in computing area, especially power wall, changes computing paradigm from computing hardwares including processor and system architecture to programming environment and application usage. The high performance computing (HPC) area, especially, has been experienced catastrophic changes, and it is now considered as a key to the national competitiveness. In the late 2000's, many leading countries rushed to develop Exascale supercomputing systems, and as a results tens of PetaFLOPS system are prevalent now. In Korea, ICT is well developed and Korea is considered as a one of leading countries in the world, but not for supercomputing area. In this paper, we describe architecture design of MAHA supercomputing system which is aimed to develop 300 TeraFLOPS system for bio-informatics applications like human genome analysis and protein-protein docking. MAHA supercomputing system is consists of four major parts - computing hardware, file system, system software and bio-applications. MAHA supercomputing system is designed to utilize heterogeneous computing accelerators (co-processors like GPGPUs and MICs) to get more performance/$, performance/area, and performance/power. To provide high speed data movement and large capacity, MAHA file system is designed to have asymmetric cluster architecture, and consists of metadata server, data server, and client file system on top of SSD and MAID storage servers. MAHA system softwares are designed to provide user-friendliness and easy-to-use based on integrated system management component - like Bio Workflow management, Integrated Cluster management and Heterogeneous Resource management. MAHA supercomputing system was first installed in Dec., 2011. The theoretical performance of MAHA system was 50 TeraFLOPS and measured performance of 30.3 TeraFLOPS with 32 computing nodes. MAHA system will be upgraded to have 100 TeraFLOPS performance at Jan., 2013.