• Title/Summary/Keyword: Resistant model

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Preclinical Activity of Lobaplatin as a Single Agent and in Combination with Taxanes for Ovarian Carcinoma Cells

  • Sun, Xu;Lou, Li-Guang;Sui, Dong-Hu;Wu, Xiao-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9939-9943
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    • 2014
  • Lobaplatin, one of the third - generation platinum compounds, has shown encouraging anticancer activity in a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemically evaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in - vitro and in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects of lobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovarian cancer cell lines. In addition, in - vitro antitumor activities were evaluated with cisplatin - sensitive and cisplatin - resistant human ovarian cancer xenografts in nude mice. The cytotoxicity of lobaplatin was similar to or higher than that of cisplatin and carboplatin, with $IC_{50}$ values from 0.9 to $13.8{\mu}mol/L$ in a variety of ovarian cancer cells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, in platinum - sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatin and carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activity in platinum - resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or in combination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Further clinical development of lobaplatin is clearly warranted.

Effects of C-Terminal Residues of 12-Mer Peptides on Antibacterial Efficacy and Mechanism

  • Son, Kkabi;Kim, Jieun;Jang, Mihee;Chauhan, Anil Kumar;Kim, Yangmee
    • Journal of Microbiology and Biotechnology
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    • v.29 no.11
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    • pp.1707-1716
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    • 2019
  • The development of new antimicrobial agents is essential for the effective treatment of diseases such as sepsis. We previously developed a new short peptide, Pap12-6, using the 12 N-terminal residues of papiliocin, which showed potent and effective antimicrobial activity against multidrug-resistant Gram-negative bacteria. Here, we investigated the antimicrobial mechanism of Pap12-6 and a newly designed peptide, Pap12-7, in which the 12th Trp residue of Pap12-6 was replaced with Val to develop a potent peptide with high bacterial selectivity and a different antibacterial mechanism. Both peptides showed high antimicrobial activity against Gram-negative bacteria, including multidrug-resistant Gram-negative bacteria. In addition, the two peptides showed similar anti-inflammatory activity against lipopolysaccharide-stimulated RAW 264.7 cells, but Pap12-7 showed very low toxicities against sheep red blood cells and mammalian cells compared to that showed by Pap12-6. A calcein dye leakage assay, membrane depolarization, and confocal microscopy observations revealed that the two peptides with one single amino acid change have different mechanisms of antibacterial action: Pap12-6 directly targets the bacterial cell membrane, whereas Pap12-7 appears to penetrate the bacterial cell membrane and exert its activities in the cell. The therapeutic efficacy of Pap12-7 was further examined in a mouse model of sepsis, which increased the survival rate of septic mice. For the first time, we showed that both peptides showed anti-septic activity by reducing the infiltration of neutrophils and the production of inflammatory factors. Overall, these results indicate Pap12-7 as a novel non-toxic peptide with potent antibacterial and anti-septic activities via penetrating the cell membrane.

Analysis of Creep Effective Stress in Austenitic Heat Resistant Steel (오스테나이트계 내열강의 크리프 유효응력 해석)

  • Nam, Ki-Woo;Park, In-Duck
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.26 no.7
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    • pp.1317-1323
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    • 2002
  • This paper describes the comparison of calculated effective stress with experimental one in austenitic heat resistant steels, STS310J1TB and STS310S with and without a small amount of Nb and N. Based on a solute atoms diffusion model, contribution from soluble nitrogen to the high-temperature strength was numerically examined for austenitic heat-resisting Fe-Cr-Ni-N(STS310J1TB) and Fe-Cr-Ni (STS310S) alloys. The solute atmosphere dragging stress of dislocation was calculated in optional dislocation velocity of STS310J1TB and STS310S at $650^{\circ}C$, $675^{\circ}C$ and $700^{\circ}C$. As a result of the numerical calculation, the solute atmosphere dragging stress of STS310J1TB was about 50 times larger than that of STS310S. When the temperature became high, the maximum value of solute atmosphere dragging stress was small and the velocity of moving dislocation was fast. From the relationship between the dislocation rate and the solute atmosphere dragging stress, the relation of both was proportional and the inclination is about 1 in the level with low velocity of moving dislocation. From above results, the mechanism of dislocation movement in STS310J1TB was the solute atmosphere dragging stress. The solute atmosphere dragging stress, which was calculated from the numerical calculation was close to the effect stress in stress relaxation tests.

A Rice Gene Homologous to Arabidopsis AGD2-LIKE DEFENSE1 Participates in Disease Resistance Response against Infection with Magnaporthe oryzae

  • Jung, Ga Young;Park, Ju Yeon;Choi, Hyo Ju;Yoo, Sung-Je;Park, Jung-Kwon;Jung, Ho Won
    • The Plant Pathology Journal
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    • v.32 no.4
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    • pp.357-362
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    • 2016
  • ALD1 (ABERRANT GROWTH AND DEATH2 [AGD2]-LIKE DEFENSE1) is one of the key defense regulators in Arabidopsis thaliana and Nicotiana benthamiana. In these model plants, ALD1 is responsible for triggering basal defense response and systemic resistance against bacterial infection. As well ALD1 is involved in the production of pipecolic acid and an unidentified compound(s) for systemic resistance and priming syndrome, respectively. These previous studies proposed that ALD1 is a potential candidate for developing genetically modified (GM) plants that may be resistant to pathogen infection. Here we introduce a role of ALD1-LIKE gene of Oryza sativa, named as OsALD1, during plant immunity. OsALD1 mRNA was strongly transcribed in the infected leaves of rice plants by Magnaporthe oryzae, the rice blast fungus. OsALD1 proteins predominantly localized at the chloroplast in the plant cells. GM rice plants over-expressing OsALD1 were resistant to the fungal infection. The stable expression of OsALD1 also triggered strong mRNA expression of PATHOGENESIS-RELATED PROTEIN1 genes in the leaves of rice plants during infection. Taken together, we conclude that OsALD1 plays a role in disease resistance response of rice against the infection with rice blast fungus.

Factors Affecting Performance Infection Control of MultiDrug-Resistant Organisms among Nurses:with focus of the Health Belief Model (종합병원 간호사의 다제내성균 감염관리 수행도에 영향을 미치는 요인: 건강신념모델 중심으로)

  • Park, Jung Hee;Lee, Mi-Hyang
    • Journal of Digital Convergence
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    • v.18 no.3
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    • pp.227-234
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    • 2020
  • This study was carried out to provide basic data for the development of an educational program by assessing the its effects on the MDROs infection management performances of nurses at general hospitals. Data was obtained through a structured questionnaire survey conducted on 202 nurses. The average of knowledge score was 17.68 and their perceived susceptibility, perceived severity, perceived benefits, and performances had correlation. There was difference in their performances in accordance with their general characteristics including marriage, clinical experiences, positions, and affiliated department. Factors that affected MDROs infection management performance included perceived benefits and affiliated department with an explanation power of 35%. Therefore, it is necessary to emphasize the benefits by including advantages and effects of performing the MDROs infection control at the time of the development. In addition, nurses are required to have MDROs infection control education.

Effects of Pyrola japonica Extracts on Osteoclast Differentiation and Bone Resorption (녹제초 추출물이 파골세포 분화 및 골 흡수에 미치는 영향)

  • Park, Jung-Sik;Lim, Hyung-Ho
    • Journal of Korean Medicine Rehabilitation
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    • v.29 no.2
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    • pp.135-147
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    • 2019
  • Objectives This study was performed to evaluate the effect of Pyrola japonica extract (NJ) and its principal constituent, homoarbutin (HA) on osteoclast differentiation and gene expression and bone resorption. The osteoclastogenesis and gene expression were determined in receptor activator of nuclear factor kappa B ligand (RANKL)-stimulated RAW264.7 cell. Methods In order to evaluate the effect of HA extracted from NJ on bone resorption, osteoclasts were used to be differentiated and formed by stimulating RAW264.7 cells with RANKL. Tartarate-resistant acid phosphatase (TRAP) (+) polynuclear osteoclast formation ability was evaluated, and differentiation control genes including cathepsin K, matrix metalloproteinases-9 (MMP-9), and TRAP in osteoclast differentiation were analyzed by real-time polymerase chain reaction (PCR). Immunoblotting was performed to measure the effect of mitogen-activated protein kinase (MAPK) factors on bone resorption, and the effect of osteoclasts on osteoclast differentiation was measured. Results Both NJ and high concentration of HA blocked RANKL-stimulated differentiation from RAW264.7 cell to TRAP-positive multinucleated cells. NJ reduced RANKL-induced expression of TRAP, cathepsin K. Both NJ and high concentration of HA inhibited RANKL-mediated expression of MMP-9, nuclear factor of activated T-cells, cytoplasmic 1, and cellular Jun-fos. NJ suppressed RANKL-stimulated expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, tumor necrosis factor-alpha, and levels of interleukins. Both NJ and HA decreased bone resorption in osteoclast-induced bone pit formation model. Conclusions These results suggest that NJ and HA blocked bone resorption by decreasing RANKL-mediated osteoclastogenesis through down-regulation of genes for osteoclast differentiation.

Wind resistance performance of a continuous welding stainless steel roof under static ultimate wind loading with testing and simulation methods

  • Wang, Dayang;Zhao, Zhendong;Ou, Tong;Xin, Zhiyong;Wang, Mingming;Zhang, Yongshan
    • Wind and Structures
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    • v.32 no.1
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    • pp.55-69
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    • 2021
  • Ultrapure ferritic stainless steel provides a new generation of long-span metal roof systems with continuous welding technology, which exhibits many unknown behaviors during wind excitation. This study focuses on the wind-resistant capacity of a new continuous welding stainless steel roof (CWSSR) system. Full-scale testing on the welding joints and the CWSSR system is performed under uniaxial tension and static ultimate wind uplift loadings, respectively. A finite element model is developed with mesh refinement optimization and is further validated with the testing results, which provides a reliable way of investigating the parameter effect on the wind-induced structural responses, namely, the width and thickness of the roof sheeting and welding height. Research results show that the CWSSR system has predominant wind-resistant performance and can bear an ultimate wind uplift loading of 10.4 kPa without observable failures. The welding joints achieve equivalent mechanical behaviors as those of base material is produced with the current of 65 A. Independent structural responses can be found for the roof sheeting of the CWSSR system, and the maximum displacement appears at the middle of the roof sheeting, while the maximum stress appears at the connection supports between the roof sheeting with a significant stress concentration effect. The responses of the CWSSR system are greatly influenced by the width and thickness of the roof sheeting but are less influenced by the welding height.

Analysis on the Dynamic Behavior of Breakwater with the DCM Method Using the Shaking Table Test (진동대시험을 이용한 DCM공법에 따른 방파제의 동적거동 분석)

  • Kim, Youngjun;Park, Innjoon
    • Journal of the Korean GEO-environmental Society
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    • v.23 no.5
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    • pp.25-32
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    • 2022
  • As recently, there have been two earthquakes with a magnitude of 5.0 or greater in Korea and the number of smaller earthquakes has increased, a lot of research and interest in earthquake-resistant design are increasing. Especially, the Pohang earthquake has also raised interest in earthquake-resistant design of port facilities. In this study, experiments and analysis were conducted on the dynamic behavior of upright and inclined breakwaters during earthquakes among port structures through the 1g shaking table test. To this end, three seismic waves were applied to the model to which the similarity law (scale effect) was applied: long period (Hachinohe), short period (Ofunato) and artificial seismic waves. The acceleration and displacement of the upright and inclined breakwaters were analyzed according to whether the DCM method was reinforced during earthquakes based on the results of shaking table test. As the result, the dynamic behavior of the upright and inclined breakwater shows a tendency to suppress the amplification of acceleration as bearing capacity and rigidity increase when DCM method is reinforced.

Investigation on the effect of vibration frequency on vortex-induced vibrations by section model tests

  • Hua, X.G.;Chen, Z.Q.;Chen, W.;Niu, H.W.;Huang, Z.W.
    • Wind and Structures
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    • v.20 no.2
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    • pp.349-361
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    • 2015
  • Higher-mode vertical vortex-induced vibrations (VIV) have been observed on several steel box-girder suspension bridges where different vertical modes are selectively excited in turn with wind velocity in accordance with the Strouhal law. Understanding the relationship of VIV amplitudes for different modes of vibration is very important for wind-resistant design of long-span box-girder suspension bridges. In this study, the basic rectangular cross-section with side ratio of B/D=6 is used to investigate the effect of different modes on VIV amplitudes by section model tests. The section model is flexibly mounted in wind tunnel with a variety of spring constants for simulating different modes of vibration and the non-dimensional vertical amplitudes are determined as a function of reduced velocity U/fD. Two 'lock-in' ranges are observed at the same onset reduced velocities of approximately 4.8 and 9.4 for all cases. The second 'lock-in' range, which is induced by the conventional vortex shedding, consistently gives larger responses than the first one and the Sc-normalized maximum non-dimensional responses are almost the same for different spring constants. The first 'lock-in' range where the vibration frequency is approximately two times the vortex shedding frequency is probably a result of super-harmonic resonance or the "frequency demultiplication". The main conclusion drawn from the section model study, central to the higher-mode VIV of suspension bridges, is that the VIV amplitude for different modes is the same provided that the Sc number for these modes is identical.

Development of an Engineering Model of Hydrogen-Fueled Ultra-micro Combustor for UMGT

  • Shimotori, Shoko;Yuasa, Saburo;Sakurai, Takashi
    • Proceedings of the Korean Society of Propulsion Engineers Conference
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    • 2008.03a
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    • pp.828-836
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    • 2008
  • To develop an engineering-model of hydrogen-fueled ultra-micro combustor for Ultra Micro Gas Turbine(UMGT), we reviewed and summarized the problems in downsizing combustors, and determined a suitable burning method. The key issue to actualize practical ultra-micro combustors is reducing heat loss from the combustor to compressor and turbine. The reduction of heat loss was discussed from 3 different viewpoints; heat-insulation material, high-space-heating-rate combustion, and combustor-insolated gas turbine structure. Use of heat-insulation material induced the heat loss reduction to the surroundings. The heat loss ratio decreased substantially in reverse proportion to space heating rate, leading the idea that it could be reduced by burning at a high space heating rate. By settling the combustor insolated from the compressor and turbine, the heat transfer from the combustor to the compressor and turbine becomes smaller. For a selection of the suitable burning method, comparison between 2 burning methods, flat-flame and swirling-flamer types, was conducted. Synthetically the flat-flame burning method was confirmed to be more suitable for ultra-micro combustors than latter one. Base on them, an engineering-model of hydrogen-fueled flat-flame ultra-micro combustor was developed. To obtain high overall heat-insulation, heat-resistant and strength, the engineering-model combustor had triple layer structure with an advanced ceramic, a heat insulation material and a stainless steel. To simplify heat transfer issue in the combustor, it was isolated from the other components. Furthermore it was designed by considering structure, size, material, velocity, pressure loss and prevention of flashback.

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