• Title/Summary/Keyword: Non-selectivity

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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.

POTENT INHIBITION OF HUMAN CYTOCHROME P450 1 ENZYMES BY DIMETHOXYPHENYL VINYL THIOPHENE

  • Lee, Sang-Kwang;Kim, Sang-Hee;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.312.3-313
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    • 2002
  • Recently we have reported that various hydroxystilbenes show strong inhibition of human P450 1 activity. A series of synthetic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human P450 1A1, 1A2 or 1B1 coexpressed with human NADPH-P450 reductase to find new candidates for cancer chemoprevention, Of the compounds tested. SY-021 (3.5-dimethoxyphenyl vinyl thiophene) exhibited a potent inhibition of human P450 181 with an IC$_{50}$ value of 2 nM. SY-021 also showed the inhibitrion of P450 1A1 with IC$_{50}$ value of 61 nM and P450 1A2 with IC$_{50}$ value of 11 nM. SY-021 showed 31-fold selectivity for P450 1B1 over P450 1A1 and 6-fold selectivity for P450 1B1 over 1A2. We have further investigated the inhibition kinetics of P450 1A1. 1A2 and 1B1 by SY-021. The modes of inhibition by SY-021were non-compeitive for all three P450 1 enzymes. Effect of preincubation with NADPH on inhibition of P450 1B1 by SY-021 was determined. These results suggest that SY-021 is one of the mostj potent inhibitor of human P450 1 enzymes and may be considered as a good candidate for a cancer chemopreventive agent in human

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Effect of Temperature and Eluent Composition on the Separation of Ketoprofen and Ibuprofen Racemates in Kromasil HPLC Column (Kromasil HPLC 칼럼에서 온도와 이동상 조성비에 따른 Ketoprofen과 Ibuprofen 라세미체의 분리특성)

  • Park, Moon-Bae;Kim, In Ho
    • Korean Chemical Engineering Research
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    • v.47 no.1
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    • pp.54-58
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    • 2009
  • Ketoprofen and ibuprofen are non-steroid anti-inflammatory drug(NSAID) that have analgesic and antipyretic properties. (S)-ketoprofen and (S)-ibuprofen have pharmacological activity, while (R)-ketoprofen and (R)-ibuprofen are either inactive or have side effect. The chiral separation of racemic ketoprofen and ibuprofen enantiomers was carried out by using a Kromasil HPLC column. Some chromatographic parameters (selectivity, resolution, number of theoretical plates and ${\Delta}H$) are calculated under different mobile phase compositions of hexane/t-BME/acetic acid and temperatures. The selectivity, resolution and number of theoretical plates were observed high at $25^{\circ}C$ and the composition of hexane/t-BME/acetic acid (80/20/0.1).

Relationship among Degree of Time-delay, Input Variables, and Model Predictability in the Development Process of Non-linear Ecological Model in a River Ecosystem (비선형 시계열 하천생태모형 개발과정 중 시간지연단계와 입력변수, 모형 예측성 간 관계평가)

  • Jeong, Kwang-Seuk;Kim, Dong-Kyun;Yoon, Ju-Duk;La, Geung-Hwan;Kim, Hyun-Woo;Joo, Gea-Jae
    • Korean Journal of Ecology and Environment
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    • v.43 no.1
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    • pp.161-167
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    • 2010
  • In this study, we implemented an experimental approach of ecological model development in order to emphasize the importance of input variable selection with respect to time-delayed arrangement between input and output variables. Time-series modeling requires relevant input variable selection for the prediction of a specific output variable (e.g. density of a species). Inadequate variable utility for input often causes increase of model construction time and low efficiency of developed model when applied to real world representation. Therefore, for future prediction, researchers have to decide number of time-delay (e.g. months, weeks or days; t-n) to predict a certain phenomenon at current time t. We prepared a total of 3,900 equation models produced by Time-Series Optimized Genetic Programming (TSOGP) algorithm, for the prediction of monthly averaged density of a potamic phytoplankton species Stephanodiscus hantzschii, considering future prediction from 0- (no future prediction) to 12-months ahead (interval by 1 month; 300 equations per each month-delay). From the investigation of model structure, input variable selectivity was obviously affected by the time-delay arrangement, and the model predictability was related with the type of input variables. From the results, we can conclude that, although Machine Learning (ML) algorithms which have popularly been used in Ecological Informatics (EI) provide high performance in future prediction of ecological entities, the efficiency of models would be lowered unless relevant input variables are selectively used.

A Study on the Nonlinear Relationship Between Volunteer Time Spending and Psychosocial Well-being in Old Life (노년기 자원봉사 시간과 심리사회적 안녕감의 관계 - 비선형성의 탐색 -)

  • Jung, Jin-Kyung
    • Korean Journal of Social Welfare
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    • v.63 no.1
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    • pp.137-158
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    • 2011
  • This study explore nonlinear relationship between volunteer time spending and psychosocial well-being among the old adults, on the ground of Socioemotional Selectivity Theory. This is secondary analysis using the 2009 National Old Aging Volunteer Survey data including 645 cases. The simple and multiple line graph method are implemented. As a result, this paper shows a nolinerar relationship which the low level of psychosocial well-being at non volunteer status is increasing to the paticular time spending, and then decreases after high level participation like U-shape. Male, over the 75 and not good health status has showed lower level of volunteer time spending. It can be founded that volunteering activity contributes to improve a psychosocial well-being in old life, but the desirable volunteer time spending is medial about 100-200 yearly not over the 700.

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Synthesis of Silica Membranes on a Porous Stainless Steel by Sol-Gel Method and Effect of Preparation Conditions on Their Permselectivity

  • Lee, Dong-Wook;Nam, Seung-Eun;Sea, Bong-Kuk;Ihm, Son-Ki;Lee, Kew-Ho
    • Bulletin of the Korean Chemical Society
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    • v.25 no.9
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    • pp.1371-1378
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    • 2004
  • A porous stainless steel (SUS) as a substrate of silica composite membranes for hydrogen purification was used to improve mechanical strength of the membranes for industrial application. The SUS support was successfully modified by using submicron Ni powder, $SiO_2$ sols with particle size of 500 nm and 150 nm in turns. Silica top layer was coated on the modified supports under various preparation conditions such as calcination temperature, dipping time and repeating number of dipping-drying process. The calcination temperature for proper sintering was between H ttig temperature and Tamman temperature of the coating materials. Maximum hydrogen selectivity was investigated by changing dipping time. As repeating number of dipping-drying process increased, permeances of nitrogen and hydrogen were decreased and $H_2/N_2$ selectivity was increased due to the reduction of non-selective pinholes and mesopores. For the silica membrane prepared under optimized conditions, permeance of hydrogen was about $3\;{\times}\;10^{-5}\;cm^3{\cdot}cm^{-2}{\cdot}s^{-1}{\cdot}cmHg^{-1}$ combined with $H_2/N_2$ seletivity of about 20.

A Study on the Selection Area Growth of GaN on Non-Planar Substrate by MOCVD (MOCVD를 이용한 비평면구조 기판에서의 GaN 선택적 성장특성연구)

  • Lee, Jae-In;Geum, Dong-Hwa;Yu, Ji-Beom
    • Korean Journal of Materials Research
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    • v.9 no.3
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    • pp.257-262
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    • 1999
  • The selective area growth of GaN by metal organic chemical vapor deposition has been carried out on GaN/ sapphire substrate using $SiO_2$ mask. We investgated the effect of growth parameters such as flow rate of $NH_3$(500­~1300sccm) and the growth temperature(TEX>$950~1060^{\circ}C$) on the growth selectivity and characteristics of GaN using the Scanning Electron Microscopy(SEM). The selectivity of GaN improved as flow rate of NH, and growth temperature in­creased. But the grown GaN shapes on the substrate windows was independent of the flow rate of $NH_3$. On the pattern shapes such as circle, stripe, and radiational pattern(rotate the stripe pattern by $30^{\circ}, 45^{\circ}$), we observed the hexagonal pyramid, the lateral over growth on the mask layer, and the difference of the lateral growth rate depending on growth condition.

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Difluoromethane Synthesis over Fluorinated Metal Oxide (불화된 금속산화물 촉매상에서 이불화메탄의 합성)

  • Lee, Youn-Woo;Lee, Kyong-Hwan;Lim, Jong Sung;Kim, Jae-Duck;Lee, Youn Yong
    • Applied Chemistry for Engineering
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    • v.9 no.5
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    • pp.619-623
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    • 1998
  • The influences of reaction temperature, HF/DCM mole ratio, contact time and catalyst type on activity and selectivity of difluoromethane synthesis via hydrofluoriation of dichloromethane over fluorinated catalyst have been studied. It has been found that fluorinated $Cr/Al_2O_3$ catalysts, show better performance compared to pure fluorinated $Al_2O_3$ catalyst and then, non-treated catalysts demonstrate better than catalysts pretreated with hydrogen and air. The results show that the optimum reaction conditions are found as follows : reaction temperature at $340^{\circ}C$, mole ratio of HF/DCM 5 or above and contact time 20 sec. or above. With these conditions the maximum attainable yield of difluoromethane has been found to be greater than 80%. In particular, the activity and the selectivity of difluoromethane do not change with the reaction time on stream up to 8 hours.

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A Characterization of Pervaporation-facilitated Esterification Reaction with non-perfect Separation (비완전 막분리시 투과증발 막촉진 에스터화 반응 거동 연구)

  • C. K Yeom;F. U. Baig
    • Membrane Journal
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    • v.13 no.4
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    • pp.268-282
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    • 2003
  • Pervaporation-facilitated esterification with slow reaction regime was characterized by using a practical model based on non-perfect separation through membrane. A non-perfect separation in which the membrane is not perfectly permselective to water was applied to the model. Thus, membrane selectivity and membrane capability to remove water were included in the simulation model to explain how they influence the membrane-facilitated reaction process and improve the reactor performance. It was shown by simulation that in the reaction systems with non-perfect separation, reaction completion can hardly be achievable when any reactant at initial molar ratio=1 or the less abundant reactant at initial molar ratio>1 permeates through membrane, and the permeation of ester accelerates the forward reaction md increase reaction conversion at any instant through removal of product species like water. The volume change causes concentrating both reactants and products that affect the reaction with time in opposite ways; reactant-concentrating effect is dominant during the initial stage of reaction, increasing the reaction rate, and then concentrating product influences more reaction by decreasing the reaction rate.

Involvement of the CXC Chemokines Mig and IP-10 in Response to M. bovis BCG in Mice

  • Hong, Seong-Tshool;Cho, Jung-Gil;Lee, Hwang-Ho
    • The Journal of the Korean Society for Microbiology
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    • v.35 no.2
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    • pp.117-127
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    • 2000
  • The non-ELR-containing CXC chemokines Mig and IP-10 have been shown to function as chemotactic cytokines for activated T lymphocytes. In this study, we examined the potential involvement of Mig and IP-10 in antimycobacterial response of mice immunized or infected with M. bovis BCG. The accumulation of Mig and IP-10 mRNA in resident peritoneal monocytes ($RPM{\Phi}$) was slightly reduced by stimulation with vBCG, and the degree was greater for 24 hr culture even though IFN-${\gamma}$ was added. Expression of Mig, IP-10, and IFN-${\gamma}$ in 24 hr delayed-type hypersensitivity (DTH) response was stronger in vBCG-immune mice than in the non-immune. The increase of DTH measured by foot-pad thickness appears to be clearly related to the levels of chemokines Mig and IP10 messages and those of IFN-${\gamma}$ and IL-12. Stimulation with vBCG for 2 days decreased or completely dropped the levels of Mig message in non-immune or immune splenocytes, respectively, whereas IP-10 message was slightly decreased in 2 days culture. Moreover, messages for IL-12 (p40) showed similar kinetics for Mig. The levels of Mig and IP-10 mRNA during the course of infection with BCG were not readily changed in lungs, livers, and spleens from BCG-infected mice. Although there was no obvious changes of Mig and IP-10 messages in the target organs during infection process, we found that the infection progressed over the first 3 wk before being contained by the emerging immune response suggested from detectable amount of IFN-${\gamma}$ mRNA around this time. In view of selectivity of chemokines Mig and IP-10 for activated T cells, these data suggest that chemokine Mig and IP-10, especially in collaboration with IL-12 and IFN-${\gamma}$, may playa role as T cell recruiters in immune response against mycobacterial infection.

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