• Title/Summary/Keyword: Shock-shock interaction

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Tazarotene-Induced Gene 1 Interacts with DNAJC8 and Regulates Glycolysis in Cervical Cancer Cells

  • Wang, Chun-Hua;Shyu, Rong-Yaun;Wu, Chang-Chieh;Chen, Mao-Liang;Lee, Ming-Cheng;Lin, Yi-Yin;Wang, Lu-Kai;Jiang, Shun-Yuan;Tsai, Fu-Ming
    • Molecules and Cells
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    • v.41 no.6
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    • pp.562-574
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    • 2018
  • The tazarotene-induced gene 1 (TIG1) protein is a retinoidinducible growth regulator and is considered a tumor suppressor. Here, we show that DnaJ heat shock protein family member C8 (DNAJC8) is a TIG1 target that regulates glycolysis. Ectopic DNAJC8 expression induced the translocation of pyruvate kinase M2 (PKM2) into the nucleus, subsequently inducing glucose transporter 1 (GLUT1) expression to promote glucose uptake. Silencing either DNAJC8 or PKM2 alleviated the upregulation of GLUT1 expression and glucose uptake induced by ectopic DNAJC8 expression. TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. In conclusion, TIG1 acts as a pivotal repressor of DNAJC8 to enhance glucose uptake by partially regulating PKM2 translocation.

Analysis of Two Dimensional and Three Dimensional Supersonic Turbulence Flow around Tandem Cavities

  • Woo Chel-Hun;Kim Jae-Soo;Lee Kyung-Hwan
    • Journal of Mechanical Science and Technology
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    • v.20 no.8
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    • pp.1256-1265
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    • 2006
  • The supersonic flows around tandem cavities were investigated by two-dimensional and three-dimensional numerical simulations using the Reynolds-Averaged Navier-Stokes (RANS) equation with the k- ω turbulence model. The flow around a cavity is characterized as unsteady flow because of the formation and dissipation of vortices due to the interaction between the freestream shear layer and cavity internal flow, the generation of shock and expansion waves, and the acoustic effect transmitted from wake flow to upstream. The upwind TVD scheme based on the flux vector split with van Leer's limiter was used as the numerical method. Numerical calculations were performed by the parallel processing with time discretizations carried out by the 4th-order Runge- Kutta method. The aspect ratios of cavities are 3 for the first cavity and 1 for the second cavity. The ratio of cavity interval to depth is 1. The ratio of cavity width to depth is 1 in the case of three dimensional flow. The Mach number and the Reynolds number were 1.5 and $4.5{\times}10^5$, respectively. The characteristics of the dominant frequency between two- dimensional and three-dimensional flows were compared, and the characteristics of the second cavity flow due to the first cavity flow was analyzed. Both two dimensional and three dimensional flow oscillations were in the 'shear layer mode', which is based on the feedback mechanism of Rossiter's formula. However, three dimensional flow was much less turbulent than two dimensional flow, depending on whether it could inflow and outflow laterally. The dominant frequencies of the two dimensional flow and three dimensional flows coincided with Rossiter's 2nd mode frequency. The another dominant frequency of the three dimensional flow corresponded to Rossiter's 1st mode frequency.

DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes

  • Shon, Jong Cheol;Joo, Jeongmin;Lee, Taeho;Kim, Nam Doo;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • v.9 no.1
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    • pp.24-29
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    • 2018
  • DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.

A Study of the Thrust Vectoring Control Using Secondary Co- and Counter-Streams (2차 순유동과 역유동을 이용한 추력벡터 제어법에 관한 연구)

  • Lim Chae-Min;Kim Heuy-Dong
    • Proceedings of the Korean Society of Propulsion Engineers Conference
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    • 2004.10a
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    • pp.109-112
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    • 2004
  • Of late, the thrust vectoring control, using fluidic co-flow and counter-flow concepts, has been received much attention since it not only improves the maneuverability of propulsive engine but also reduces an additional material load due to the trailing control wings, which in turn reduce the aerodynamic drag. However, the control effects are not understood well since the flow field involves very complicated non: physics such as shock wave/boundary layer interaction, separation and significant unsteadiness. Existing data are not enough to achieve the effectiveness and usefulness of the thrust vectoring control, and systematic work is required for the purpose of practical applications In the present study, computational study has been performed to investigate the effects of the thrust vector control using the fluidic co-and counter-flow concepts. The results obtained show that, for a given pressure ratio, the thrust deflection angle has a maximum value at a certain suction flow rate, which is at less than $5\%$ of the mass flow rate of the primary jet. With a longer collar, the same vector angle is achievable with smaller mass flow rate.

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Characterization of Gel16 as a Cytochrome P450 in Geldanamycin Biosynthesis and in-silico Analysis for an Endogenous Electron Transport System

  • Rimal, Hemraj;Yu, Sang-Cheol;Lee, Byeongsan;Hong, Young-Soo;Oh, Tae-Jin
    • Journal of Microbiology and Biotechnology
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    • v.29 no.1
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    • pp.44-54
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    • 2019
  • Geldanamycin and its derivatives, inhibitors of heat shock protein 90, are considered potent anticancer drugs, although their biosynthetic pathways have not yet been fully elucidated. The key step of conversion of 4,5-dihydrogeldanamycin to geldanamycin was expected to catalyze by a P450 monooxygenase, Gel16. The adequate bioconversions by cytochrome P450 mostly rely upon its interaction with redox partners. Several ferredoxin and ferredoxin reductases are available in the genome of certain organisms, but only a few suitable partners can operate in full efficiency. In this study, we have expressed cytochrome P450 gel16 in Escherichia coli and performed an in vitro assay using 4,5-dihydrogeldanamycin as a substrate. We demonstrated that the in silico method can be applicable for the efficient mining of convenient endogenous redox partners (9 ferredoxins and 6 ferredoxin reductases) against CYP Gel16 from Streptomyces hygroscopicus. The distances for ligand FDX4-FDR6 were found to be $9.384{\AA}$. Similarly, the binding energy between Gel16-FDX4 and FDX4-FDR6 were -611.88 kcal/mol and -834.48 kcal/mol, respectively, suggesting the lowest distance and binding energy rather than other redox partners. These findings suggest that the best redox partners of Gel16 could be NADPH ${\rightarrow}$ FDR6 ${\rightarrow}$ FDX4 ${\rightarrow}$ Gel16.

Anti-Endotoxin 9-Meric Peptide with Therapeutic Potential for the Treatment of Endotoxemia

  • Krishnan, Manigandan;Choi, Joonhyeok;Choi, Sungjae;Kim, Yangmee
    • Journal of Microbiology and Biotechnology
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    • v.31 no.1
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    • pp.25-32
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    • 2021
  • Inflammatory reactions activated by lipopolysaccharide (LPS) of gram-negative bacteria can lead to severe septic shock. With the recent emergence of multidrug-resistant gram-negative bacteria and a lack of efficient ways to treat resulting infections, there is a need to develop novel anti-endotoxin agents. Antimicrobial peptides have been noticed as potential therapeutic molecules for bacterial infection and as candidates for new antibiotic drugs. We previously designed the 9-meric antimicrobial peptide Pro9-3 and it showed high antimicrobial activity against gram-negative bacteria. Here, to further examine its potency as an anti-endotoxin agent, we examined the anti-endotoxin activities of Pro9-3 and elucidated its mechanism of action. We performed a dye-leakage experiment and BODIPY-TR cadaverine and limulus amebocyte lysate assays for Pro9-3 as well as its lysine-substituted analogue and their enantiomers. The results confirmed that Pro9-3 targets the bacterial membrane and the arginine residues play key roles in its antimicrobial activity. Pro9-3 showed excellent LPS-neutralizing activity and LPS-binding properties, which were superior to those of other peptides. Saturation transfer difference-nuclear magnetic resonance experiments to explore the interaction between LPS and Pro9-3 revealed that Trp3 and Tlr7 in Pro9-3 are critical for attracting Pro9-3 to the LPS in the gram-negative bacterial membrane. Moreover, the anti-septic effect of Pro9-3 in vivo was investigated using an LPS-induced endotoxemia mouse model, demonstrating its dual activities: antibacterial activity against gram-negative bacteria and immunosuppressive effect preventing LPS-induced endotoxemia. Collectively, these results confirmed the therapeutic potential of Pro9-3 against infection of gram-negative bacteria.

Definition, Role and Method of Yinyang Pattern Differentiation (음양변증(陰陽辨證)의 정의와 기능 및 판별방법 연구)

  • Chi, Gyoo-yong;Park, Shin-hyung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.35 no.2
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    • pp.47-55
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    • 2021
  • In order to ensure the fact that eight principle pattern differentiation is used clinically as a basic guideline for Korean medicine practice, the definition, role and method of yin-yang pattern differentiation with its case report were explored at first. Yinyang Pattern Differentiation is a method of discriminating human tendencies or morbidity based on the yin and yang characteristics expressed in living bodies. And yin and yang are the two contrasting characteristics and aspects of the interaction when certain physical conditions that have a lasting effect on the human physiological metabolic function are correlated with the morbidity. Specific methods of yinyang pattern differentiation can be divided into several types of yin and yang indicators. First, time and space factors like day and night, hot and cold seasons, above and below, topographical districts. Second, colors and pulse and their/or relative clearness and muddiness, hardness and softness, moving and resting. Third, diagnose yin and yang patterns through distinguishing the true and false of a fever and cold in an emergency phase such as increase of brain pressure and shock state. Fourth, general characteristics of the propensity and constitution of a subject such as body type, speech, behavior, and physiological metabolism. And for clinical use, these were summarized again as a symptom indicators of physical signs and color, pulse, tongue and questionnaire indicators of propensity, body type, and space-time characteristics. Conclusively, it was confirmed that yinyang pattern differentiation has its own diagnostic significance which is distinct from exterior-interior, cold-heat and deficiency-excess pattern differentiation.

A novel mechanism of Korean Red Ginseng-mediated anti-inflammatory action via targeting caspase-11 non-canonical inflammasome in macrophages

  • Min, Ji-Hyun;Cho, Hui-Jin;Yi, Young-Su
    • Journal of Ginseng Research
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    • v.46 no.5
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    • pp.675-682
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    • 2022
  • Background: Korean Red Ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Methods: Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. Results: KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. Conclusion: The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response.

Effects of L-proline on the Growth Performance, and Blood Parameters in Weaned Lipopolysaccharide (LPS)-challenged Pigs

  • Kang, Ping;Zhang, Lili;Hou, Yongqing;Ding, Binying;Yi, Dan;Wang, Lei;Zhu, Huiling;Liu, Yulan;Yin, Yulong;Wu, Guoyao
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.8
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    • pp.1150-1156
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    • 2014
  • This trail was conducted to study the effect of L-proline on the growth performance, and blood parameter in the weaned lipopolysaccharide (LPS)-challenged pigs. Thirty six pigs ($9.13{\pm}0.85$ kg) were assigned randomly to dietary treatments in a $2{\times}3$ factorial arrangement in a 20-d growth assay. Factors were intraperitoneal injection with saline or LPS, and three dietary L-proline supplement levels (0%, 0.5%, or 1.0%). On d 10, blood samples were collected at 3 h after LPS (100 ${\mu}g$ LPS/kg body weight [BW]) or saline injection. On d 20 of the trial, all pigs were orally administrated D-xylose (0.1 g/kg BW) at 2 h, and blood samples were collected at 3 h after LPS or saline injection. As a result, dietary supplementation with 0.5% proline had a tendency to increase average daily gain (ADG) in piglets during d 10 to 20 (p = 0.088). Without LPS challenge, dietary supplementation with 1.0% proline had no effect on growth hormone (GH) concentrations on d 10 (p>0.05), but decreased it after LPS challenge (p<0.05). There was LPS challenge${\times}$proline interaction for GH concentrations on d 10 (p<0.05). Dietary supplementation with 1.0% proline decreased glucagon concentration on d 10 after LPS challenge (p<0.05). In addition, dietary supplementation with proline increased superoxide dismutase (SOD) activity significantly on d 10 and 20 (p<0.05), and 1.0% proline increased heat shock proteins-70 concentration on d 10 (p<0.05). Moreover, proline supplementation increased diamine oxidase (DAO) concentrations after LPS challenge (p<0.05). There was LPS challenge${\times}$proline interaction for DAO (p<0.05). Furthermore, dietary supplementation with 1.0% proline increased the D-xylose level when no LPS challenge (p<0.05). These results indicate that proline supplementation could improve growth performance, increase SOD activities, and has a positive effect on the gastrointestinal tract digestibility in early weaned pigs.

A Study on the Children's Adaptation in the Foster Care : An Approach based on Grounded Theory (일반위탁가정 아동의 적응에 대한 연구: 근거이론적 접근)

  • Kim, Jin-Sook;Lee, Hyuk-Koo
    • Korean Journal of Social Welfare
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    • v.59 no.1
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    • pp.87-116
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    • 2007
  • The purpose of this study is to identify the adaptation experience of foster children. This qualitative research was conducted through in-depth interview of 8 foster children in and over 4th grade. In data analysis of this qualitative study, the grounded theory suggested by Strauss and Corbin(1998) was used. The raw data collected from in-depth interview with the participants were analyzed in open coding, through theoretically sensitive and constant comparisons method. As a result, total 11 categories, 30 subcategories and 96 concepts were generated. In summary, the casual condition that caused the core phenomenon was 'family stability collapse'. The core phenomenon that foster children experience during the process of adaptation was 'marginalization'. The contextual condition that affected the outcome was 'cultural shock' and 'loyalty conflict.' The intervening condition that promote or restrain the action/interaction on core phenomenon were, 'support system', 'resilience menifestation', 'negative predestination'. The action/interaction strategy on core phenomenon were 'will to power' and 'pursuing moral superiority'. As a result, two concepts, 'mechanical adaptation to foster care environment' and 'active formation' of foster care environment' were assumed.

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