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Gallic Acid Inhibits STAT3 Phosphorylation and Alleviates DDS-induced Colitis via Regulating Cytokine Production

  • Jeong, Ji Hyun;Kim, Eun Yeong;Choi, Hee Jung;Chung, Tae Wook;Kim, Keuk Jun;Kim, So Yeon;Ha, Ki Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.30 no.5
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    • pp.338-346
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    • 2016
  • Signal transducer and activator of transcription 3 (STAT3) is associated with various human diseases, such as cancer, auto-immune disease, and intestinal inflammation. The limited and inadequate effect of standard approaches for treating inflammatory bowel disease (IBD) has prompted to develop alternative anti-colitis agents through inhibition of STAT3. Here, we show that gallic acid (GA), a 3,4,5-trihydroxybenzoic acid, markedly reduced phosphorylation of STAT3. Among the derivatives of benzoic acids, GA showed significant inhibition on STAT3 phosphorylation. In addition, GA ameliorated the dextran sodium sulfate (DSS)-induced acute colitis as determined by the measurement of symptomatic and histological indices. The suppression of DSS-induced acute colitis by GA treatment may be related to the regulation of cytokines and growth factors. Furthermore, GA inhibited phosphorylation of STAT3 in the colon tissue of DSS-treated mice. These findings may be useful in comprehending the molecular action of GA on STAT3 phosphorylation and provide novel insights into the potential application of GA in the treatment of STAT3-related inflammatory disease, such as IBD.

Numerical Simulation of Directivity for Probe and Surface Defect (탐촉자와 표면 결함에 대한 지향성의 수치 실험에 관한 연구)

  • Nam, Young-Hyun
    • Journal of the Korean Society for Nondestructive Testing
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    • v.15 no.1
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    • pp.291-298
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    • 1995
  • An ultrasonic testing uses the directivity of the ultrasonic wave which propagates in one direction. The directivity is expressed as the relationship between the propagate direction and its sound pressure. This paper studied the directivity of shear waves emitted from angle probes and scattered from surface defects by using visualization method. These experimental results were compared with the theory which was based on the continuous wave. The applicability of continuous wave theory was discussed in terms of the parameter $d/{\lambda}$; where d is transducer or defect size and ${\lambda}$ is the wavelength. In the case of angle probes, the experimental results show good agreement with theoretical directivity on the principal lobe. When defect size was smaller than the wavelengths, clear directivity in the reflected wave was observed. In the case of the same ratio of defect size to wavelength, the directivity of reflected waves from the defect show almost the same directivity in spite of frequency differences. When the $d/{\lambda}$ is greater than 1.5, measured directivities almost agreed with the theoretical one.

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Cyclic Mechanical Stretch Stimulates the Proliferation of C2C12 Myoblasts and Inhibits Their Differentiation via Prolonged Activation of p38 MAPK

  • Kook, Sung-Ho;Lee, Hyun-Jeong;Chung, Wan-Tae;Hwang, In-Ho;Lee, Seung-Ah;Kim, Beom-Soo;Lee, Jeong-Chae
    • Molecules and Cells
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    • v.25 no.4
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    • pp.479-486
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    • 2008
  • Mitogen-activated protein kinases (MAPKs) play an indispensable role in activation of the myogenic program, which is responsive to mechanical stimulation. Although there is accumulating evidence of mechanical force-mediated cellular responses, the role of MAPK in regulating the myogenic process in myoblasts exposed to cyclic stretch is unclear. Cyclic stretch induced the proliferation of C2C12 myoblasts and inhibited their differentiation into myotubes. In particular, it induced persistent phosphorylation of p38 kinase, and decreased the level of phosphorylation of extracellular-signal regulated kinase (ERK). Partial inhibition of p38 phosphorylation increased cellular levels of MyoD and p-ERK in stretched C2C12 cells, along with increased myotube formation. Treatment with $10{\mu}M$ PD98059 prevented myogenin expression in response to a low dose of SB203580 ($3{\mu}M$) in the stretched cells, suggesting that adequate ERK activation is also needed to allow the cells to differentiate into myotubes. These results suggest that cyclic stretch inhibits the myogenic differentiation of C2C12 cells by activating p38-mediated signaling and inhibiting ERK phosphorylation. We conclude that p38 kinase, not ERK, is the upstream signal transducer regulating cellular responses to mechanical stretch in skeletal muscle cells.

Effect of Ovum Pick-up Frequency on In Vitro Production of Embryos in Hanwoo Cattle (한우에 있어서 초음파기기를 이용한 생체내 개체별 난자 채취 빈도 및 수정란 생산효율에 관한 연구)

  • 박성재;양보석;임기순;성환후;양병철;장원경;정일정;정기화;심보웅
    • Journal of Embryo Transfer
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    • v.15 no.1
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    • pp.1-8
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    • 2000
  • The ultrasound-guided oocytes cllection (ovum pick-up ; OPU) has become a substitution for superovlation in cattle. The objective of this study was to examine the effect of OPU frequency on the in vitro production of embryos in Hanwoo cattle. Six cycling Hanwoo cows were distributed into two groups for either once or twice weekly OPU sessions. Oocytes were collected by ultrasound-guided follicle aspiration(SA600) using a 6.5HMz transducer and attached with 18 gauge needle, with vacuum pressure of 40 mmHg. The cumulus-oocyte complexes (COCs) collected from each donor were matured in TCM 199 supplemented with 10% fetal bovine serum at 5% CO2 in air at 38.5$^{\circ}C$ for 22h and in vitro matured oocytes were co-incubated with sperm(separated by Percoll gradient) for 6h. The zygotes were co-cultured on cumulus cell monolayer in 10ul droplets in the same culture medium and conditions used for IVM for 7 days. On Day 7 of culture, development to blastocysts was examined. Although the number of oocytes collected was variable depending on individuals, overall embryo production in the twice per week OPU sessions was better that in the once per week sessions(6~21 vs 2~7 blastocysts produced, respectively). Two cows(E, A) were good oocyte donors and embryo production was superior in cow C ; however, cow F was a poor donor as compared to the others. In conclusion, these results suggest that for embryo production, twice weekly OPU sessions were better than once per week for producing embryos in vitro from Hanwoo cattle.

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Role of Spinal Adenosine $A_2$ Receptor in the cardiovascular Regulation in Rats (흰쥐에서 실혈관 조절기전에 대한 척수의 Adenosine $A_2$수용체의 역할)

  • 문삼영;신현진;신인철;고현철;엄애선;박정로;김범수;강주섭
    • Biomolecules & Therapeutics
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    • v.8 no.4
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    • pp.325-331
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    • 2000
  • The present study was designed to assess the role of spinal adenosine $A_2$ receptor in the regulation of cardiovascular functions such as mean arterial pressure (MAP) and heart rate (HR) in male Sprague-Dawley rats. Rats (250~300 g) were anesthetized with urethane and paralyzed with d-tubocurarine and artificially ventilated. blood pressure and HR were continuously monitored via a femoral catheter connected to a pressure transducer and a polygraph. Drugs were administered intrathecally using injection cannula through guide cannula which was inserted inthrathecally at lower thoracic level through a puncture of an atlantooccipital mombrane. Intrathecal injection of an adenosine $A_2$ receptor agonist, 5'-(N-cyclopropyl)-carboxamaidoadenosine (CPCA; 1, 2 and 3 nmol, respectively), produced a dose-dependent decrease in MAP and HR. Pretreatment with $N^{G}$-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or 10 nmol of MDL-12,330, an adenylate cyclase inhibitor blocked significantly the depressor and bradycardic effect of 2 nmol of CPCA. But, Pretreatment with 3 nmol of bicuculline, gamma-aminobutyric acid A (GAB $A_{A}$) receptor antagonist, or 50 nmol of 5-aminovaleric acid, GAB $A_{B}$ receptor antagonist did not inhibit the depressor and bradycardic effect of 2 nmol of CPCA. These results indicate that adenosine $A_2$ receptor in the spinal cord plays an inhibitory role in the regulation of cardiovascular function and that the depressor and bradycardic action of adonosine $A_2$ receptor are mediated via the synthesis of nitric oxide and the activation of adenylate cyclase in the spinal cord of rats.s.s.s.

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IL-4 Independent Nuclear Translocalization of STAT6 in HeLa Cells by Entry of Toxoplasma gondii

  • Ahn, Hye-Jin;Kim, Ji-Yeon;Nam, Ho-Woo
    • Parasites, Hosts and Diseases
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    • v.47 no.2
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    • pp.117-124
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    • 2009
  • Toxoplasma gondii provokes rapid and sustained nuclear translocation of the signal transducer and activator of transcription 6 (STAT6) in HeLa cells. We observed activation of STAT6 as early as 2hr after infection with T. gondii by the nuclear translocation of fluorescence expressed from exogenously transfected pDsRed2-STAT6 plasmid and by the detection of phosphotyrosine-STAT6 in Western blot. STAT6 activation occurred only by infection with live tachyzoites but not by co-culture with killed tachyzoites or soluble T. gondii extracts. STAT6 phosphorylation was inhibited by small interfering RNA of STAT6 (siSTAT6). In view of the fact that STAT6 is a central mediator of IL-4 induced gene expression, activation of STAT6 by T. gondii infection resembles that infected host cells has been stimulated by IL-4 treatment. STAT1 was affected to increase the transcription and expression by the treatment of siSTAT6. STAT6 activation was not affected by any excess SOCS's whereas that with IL-4 was inhibited by SOCS-1 and SOCS-3. T. gondii infection induced Eotaxin-3 gene expression which was reduced by $IFN-{\gamma}$. These results demonstrate that T. gondii exploits host STAT6 to take away various harmful reactions by $IFN-{\gamma}$. This shows, for the first time, IL-4-like action by T. gondii infection modulates microbicidal action by $IFN-{\gamma}$ in infected cells.

Cripto Enhances Proliferation and Survival of Mesenchymal Stem Cells by Up-Regulating JAK2/STAT3 Pathway in a GRP78-Dependent Manner

  • Yun, SeungPil;Yun, Chul Won;Lee, Jun Hee;Kim, SangMin;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.464-473
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    • 2018
  • Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1. Notably, treatment with an anti-GRP78 antibody blocked these effects. In addition, pretreatment with STAT3 short interfering RNA (siRNA) inhibited the increase in p-JAK2, c-Myc, cyclin D1, and BCL3 levels caused by Cripto and attenuated the pro-survival action of Cripto on MSCs. We also found that incubation with Cripto protected MSCs from apoptosis caused by hypoxia or $H_2O_2$ exposure, and the level of caspase-3 decreased by the Cripto-induced expression of B-cell lymphoma 3-encoded protein (BCL3). These effects were sensitive to down-regulation of BCL3 expression by BCL3 siRNA. Finally, we showed that Cripto enhanced expression levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). In summary, our results demonstrated that Cripto activated a novel biochemical cascade that potentiated MSC proliferation and survival. This cascade relied on phosphorylation of JAK2 and STAT3 and was regulated by GRP78. Our findings may facilitate clinical applications of MSCs, as these cells may benefit from positive effects of Cripto on their survival and biological properties.

Ultrasonic Nondestructive On-Site Evaluation of Decks in-Service (초음파 비파괴시험법을 이용한 데크재의 현장평가)

  • Oh, Sei-Chang
    • Journal of the Korean Wood Science and Technology
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    • v.43 no.4
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    • pp.486-493
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    • 2015
  • The ultrasonic nondestructive test (NDT) was applied to deck in-service to inspect and evaluate the performance of decking materials using ultrasonic pulse velocity. First, the measuring method between direct and indirect method according to transducer arrangement was studied. Second, the ultrasonic pulse velocity of decks in-service was compared with the passage of time. Finally, the change of ultrasonic pulse velocity was evaluated to expect service life of decking materials. The results of comparison between direct and indirect method was statistically insignificant and the ratio of direct to indirect method was 1.02. 1.05 respectively. The ultrasonic pulse velocity of decks in-service was decreased as the passage of time and the linear relationship in the ultrasonic pulse velocity to passage of time was found. From the results, The ultrasonic NDT will be helpful as an efficient method of on-site management of decks in-service.

Ultrasonic Characterization of a Resonating High-Speed Microcantilever (초음파 기법을 이용한 고속 마이크로 캔틸레버의 공진 특성평가)

  • Kim, Yun Young;Lee, Seonwook;Park, Jiwon;Cho, Younho
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.41 no.6
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    • pp.483-489
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    • 2017
  • An ultrasonic technique was developed to characterize the resonance behavior of a microcantilever operating in a megahertz regime. A high-power ultrasonic pulser and a contact transducer were employed to excite the silicon microcantilever, and a Michelson interferometer was used to obtain the time domain waveform. The natural frequency of the microcantilever was evaluated through the fast Fourier transform of the signal, and a numerical analysis using the finite element method confirmed the measurement data. The present study proposes a novel and facile method to evaluate nanoscale materials and structures with high sensitivity compared to conventional approaches.

The Determination of Transducer Locations for Active Structural Acoustic Control of the Radiated Sound from Vibrating Plate (평판에서 방사되는 소음의 능동구조소음제어를 위한 변환기의 위치결정)

  • 김흥섭;홍진석;이충휘;오재응
    • Transactions of the Korean Society for Noise and Vibration Engineering
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    • v.12 no.9
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    • pp.694-701
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    • 2002
  • In this paper, through the study on locations of structural transducers for active control of the radiated sound from the vibrating plate, the active structural acoustic control (ASAC) system is proposed. And, for the evaluation of the proposed location, the experiment of the active structural acoustic control is implemented using the multi-channel filtered-x LMS algorithm and an additional filter (Acoustic Prediction Filter) to estimate the radiated sound using the acceleration signals of the plate. The structural transducers are piezoceramic actuator (PZT) and accelerometer. PZT is used as an actuator to reduce the vibration and the radiated sound. To maximize the control performance, each PZT actuator is located at the position that has the largest control sensitivity of the plate bending moment in the direction of x and y coordinates and the optimal PZT location is validated experimentally. Also, to find the acoustic prediction filter accurately, two accelerometers are located at the positions that have the largest radiation efficiencies of the plate, and the proposed locations are validated by simulation using the Rayleigh integral. The multi-channel filtered-x LMS algorithm is introduced to control a complex 2-D structural vibration mode. Finding the locations of structural transducers for active structural acoustic control of the radiated sound, the active structural acoustic control (ASAC) system can be presented and validated by experiments using a real time control system.