• Title/Summary/Keyword: Inhibitor switch

검색결과 15건 처리시간 0.029초

CAM을 활용한 인히비터 스위치 가공 (Manufacture of Inhibitor Switch using CAM)

  • 김세환;이종선;김정훈
    • 한국산학기술학회논문지
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    • 제5권1호
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    • pp.49-54
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    • 2004
  • 본 논문은 자동차용 자동변속기의 변속전환 핵심 부품인 인히비터 스위치 케이스를 CAM을 활용하여 직접 제작하였다. 자동차 부품의 대부분은 주조로 만들어 대량생산과 복잡한 형상의 가공이 용이하지만 기계적 성질의 저하, 정밀도의 저하, 환경의 문제, 후처리를 해야하는 문제점이 있다. 이러한 문제점을 해결하기 위하여 CAM을 활용하여 제작함으로서 새로운 가공 방향을 제시하였다.

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비 접촉식 차량용 Transmitter Switch에 관한 연구 (A study on Non-contacted Transmitter Switch for Vehicle)

  • 안종영;김영섭;김성수;허강인
    • 한국인터넷방송통신학회논문지
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    • 제10권5호
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    • pp.245-249
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    • 2010
  • 현재 차량에서 일반적으로 많이 쓰이고 있는 변속 스위치의 방법은 전위차를 신호로하는 접촉식이다. 접촉식은 신호전달에 있어서 정확한 방식의 하나이지만 장시간 사용 시 접촉면의 노후화로 인하여 수명이 짧아진다. 비 접촉 방식으로 사용될 수 있는 자기센서를 사용 한다면 접촉면의 노후화를 해결 할 수 있다. 본 논문에서는 자기센서의 특징을 살려서 비 접촉식 방법으로 차량용 변속스위치에 적용 하여 기존 접촉식 방법의 문제를 해결하였다. 센서 출력 전압은 가변적인 전위차를 가지는데 스위치의 각동에 따라 통상 0mV에서 150mV의 값을 가진다. 본 연구에서는 5개의 상태 신호에 대한 두 개의 사인 신호를 사용 하였다.

Effects of the Myosin ATPase Inhibitor, 2,3-Butanedione-2-Monoxime, on Growth and Dimorphic Switches of Candida albicans

  • Woo, Mi-Young;Jwa, Mi-Ri;Kim, Jin-Mi;Song, Ki-Won
    • Journal of Microbiology and Biotechnology
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    • 제10권5호
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    • pp.606-611
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    • 2000
  • Dimorphic yeast Candida albicans reversibly switches between the form of yeast and hyphae depending on external conditions. We investigated possible roles of the myosin family in the growth and dimorphic switches of C. albicans with a general myosin ATPase inhibitor, 2,3-butanedione-2-monoxime (BDM). Transition to hyphae as well as proliferation by budding was completely inhibited by BDM at 16 mM. Presence of 16 mM BDM did not affect hyphae-to-bud transition but it blocked budding. The effects of BDM on yeast growth and dimorphic switches were reversible. More than 70% of the BDM-treated cells demonstrated defects in the amount and the polarized localization of F-actin as well as in the shape and migration of the nucleus, suggesting that myosin activities are needed in these cellular processes of C. albicans.

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Activin A Stimulates Mouse APCs to Express BAFF via ALK4-Smad3 Pathway

  • Kim, Jae-Hee;Seo, Goo-Young;Kim, Pyeung-Hyeun
    • IMMUNE NETWORK
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    • 제11권4호
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    • pp.196-202
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    • 2011
  • Background: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. Methods: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. Results: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. Conclusion: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.

암모니아와 glutamine에 의한 Rhodopseudomonas sphaeroides의 질소 고정 효소활성에 미치는 Methionine Sulfoximine의 영향 (Effect of Methionine Sulfoximine in nitrogenase activity by ammonia and glutamine in Rhodopseudomonas sphaeroides)

  • 이혜주
    • 미생물학회지
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    • 제26권3호
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    • pp.215-222
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    • 1988
  • 광합성 세균인 Rhodopsedomonas sphaeroides의 질소 고정 효소 활성에 미치는 암모니아와 glutamine의 영향을 조사하였다. 그 결과 RP. sphaeroides의 질소 고정 효소 활성은 암모니아와 glutamine에 의해 저해를 받았으며, 이들의 저해는 암모니아와 glutamine이 다 사용된 후에는 질소 고정 효소의 활성이 되살아나는 가역적인 반응이었다. glutamine synthetase의 활성을 비가역적으로 저해하는 methionine sulfoximine (MSX)를 사용하여 암모니아와 glutamine이 직접 질소 고정 효소의 활성을 저해하는지를 일아보았다. 암모니아에 의한 질소 고정 효소의 switch-off에 미치는 MSX의 영향은 균의 배양 시기에 의존함을 알 수 있었다 . 12시간 배양한 경우, $500{\mu}M$ NH,Cl에 의해 질소 고정 효소는 저해를 받았으며, $500{\mu}M$의 MSX를 주가로 처리하였을 경우, GS는 21% 저해를 받았으며, 이때 유리된 암모니아의 량은 감소하였고, 질소 고정 효소의 활성은 회복되지 않았다. 그러나 20시간 배양한 경우, $500{\mu}M$ NH,CI을 처리한 후 $100{\mu}M$ MSX플 첨가하면, GS의 활성은 완전히 저해되고, 유리된 암모니아의 량은 약간 증가하였으나 질소 고정 효소의 활성의 저해는 MSX에 의해 회복되었다. 따라서 Rp. sphaeroides의 경우, in vivo 상태에서 암모니아에 의한 질소 고정 효소의 활성 저해는 암모니아 자체에 의한 것이 아니라 암모니아 동화산물에 의한 것임을 알 수 있었다.

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Elucidation of Serpin's Conformational Switch Mechanism By Rapid Kinetic Study

  • Kang, Un-Beom;Lee, Cheolju;Baek, Je-Hyun;Seunghyun Ryu;Kim, Joon;Yu, Myeong-Hee
    • 한국생물물리학회:학술대회논문집
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    • 한국생물물리학회 2003년도 정기총회 및 학술발표회
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    • pp.62-62
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    • 2003
  • The native form of serpin (serine protease inhibitor) is kinetically trapped in metastable state. Metastability in these proteins is critical to their biological function. Serpins inhibit target proteases by forming a stable covalent complex in which the cleaved reactive site loop of the serpin is inserted into $\beta$-sheet A of the serpin with concomitant translocation of the protease to the opposite of the initial binding site. Despite recent determination of the crystal structures of a Michaelis protease-serpin complex as well as a stable covalent complex, details on the kinetic mechanism remain unsolved. In this study we constructed several $\alpha$$_1$-antitrypsin variants and examined their kinetic mechanism of loop translocation and formation of protease-serpin complex by stopped-flow experiments of fluorescence resonance energy transfer as well as quenched-flow experiment. We report here the relationship of serpin's conformational switch mechanism with Inhibitory activity. There is little direct correlation between loop insertion rate and inhibitory activity. Rather, disrupting a salt bridge between R196 and E354 accelerates loop translocation even though it impairs the inhibitory activity. Moreover, the serpin's reactive site loop is translocated, at least partially, prior to loop cleavage.

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G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells

  • Cho, Eunah;Kwon, Yeo-Jung;Ye, Dong-Jin;Baek, Hyoung-Seok;Kwon, Tae-Uk;Choi, Hyung-Kyoon;Chun, Young-Jin
    • Biomolecules & Therapeutics
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    • 제27권6호
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    • pp.591-602
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    • 2019
  • Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.

Tyrosine Kinase Inhibitor as Clinical Application Feasibility in Canine Intractable Tumor Diseases

  • Choi, Eul-Soo;Song, Joong-Hyun;Shin, Jong-Il;Sur, Jung-Hyang;Kang, Byeong-Teck;An, Su-Jin;Cho, Kyu-Woan;Jung, Dong-In
    • 한국임상수의학회지
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    • 제33권4호
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    • pp.187-193
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    • 2016
  • A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions. This study aims to show that the actions of growth factors associated with PDGFR-${\alpha}$, PDGFR-${\beta}$, VEGFR-2, c-KIT, and c-ABL, which are used in veterinary medicine, are expressed in canine intractable tumors. This study used archival cases of canine paraganglioma, gastrointestinal adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma. Tissues had been immunohistochemical analysis. The antibodies used were PDGFR-${\alpha}$, PDGFR-${\beta}$, c-kit, VEGFR-2, and c-Abl. PDGFR-${\alpha}$ was expressed only in HCC, and PDGFR-${\beta}$ was expressed in all tumors. VEGFR was also only expressed in HCC, and c-KIT has been expressed in HCC, paraganglioma, and small intestinal adenocarcinoma. c-Abl was expressed in all cancers, but was weakly expressed in paraganglioma, while more than moderately expressed in other tissues. In conclusion, this study investigated how TKIs used in human medicine can be applied to canine intractable tumors, through immunohistochemistry. The results indicate that there may be an application for TKIs in treating canine intractable tumors.

Crosstalk between BMP signaling and KCNK3 in phenotypic switching of pulmonary vascular smooth muscle cells

  • Yeongju, Yeo;Hayoung, Jeong;Minju, Kim;Yanghee, Choi;Koung Li, Kim;Wonhee, Suh
    • BMB Reports
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    • 제55권11호
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    • pp.565-570
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    • 2022
  • Pulmonary arterial hypertension (PAH) is a progressive and devastating disease whose pathogenesis is associated with a phenotypic switch of pulmonary arterial vascular smooth muscle cells (PASMCs). Bone morphogenetic protein (BMP) signaling and potassium two pore domain channel subfamily K member 3 (KCNK3) play crucial roles in PAH pathogenesis. However, the relationship between BMP signaling and KCNK3 expression in the PASMC phenotypic switching process has not been studied. In this study, we explored the effect of BMPs on KCNK3 expression and the role of KCNK3 in the BMP-mediated PASMC phenotypic switch. Expression levels of BMP receptor 2 (BMPR2) and KCNK3 were downregulated in PASMCs of rats with PAH compared to those in normal controls, implying a possible association between BMP/BMPR2 signaling and KCNK3 expression in the pulmonary vasculature. Treatment with BMP2, BMP4, and BMP7 significantly increased KCNK3 expression in primary human PASMCs (HPASMCs). BMPR2 knockdown and treatment with Smad1/5 signaling inhibitor substantially abrogated the BMP-induced increase in KCNK3 expression, suggesting that KCNK3 expression in HPASMCs is regulated by the canonical BMP-BMPR2-Smad1/5 signaling pathway. Furthermore, KCNK3 knockdown and treatment with a KCNK3 channel blocker completely blocked BMP-mediated anti-proliferation and expression of contractile marker genes in HPAMSCs, suggesting that the expression and functional activity of KCNK3 are required for BMP-mediated acquisition of the quiescent PASMC phenotype. Overall, our findings show a crosstalk between BMP signaling and KCNK3 in regulating the PASMC phenotype, wherein BMPs upregulate KCNK3 expression and KCNK3 then mediates BMP-induced phenotypic switching of PASMCs. Our results indicate that the dysfunction and/or downregulation of BMPR2 and KCNK3 observed in PAH work together to induce aberrant changes in the PASMC phenotype, providing insights into the complex molecular pathogenesis of PAH.

Immunosuppressive Properties of Catfish Bile from Silurus asotus: Inhibition of T Cell Activation in Mouse Splenocytes

  • Joo, Seong-Soo
    • Food Science and Biotechnology
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    • 제17권3호
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    • pp.598-602
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    • 2008
  • Concentrated catfish Silurus asotus bile (SAB) containing high amounts of ursodeoxycholic acid (UDCA) and taurocholic acid may have immunosuppressive properties. To investigate the putative immunosuppressive properties of SAB, the anti-proliferation and suppression of early T cell activation markers, and the inhibition of cytokines induced by T cells in response to anti-CD3 mAb activation in mouse splenocytes were examined. The suppression of these activation repertoires are the main properties of calcineurin inhibitors. It was found that SAB effectively suppressed the activation of T cells, and cytokines from T cell activation, at levels similar to cyclosporine A, a calcineurin inhibitor. Although the mechanism in which suppression occurs is not clear, we speculate that SAB from Silurus asotus, which has been known to switch their intake habits to zoophagy during an early adult stage, may explain the suppressive effect of SAB as a result of high amounts of functional UDCA in bile. Our results suggest that the treatment or intake of SAB, either in therapy or as a food supplement, may act as an adjuvant therapy for the prevention of transplant rejection, although further investigation is required before this treatment can be applied clinically.