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Kim, H. J.,Yoo, H. Y.,Jang, J. H.,Lin, H. Y.,Seo, E. Y.,Zhang, Y. H.,Kim, S. J. Springer Science + Business Media 2016 Pfl ugers Arch Vol.468 No.4
<P>Pulmonary arteries (PAs) have high compliance, buffering the wide ranges of blood flow. Here, we addressed a hypothesis that PA smooth muscle cells (PASMCs) express nitric oxide synthases (NOS) that might be activated by mechanical stress and vasoactive agonists. In the myograph study of endothelium-denuded rat PAs, NOS inhibition (L-NAME) induced strong contraction (96 % of 80 mM KCl-induced contraction (80K)) in the presence of 5 nM U46619 (thromboxane A(2) (TXA(2)) analogue) with relatively high basal stretch (2.94 mN, S(+)). With lower basal stretch (0.98 mN, S(-)), however, L-NAME application following U46619 (TXA(2)/L-NAME) induced weak contraction (27 % of 80K). Inhibitors of nNOS and iNOS had no such effect in S(+) PAs. In endothelium-denuded S(+) mesenteric and renal arteries, TXA(2)/L-NAME-induced contraction was only 18 and 21 % of 80K, respectively. Expression of endothelial-type NOS (eNOS) in rat PASMCs was confirmed by RT-PCR and immunohistochemistry. Even in S(-) PAs, pretreatment with H2O2 (0.1-10 mu M) effectively increased the sensitivity to TXA(2)/L-NAME (105 % of 80K). Vice versa, NADPH oxidase inhibitors, reactive oxygen species scavengers, or an Akt inhibitor (SC-66) suppressed TXA(2)/L-NAME-induced contraction in S(+) PAs. In a human PASMC line, immunoblot analysis showed the following: (1) eNOS expression, (2) Ser(1177) phosphorylation by U46619 and H2O2, and (3) Akt activation (Ser(473) phosphorylation) by U46619. In the cell-attached patch clamp study, H2O2 facilitated membrane stretch-activated cation channels in rat PASMCs. Taken together, the muscular eNOS in PAs can be activated by TXA(2) and mechanical stress via H2O2 and Akt-mediated signaling, which may counterbalance the contractile signals from TXA(2) and mechanical stimuli.</P>
CAN통신을 이용한 H-브릿지 멀티레벨 인버터의 PWM 동기화 및 위상전이 방법
박영민(Y.M.Park),유한승(H.S.Yoo),장성영(S.Y.Jang),이현원(H.W.Lee),이세현(S.H.Lee),서광덕(K.D.Seo) 전력전자학회 2004 전력전자학술대회 논문집 Vol.- No.-
H-브릿지 멀티레벨 인버터는 여러 개의 단상 Power Cell을 직렬로 연결함으로써 저전압 전력용 반도체를 사용하여 고전압을 얻을 수 있고, 정현파에 가까운 출력전압 파형을 얻을 수 있는 멀티레벨 인버터 토폴로지이다. 본 토폴로지는 출력전압 레벨에 비례하여 Power Cell의 수가 증가하므로, 주제어기의 연산능력에 대한 부담증가와 신호선의 많아지는 단점이 있다. 따라서 Power Cell제어를 직접적인 PWM 신호가 아닌 통신을 사용함으로써 이러한 단점을 극복할수 있으며, 신뢰성 측면이나 보수/유지 측면에서도 유리하다. 본 논문은 산업현장에서 신뢰성을 인정받아 많이 사용되고 있는 직렬통신 방식의 일종인 CAN통신 인터럽터를 이용한 H-브릿지 멀티레벨 인버터 Power Cell의 PWM 동기화 및 위상전이 방법에 관한 것이다. 제안된 방법의 주요 장점은 주제어기와 셀 제어기 사이에 직렬통신(CAN)을 사용함으로써 주제어기와 셀 제어기의 신호선의 단순화, 주제어기의 부담 감소, Power Cell의 모듈화, 셀 단위의 보호동작 용이, 확장성 향상 그리고 제어 신호 및 Power Cell의 신뢰성을 향상에 있다. 13레벨로 구성된 H-브릿지 멀티레벨 인버터 시험을 통해 제안된 방법의 타당성과 신뢰성을 입증하였다.
Seo, S H,Kim, K S,Park, S H,Suh, Y S,Kim, S J,Jeun, S-S,Sung, Y C Nature Publishing Group 2011 Gene Therapy Vol.18 No.5
<P>Owing to its tumor tropism and prolonged transgene expression, mesenchymal stem cell (MSC) has been considered as an ideal delivery vehicle for cancer gene therapies or therapeutic vaccines. In this study, we demonstrated that intratumoral (i.t.) injection of MSCs expressing modified interleukin-12 (MSCs/IL-12M) exhibited stronger tumor-specific T-cell responses and antitumor effects as well as more sustained expressions of IL-12 and interferon (IFN)-γ in both sera and tumor sites than did IL-12M-expressing adenovirus (rAd/IL-12M) in mice bearing both solid and metastatic tumors. Subcutaneous (s.c.) injection of MSCs/IL-12M at contralateral site of tumor exhibited similar levels of serum IL-12 and IFN-γ as i.t. injection, but much weaker antitumor effects in both B16F10 melanoma and TC-1 cervical cancer models than i.t. injection. Although intravenous (i.v.) injection elicited earlier peak serum levels of cytokines, it induced weaker tumor-specific T-cell responses and antitumor effects than i.t. injection, indicating that serum cytokine levels are not surrogate indicators of antitumor effects. Taken together, these results indicated that MSC is more efficient than adenovirus as a cytokine gene delivery vehicle and that i.t. injection of MSCs/IL-12M is the best approach to induce strong tumor-specific T-cell responses that correlate with anti-metastatic effects as well as inhibition of solid tumor growth, although MSCs themselves have an ability to migrate into the tumor site. In addition, MSCs/IL-12M embedded in Matrigel (MSCs/IL-12M/Matrigel) exhibited significant antitumor effects even in immunodeficient mice such as SCID and BNX mice lacking T, B and natural killer (NK) cells, but not in IFN-γ knockout mice. Our findings provide an optimal approach for designing an efficient clinical protocol of MSC-based cytokine gene therapy to induce strong tumor-specific T-cell responses and therapeutic anticancer efficacy.</P>
Kim, J.Y.,Kim, K.B.,Son, H.J.,Chae, Y.C.,Oh, S.T.,Kim, D.W.,Pak, J.H.,Seo, S.B. North-Holland Pub ; Elsevier Science Ltd 2012 FEBS letters Vol.586 No.19
Significant progress has been made in understanding the relationship between histone modifications and 'reader' molecules and their effects on transcriptional regulation. A previously identified INHAT complex subunit, SET/TAF-Iβ, binds to histones and inhibits histone acetylation. To investigate the binding specificities of SET/TAF-Iβ to various histone modifications, we employed modified histone tail peptide array analyses. SET/TAF-Iβ strongly recognized PRC2-mediated H3K27me½/3; however, the bindings were completely disrupted by H3S28 phosphorylation. We have demonstrated that SET/TAF-Iβ is sequentially recruited to the target gene promoter ATF3 after the PRC2 complex via H3K27me recognition and may offer additive effects in the repression of the target gene.
Jeong, J.H.,Oh, Y.J.,Lho, Y.,Park, S.Y.,Liu, K.H.,Ha, E.,Seo, Y.H. S.E.C.T. [etc.] ; Elsevier Science Ltd 2016 European journal of medicinal chemistry Vol.124 No.-
The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC<SUB>50</SUB> = 50.3 nM). Furthermore, it effectively inhibits the proliferation of H1975 non-small cell lung cancer (NSCLC) and Skbr3 breast cancer cell lines with GI<SUB>50</SUB> values of 0.31 μM and 0.11 μM, respectively. Compound 19 induces the degradation of the Hsp90 client proteins including EGFR, Her2, Met, c-Raf, and Akt, and consequently promotes apoptotic cancer cell death. Compound 19 also inhibits the growth of H1975 xenografts in NOD-scid IL2R gamma<SUP>null</SUP> mice without any apparent body-weight loss. The immunohistologic evaluation indicates that compound 19 decreases the expression of Akt in xenograft tumor tissue via an inhibition of the Hsp90 chaperon function. Additionally, the cytochrome P450 assay indicates that compound 19 has no effect on the activities of five major P450 isoforms (IC<SUB>50</SUB> > 50 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between compound 19 and the substrate drugs of the five major P450 isoforms are not expected. Overall, compound 19 represents a new class of Hsp90 inhibitor with its 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-amide structure, and it has the therapeutic potential to overcome drug resistance in cancer chemotherapy.
Seo, D.W.,Lim, Y.D.,Lee, S.H.,Jeong, Y.G.,Hong, T.W.,Kim, W.G. Pergamon Press ; Elsevier Science Ltd 2010 International journal of hydrogen energy Vol.35 No.23
Sulfonated amine-poly(ether sulfone)s (S-APES)s were prepared by nitration, reduction and sulfonation of poly(ether sulfone) (ultrason<SUP>(</SUP>R)-S6010). Poly(ether sulfone) was reacted with ammonium nitrate and trifluoroacetic anhydride to produce the nitrated poly(ether sulfone), and was followed by reduction using tin(II)chloride and sodium iodide as reducing agents to give the amino-poly(ether sulfone). The S-APES was obtained by reaction of 1,3-propanesultone and the amino-poly(ether sulfone) (NH<SUB>2</SUB>-PES) with sodium methoxide. The different degrees of nitration and reduction of poly(ether sulfone) were successfully synthesized by an optimized process. The reduction of nitro group to amino was done quantitatively, and this controlled the contents of the sulfonic acid group. The films were converted from salt to acid forms with dilute hydrochloric acid. Different contents of sulfonated unit of the S-APES were studied by FT-IR, <SUP>1</SUP>H NMR spectroscopy, differential scanning calorimetry (DSC), and thermo gravimetric analysis (TGA). Sorption experiments were conducted to observe the interaction of sulfonated polymers with water and methanol. The ion exchange capacity (IEC), a measure of proton conductivity, was evaluated. The S-APES membranes exhibit conductivities (25 <SUP>o</SUP>C) from 1.05 x 10<SUP>-3</SUP> to 4.83 x 10<SUP>-3</SUP> S/cm, water swell from 30.25 to 66.50%, IEC from 0.38 to 0.82 meq/g, and methanol diffusion coefficients from 3.10 x 10<SUP>-7</SUP> to 4.82 x 10<SUP>-7</SUP> cm<SUP>2</SUP>/S at 25 <SUP>o</SUP>C.
Kim, S.J.,Geballe, T.R.,Seo, H.J.,Kim, J.H. Academic Press 2009 Icarus Vol.202 No.1
Jupiter exhibits bright H<SUP>+</SUP><SUB>3</SUB> auroral arcs at 3-4 microns that cool the hot (>1000 K) ionosphere above the ~10<SUP>-7</SUP> bar level through the infrared bands of this trace constituent. Below the 10<SUP>-7</SUP> bar level significant cooling proceeds through infrared active bands of CH<SUB>4</SUB>, C<SUB>2</SUB>H<SUB>2</SUB>, and C<SUB>2</SUB>H<SUB>6</SUB>. We report the discovery of 3-micron line emission from these hydrocarbon species in spectra of the jovian south polar region obtained on April 18 and 20, 2006 (UT) with CGS4 on the United Kingdom Infrared Telescope. Estimated cooling rates through these molecules are 7.5x10<SUP>-3</SUP>, 1.4x10<SUP>-3</SUP>, and 0.72x10<SUP>-3</SUP> Wm<SUP>-2</SUP>, respectively, for a total nearly half that of H<SUP>+</SUP><SUB>3</SUB>. We derive a temperature of 450@?+/-@?50 K in the 10<SUP>-7</SUP>-10<SUP>-5</SUP> bar region from the C<SUB>2</SUB>H<SUB>2</SUB> lines.