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      • Effects of sevoflurane on collagen production and growth factor expression in rats with an excision wound

        LEE, H.-J.,KWON, J.-Y.,SHIN, S.-W.,BAEK, S.-H.,CHOI, K.-U.,JEON, Y.-H.,KIM, W.-S.,BAE, J.-H.,CHOI, H.-J.,KIM, H.-K.,BAIK, S.-W. Blackwell Publishing Ltd 2010 Acta anaesthesiologica Scandinavica Vol.54 No.7

        <P>Background</P><P>Sevoflurane is a widely used inhalation anesthetic, but there are no studies on its effect on the wound-healing process. This study was undertaken to evaluate the effect of exposure time to sevoflurane on wound healing.</P><P>Method</P><P>Male Sprague–Dawley rats were used. Two circular full-thickness skin defects 8 mm in diameter were made on the dorsum of the rats. The animals were divided into six groups according to exposed gas type and time: S1 (sevoflurane, 1 h), S4 (sevoflurane, 4 h), S8 (sevoflurane, 8 h), O1 (oxygen, 1 h), O4 (oxygen, 4 h), and O8 (oxygen, 8 h). The surface area of the wounds was measured 0, 1, 3, and 7 days after surgery. Separately, the mean blood pressures (MBP) and arterial oxygen pressures (PaO<SUB>2</SUB>) were monitored during the sevoflurane exposure. Collagen type I production and transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF) expression on the wound surface were analyzed. Routine histological analysis was also performed.</P><P>Result</P><P>Exposure duration to sevoflurane had no influence on MBP and PaO<SUB>2</SUB>. The reduction in wound size and collagen type I production was delayed in S8. The expression of TGF-β1 and bFGF on the wound surface in S8 was significantly attenuated in S8. The histology of the S8 demonstrated a delayed healing status.</P><P>Conclusions</P><P>Prolonged exposure to sevoflurane might alter the inflammatory phase of the wound-healing process by attenuation of growth factor expression such as TGF-β1 and bFGF and subsequently by reduced collagen production.</P>

      • Sphingosine-1-phosphate-induced Flk-1 transactivation stimulates mouse embryonic stem cell proliferation through S1P<sub>1</sub>/S1P<sub>3</sub>-dependent β-arrestin/c-Src pathways

        Ryu, J.M.,Baek, Y.B.,Shin, M.S.,Park, J.H.,Park, S.H.,Lee, J.H.,Han, H.J. Elsevier 2014 Stem cell research Vol.12 No.1

        Although recent findings showed that the bioactive lipid metabolites can regulate the ES cell functions, the physiological relevance of interaction between sphingosine-1-phosphate (S1P) and Flk-1 and its related signaling molecules are not yet clear in ES cell proliferation. In the present study, S1P<SUB>1-5</SUB> receptors were expressed in mouse ES cells and S1P increased S1P<SUB>1-3</SUB> receptor expression level. S1P treatment stimulated the cellular proliferation in S1P<SUB>1/3</SUB>-dependent manner, located in lipid rafts. In response to S1P, β-arrestin was recruited to S1P<SUB>1/3</SUB> receptor and c-Src was activated. S1P also increased the binding of S1P<SUB>1/3</SUB> receptor with Flk-1. Similar to responses for VEGF, S1P increased Flk-1 phosphorylation, which was blocked by β-arrestin siRNA, and PP2, but not by VEGF-A<SUB>164</SUB> antibody or VEGF siRNA. In addition, S1P induced VEGF expression and VEGFR2 kinase inhibitor (SU1498) blocked the S1P-induced cellular proliferation. However, VEGF-A<SUB>164</SUB> antibody or VEGF siRNA partially blocked S1P-induced cellular proliferation, suggesting that both VEGF-dependent Flk-1 activation and VEGF-independent Flk-1 activation are involved in S1P-induced ES cell proliferation. S1P and VEGF-induced phosphorylation of ERK and JNK were blocked by pretreatment with SU1498. Moreover, inhibition of ERK and JNK blocked S1P-induced cellular proliferation. In conclusion, S1P-elicited transactivation of Flk-1 mediated by S1P<SUB>1/3</SUB>-dependent β-arrestin/c-Src pathways stimulated mouse ES cell proliferation.

      • Efficient xeno-free culture system for human embryonic stem cells

        Baek J.A.,Seol H.W.,Jung J.,Yoon B.A.,Kim H.S.,Oh S.K.,Koo S.,Kim S.H.,Moon S.Y.,Choi Y.M. 한국발생생물학회 2011 한국발생생물학회 학술발표대회 Vol.30 No.-

        The development of humanized culture system of human embryonic stem cells (hESCs) hold promise for therapeutic applications. However, conventional culture system contain animal-derived components such as fetal bovine serum and mouse embryonic fibroblasts that bear a risk of transmitting non-human pathogens and incorporation of non-human immunogenic molecules to hESCs. In this study, we developed an efficient xeno-free hESCs culture system using humanized materials, the CELLstartTM, human foreskin feeder and xeno-free medium containing knockOutTM SR XenoFree (XF-medium) without animal-derived material. The hESCs were gradually adapted to the XF-medium; 25:75, 50:50, 75:25 and 100:0. Two karyotypically normal hESC lines, SNUhES4 and H1, were used for the experiments of xeno-free culture condition. The attachment rates at xeno-free culture system were 52.6±12.4%, 67.0±16.6%, 59.0±13.9%, 28.3±2.9% in SNUhES4, 79.3±5.4%, 53.8±20.9%, 69.4 ±6.4%, 59.8±12.6% in H1 and the spontaneous differentiation rates were 42.2±12.7%, 31.4±2.9%, 40.8±14.5%, 55.2±35.5% in SNUhES4, 35.6±8.5%, 36.4±13.5%, 48.4±7.8%, 80.1±6.0% in H1 in the first four passage. Although the attachment rates were low and the spontaneous differentiation rates were high compared to that of conventional system in the early passages using this humanized culture condition, hESCs in this culture condition were found to maintain hESC characterizations; morphology, expression of cell surface markers and stable karyotype. Our results indicate that simplified compositions of humanized culture system can be applicable to the further optimization for a xeno-free culture of hESCs without the loss of pluripotency and contamination from xenogenic sources.

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        S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis

        Kim, S Y,S Hong, Y,K Shim, E,Kong, S-Y,Shin, A,Baek, J Y,Jung, K H Nature Publishing Group 2013 The British journal of cancer Vol.109 No.6

        <P><B>Background:</B></P><P>S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.</P><P><B>Methods:</B></P><P>Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m<SUP>−2</SUP> followed by oxaliplatin 85 mg m<SUP>−2</SUP> on day 1 and S-1 80 mg m<SUP>−2</SUP> per day from day 1 to 14 every 3 weeks. Polymorphisms in the <I>UGT1A1</I>, <I>UGT1A6</I>, <I>UGT1A7</I> and <I>CYP2A6</I> genes were analysed.</P><P><B>Results:</B></P><P>Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval: 53.4–81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of <I>UGT1A6*2</I> or <I>UGT1A7*3</I> and an improved tumour response was noted in those without variant alleles of <I>CYP2A6</I> or <I>UGT1A1*60</I>.</P><P><B>Conclusion:</B></P><P>The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.</P>

      • Dependence of the exchange bias and coercivity of [Pd/Ferromagnet]<sub>N</sub>/FeMn multilayers on the stack number N

        Joo, H.W.,Lee, M.S.,Kim, S.W.,Kim, S.S.,Lee, J.Y.,Baek, J.Y.,You, C.-Y.,Lee, K.A.,Rhee, J.R.,Lee, S.S.,Hwang, D.G. IEEE 2006 IEEE transactions on magnetics Vol.42 No.10

        The dependencies of the stack number N on perpendicular exchange-biasing (H<SUB>ex</SUB>) and coercivity H<SUB>c</SUB>) in [Pd/Co]<SUB>N</SUB> and [Pd/Co (or CoFe)]<SUB>N</SUB>/FeMn multilayers were investigated. With the help of the careful designs of layer structures, a series of samples whose surface anisotropies have the linear function N was prepared with constant bulk anisotropies. From the experimental data obtained, it was found that H<SUB>ex</SUB> does not depend on the surface anisotropy, while H<SUB>c</SUB> shows a strong dependence. Therefore, it is possible to tailor wide ranges of H<SUB>c</SUB> (300-600 Oe) without varying H<SUB>ex</SUB>(∼200 Oe) through the single control parameter stack number N.

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        Performance and carrier transport analysis of In<sub>0.7</sub>Ga<sub>0.3</sub>As quantum-well MOSFETs with Al<sub>2</sub>O<sub>3</sub>/HfO<sub>2</sub> gate stack

        Son, S.W.,Park, J.H.,Baek, J.M.,Kim, J.S.,Kim, D.K.,Shin, S.H.,Banerjee, S.K.,Lee, J.H.,Kim, T.W.,Kim, D.H. Pergamon Press ; Elsevier Science Ltd 2016 Solid-State Electronics Vol.123 No.-

        In this paper, we have fabricated and characterized In<SUB>0.7</SUB>Ga<SUB>0.3</SUB>As quantum-well (QW) metal-oxide-semiconductor field-effect-transistors (MOSFETs). We have employed the gate dielectric of the Al<SUB>2</SUB>O<SUB>3</SUB>/HfO<SUB>2</SUB> (0.6/2nm) bi-layer stack by ALD. The fabricated device with L<SUB>g</SUB>=4μm exhibits a record maximum transconductance (g<SUB>m_max</SUB>) in excess of 520μS/μm at >1μm region, and reasonably good electrostatic integrity, such as SS=110mV/decade and DIBL=43mV/V. Also, we have investigated the gate length scaling behavior in terms of output, transconductance, and transfer characteristics. In particular, our devices feature very uniform values of the electrostatic integrity, such as SS=100-110mV/decade, V<SUB>T</SUB>=-0.25V to -0.2V and DIBL=40-50mV/V, as L<SUB>g</SUB> decreases from 10μm to 4μm. Furthermore, we have explored the impact of source resistance (R<SUB>S</SUB>) onto the device characteristics of the InGaAs QW MOSFETs. In doing so, we have modeled both measured extrinsic transconductance (g<SUB>m_ext</SUB>) and intrinsic transconductance (g<SUB>m_int</SUB>) as a function of L<SUB>g</SUB>.

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        Status of the KSTAR superconducting magnet system development

        Kim, K.,Park, H.K.,Park, K.R.,Lim, B.S.,Lee, S.I.,Chu, Y.,Chung, W.H.,Oh, Y.K.,Baek, S.H.,Lee, S.J.,Yonekawa, H.,Kim, J.S.,Kim, C.S.,Choi, J.Y.,Chang, Y.B.,Park, S.H.,Kim, D.J.,Song, N.H.,Kim, K.P.,So International Atomic Energy Agency 2005 Nuclear fusion Vol.45 No.8

        <P>The aim of the Korea superconducting tokamak advanced research (KSTAR) project is to develop a steady-state-capable advanced superconducting tokamak for establishing a scientific and technological basis for an attractive fusion reactor. Since the KSTAR mission includes the achievement of a steady-state-capable operation, the use of superconducting coils is an obvious choice for the magnet system. The KSTAR superconducting magnet system consists of 16 toroidal field (TF) and 14 poloidal field (PF) coils which include 8 central solenoid coils. Both the TF and PF coil systems use internally-cooled cable-in-conduit conductors (CICC). The TF coil system provides a magnetic field of 3.5 T at the plasma centre and the PF coil system provide a flux swing of 17 V s. The major achievement in the KSTAR magnet system development includes the development of CICC, a full size TF model coil, a background magnetic field generation coil system and the construction of a large scale superconducting magnet and the CICC test facility. TF and PF coils are at the stage of fabrication for the KSTAR completion in the year 2007.</P>

      • In vivo imaging of tumor apoptosis using histone H1-targeting peptide

        Wang, K.,Purushotham, S.,Lee, J.Y.,Na, M.H.,Park, H.,Oh, S.J.,Park, R.W.,Park, J.Y.,Lee, E.,Cho, B.C.,Song, M.N.,Baek, M.C.,Kwak, W.,Yoo, J.,Hoffman, A.S.,Oh, Y.K.,Kim, I.S.,Lee, B.H. Elsevier Science Publishers 2010 Journal of controlled release Vol.148 No.3

        In vivo imaging of apoptosis could allow monitoring of tumor response to cancer treatments such as chemotherapy. Using phage display, we identified the CQRPPR peptide, named ApoPep-1(Apoptosis-targeting Peptide-1), that was able to home to apoptotic and necrotic cells in tumor tissue. ApoPep-1 also bound to apoptotic and necrotic cells in culture, while only little binding to live cells was observed. Its binding to apoptotic cells was not dependent on calcium ion and not competed by annexin V. The receptor for ApoPep-1 was identified to be histone H1 that was exposed on the surface of apoptotic cells. In necrotic cells, ApoPep-1 entered the cells and bound to histone H1 in the nucleus. The imaging signals produced during monitoring of tumor apoptosis in response to chemotherapy was enhanced by the homing of a fluorescent dye- or radioisotope-labeled ApoPep-1 to tumor treated with anti-cancer drugs, whereas its uptake of the liver and lung was minimal. These results suggest that ApoPep-1 holds great promise as a probe for in vivo imaging of apoptosis, while histone H1 is a unique molecular signature for this purpose.

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        Apoptotic cell death in rat epididymis following epichlorohydrin treatment

        Lee, I.-C.,Kim, K.-H.,Kim, S.-H.,Baek, H.-S.,Moon, C.,Yun, W.-K.,Nam, K.-H.,Kim, H.-C.,Kim, J.-C. SAGE Publications 2013 Human & experimental toxicology Vol.32 No.6

        <P>Epichlorohydrin (ECH) is an antifertility agent that acts both as an epididymal toxicant and an agent capable of directly affecting sperm motility. This study identified the time course of apoptotic cell death in rat epididymides after ECH treatment. Rats were administrated with a single oral dose of ECH (50 mg/kg). ECH-induced apoptotic changes were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and its related mechanism was confirmed by Western blot analysis and colorimetric assay. The TUNEL assay showed that the number of apoptotic cells increased at 8 h, reached a maximum level at 12 h, and then decreased progressively. The Western blot analysis demonstrated no significant changes in proapoptotic Bcl-2-associated X (Bax) and anti-apoptotic Bcl-2 expression during the time course of the study. However, phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and phospho-c-Jun amino-terminal kinase (p-JNK) expression increased at 8–24 h. Caspase-3 and caspase-8 activities also increased at 8–48 h and 12–48 h, respectively, in the same manner as p-p38 MAPK and p-JNK expression. These results indicate that ECH induced apoptotic changes in rat epididymides and that the apoptotic cell death may be related more to the MAPK pathway than to the mitochondrial pathway.</P>

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        PdO-doped BaZr<sub>0.8</sub>Y<sub>0.2</sub>O<sub>3-δ</sub> electrolyte for intermediate-temperature protonic ceramic fuel cells

        Baek, S.S.,Park, K.Y.,Lee, T.H.,Lee, N.,Seo, Y.,Song, S.J.,Park, J.Y. Elsevier Science 2014 Acta materialia Vol.66 No.-

        This paper explores the potential to design a ''superprotonic conductor'' for operation in the intermediate temperature (IT) range through a doping approach with a conventional proton conductor. This approach is validated scientifically, based on the enhanced macroscopic transport properties of the oxide ion conductor. This system consists of a BaZr<SUB>0.8</SUB>Y<SUB>0.2</SUB>O<SUB>3-δ</SUB> (BZY) proton conductor and a small amount of palladium oxide (PdO). The influence of the PdO on the sinter activity of the highly refractory BZY material is not significant, with low rates of grain growth under typical sintering conditions, even though the addition of some PdO favors the grain growth of BZY materials to some extent. The conductivity of PdO-modified BZY (BZPY) is higher than that of BZY in the IT range, in all atmospheres and at all temperatures. The conductivity of 3mol.% PdO-modified BZPY was 8.60x10<SUP>-3</SUP>Scm<SUP>-1</SUP> at 600<SUP>o</SUP>C in wet 5% H<SUB>2</SUB>. The electrical conductivity of BZPY increases systematically with increasing PdO content (0.5-3mol.%) in all atmospheres investigated.

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