Sphingosine-1-phosphate-induced Flk-1 transactivation stimulates mouse embryonic stem cell proliferation through S1P₁/S1P₃-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.

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>

Ultraviolet photodissociation spectroscopy of cold, isolated adenine complexes with a potassium cation

Baek, J.Y.,Choi, C.M.,Eun, H.J.,Park, K.S.,Choi, M.C.,Heo, J.,Kim, N.J. North Holland 2015 Chemical physics letters Vol.635 No.-

We obtain the ultraviolet photodissociation spectrum of adenine complexes with K<SUP>+</SUP> ion stored in a cold ion trap. The spectrum near the origin band of the S<SUB>0</SUB>-S<SUB>1</SUB> transition exhibits well-resolved vibronic bands, all of which are assigned from a single isomer by UV-UV hole-burning (HB) spectroscopy. Comparing the spectrum with theoretical spectra, we determine the structure of the isomer, where K<SUP>+</SUP> is bound not to 9H-adenine (A9) but to 7H-adenine (A7). We suggest that K<SUP>+</SUP>A7 ions are formed in solution through tautomerization, for which the energy barrier varies greatly depending on the binding site of the K<SUP>+</SUP> ion on A9.

Prevalence of antimicrobial resistant Streptococcus pneumoniae serotype 11A isolates in Korea, during 2004-2013, due to the increase of multidrug-resistant clone, CC166

Baek, J.Y.,Kim, S.H.,Kang, C.I.,Chung, D.R.,Peck, K.R.,Ko, K.S.,Song, J.H. Elsevier Science 2016 INFECTION GENETICS AND EVOLUTION Vol.38 No.-

Since the introduction of the pneumococcal conjugate vaccine (PCV7) in Korea in 2003, the proportion of non-vaccine serotypes has increased. Among non-vaccine serotypes, serotype 11A is highly prevalent in Korea. We investigated the prevalence and characteristics of Streptococcus pneumoniae serotype 11A isolates in a Korean tertiary-care hospital, during 2004-2013. A total of 1579 non-duplicate clinical S. pneumoniae isolates, collected from 2004 to 2013, were included in this study. Serotype was determined by the capsular Quellung method, and in vitro susceptibility testing was performed by broth microdilution method. Multilocus sequence typing was performed to determine the genotypes of the S. pneumoniae isolates. We identified 90 serotype 11A isolates (5.7%). During this period, the proportion of serotype 11A has increased from 3.2% up to 13.2% (in 2012). Among the serotype 11A isolates, two main clonal complexes (CCs), CC166 and CC99, were identified. The increase of serotype 11A was mainly due to the increase of CC166 isolates, which have high antimicrobial resistance rates. In addition, we identified that 14 isolates, belonging to ST8279, ST9875, and ST3598 of CC166, were non-susceptible to all antimicrobial agents tested in this study. We identified the increase of S. pneumoniae serotype 11A in Korea, which mainly due to the expansion of a resistant clonal group, CC166.

능동 현가 장치가 차량의 핸들링에 미치는 영향에 관한 연구

이증섭(J. S. Lee),강준원(J W. Kang),백승주(S. J. Baek),박성문(S. M. Park),오재윤(C. Y. Oh) 한국자동차공학회 1996 한국자동차공학회 춘 추계 학술대회 논문집 Vol.1996 No.11_1

This paper develops a 7 DOF vehicle model to study the effects of the active suspension on ride. The model is used to derive a control law for the active suspension using a full state linear optimal control technique. A wheelbase preview type active suspension is also considered in the control law derivation. The time delay between wheelbases is approximated using Pade approximation technique. The ride model is extended to a 14 DOF handling model to include lateral, longitudinal, yaw and four wheel spin motions. A control law which is derived by considering only ride related parameters is used to study the effects of the active suspension on a vehicle handling. J-tum maneuver simulation results show that the active suspension has a slower response in lateral acceleration and yaw rate, a bigger steady state lateral acceleration and an oversteer tendency. Lane changing maneuver simulation results show that the active suspension has a little bigger lateral acceleration but a much smaller roll angle and roll motion. Braking maneuver simulation results show that the active suspension has a much smaller pitch angle and pitch motion.<br/>

Performance and carrier transport analysis of In_0.7Ga_0.3As quantum-well MOSFETs with Al₂O₃/HfO₂ 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>.

기능 안전 설계/평가 프로세스(ISO 13849) 적용한 지게차용 변속기 제어 유닛(TCU) 개발과 H/W-S/W 레벨 및 실차 레벨 검증

백종희(J. H. Baek),김경수(K. S. Kim),조성진(S. J. Cho),정명길(M. K. Jung) 유공압건설기계학회 2022 유공압건설기계학회 학술대회논문집 Vol.2022 No.06

As the application of automation, intelligent technologies in construction equipment has been increased rapidly, nowadays functional safety regulation on the SRP/CS(Safety Related Parts of Control System) of fork-lift trucks become more strictly applied based on ISO 13849, EN 1175, etc. So, we applied functional safety principles in TCU(Transmission Control Unit) for industrial trucks and performed verification and validation in accordance with ISO 13849, for the first time in Korea. As a result, we developed TCU H/W with the PFHd of 0.392 × 10<SUP>-6</SUP>(1/h). We also conducted S/W tests such as static analysis for MISRA-C compliant rate, dynamic tests for white-box and black-box test, all of which are compliant to PLc/Category 2 or the higher level.

Baicalin-induced Akt activation decreases melanogenesis through downregulation of microphthalmia-associated transcription factor and tyrosinase

Jeong, H.S.,Gu, G.E.,Jo, A.R.,Bang, J.S.,Yun, H.Y.,Baek, K.J.,Kwon, N.S.,Park, K.C.,Kim, D.S. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.761 No.-

Scutellaria baicalensis has been used topically to treat inflammatory skin diseases in traditional East Asian medicine. Because post-inflammatory hyperpigmentation of the skin is difficult to manage, we investigated the effects of baicalin, a major component of S. baicalensis, on melanin synthesis in Mel-Ab cells. Our data showed that baicalin significantly inhibited melanin production and tyrosinase activity in a dose-dependent fashion, but it did not directly influence tyrosinase activity. Moreover, baicalin treatment triggered decreases in both mRNA and protein levels of microphthalmia-associated transcription factor (MITF) and tyrosinase. Although AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK) activation were induced in baicalin-treated Mel-Ab cells, they were not responsible for baicalin-induced hypopigmentation. Because the Akt pathway is also known to be involved in regulation of melanogenic protein expression and melanin synthesis, we examined the effects of baicalin on the Akt pathway. Our results showed that baicalin treatment stimulated Akt activation. Treatment with LY294002, a specific Akt inhibitor, restored baicalin-induced melanogenesis inhibition and abolished MITF and tyrosinase downregulation by baicalin. Taken together, our data suggest that Akt activation by baicalin inhibits melanin production via downregulation of MITF and tyrosinase in Mel-Ab cells.

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>

Lactobacillus casei LM -1 의 Bacteriophage 저항성 기작에 관한 연구

임광세(K . S . Lim),장영호(Y . H . Jang),백영진(Y . J . Baek),김현욱(H . U . Kim) 한국축산학회 1991 한국축산학회지 Vol.33 No.10

This study was carried out to elucidate the phage defense mechanism of Lactobacillus casei LM-1, the phage-resistant mutant of L. cased S-1, and to obtaine the basic knowledge for developing a better lactic starter bacteria resistant to the phages. The results obtained are summarized as follows ; 1. No differences were found in growth, acid production, and carbohydrate fermentation between L. casei S-1 and L. casei LM-1 in the MRS broth. and transmission electron microscopic studies of L. case; LM-1 revealed that cells were covered with the hairly capsular layer, that is presumed to cover up the phage receptor sites on the surface of the cells. 2. When the cells of L. casei S-1 were treated with mutanolysin, the adsorption rate of phage J-I and ø-I was decreased rapidly. In case of L. casei LM-l, the adsorption rate of phage J-1 and ø-1 was increased around 30 minutes after addition of mutanolysin and then decreased. 3. Based upon the knowledge obtained from enzymatie treatment; and electron micrographs of L. casei LM-I, it is safe to say that the phage-resistant harrier of L. case; LM-1 is the extension of the modified pep-tidoglycan layer of the normal cell wall. 4. Treatment of L. casei LM-1 with 3 kinds of enzymes (subtilisin. α-amylase, β-amylase) did not affect the low adsorption of phage J-I and ø-1 on the host cells. which tells the capsular layer of L. casei LM-1 was not hydrolyzed by these enzymes. 5. No plasmids of L. casei S-1 and L. easei LM-1 were found on agarose gel electrophoresis, which suggests that the gene responsible for the formation of capsular layer was possibly induced due to the chromosomal mutation.