<i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

<P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

Induction of bone formation by <i>Escherichia coli</i>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models

Park, J‐,C.,So, S‐,S.,Jung, I‐,H.,Yun, J‐,H.,Choi, S‐,H.,Cho, K‐,S.,Kim, C‐,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.6

<P><I>Park J‐C, So S‐S, Jung I‐H, Yun J‐H, Choi S‐H, Cho K‐S, Kim C‐S. Induction of bone formation by</I> Escherichia coli<I>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models. J Periodont Res 2011; 46: 682–690. © 2011 John Wiley & Sons A/S</I></P><P><B>Background and Objective: </B> The potential of the <I>Escherichia coli</I>‐expressed recombinant human bone morphogenetic protein‐2 (ErhBMP‐2) to support new bone formation/maturation using a block‐type of macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in an orthotopic and ectopic rat model.</P><P><B>Material and Methods: </B> Critical‐size (Φ 8 mm) calvarial defects and subcutaneous pockets in 32 Sprague–Dawley rats received implants of rhBMP‐2 (2.5 μg) in a bMBCP carrier or bMBCP alone (control). Implant sites were evaluated using histological and histometric analysis following 2‐ and 8‐wk healing intervals (eight animals/group/interval).</P><P><B>Results: </B> ErhBMP‐2/bMBCP supported significantly greater bone formation at 2 and 8 wk (10.8% and 25.4%, respectively) than the control at 2 and 8 wk (5.3% and 14.0%, respectively) in calvarial defects (<I>p</I> < 0.01). Bone formation was only observed for the ErhBMP‐2/bMBCP ectopic sites and was significantly greater at 8 wk (7.5%) than at 2 wk (4.5%) (<I>p</I> < 0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8 wk. The bMBCP carrier showed no evidence of bioresorption.</P><P><B>Conclusion: </B> ErhBMP‐2/bMBCP induced significant bone formation in both calvarial and ectopic sites. Further study appears to be required to evaluate the relevance of the bMBCP carrier.</P>

Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein‐2 on periodontal regeneration

Song, D‐,S.,Park, J‐,C.,Jung, I‐,H.,Choi, S‐,H.,Cho, K‐,S.,Kim, C‐,K.,Kim, C‐,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.2

<P> <I>Song D‐S, Park J‐C, Jung I‐H, Choi S‐H, Cho K‐S, Kim C‐K, Kim C‐S. Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein‐2 on periodontal regeneration. J Periodont Res 2011; 46: 193–203. © 2010 John Wiley & Sons A/S</I> </P><P><B>Background and Objective: </B> Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) is a potent inducer for the regeneration of mineralized tissue, but has a limited effect on the regeneration of cementum and periodontal ligament (PDL). The aim of the present study was to determine the effects of rhBMP‐2 on the <I>in vitro</I> and <I>in vivo</I> biologic activity of well‐characterized human PDL stem cells (hPDLSCs) and to elucidate the underlying mechanism of minimal periodontal regeneration by rhBMP‐2.</P><P><B>Material and Methods: </B> hPDLSCs were isolated and cultured, and then transplanted into an ectopic subcutaneous mouse model using a carrier treated either with or without rhBMP‐2. Comprehensive histologic, histometric and immunohistochemical analyses were performed after an 8‐wk healing period. The effects of rhBMP‐2 on the adipogenic and osteogenic/cementogenic differentiation of hPDLSCs were also evaluated. The effect of rhBMP‐2 on both soluble and insoluble collagen synthesis was analyzed, and the expression of mRNA and protein for collagen types I, II, III and V was assessed.</P><P><B>Results: </B> In the present study, rhBMP‐2 promoted both adipogenic and osteogenic/cementogenic differentiation of hPDLSCs <I>in vitro</I>, and the <I>in vivo</I> potential of hPDLSCs to form mineralized cementum and organized PDL tissue was down‐regulated following treatment with rhBMP‐2. Collagen synthesis, which plays a crucial role in the regeneration of cementum and the periodontal attachment, was significantly reduced, with associated modification of the relevant mRNA and protein expression profiles.</P><P><B>Conclusion: </B> In summary, the findings of the present study suggest that enhanced adipogenic differentiation and inhibition of collagen synthesis by hPDLSCs appear to be partly responsible for the minimal effect of rhBMP‐2 on cementum and PDL tissue regeneration by hPDLSCs.</P>

Overexpression of PtrMYB119, a R2R3-MYB transcription factor from Populus trichocarpa, promotes anthocyanin production in hybrid poplar

Cho, J. S.,Nguyen, V. P.,Jeon, H. W.,Kim, M. H.,Eom, S. H.,Lim, Y. J.,Kim, W. C.,Park, E. J.,Choi, Y. I.,Ko, J. H. Oxford University Press 2016 Tree physiology Vol.36 No.9

<P>Anthocyanins are a group of colorful and bioactive natural pigments with important physiological and ecological functions in plants. We found an MYB transcription factor (PtrMYB119) from Populus trichocarpa that positively regulates anthocyanin production when expressed under the control of the CaMV 35S promoter in transgenic Arabidopsis. Amino acid sequence analysis revealed that PtrMYB119 is highly homologous to Arabidopsis PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT1), a well-known transcriptional activator of anthocyanin biosynthesis. Independently produced transgenic poplars overexpressing PtrMYB119 or PtrMYB120 (a paralogous gene to PtrMYB119) (i.e., 35S::PtrMYB119 and 35S::PtrMYB120, respectively) showed elevated accumulation of anthocyanins in the whole plants, including leaf, stem and even root tissues. Using a reverse-phase high-performance liquid chromatography, we confirmed that the majority of the accumulated anthocyanin in our transgenic poplar is cyanidin-3-O-glucoside. Gene expression analyses revealed that most of the genes involved in the anthocyanin biosynthetic pathway were highly upregulated in 35S::PtrMYB119 poplars compared with the nontransformed control poplar. Among these genes, expression of PtrCHS1 (Chalcone Synthase1) and PtrANS2 (Anthocyanin Synthase2), which catalyze the initial and last steps of anthocyanin biosynthesis, respectively, was upregulated by up to 350-fold. Subsequent transient activation assays confirmed that PtrMYB119 activated the transcription of both PtrCHS1 and PtrANS2. Interestingly, expression of MYB182, a repressor of both anthocyanin and proanthocyanidin (PA) biosynthesis, was largely suppressed in 35S::PtrMYB119 poplars, while expression of MYB134, an activator of PA biosynthesis, was not changed significantly. More interestingly, high-level accumulation of anthocyanins in 35S::PtrMYB119 poplars did not have an adverse effect on plant growth. Taken together, our results demonstrate that PtrMYB119 and PtrMYB120 function as transcriptional activators of anthocyanin accumulation in both Arabidopsis and poplar.</P>

Effect of bedrock stiffness and thickness of weathered rock on response spectrum in Korea

Manandhar, S.,Cho, H. I.,Kim, D. S. Springer Science + Business Media 2016 KSCE JOURNAL OF CIVIL ENGINEERING Vol.20 No.7

<P>The Standard Penetration Test (SPT) is increasingly used to generate shear wave velocity (V (S) ) profile of a site for seismic hazard assessment. However, it is difficult to perform site investigation using the SPT for weathered rock and bedrock even at shallow depths in most cases. Consequently, the stiffness of bedrock (V (Sb) ) is assumed to be 760 m/s, and only partial thickness of weathered rock is used for site response assessment in Korea. The increase in V (Sb) and thickness of weathered rock (H (w) ) may affect the overall seismic response of a site, even though the site response is mostly governed by the upper soil layers. In this study, the effect of V (Sb) and H (w) on response spectrum in Korea was investigated by performing equivalent-linear site response analyses on three representative sites each of S (C) and S (D) soil categories as defined in the Korean seismic code based on the average shear wave velocity of top 30 m of a site (V-S30). The S (C) and S (D) categories are defined similar to that in the International Building Code (IBC). Further, the effect of increase in V-Sb and H-w on the selection of design response spectrum based on seismic codes was also investigated. An increase in V (Sb) resulted in an increase in spectral amplification, while the effect of increase in H-w was not substantial for the representative sites considered in this study. This means that the V (S) of bedrock needs to be assessed properly. On the other hand, it is possible to get a reliable seismic response even if the H-w cannot be determined accurately. The incorporation of V (Sb) in V (S30) for shallow bedrock sites (bedrock depth < 30 m) fails to consider the effect of increase in seismic amplification at large V (Sb) . Hence, it is preferable to consider the effect of V (Sb) separately on the design response spectrum. In addition, the effect on soil non-linearity due to variation in the V (Sb) and H (w) was found to be insignificant.</P>

SHRIMP U-Pb dating and geochemistry of the Cretaceous plutonic rocks in the Korean Peninsula: A new tectonic model of the Cretaceous Korean Peninsula

Kim, S.W.,Kwon, S.,Park, S.I.,Lee, C.,Cho, D.L.,Lee, H.J.,Ko, K.,Kim, S.J. Universitetsforlaget ; Elsevier Science Ltd 2016 Lithos Vol.262 No.-

<P>The Cretaceous tectonomagmatism of the Korean Peninsula was examined based on geochemical and geochronological data of the Cretaceous plutonic rocks, along with distribution of volcano-sedimentary nonmarine N- to NE-trending fault bounded sedimentary basins. We conducted sensitive high-resolution ion microprobe (SHRIMP) zircon U-Pb ages and whole-rock geochemical compositions of 21 Cretaceous plutonic rocks, together with previously published data, from the central to southern Korean Peninsula. Four age groups of plutonic rocks were identified: Group I (ca. 119-106 Ma) in the northern to central area, Group II (ca. 99-87 Ma) in the central southern area, Group III (ca. 85-82 Ma) in the central to southern area, and Group IV (ca. 76-67 Ma) in the southernmost area. These results indicate a sporadic trenchward-younging trend of the Cretaceous magmatism in the Korean Peninsula. The Group I, II, and III rocks are dominated by high-K calc-alkaline I-type rocks with rift-related A-type granitoids. In contrast, the Group IV rocks are high-K calc-alkaline I-type plutonic rocks with no A-type rocks. The geochemical signatures of the entire groups indicated LREEs (light rare earth elements) enrichments and negative Nb, Ta, and Ti anomalies, indicating normal arc magmatism. A new tectonic model of the Cretaceous Korean Peninsula was proposed based on temporal and spatial distribution of the Cretaceous plutons represented by four age groups; 1) magmatic quiescence throughout the Korean Peninsula from ca. 160 to 120 Ma, 2) intrusions of the I- and A-type granitoids in the northern and central Korean Peninsula (Group I plutonic rocks from ca. 120 to 100 Ma) resulted from the partial melting of the lower continental crust due to the rollback of the Izanagi plate expressed as the conversion from flat-lying subduction to normal subduction. The Gyeongsang nonmarine sedimentary rift basin in the Korean Peninsula and adakite magmatism preserved in the present-day Japanese Islands supported the slab rollback followed by steepening of the Izanagi plate with an injection of upwelling of the hot asthenosphere into the mantle wedge. 3) Alternating shallow (from similar to 100 to 85 Ma) to steep (from similar to 85 to 65 Ma) subduction resulted in the migration of the normal arc magmatism in the southern Korean Peninsula, expressed as the intruded I- and A-type (Group III) and I-type granitoids (Group IV), respectively. The tectonomagmatism of, the Korean Peninsula showed the unique style of evolution, different from those of South China and Japanese Islands. (C) 2016 Elsevier B.V. All rights reserved.</P>

Simulation study on effect of drain underlap in gate-all-around tunneling field-effect transistors

Lee, J.S.,Seo, J.H.,Cho, S.,Lee, J.H.,Kang, S.W.,Bae, J.H.,Cho, E.S.,Kang, I.M. Elsevier 2013 Current Applied Physics Vol.13 No.6

In this work, the effects of underlapping drain junction on the performances of gate-all-around (GAA) tunneling field-effect transistors (TFETs) have been studied in terms of direct-current (DC) characteristics including on-current (I<SUB>on</SUB>), off-current (I<SUB>off</SUB>), subthreshold swing (S), and I<SUB>on</SUB>/I<SUB>off</SUB> ratio. In addition, the dependences of intrinsic delay time (τ) and radio-frequency (RF) performances including cut-off frequency (f<SUB>T</SUB>) and maximum oscillation frequency (f<SUB>max</SUB>) on gate-drain capacitance (C<SUB>gd</SUB>) with the underlapping were investigated as the gate length (L<SUB>gate</SUB>) is scaled. A GAA TFET with asymmetric junctions, with an underlap at the drain side, demonstrated DC and RF performances superior to those of a device with symmetric junctions.

200 GeV/핵자 유황이온과 핵건판핵의 충돌에 의해 생성된 헬륨 파쇄핵의 극한파쇄 연구

김동철,송진섭,윤천실,정성헌,박인곤,김종오,김철수,김태연,이승희,조재희,천병구,김재률,김준원,김태익,박명렬,장한일,임인택 慶尙大學校 기초과학연구소 1992 基礎科學硏究所報 Vol.8 No.-

고에너지 중이온 원자핵과 핵건판의 충돌에서, 200GeV/핵자 유황이온에 의해 생성된 파쇄 헬륨핵(Z=2)의 실험실계의 방출각 분포는 표적핵에 무관한 회귀공식. dN=exp[a+k exp(η-y_b)]d[exp(η-y_b)]로 잘 표현된다. 여기에서 의사신속도 η=-ln[tan(θ/2)]이고, y_b는 실험실계의 입사입자(^32S)의 신속도이다. 이 공식에 의한 적합에서 k=-0.057±0.008로 얻어진다. 즉, 핵건판과 고에너지 중이온의 충돌에서 파쇄 헬륨핵의 exp(η-y_b)의 분포는 "극한파쇄" 현상을 잘 설명하고 있다. The angular distribution of emission angle θ of helium (Z=2) produced in the collisions of incident particles of 200 GeV/nucleon ^32S in nuclear emulsion is well expressed by dN=exp[a+k exp(η-y_b)]d[exp(η-y_b)] where the pseudorapidity is η=-ln[tan(θ/2)], the laboratory system primary rapidity is y_b, and k=-0.057+0.008. The shape of this frequency of occurrence distributions in terms of exp(η-y_b) attests to the validity of the concept of "limiting fragmentation" for helium projectile fragments produced in the projectile fragmentation regions of heavy ion collisions in nuclear emulsion.

Polymorphisms in the neurokinin-2 receptor gene are associated with angiotensin-converting enzyme inhibitor-induced cough

Kim, T.-B.,Oh, S.-Y.,Park, H.-K.,Jeon, S.-G.,Chang, Y.-S.,Lee, K.-Y.,Cho, Y. S.,Chae, I.-H.,Kim, Y.-K.,Cho, S.-H.,Moon, H.-B.,Min, K.-U.,Kim, Y.-Y. Blackwell Publishing Ltd 2009 Journal of clinical pharmacy and therapeutics Vol.34 No.4

<P>Summary</P><P>Background and objective: </P><P>Treatment with angiotensin-converting enzyme (ACE) inhibitors can induce chronic cough in many patients. Genetic variations in the neurokinin 2 receptor gene (NK2R) are significantly associated with cough sensitivity to capsaicin.</P><P>Methods: </P><P>This study assessed the relationship between genetic polymorphisms in the NK2R gene and chronic cough in 91 patients taking ACE inhibitors. Patients included in the study did not have chest abnormalities, postnasal drip, gastroesophageal reflux or a recent history of upper respiratory infection.</P><P>Results: </P><P>We detected two single nucleotide polymorphisms in the NK2R gene (i.e., Gly231Glu and Arg375His). The allelic frequencies at amino acid 231 were 36·3% for Gly/Gly, 49·5% for Gly/Glu and 14·3% for Glu/Glu. The allelic frequencies at amino acid 375 were 74·7% for Arg/Arg, 24·2% for Arg/His and 1·1% for His/His. The prevalence of chronic cough in patients with the amino acid 231 genotype was 33·3% in Gly/Gly homozygotes, 24·4% in Gly/Glu heterozygotes and 0% in Glu/Glu homozygotes. There was a statistically significant association between chronic cough and the Glu/Glu allele (<I>P</I> = 0·028) when the data were analyzed with a recessive model. In addition, there was a significant inverse linear association between the number of Glu231 alleles and ACE inhibitor-related cough (<I>P </I>=<I> </I>0·026). The prevalence of chronic cough in patients with the amino acid 375 genotype was 22·1% in Arg/Arg homozygotes, 31·8% in Arg/His heterozygotes and 0% in His/His homozygotes, although none of these association were statistically significant.</P><P>Conclusion: </P><P>Our findings indicate that the Gly231Glu polymorphism is associated with a lower prevalence of ACE inhibitor-related cough.</P>

Predicting temporal shifts in the spring occurrence of overwintered Scotinophara lurida (Hemiptera: Pentatomidae) and rice phenology in Korea with climate change

Lee, H.,Kang, W. S.,Ahn, M. I.,Cho, K.,Lee, J. H. Springer Science + Business Media 2016 International journal of biometeorology Vol.60 No.1

<P>Climate change could shift the phenology of insects and plants and alter their linkage in space and time. We examined the synchrony of rice and its insect pest, Scotinophara lurida (Burmeister), under the representative concentration pathways (RCP) 8.5 climate change scenario by comparing the mean spring immigration time of overwintered S. lurida with the mean rice transplanting times in Korea. The immigration time of S. lurida was estimated using an overwintered adult flight model. The rice transplanting time of three cultivars (early, medium, and medium-late maturing) was estimated by forecasting the optimal cultivation period using leaf appearance and final leaf number models. A temperature increase significantly advanced the 99 % immigration time of S. lurida from Julian day 192.1 in the 2000s to 178.4 in the 2050s and 163.1 in the 2090s. In contrast, rice transplanting time was significantly delayed in the early-maturing cultivar from day 141.2 in the 2000s to 166.7 in the 2050s and 190.6 in the 2090s, in the medium-maturing cultivar from day 130.6 in the 2000s to 156.6 in the 2050s and 184.7 in the 2090s, and in the medium-late maturing cultivar from day 128.5 in 2000s to 152.9 in the 2050s and 182.3 in the 2090s. These simulation results predict a significant future phenological asynchrony between S. lurida and rice in Korea.</P>