Characteristic polynomial of a generalized complete product of matrices

Hwang, S.G.,Park, J.W. North Holland [etc.] 2011 Linear algebra and its applications Vol.434 No.5

For a simple graph G, let G@? denote the complement of G relative to the complete graph and let P<SUB>G</SUB>(x)=det(xI-A(G)) where A(G) denotes the adjacency matrix of G. The complete product G@?H of two simple graphs G and H is the graph obtained from G and H by joining every vertex of G to every vertex of H. In [2]P<SUB>G@?H</SUB>(x) is represented in terms of P<SUB>G</SUB>, P<SUB>G@?</SUB>, P<SUB>H</SUB> and P<SUB>H@?</SUB>. In this paper we extend the notion of complete product of simple graphs to that of generalized complete product of matrices and obtain their characteristic polynomials.

Gα₁₂ gep oncogene deregulation of p53-responsive microRNAs promotes epithelial–mesenchymal transition of hepatocellular carcinoma

Yang, Y M,Lee, W H,Lee, C G,An, J,Kim, E-S,Kim, S H,Lee, S-K,Lee, C H,Dhanasekaran, D N,Moon, A,Hwang, S,Lee, S J,Park, J-W,Kim, K M,Kim, S G Macmillan Publishers Limited 2015 Oncogene Vol.34 No.22

Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive phenotype. Gα<SUB>12</SUB> gep oncogene product couples to G-protein-coupled receptors, whose ligand levels are frequently increased in tumor microenvironments. Here, we report Gα<SUB>12</SUB> overexpression in human HCC and the resultant induction of zinc-finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation. Gα<SUB>12</SUB> expression was higher in HCC than surrounding non-tumorous tissue. Transfection of Huh7 cell with an activated mutant of Gα<SUB>12</SUB> (Gα<SUB>12</SUB>QL) deregulated microRNA (miRNA or miR)-200b/a/429, -194-2/192 and -194-1/215 clusters in the miRNome. cDNA microarray analyses disclosed the targets affected by Gα<SUB>12</SUB> gene knockout. An integrative network of miRNAs and mRNA changes enabled us to predict ZEB1 as a key molecule governed by Gα<SUB>12</SUB>. Decreases of miR-200a/b, -192 and -215 by Gα<SUB>12</SUB> caused ZEB1 induction. The ability of Gα<SUB>12</SUB> to decrease p53 levels, as a result of activating protein-1 (AP-1)/c-Jun-mediated mouse double minute 2 homolog induction, contributed to transcriptional deregulation of the miRNAs. Gα<SUB>12</SUB>QL induced ZEB1 and other epithelial–mesenchymal transition markers with fibroblastoid phenotype change. Consistently, transfection with miR-200b, -192 or -215 mimic prevented the ability of Gα<SUB>12</SUB>QL to increase tumor cell migration/invasion. In xenograft studies, sustained knockdown of Gα<SUB>12</SUB> decreased the overall growth rate and average volume of tumors derived from SK-Hep1 cell (mesenchymal-typed). In HCC patients, miR-192, -215 and/or -200a were deregulated with microvascular invasion or growth advantage. In the HCC samples with higher Gα<SUB>12</SUB> level, a correlation existed in the comparison of relative changes of Gα<SUB>12</SUB> and ZEB1. In conclusion, Gα<SUB>12</SUB> overexpressed in HCC causes ZEB1 induction by deregulating p53-responsive miRNAs, which may facilitate epithelial–mesenchymal transition and growth of liver tumor. These findings highlight the significance of Gα<SUB>12</SUB> upregulation in liver tumor progression, implicating Gα<SUB>12</SUB> as an attractive therapeutic target.

One-pass antibacterial efficacy of bipolar air ions against aerosolized Staphylococcus epidermidis in a duct flow

Lee, S.G.,Hyun, J.,Hwa Lee, S.,Hwang, J. Pergamon Press ; Elsevier Science Ltd 2014 Journal of aerosol science Vol.69 No.-

While heating, ventilating, and air-conditioning (HVAC) systems can provide healthy and comfortable indoor environments, virtually any part of an HVAC system can support active microbial growth if sufficient nutrients are present. In this study, we introduced a methodology to enhance the one-pass antibacterial performance of air ions against aerosolized bacteria in a ventilation duct flow. Staphylococcus epidermidis (S. epidermidis) was aerosolized, mixed with the duct flow, and exposed to air ions generated by carbon fiber ionizers installed inside the duct. The S. epidermidis was then sampled at the exit of the duct and incubated to evaluate their cultivability as functions of the ion exposure time, ion concentration, and ion polarity. When the ionizers produced bipolar air ions for 2s, a high antibacterial efficiency of 85% was obtained when four ionizers were positioned both at the top and bottom walls of the duct in a configuration in which there were three changes in ion polarity (one positive ionizer, one negative ionizer, one positive ionizer, and one negative ionizer in series along the flow direction). When the ion exposure time was decreased to 0.2s, an antibacterial efficiency of 50% was realized by applying a configuration with seven changes in ion polarity. By using a scanning electron microscope (SEM), cell contraction of S. epidermidis caused by the bipolar ion treatment was observed.

Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

Kim, E-S,Cha, Y,Ham, M,Jung, J,Kim, S G,Hwang, S,Kleemann, R,Moon, A Macmillan Publishers Limited 2014 Oncogene Vol.33 No.27

A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional significance in breast cell invasion. The present study aimed to elucidate the molecular link between S1P and CRP during the invasive process of breast epithelial cells. This is the first report showing that transcription of CRP was markedly activated by S1P in breast cells. Our data suggest that not only S1P treatment but also the endogenously produced S1P may upregulate CRP in breast carcinoma cells. Transcription factors CCAAT/enhancer-binding protein beta and c-fos were required for S1P-induced CRP expression. Coupling of S1P<SUB>3</SUB> to heterotrimeric G<SUB>αq</SUB> triggered the expression of CRP, utilizing signaling pathways involving reactive oxygen species (ROS), Ca<SUP>2+</SUP> and extracellular signal-related kinases (ERKs). S1P-induced CRP expression was crucial for the transcriptional activation of matrix metalloproteinase-9 through ERKs, ROS and c-fos, leading to breast cell invasion. Using a xenograft mice tumor model, we demonstrated that S1P induced CRP expression both in vitro and in vivo. Taken together, our findings have revealed a molecular basis for S1P-induced transcriptional activation of CRP and its functional significance in the acquisition of the invasive phenotype of human breast epithelial cells under inflammatory conditions. Our findings may provide useful information on the identification of useful therapeutic targets for inflammatory breast cancer.

Progress in the development of heating systems towards long pulse operation for KSTAR

Kwak, J.G.,Bae, Y.D.,Chang, D.H.,Chang, D.S.,Hong, B.G.,Hwang, C.K.,In, S.R.,Jeong, S.H.,Jin, J.T.,Jung, K.S.,Kim, B.R.,Kim, J.,Kim, S.K.,Kim, T.S.,Lee, D.W.,Lee, K.W.,Oh, B.H.,Seo, C.S.,Seo, M.S.,Yoo International Atomic Energy Agency 2007 Nuclear fusion Vol.47 No.5

<P>Construction of the Korea superconducting tokamak advanced research (KSTAR) tokamak is in its final phase. For the long-pulse KSTAR discharges, the ion cyclotron range of frequencies (ICRF) and neutral beam injection (NBI) heating systems are expected to play important roles through a selective heating of ions and electrons, control of the plasma pressure and current profiles, a core fuelling and beam diagnostics for the KSTAR. In addition, the ICRF system is expected to be used for possible discharge cleaning and assisting in the tokamak startup. In this paper, the recent progress in the development of the ICRF and the NBI heating systems is described. The four-strap ICRF antenna has been successfully tested for a voltage up to 41 kV for a pulse length of 300 s (to 46 kV for 20 s) in a test chamber. A prototype KSTAR NBI system has been developed. At present, the system has successfully produced a 1 MW beam power for 200 s and a 3.5 MW output beam power for 4 s.</P>

Investigation on Antibacterial and Antioxidant Activities, Phenolic and Flavonoid Contents of Some Thai Edible Plants as an Alternative for Antibiotics

Lee, J.H.,Cho, S.,Paik, H.D.,Choi, C.W.,Nam, K.T.,Hwang, S.G.,Kim, Soo-Ki Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.10

This study was aimed to examine the antibacterial and antioxidative properties of seven edible plants from Thailand to develop alternative antibiotics as feed additives. The plants include Citrus aurantifolia Swingle (Lime) fruits and its leaves, Sesbania grandiflora L. (Agati sesbania) leaves, Piper sarmentosum Roxb (Wild betal) leaves, Curcuma domestica Valeton (Turmeric) roots, Morinda citrifolia L. (Beach mulberry) leaves, Cassia siamea britt (Siamea cassia) leaves, and Cocos nucifera L. (Coconut) peels. The plants were extracted by methanol, n-hexane, chloroform, ethyl acetate, butanol and water. Antibacterial activities with minimum inhibitory concentration (MIC) were determined by agar diffusion assay against Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus parasuis, and Clostridium perfringens that were considered pathogenic strains in livestock infection. Methanol extracts of C. aurantifolia Swingle fruits and leaves showed the broadest spectrum of antibacterial activities except for C. perfringens. Butanol extract of S. grandiflora L. leaves showed the strongest activity against Burkholderia sp. with MIC, $135{\mu}g/mL$. P. sarmentosum Roxb leaves showed antibacterial activities against E. coli, Burkholderia sp. and H. parasuis. Ethyl acetate and water extracts from C. domesitca Valeton roots showed MIC of $306{\mu}g/mL$ and $183{\mu}g/mL$, respectively against only C. perfringens. Antioxidative activity was determined by 2-diphenyl-2-picryl hydrazyl photometric assay. The methanol extracts of C. aurantifolia Swingle fruits and P. sarmentosum Roxb leaves showed the highest antioxidant activity among all the extracts with 3.46 mg/mL and 2.70 mg/mL effective concentration 50% ($EC_{50}$) values, respectively. Total contents of phenolics and flavonoids were measured from the plant extracts. Methanol extracts of S. grandiflora L. and chloroform extracts of C. domestica Valeton were found to have the highest amount of total phenolics, 41.7 and $47.8{\mu}g/mL$, respectively. Flavonoid content of methanol extracts in S. grandiflora L. T was $22.5{\mu}g/mL$ and the highest among plant extracts tested. These results indicated that C. aurantifolia Swingle, S. grandiflora L., P. sarmentosum Roxb, and C. domestica Valeton have antibacterial and antioxidant activities and can be used as alternative antibiotics or potential feed additives for the control of animal pathogenic bacteria.

Bioequivalence Study of a New Fixed-dose Combination Tablet Containing S-Amlodipine Nicotinate and Olmesartan Medoxomil in Healthy Korean Male Subjects

Oh, M.J.,Hwang, H.H.,Kim, H.G.,Lee, G.H.,Cho, Y.S.,Lee, S.Y.,Kang, S.Y.,Cho, K.H.,Lee, Y.Y.,Lee, Y.J.,Jang, C.G.,Lee, S.Y. Excerpta Medica] ; Elsevier Science Ltd 2017 Clinical therapeutics Vol.39 No.7

Purpose: A fixed-dose combination (FDC) pill of amlodipine (relatively old calcium channel blocker as dihydropyridine) and olmesartan (relatively new angiotensin II receptor blocker) is used for hypertension that is not adequately controlled with a single-formulation drug. Because the FDC is a one-pill formulation, and amlodipine and olmesartan have different mechanisms of action, it is expected to improve patients' medication compliance and have an increased blood pressure-lowering efficacy. The purpose of this study was to assess the safety profile and the bioequivalence of two different FDC formulations [amlodipine besylate/olmesartan medoxomil 10/40 mg (reference product) and S-amlodipine nicotinate/olmesartan medoxomil 5/40 mg (test product)]. Methods: A randomized, open-label, single-dose, 2-treatment, 2-way, and 2-period crossover study, including a 3-week washout period, was performed in 32 healthy Korean male volunteers. To analyze the concentration of S-amlodipine or olmesartan, plasma samples were collected up to 144 hours after the dose for S-amlodipine and 48 hours after the dose for olmesartan. Pharmacokinetic parameters, including the C<SUB>max</SUB> and the area under the curve from time 0 to the last measurable concentration (AUC<SUB>0-last</SUB>) for the time versus concentration plot, were calculated. Analysis of variance for bioequivalence was conducted using C<SUB>max</SUB> and AUC<SUB>0-last</SUB> converted to log scale, and the mean ratios and 90% CIs were determined. Safety data included analysis of adverse events (AEs), vital signs, physical examinations, clinical laboratory test, and 12-lead ECGs. Findings: Of the 32 enrolled participants, 29 healthy volunteers completed the study. For both S-amlodipine and olmesartan, the main pharmacokinetic parameters were all within the acceptable range for regulatory bioequivalence. The 90% CIs for the geometric mean ratios of C<SUB>max</SUB> and AUC<SUB>0-last</SUB> were 0.8766 to 0.9760 and 0.8288 to 0.9224, respectively, for S-amlodipine and 0.9097 to 1.1229 and 0.8904 to 1.0407, respectively, for olmesartan. Hypotension was the most frequent AE, and it was observed in 4 volunteers with the test product and 7 volunteers with the reference product. Both the test and reference formulations were well tolerated. Implications: The present study demonstrates that the newly developed FDC product (test drug) and the conventional FDC product (reference drug) have comparable pharmacokinetic characteristics in healthy adult male volunteers. Both the test and reference products indicated good tolerance in this population, and no serious AEs were observed.

284 KINETICS OF OOCYTE MATURATION AND SUBSEQUENT DEVELOPMENT OF PARTHENOGENETIC PORCINE EMBRYOS AFTER MEIOTIC INHIBITION WITH ROSCOVITINE

Kim, D.H.,Kim, S.W.,Im, G.S.,Yang, B.C.,Lee, D.R.,Park, H.S.,Hwang, I.S.,S Seo, J.,Yang, B.S.,Chang, W.K. CSIRO Publishing 2005 Reproduction, fertility, and development Vol.17 No.1-2

<P> Maturation of mammalian oocytes is a very important process for subsequent embryo development after fertilization. Prolonged maturation time by meiotic inhibitors could be an effective method for improvement in the meiotic and developmental competence of mammalian oocytes. Roscovitine, a cyclin dependent kinase inhibitor, is known to specifically inhibit M-phase promoting factor (MPF) kinase activity and prevent the resumption of meiosis. The aim of this study was to examine the effect of roscovitine on the maturation and subsequent development of porcine oocytes. Ovaries were collected from slaughtered prepubertal gilts and COCs were aspirated from 2- to 5-mm antral follicles. In control, porcine cumulus oocyte complexes (COCs) were cultured in the maturation medium (TCM-199 supplemented with 0.3% BSA, 1 μg/mL FSH, 1 μg/mL LH, and 10 ng/mL EGF) for 44 h. In the experimental group, COCs were cultured in the inhibition medium (TCM-199 supplemented with 0.3% BSA and roscovitine) for 24 h, and then further cultured in the maturation medium for 44 h. Matured oocytes from both groups were activated by electrical pulse (1.2 kV/cm for 30 μs), and then cultured in PZM-3 medium for 6 days. Apoptotic cells in blastocysts were detected by TUNEL assay and total cell number was examined by propidium iodide (PI) counterstaining. Data were analyzed by chi-square and Student's t-test. The first experiment was conducted to determine the effect of roscovitine (0, 12.5, 25, 50, and 100 μM) on meiotic inhibition of GV oocytes. This effect was dose-dependent, and a concentration of 50 μM was sufficient to prevent meiotic resumption in 79.2% (76/96, 5 replicates) of the porcine oocytes after 24 h of culture when compared to 0 (15.4%, 15/97), 12.5 (32.1%, 36/112), 25 (57.4%, 54/94), and 100 μM (77.8%, 77/99). The second experiment was carried out to examine the kinetics of maturation of roscovitine-treated porcine oocytes. The concentration of roscovitine used was 50 μM. A total of 75.8% (50/66, 3 replicates) of roscovitine-treated oocytes reached metaphase II stage compared with 70.8% (46/65) of control. The third experiment was performed to compare embryo development between control and treated group after parthenogenetic activation. No differences (P > 0.05) were found between the control and the treated group in cleavage rate (77.2%, 132/171 vs. 68.0%, 115/169), blastocyst rate (26.9%, 46/171 vs. 17.8%, 30/169), and total (33.7 ± 12.4 vs. 35.1 ± 12.6) and apoptotic (2.2 ± 2.4 vs. 2.2 ± 1.2) cell number per blastocyst (4 replicates). The results suggest that roscovitine can be used to prolong maturation time of porcine oocytes without reducing meiotic maturation but also without significantly decreasing their subsequent developmental competence. Further studies are necessary to improve the developmental competence of porcine oocytes treated with roscovitine.</P>

세관 양광주 방전에서 플라즈마 확산의 완전 해

김동준,정종문,김정현,황하청,정재윤,조윤희,임현교,구제환,최은하,조광섭,Jin, D.J.,Jeong, J.M.,Kim, J.H.,Hwang, H.C.,Chung, J.Y.,Cho, Y.H.,Lim, H.K.,Koo, J.H.,Choi, E.H.,Cho, G.S. 한국진공학회 2010 Applied Science and Convergence Technology Vol.19 No.1

관경이 수 mm인 세관 램프 내부에서 플라즈마의 확산을 조사하기 위하여 이극성(ambipolar) 확산방정식을 해하였다. 반경 방향의 확산에 의한 유리관 벽에서의 플라즈마 소멸 특성시간은 $\tau_r\;=\;(r_0/2.4)^2/D_a$로 주어진다. 반경 $r_0{\sim}1\;mm$이고 이극성 확산계수 $D_a{\sim}0.01\;m^2/s$ 이면, $\tau_r{\sim}17\;{\mu}s$이다. 이는 램프의 교류전원 구동에서 플라즈마를 유지하기 위한 구동 최소 주파수 ~30 kHz에 해당한다. 고전압이 인가되는 전극부에 발생한 고밀도의 플라즈마가 양광주로 확산되는 특성시간은 $\tau_z{\sim}0.1\;s$이다. 고밀도 플라즈마 경계에서의 시간에 대한 확산속도는 $t{\sim}10^{-6}\;s$일 때 $u_D{\sim}10^2\;m/s$이고, $t{\sim}10^{-3}\;s$이면 그 속도는 $u_D{\sim}1\;m/s$로 느려진다. 따라서 램프 길이 ~1 m에 대하여 전극부에서 생성된 고밀도 플라즈마가 양광주 전체로 확산되는 시간은 수 초가 걸린다. The ambipolar diffusion equation has been solved in a fine-tube lamp of a few mm in diameter. In the diffusion of radial direction, the plasma diffuses and vanishes away at the glass wall by recombination with the characteristic time of plasma loss is given by $\tau_r\;=\;(r_0/2.4)^2/D_a$. With the radius $r_0{\sim}1\;mm$ and the ambipolar diffusion coefficient $D_a{\sim}0.01\;m^2/s$, the vanishing time is calculated $\tau_r{\sim}10\;{\mu}s$ which corresponds to the least value of frequency 30 kHz for the sustaining the plasma in the operation of high voltage AC-power. In the diffusion of longitudinal z-direction, a high density plasma generated at the area of a high voltage electrode, diffuses into the positive column with the characteristic time $\tau_z{\sim}0.1\;s$. The plasma diffusion velocity at the boundary of high density plasma is $u_D{\sim}10^2\;m/s$ at the time $t{\sim}10^{-6}$ s and the diffusion velocity becomes slow as $u_D{\sim}1\;m/s$ at $t{\sim}10^{-3}\;s$. Therefore, for the long lamp of 1 m, it takes about several seconds for the high density plasma at the area of electrode to diffuse through the whole positive column space.

Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor

Cui, Y-H,Suh, Y,Lee, H-J,Yoo, K-C,Uddin, N,Jeong, Y-J,Lee, J-S,Hwang, S-G,Nam, S-Y,Kim, M-J,Lee, S-J Macmillan Publishers Limited 2015 Oncogene Vol.34 No.42

Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial–mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.