Finite-time H_~ static output control of Markov jump systems with an auxiliary approach

Shen, M.,Yan, S.,Zhang, G.,Park, J.H. Elsevier [etc.] 2016 Applied Mathematics and Computation Vol.273 No.-

<P>This paper considers the finite time H-infinity static output feedback control of Markov jump systems. With the help of introducing two new variables related to the original system state and output, sufficient conditions for the closed loop system to be stochastic finite time boundedness with the prescribed H-infinity performance level are proposed in terms of linear matrix inequalities (LMIs). Meanwhile, the static output control gains are solved explicitly by the proposed conditions. It is shown that the proposed method is less or at least the same conservative than the existing result. Lastly, a numerical example is given to demonstrate the effectiveness of the proposed method. (C) 2015 Elsevier Inc. All rights reserved.</P>

MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer

Bae, H.J.,Jung, K.H.,Eun, J.W.,Shen, Q.,Kim, H.S.,Park, S.J.,Shin, W.C.,Yang, H.D.,Park, W.S.,Lee, J.Y.,Nam, S.W. Elsevier Science Publishers 2015 Journal of hepatology Vol.63 No.2

Background & Aims: Most common reason behind changes in histone deacetylase (HDAC) function is its overexpression in cancer. However, among HDACs in liver cancer, HDAC6 is uniquely endowed with a tumor suppressor, but the mechanism underlying HDAC6 inactivation has yet to be uncovered. Methods: Microarray profiling and target prediction programs were used to identify miRNAs targeting HDAC6. A series of inhibitors, activators and siRNAs was introduced to validate regulatory mechanisms for microRNA-221-3p (miR-221) governing HDAC6 in hepatocarcinogenesis. Results: Comprehensive miRNA profiling analysis identified seven putative endogenous miRNAs that are significantly upregulated in hepatocellular carcinoma (HCC). While miR-221 was identified as a suppressor of HDAC6 by ectopic expression of miRNA mimics in Dicer knockdown cells, targeted-disruption of miR-221 repressed cancer cell growth through derepressing HDAC6 expression. Suppression of HDAC6 via miR-221 was induced by JNK/c-Jun signaling in liver cancer cells but not in normal hepatic cells. Additionally, cytokine-induced NF-κBp65 independently regulated miR-221, thereby suppressing HDAC6 expression in HCC cells. HCC tissues derived from chemical-induced rat and H-ras12V transgenic mice liver cancer models validated that JNK/c-Jun activation and NF-κBp65 nuclear translocation are essential for the transcription of miR-221 leading to repression of HDAC6 in HCC. Conclusions: Our findings suggest that the functional loss or suppression of the tumor suppressor HDAC6 is caused by induction of miR-221 through coordinated JNK/c-Jun- and NF-κB-signaling pathways during liver tumorigenesis, providing a novel target for the molecular treatment of liver malignancies.

DNA 분석을 통한 한우 , 연변황우 및 화우의 유전적 특성

신원집,여정수,김재우,신수길,정진우,이지홍 한국축산학회 1999 한국축산학회지 Vol.41 No.4

This study was conducted to identify the genetic parameters and genetic relationships among 3 cattle breeds of Hanwoo (Korea), Yanbian yellow cattle (China), and Wagyu (Japan). DNA fingerprinting was prepared using M13 probe and Pst 1 enzyme. Genetic homogencities of Hanwoo and Yanbian yellow cattle were comparatively lower than that of Wagyu, suggesting genetic improvement by active breeding program for Wagyu compared to Hanwoo and Yanbian yellow cattle and possibility of improvement capacity for Hanwoo and Yanbian yellow cattle. Genetic similarities between breeds were not significantly different among them, suggesting that these 3 breeds have been raised independently without any inflow or outflow of gene source for a while.

Search for the 0−− glueball in ϒ(1S) and ϒ(2S) decays

Jia, S.,Shen, C. P.,Yuan, C. Z.,Adachi, I.,Aihara, H.,Al Said, S.,Asner, D. M.,Aushev, T.,Ayad, R.,Babu, V.,Badhrees, I.,Bakich, A. M.,Bansal, V.,Barberio, E.,Behera, P.,Bhuyan, B.,Biswal, J.,Bonvicin American Physical Society 2017 Physical Review D Vol.95 No.1

<P>We report the first search for the J(PC) = 0(--) glueball in Upsilon(1S) and Upsilon(2S) decays with data samples of (102 +/- 2) x 10(6) and (158 +/- 4) x 10(6) events, respectively, collected with the Belle detector. No significant signals are observed in any of the proposed production modes, and the 90% credibility level upper limits on their branching fractions in Upsilon(1S) and Upsilon(2S) decays are obtained. The inclusive branching fractions of the Upsilon(1S) and Upsilon(2S) decays into final states with chi(c1) are measured to be B(Upsilon(1S) -> chi(c1) + anything) = (1.90 +/- 0.43(stat) +/- 0.14(syst) x 10(-4) with an improved precision over prior measurements and B Upsilon(2S) -> chi(c1) + anything) = (2.24 +/- 0.44(stat) +/- 0.20(syst) x 10(-4) for the first time.</P>

Search for light tetraquark states in ϒ(1S) and ϒ(2S) decays

Jia, S.,Shen, C. P.,Yuan, C. Z.,Adachi, I.,Ahn, J. K.,Aihara, H.,Al Said, S.,Asner, D. M.,Atmacan, H.,Aushev, T.,Ayad, R.,Babu, V.,Badhrees, I.,Bahinipati, S.,Bakich, A. M.,Bansal, V.,Behera, P.,Berge American Physical Society 2017 Physical review. D Vol.96 No.11

<P>We search for the J(PC) = 0(--) and 1(+-) light tetraquark states with masses up to 2.46 GeV/c(2) in gamma(1S) and gamma(2S) decays with data samples of (102 +/- 2) million and (158 +/- 4) million events, respectively, collected with the Belle detector. No significant signals are observed in any of the studied production modes, and 90% credibility level (C. L.) upper limits on their branching fractions in Upsilon(1S) and Upsilon(2S) decays are obtained. The inclusive branching fractions of the Upsilon(1S) and Upsilon(2S) decays into final states with f(1)(1285) are measured to be B(Upsilon(1S) -> f(1)(1285) + anything) = (46 +/- 28(stat) +/- 13(syst)) x 10(-4) and B(Upsilon(2S) -> f(1)(1285) + anything) = (22 +/- 15(stat) +/- 6.3(syst)) x 10(-4). The measured chi(b2) -> J/Psi + anything branching fraction is measured to be (1.50 +/- 0.34(stat) +/- 0.22(syst)) x 10(-3), and 90% C. L. upper limits for the chi(b0;b1) -> J/Psi + anything branching fractions are found to be 2.3 x 10(-3) and 1.1 x 10(-3), respectively. For B(chi(b1) -> omega + anything), the branching fraction is measured to be (4.9 +/- 1.3(stat) +/- 0.6(syst) x 10(-2). All results reported here are the first measurements for these modes.</P>

Nicotinamide adenine dinucleotide: An essential factor in preserving hearing in cisplatin-induced ototoxicity

Kim, H.J.,Oh, G.S.,Shen, A.,Lee, S.B.,Khadka, D.,Pandit, A.,Shim, H.,Yang, S.H.,Cho, E.Y.,Song, J.,Kwak, T.H.,Choe, S.K.,Park, R.,So, H.S. Elsevier/North-Holland, Biomedical Press ; Elsevie 2015 Hearing research Vol.326 No.-

Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced ototoxicity. Although much attention has been directed at identifying ways to protect the inner ear from cisplatin-induced damage, the precise underlying mechanisms have not yet been elucidated. The cofactor nicotinamide adenine dinucleotide (NAD<SUP>+</SUP>) has emerged as an important regulator of cellular energy metabolism and homeostasis. NAD<SUP>+</SUP> acts as a cofactor for various enzymes including sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs), and therefore, maintaining adequate NAD<SUP>+</SUP> levels has therapeutic benefits because of its effect on NAD<SUP>+</SUP>-dependent enzymes. Recent studies demonstrated that disturbance in intracellular NAD<SUP>+</SUP> levels is critically involved in cisplatin-induced cochlear damage associated with oxidative stress, DNA damage, and inflammatory responses. In this review, we describe the importance of NAD<SUP>+</SUP> in cisplatin-induced ototoxicity and discuss potential strategies for the prevention or treatment of cisplatin-induced ototoxicity with a particular focus on NAD<SUP>+</SUP>-dependent cellular pathways.

Dunnione ameliorates cisplatin ototoxicity through modulation of NAD⁺ metabolism

Kim, H.J.,Pandit, A.,Oh, G.S.,Shen, A.,Lee, S.B.,Khadka, D.,Lee, S.,Shim, H.,Yang, S.H.,Cho, E.Y.,Kwak, T.H.,Choe, S.K.,Park, R.,So, H.S. Elsevier/North-Holland, Biomedical Press ; Elsevie 2016 Hearing research Vol.333 No.-

<P>Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that cisplatin-induced ototoxicity is related to oxidative stress and DNA damage. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as an important regulator of energy metabolism and cellular homeostasis. Here, we demonstrate that the levels and activities of sirtuin-1 (SIRT1) are suppressed by the reduction of intracellular NAD(+) levels in cisplatin-mediated ototoxicity. We provide evidence that the decreases in SIRT1 activity and expression facilitated by increasing poly(ADP-ribose) polymerase-1 (PARP-1) activation and microRNA-34a levels through cisplatin-mediated p53 activation aggravate the associated ototoxicity. Furthermore, we show that the induction of cellular NAD(+) levels using dunnione, which targets intracellular NQO1, prevents the toxic effects of cisplatin through the regulation of PARP-1 and SIRT1 activity. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological agents could be a promising therapeutic approach for protection from cisplatin-induced ototoxicity. (C) 2015 Elsevier B.V. All rights reserved.</P>

Augmentation of NAD+ levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiomyopathy

Khadka, D.,Oh, G.-S.,Kim, H.-J.,Lee, S.-H.,Shen, A.,Lee, S.-B.,Pandit, A.,Sharma, S.,Yang, S.-H.,So, H.-S. Elsevier 2018 ANNALS OF ONCOLOGY Vol.29 No.3

Glucocorticoid Suppresses Connexin 43 Expression by Inhibiting the Akt/mTOR Signaling Pathway in Osteoblasts

Shen, C.,Kim, M. R.,Noh, J. M.,Kim, S. J.,Ka, S. O.,Kim, J. H.,Park, B. H.,Park, J. H. Springer Science + Business Media 2016 Calcified tissue international Vol.99 No.1

<P>The inhibition of proliferation or functional alteration of osteoblasts by glucocorticoids (GCs) has been recognized as an important etiology of GC-induced osteoporosis (GIO). Connexin 43 (Cx43) is the most abundant connexin isoform in bone cells and plays important roles in bone remodeling. Despite the important role of Cx43 in bone homeostasis and the prevalence of GIO, the direct action of GCs on Cx43 expression in osteoblasts has been poorly described. The aim of the present study was to evaluate how GCs affect Cx43 expression in osteoblasts. Dexamethasone (Dex) treatment decreased expression of Cx43 RNA and protein in MC3T3-E1 mouse osteoblastic cells. Reduction of Cx43 expression by Dex was dependent on the glucocorticoid receptor (GR), as it was abolished by pretreatment with a GR blocker. Treatment with PTH (1-34), a medication used for GIO management, counteracted the suppression of Cx43 by Dex. Akt or mTOR signaling modulators revealed the involvement of the Akt/mTOR signaling pathway in Dex-induced reduction of Cx43 expression. Moreover, overexpression of Cx43 significantly attenuated Dex-inhibited cell viability and proliferation, as evidenced by MTT and bromodeoxyuridine (BrdU) incorporation assay of MC3T3-E1 cells. To account for possible species or cell type differences, human primary osteoblasts were treated with Dex and similar downregulation of Cx43 by Dex was observed. In addition, immunofluorescent staining for Cx43 further demonstrated an apparent decrease in Dex-treated human osteoblasts, while analysis of lucifer yellow propagation revealed reduced gap junction intercellular communication by Dex. Collectively, these findings indicate that GCs suppress Cx43 expression in osteoblasts via GR and the Akt/mTOR signaling pathway and overexpression of Cx43 may, at least in part, rescue osteoblasts from GC-induced reductions in proliferation.</P>

Metformin and AICAR regulate NANOG expression via the JNK pathway in HepG2 cells independently of AMPK

Shen, C.,Ka, S. O.,Kim, S. J.,Kim, J. H.,Park, B. H.,Park, J. H. Springer Science + Business Media 2016 TUMOR BIOLOGY Vol.37 No.8

<P>NANOG, a marker of stemness, impacts tumor progression and therapeutic resistance in cancer cells. In human hepatocellular carcinoma (HCC), upregulation of NANOG is associated with metastasis and a low survival rate, while its downregulation results in a lower colony formation rate and enhanced chemosensitivity. Metformin, an agent widely used for diabetes treatment, and AICAR, another AMP-activated protein kinase (AMPK) activator, have been reported to inhibit the growth of several types of cancer. Although inhibitory effects of metformin on NANOG in pancreatic cancer cells and of AICAR in mouse embryonic stem cells have been described, the underlying molecular mechanisms remain uncertain in HCC. In this study, we used the HepG2 cell line and found that metformin/AICAR downregulated NANOG expression with decreased cell viability and enhanced chemosensitivity to 5-fluorouracil (5-FU). Moreover, metformin/AICAR inhibited c-Jun N-terminal kinase (JNK) activity, and blockade of either the JNK MAPK pathway or knockdown of JNK1 gene expression reduced NANOG levels. The upregulation of NANOG and phospho-JNK by basic fibroblast growth factor (bFGF) was abrogated by metformin/AICAR. Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.</P>