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Oh, H.,Kwak, J.S.,Yang, S.,Gong, M.K.,Kim, J.H.,Rhee, J.,Kim, S.K.,Kim, H.E.,Ryu, J.H.,Chun, J.S. Published for the Society by Baillère Tinda 2015 Osteoarthritis and cartilage Vol.23 No.12
Objective: Hypoxia-inducible factor-2α (HIF-2α) transcriptionally upregulates Nampt in articular chondrocytes. NAMPT, which exhibits nicotinamide phosphoribosyltransferase activity, in turn causes osteoarthritis (OA) in mice by stimulating the expression of matrix-degrading enzymes. Here, we sought to elucidate whether HIF-2α activates the NAMPT-NAD<SUP>+</SUP>-SIRT axis in chondrocytes and thereby contributes to the pathogenesis of OA. Methods: Assays of NAD levels, SIRT activity, reporter gene activity, mRNA, and protein levels were conducted in primary cultured mouse articular chondrocytes. Experimental OA in mice was induced by intra-articular (IA) injection of adenovirus expressing HIF-2α (Ad-Epas1) or NAMPT (Ad-Nampt). The functions of SIRT in OA were examined by IA co-injection of SIRT inhibitors or adenovirus expressing individual SIRT isoforms or shRNA targeting specific SIRT isoforms. Results: HIF-2α activated the NAMPT-NAD<SUP>+</SUP>-SIRT axis in chondrocytes by upregulating NAMPT, which stimulated NAD<SUP>+</SUP> synthesis and thereby activated SIRT family members. The activated NAMPT-SIRT pathway, in turn, promoted HIF-2α protein stability by negatively regulating its hydroxylation and 26S proteasome-mediated degradation, resulting in increased HIF-2α transcriptional activity. Among SIRT family members (SIRT1-7), SIRT2 and SIRT4 were positively associated with HIF-2α stability and transcriptional activity in chondrocytes. This reciprocal regulation was required for the expression of catabolic matrix metalloproteinases (MMP3, MMP12, and MMP13) and OA cartilage destruction caused by IA injection of Ad-Epas1 Ad-Nampt. Conclusion: The reciprocal regulation of HIF-2α and the NAMPT-NAD<SUP>+</SUP>-SIRT axis in articular chondrocytes is involved in OA cartilage destruction caused by HIF-2α or NAMPT.
Oh, H.,Kim, J.,Son, H.,Youn, B. D.,Jung, B. C. Springer Science + Business Media 2016 Structural and multidisciplinary optimization Vol.54 No.6
<P>In recent years, virtual testing has played an increasingly important role in the design and evaluation of engineered products. However, it is challenging to build the highly accurate computational models for virtual testing. Blind and recognized uncertainties are often unintentionally incorporated. These uncertainties consequently decrease the predictive capability of the models. To this end, this paper proposes a systematic approach for model refinement that minimizes the impact of unrecognized blind and recognized epistemic uncertainties in computational modeling. The approach consists of three steps: model invalidity analysis (MIA), development of an invalidity reasoning tree (IRT), and invalidity sensitivity analysis (ISA). First, in the MIA, possible causes that lead to discrepancies between the experimental and simulation responses are identified through brainstorming. Next, the IRT is built using the affinity diagram. It sequentially lists and screens potential candidate issues for model refinement at the stages of conceptual, mathematical, and computational modeling. Finally, the ISA quantifies the effect of incorporating updates in the model to address potential candidate issues with the goal of reducing the impact of the blind and recognized uncertainties. The most critical candidates are determined by using a weighted decision matrix. To demonstrate the effectiveness of the proposed approach, a case study examining a smartphone liquid crystal display fracture is presented.</P>
Oh, H.,Yoon, G.,Shin, J.-C.,Park, S.-M.,Cho, S.-S.,Cho, J. H.,Lee, M.-H.,Liu, K.,Cho, Y. S.,Chae, J.-I. Spandidos Publications 2016 International journal of oncology Vol.48 No.4
<P>Licochalcone B (Lico B), which belongs to the retrochalcone family, is isolated from the roots of Chinese licorice. Lico B has been reported to have several other useful pharmacological properties, such as anti-inflammatory, antibacterial, antioxidant, antiulcer, anticancer, and anti-metastasis activities. We elucidated the underlying mechanism by which Lico B can induce apoptosis in oral squamous cell carcinoma (OSCC). Our results showed that exposure of OSCC cells (HN22 and HSC4) to Lico B significantly inhibited cell proliferation in a time- and concentration-dependent manner. Lico B caused cell cycle arrest at G1 phase along with downregulation of cyclin D1 and upregulation of p21 and p27 proteins. Lico B also facilitated the diffusion of phospholipid phosphatidylserine (PS) from inner to outer leaflets of the plasma membrane with chromatin condensation, DNA fragmentation, accumulated sub-G1 population in a concentration-dependent manner. Moreover, Lico B promoted the generation of reactive oxygen species (ROS), which, in turn, can induce CHOP, death receptor (DR) 4 and DR5. Lico B treatment induced downregulation of anti-apoptotic proteins (Bid and Bcl-(xl) and Mcl-1), and up-regulation of pro-apoptotic protein (Bax). Lico B also led to the loss of mitochondrial membrane potential (MMP), resulting in cytochrome c release. As can be expected from the above results, the apoptotic protease activating factor-1 (Apaf-1) and survivin were oppositely expressed in favor of apoptotic cell death. This notion was supported by the fact that Lico B activated multi-caspases with cleavage of poly (ADP-ribose) polymerase (PARP) protein. Therefore, it is suggested that Lico B is a promising drug for the treatment of human oral cancer via the induction of apoptotic cell death.</P>
Prime number theorems and holonomies for hyperbolic rational maps
Oh, H.,Winter, D. Springer Science + Business Media 2017 Inventiones mathematicae Vol.208 No.2
<P>For a hyperbolic rational map f of degree at least two on the Riemann sphere, we obtain estimates for the number of primitive periodic orbits of f ordered by their multiplier, and establish equidistribution of the associated holonomies, both with power saving error terms.</P>
Oh, H.,Park, J.,Han, S.H.,Mishra, N.K.,Lee, S.H.,Oh, Y.,Jeon, M.,Seong, G.J.,Chung, K.Y.,Kim, I.S. Pergamon Press 2017 Tetrahedron Vol.73 No.32
The rhodium(III)-catalyzed C-H alkylations of indolines with enones and enals is described. This reaction can proceed through 1,4-conjugate addition and protonation process providing β-indolinic ketone compounds, which are known to be crucial scaffolds of biologically active compounds.
Laser-induced electrical property patterning of Ag nanowire transparent electrode
Oh, H.,Lee, M. North-Holland 2016 Materials Letters Vol.176 No.-
We here introduce a laser-driven method to pattern Ag nanowire (AgNW) transparent electrode without material removal. Our approach is to block the current flow in selected areas by cutting nanowires, which is fundamentally based on the Rayleigh instability. AgNW film spin-coated onto a glass substrate was selectively irradiated using a nanosecond-pulsed ultraviolet laser beam. This made it possible to fabricate a patterned structure consisting of spatially separated conducting and insulating regions. The feasibility of this electrical property patterning was demonstrated with white light emitting diodes attached to the fabricated pattern.