• Biomolecules & Therapeutics
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• 제26권2호
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• pp.201-209
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• 2018

G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.

• Bulletin of the Korean Chemical Society
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• 제27권9호
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• pp.1329-1334
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• 2006

The electrochemical reduction of coumarin, 7-acetoxy-4-methyl coumarin (AMC), and 7-acetoxy-4-bromomethyl coumarin (ABMC), in 0.1 M tetraethyl ammonium perchlorate/acetonitrile solution was carried out by direct current, differential pulse polarography, cyclic voltammetry, and controlled potential coulometry. The electrochemical reduction of ABMC was proceeded through three steps of electron transfer coupled with the chemical reactions. The color of solution was changed to yellow when the carbonyl group was reduced during 2nd step (-1.8 volts) and independented with cleavage of bromo group. Highest fluorescence intensity showed when the electrochemical reduction of AMC was controlled at near the potential (-2.3 volts vs. Ag/AgCl).

• Biotechnology and Bioprocess Engineering:BBE
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• 제9권1호
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• pp.23-34
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• 2004

Escherichia coli transcription termination factor Rho catalyzes the unwinding of RNA/DNA duplex in reactions that are coupled to ATP binding and hydrolysis. Fluorescence stopped-flow methods using ATP and the fluorescent 2'(3')-O-( N-methylanthraniloyl) derivatives (mant-derivatives) of ATP and ADP were used to probe the kinetics of nucleotide binding to and dissociation from the Rho-RNA complex. Presteady state nucleotide binding kinetics provides evidence for the presence of negative cooperativity in nucleotide binding among the multiple nucleotide binding sites on Rho hexamer. The binding of the first nucleotide to the Rho-RNA complex occurs at a bimolecular rate of 3.6${\times}$10$\^$6/ M$\^$-1/ sec$\^$-1/ whereas the second nucleotide binds at a slower rate of 4.7${\times}$10$\^$5/ M$\^$-1/ sec$\^$-1/ at 18$^{\circ}C$, RNA complexed with Rho affects the kinetics of nucleotide interaction with the active sites through conformational changes to the Rho hexamer, allowing the incoming nucleotide to be more accessible to the sites. Adenine nucleotide binding and dissociation is more favorable when RNA is bound to Rho, whereas ATP binding and dissociation step in the absence of RNA occurs significantly slower, at a rate ∼70- and ∼40-fold slower than those observed with the Rho-RNA complex, respectively.

• 분석과학
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• 제18권1호
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• pp.89-95
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• 2005

Studies on the electrochemical reduction of 7-acetoxy-4-bromomethyl-coumarin (ABMC), 7-acetoxymethyl coumarin (AMC), and coumarin in 0.1 M tetraethyl ammonium perchlorate acetonitrile solution were carried out with direct current, differential pulse polarography, cyclic voltammetry, and controlled potential coulometry. The electrochemical reduction of ABMC was proceeded through three irreversible steps coupled with the chemical reactions. The solution color was changed to yellow when the carbonyl group was reduced during second step and the color change was independent with bromo group of ABMC. Fluorescent intensity was highest when the electrochemical reduction was controlled at near the overpotential of supporting electrolyte (-2.3 volts).

• 대한기계학회논문집A
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• 제25권2호
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• pp.182-191
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• 2001

The paper describes the improvement on concurrent subspace optimization(CSSO) via automatic differentiation. CSSO is an efficient strategy to coupled multidisciplinary design optimization(MDO), wherein the original design problem is non-hierarchically decomposed into a set of smaller, more tractable subspaces. Key elements in CSSO are consisted of global sensitivity equation, subspace optimization, optimum sensitivity analysis, and coordination optimization problem that require frequent use of 1st order derivatives to obtain design sensitivity information. The current version of CSSO adopts automatic differentiation scheme to provide a robust sensitivity solution. Automatic differentiation has numerical effectiveness over finite difference schemes tat require the perturbed finite step size in design variable. ADIFOR(Automatic Differentiation In FORtran) is employed to evaluate sensitivities in the present work. The use of exact function derivatives facilitates to enhance the numerical accuracy during the iterative design process. The paper discusses how much the automatic differentiation based approach contributes design performance, compared with traditional all-in-one(non-decomposed) and finite difference based approaches.

• Wind and Structures
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• 제25권4호
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• pp.343-360
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• 2017

The post-flutter state of streamlined steel box girder is studied in this paper. Firstly, the nonlinear aerodynamic self-excited forces of the bridge deck cross section were investigated by CFD dynamic mesh technique and then the nonlinear flutter derivatives were identified on this basis. Secondly, based on the 2-degree-of-freedom (DOF) coupling flutter theory, the torsional amplitude and the nonlinear flutter derivatives were introduced into the traditional direct flutter calculation method, and the original program was improved to the "post-flutter state analysis program" so that it can predict not only the critical flutter velocity but also the movement of the girder in the post-flutter state. Finally, wind tunnel tests were set to verify the method proposed in this paper. The results show that the effect of vertical amplitude on the nonlinear flutter derivatives is negligible, but the torsional amplitude is not; with the increase of wind speed, the post-flutter state of streamlined steel box girder includes four stages, namely, "little amplitude zone", "step amplitude zone", "linearly growing amplitude zone" and "divergence zone"; damping ratio has limited effect on the critical flutter velocity and the steady state response in the post-flutter state; after flutter occurs, the vibration form is a single frequency vibration coupled with torsional and vertical DOF.

• Wind and Structures
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• 제10권1호
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• pp.61-82
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• 2007

This paper presents a novel finite element (FE) model for analyzing coupled flutter of long-span bridges using the commercial FE package ANSYS. This model utilizes a specific user-defined element Matrix27 in ANSYS to model the aeroelastic forces acting on the bridge, wherein the stiffness and damping matrices are expressed in terms of the reduced wind velocity and flutter derivatives. Making use of this FE model, damped complex eigenvalue analysis is carried out to determine the complex eigenvalues, of which the real part is the logarithm decay rate and the imaginary part is the damped vibration frequency. The condition for onset of flutter instability becomes that, at a certain wind velocity, the structural system incorporating fictitious Matrix27 elements has a complex eigenvalue with zero or near-zero real part, with the imaginary part of this eigenvalue being the flutter frequency. Case studies are provided to validate the developed procedure as well as to demonstrate the flutter analysis of cable-supported bridges using ANSYS. The proposed method enables the bridge designers and engineering practitioners to analyze flutter instability by using the commercial FE package ANSYS.

• Coupled systems mechanics
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• 제1권2호
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• pp.133-154
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• 2012

In this paper a bridge flutter prediction is performed by using advanced numerical simulation. Two novel approaches were developed simultaneously by utilizing the ANSYS v12.1 commercial software package. The first one is a fluid-structure interaction simulation involving the three-dimensional elastic motion of a bridge deck and the fluid flow around it. The second one is an updated forced oscillation technique based on the dynamic mode shapes of the bridge. An aeroelastic wind tunnel model was constructed in order to validate the numerical results. Good agreement between the numerical results and the measurements proves the applicability of the novel methods in bridge flutter assessment.

• 대한기계학회논문집
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• 제17권9호
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• pp.2138-2144
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• 1993

An integral equation representation of cracks was presented which differs from well-known "dislocation layer" representation. In this new representation, the equations are written in terms of the displacement discontinuity across the crack surfaces rather than derivatives of the displacement-discontinuity. It was shown in that the new technique is well-suited to the treatment of kinked cracks. In the present paper, this integral equation representation is coupled to the direct boundary-element method for the treatment of finite bodies containing kinked cracks. The method is demonstrated for two-dimensional finite domains but extension to three-dimensional problems would appear to be possible. The resulting approach is shown to be simple, yet very accurate. accurate.

• Journal of applied mathematics & informatics
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• 제34권5_6호
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• pp.495-508
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• 2016

A singularly perturbed reaction-diffusion fourth-order ordinary differential equation(ODE) with discontinuous source term is considered. Due to the discontinuity, interior layers also exist. The considered problem is converted into a system of weakly coupled system of two second-order ODEs, one without parameter and another with parameter ε multiplying highest derivatives and suitable boundary conditions. In this paper a computational method for solving this system is presented. A zero-order asymptotic approximation expansion is applied in the second equation. Then, the resulting equation is solved by the numerical method which is constructed. This involves non-overlapping Schwarz method using Shishkin mesh. The computation shows quick convergence and results presented numerically support the theoretical results.