A predictive kinetic model for inhibitory effect of nitrite on myeloperoxidase catalytic activity towards oxidation of chloride

Myeloperoxidase (MPO) is a neutrophil enzyme that employs hydrogen peroxide (H2O2) to catalyze the oxidation of chloride (Cl–) to hypochlorous acid (HOCl). Accepted mechanism is based on rapid reaction of native MPO with H2O2to produce Compound I (MPO-I) which oxidizes Cl– through a 2e– transition generating MPO and HOCl. MPO-I also reacts with H2O2 to generate Compound II (MPO-II) which is inactive in 2e oxidation of Cl–. Nitrite ( NO2-) inhibits the 2e oxidation of Cl– by reaction with MPO-I through 1e transition generating MPO-II and nitrite radical. H2O2 consumption during steady- state catalysis was monitored amperometrically by a carbon fiber based H2O2-biosensor at 25oC. Results demonstrated that in absence of NO2- reactions were monophasic and rapid (complete H2O2 consumption occurs in 2- increases, reactions change to biphasic (rapid step followed by a slow step) and both steps have been inhibited by NO2- . A predictive kinetic model describing the inhibittory effect of NO2- was developed and applied to experimental results The model is based on the assumption that MPO–I cannot be detected during steady-state catalysis. Calculated rate constants are in agreement with those obtained from pre-steady state kinetic methods.

Study of a Novel Antiosteoporosis Screening Model Targeted on Cathepsin K

Objective To establish an effective assay to access the effects of natural products on cathepsin K for screening antiosteoporosis drugs. Methods To obtain the purified cathepsin K, we cloned the target fragment from the mRNA of human osteosacoma cell line MG63 and demonstrated its correctness through DNA sequencing. Cathepsin K was expressed in a high amount in E.coli after IPTG induction, and was purified to near homogenetity through resolution and column purification. The specificity of the protein was shown by Western blotting experiment. The biological activity of the components in the fermentation broth was assayed by their inhibitory effects on cathepsin K and its analog papain. Results With the inhibition of papain activity as a screen index, the fermentation samples of one thousand strains of fungi were tested and 9 strains among them showed strong inhibitory effects. The crude products of the fermentation broth were tested for their specific inhibitory effects on the purified human cathepsin K, the product of fungi 2358 shows the highest specificity against cathepsin K. Conclusions The compounds isolated from fungi 2358 show the highest biological activity and are worth further structure elucidation and function characterization.

Strong ground motion simulation for the 2013 Lushan M_W6.6 earthquake, Sichuan, China, based on the inverted and synthetic slip models

It is well known that quantitative estimation of slip distributions on fault plane is one of the most important issues for earthquake source inversion related to the fault rupture process. The characteristics of slip distribution on the main fault play a fundamental role to control strong ground motion pattern. A large amount of works have also suggested that variable slip models inverted from longer period ground motion recordings are relevant for the prediction of higher frequency ground motions. Zhang et al. （Chin J Geophys 56：1412-1417, 2013） and Wang et al. （Chin J Geophys 56：1408-1411,2013） published their source inversions for the fault rupturing process soon after the April 20, 2013 Lushan earthquake in Sichuan, China. In this study, first, we synthesize two forward source slip models： the value of maximum slip, fault dimension, size, and dimension of major asperities, and comer wave number obtained from Wang＇s model is adopted to constrain the gen- eration of k-2 model and crack model. Next, both inverted and synthetic slip models are employed to simulate the ground motions for the Lushan earthquake based on the stochastic finite-fault method. In addition, for a comparison purpose, a stochastic slip model and another k-2 model （k 2 model II） with 2 times value of comer wave number of the original k-2 model （k 2 model I） are also employed for simulation for Lushan event. The simulated results characterized by Modified Mer- calli Intensity （MMI） show that the source slip models based on the inverted and synthetic slip distributions could capture many basic features associated with the ground motion patterns. Moreover, the simulated MMI distributions reflect the rupture directivity effect and the influence of the shallow velocity structure well. On the other hand, the simulated MMI bystochastic slip model and k 2 model II is apparently higher than observed intensity. By contrast, our simulation results show that the higher frequency ground motion is sensitive to the degree of slip roughness; therefore, we suggest that, for realistic ground- motion simulations due to future earthquake, it is imperative to properly estimate the slip roughness distribution.

一般的Activator-Inhibitor模型的分支解的稳定性

本文利用线性稳定性及分支解稳定性的一般定理讨论了 Activator-Inhibitor模型所对应的平衡态方程组的分支解的稳定性,得出了其分支解在一定条件下是稳定的,从而在理论上保证了 Activator-Inhibitor 模型的稳定的非常数平衡解的存在性.

Experimental and Numerical Study of Dilute Gas-Solid Flow inside a 90°Horizontal Square Pipe Bend

A pneumatic test rig is built to test a curved 90° square bend in an open-circuit horizontal-to-horizontal suction wind tunnel system. Sand particles are used to represent the solid phase with a wide range of particle diameters. Velocity profiles are constructed by measuring the gas velocity using a 3-hole probe. Flow patterns inside the bend duct are introduced using sparks caused by burning sticks of incense with the air flow inside the piping system for flow visualization purpose. Numerical calculations are performed by Lagrangian-particle tracking model for predicting particle trajectories of dispersed phase, and standard k-ε model for predicting the turbulent gas-solid flows in bends. Comparisons made between the theoretical results and experimental data for the velocity vectors and particle trajectories show good agreement.

NUMERICAL SIMULATION OF 3-D TURBULENT FLOWS OVER DREDGED TRENCHES

A 3- D free surface flow in open channels based on the Reynolds equations with the k-ε turbulence closure model is presented in this paper. Insted of the 'rigid lid' approximation, the solution of the free surface equation is implemented in the velocity-pressure iterative procedure on the basis of the conventional SIMPLE method. This model was used to compute the flow in rectangular channels with trenches dredged across the bottom. The velocity, eddy viscosity coefficient, turbulent shear stress, turbulent kinetic energy and elevation of the free surface can be obtained. The computed results are in good agreement with previous experimental data.

The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice

AIM: To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE(+/-) mice (AChE knockout mice) of various ages. METHODS: Cultured ARPE -19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 mu mol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE4- mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by cardiac perfusion and retinal samples were taken. AChE(+/-) deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer. RESULTS: Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE(+/-) mice retina were thinner than those in wild -type mice (P< 0.05); the retinal structure was still intact at 2mo but became thinner with increasing age(P <0.05); furthermore, AChE'l- mice developed more slowly than wild-type mice (P <0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P >0.05). CONCLUSION: in viva, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.

A New Efficient Finite Volume Modeling of Small Amplitude Free Surface Flows with Unstructured Grid

A staggered finite-volume technique for non-hydrostatic, small amplitude free surface flow governed by the incompressible Navier-Stokes equations is presented there is a proper balance between accuracy and computing time. The advection and horizontal diffusion terms in the momentum equation are discretized by an integral interpolation method on the orthogonal unstructured staggered mesh and, while it has the attractive property of being conservative. The pressure-correction algorithm is employed for the non-hydrostatic pressure in order to achieve second-order temporal accuracy. A conservative scalar transport algorithm is also applied to discretize k - c equations in this model. The eddy viscosity is calculated from the k-c turbulent model. The resulting model is mass and momentum conservative. The model is verified by two examples to simulate unsteady small amplitude free surface flows where non-hydrostatic pressures have a considerable effect on the velocity field, and then applied to simulate the tidal flow in the Bohai Sea.

Computational Evaluation of Selectivity of Triazole-and Amide-Based Drug Candidates, Flavanone Derivatives and Synthesized Steroid Compounds for Treatment of Diabetes Type II

Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.

射影平面上k-inhibitor模型的构作及其性质

κ-inhibitor模型是一个能够检测带有抑制因子的群测模型,它在许多领域有着广泛的应用.在m^2阶射影平面上构作了κ-inhibitor模型,计算了它的参数并研究了它的性质.

Binding Model and 3D-QSAR of 3-（2-Chloropyrid-5- ylmethylamino）-2-cyanoacrylates as PSⅡ Electron Transport Inhibitor

The binding model of 3-（2-chloropyrid-5-ylmethylamino）-2-cyanoacrylate photosystem Ⅱ （PSⅡ） electron transport inhibitors with the D 1 protein of PSII was built. The high herbicidal activity of this kind of inhibitors was explained by docking studies： in addition to usual factors, the N atom on the pyridine ring could form an H-bond with the backbone amide of Phe265 on the D1 protein. 3D-QSAR analysis on sixteen 3-（2-chloropyrid-5-yl- methylamino）-2-cyanoacrylate compounds was performed using CoMFA method to explain the nature of interactions between the compounds and D1 protein. These studies may provide useful insights for designing new PSII electron transport inhibitors.

NUMERICAL MODELLING OF FREE-SURFACE FLOWS WITH BOTTOM AND SURFACE-LAYER PRESSURE TREATMENT

A new non-hydrostatic numerical model with the three-dimensional Navier-Stokes equations on structured grids was constructed and discussed. The algorithm is based upon a staggered finite difference Crank-Nicholson scheme on a Cartesian grid. The eddy viscosity coefficient was calculated by the efficient k-ε turbulence model. A new surface-layer non-hydrostatic treatment and a local cell bottom treatment were introduced so that the three-dimensional model is fully non-hydrostatic and is free of any hydrostatic assumption. The developed model is second-order accuracy in both time and space when semi-implicit coefficient is set to 0.5. The validity of the present solution algorithm was demonstrated from its application to the three-dimension channel flow and the wave propagation over a submerged bar problems.

Numerical simulation of flow past circular duct

The Renormalization Group （RNG） k- ε turbulence model and Volume of Fluid （VOF） method were employed to simulate the flow past a circular duct in order to obtain and analyze hydraulic parameters. According to various upper and bottom gap ratios, the force on the duct was calculated. When the bottom gap ratio is 0, the drag force coefficient, lift force coefficient, and composite force reach their maximum values, and the azimuth reaches its minimum. With an increase of the bottom gap ratio from 0 to 1, the drag force coefficient and composite force decrease sharply, and the lift force coefficient does not decreases so much, but the azimuth increases dramatically. With a continuous increase of the bottom gap ratio from 1 upward, the drag force coefficient, lift force coefficient, composite force, and azimuth vary little. Thus, the bottom gap ratio is the key factor influencing the force on the circular duct. When the bottom gap ratio is less than 1, the upper gap ratio has a remarkable influence on the force of the circular duct. When the bottom gap ratio is greater than 1, the variation of the upper gap ratio has little influence on the force of the circular duct.

一个Inhibitor模型的构作及其应用

Inhibitor模型是群测理论的一个特殊的数学模型，（d＋（moutofr））-析取矩阵是Inhibitor模型．利用有限n阶仿射平面的性质构作了（d＋（moutofr））一析取矩阵并计算了它的参数，论述了它的应用．

DETACHED EDDY SIMULATION OF HYDRAULIC CHARACTERISTICS ALONG THE SIDE-WALL AFTER A NEW ARRANGEMENT-SCHEME OF THE SUDDEN LATERAL ENLARGEMENT AND THE VERTICAL DROP

In order to study the cavitation damage in a side-wall when a sudden lateral enlargement and a vertical drop are imposed at the radial gate, a new arrangement-scheme is proposed, where the sudden lateral enlargement and the vertical drop can be imposed at the outlet of the gate chamber. The hydraulic characteristics along the side-wall are simulated by the detached eddy simulation and the Volume Of Fluid （VOF） method. The numerical results agree well with those of experiment. The experimental and numerical results show that the flow condition is smooth with only a weak water-wing appearing behind the lateral cavity, and the length of the lateral cavity becomes longer and is mainly affected by the size of the lateral enlargement and the zone of negative pressure after the water impacts the side-wall would disappear. The hydraulic characteristics of the new arrangement-scheme are beneficial to the prevention of the cavitation damage in the side-wall and the Detached Eddy Simulation （DES） with the VOF method can well predict the hydraulic characteristics after the new arrangement-scheme of the sudden lateral enlargement and the vertical drop.

Influence of uniaxial tensile pre-strain on forming limit curve by using biaxial tensile test

This paper focused on the effect of pre-strain on forming limit curves(FLC)of 5754-O aluminum alloy sheet through utilizing biaxial tensile approach.Based on Swift model and Yld2000-2 d yield criterion,the dimensions of cruciform specimen was optimized through applying finite element method for increasing the strain at specimen center.After that,with the recommended specimen size,the cruciform specimen was tested under various stroke ratios to experimentally characterize the limit strains under different pre-strain levels.Subsequently,the biaxial tensile tests were simulated by Abaqus to obtain the limit strains and validate the material models.It can be observed in both experiments and simulations that the pre-strained uniaxial tension followed by plane tension or equi-biaxial tension can improve the formability of sheet metals.Besides,the strain path change affects the trend of first derivative of strain rate difference between neighboring points with respect to time.An early increase occurred and then fell back to the stable value,the steady evolution continued until to a new increase reaching the critical value.The M–K prediction approach was simulated to verify the influence of pre-strain on FLC.It can be found that the early increase peaks of the major strain incremental ratio rose with the amplitude of pre-strain.Finally,the phenomenon of pseudolocalization caused by the strain path change was explained through evolution of stress state inside the groove.

NUMERICAL SIMULATION OF PROPAGATION AND BREAKING PROCESSES OF A FOCUSED WAVES GROUP

A two-dimensional numerical wave flume is developed to study the focused waves group propagation and the consequent breaking processes. The numerical model is based on the Reynolds-Averaged Navier-Stokes （PANS） equations, with the standard k - c turbulence model to simulate the turbulence effects. To track the complicated and broken free-surface, the Volume Of Fluid （VOF） method is employed. The numerical model combines the ＂Partial Cell Treatment （PCT）＂ method with the ＂Locally Relative Stationary （LRS）＂ concept to treat the moving wave paddle so that various waves can be generated directly in a fixed Cartesian grid system. The theoretical results of the linear and nonlinear waves are used to validate the numerical wave flume firstly, and then a plunging breaking wave created by a focused waves group is simulated. The numerical results are compared to the experimental data and other simulation results, with very good agreements. The turbulence intensity, the flow field and the energy dissipation in the breaking processes are analyzed based on the numerical results. It is shown that the present numerical model is efficient and accurate for studying the waves group generation, the waves packet propagation, and the wave breaking processes.

Simulation of buoyancy-induced turbulent flow from a hot horizontal jet

Experimental visualizations and numerical simulations of a horizontal hot water jet entering cold water into a rectangular storage tank are described. Three different temperature differences and their corresponding Reynolds numbers are considered. Both experimental visualization and numerical computations are carried out for the same flow and thermal conditions. The realizable k-e model is used for modeling the turbulent flow while the buoyancy is modeled using the Boussinesq approximation. Polynomial approximations of the water properties are used to compare with the Boussinesq approximation. Numerical solutions are obtained for unsteady flow while pressure, velocity, temperature and turbulence distributions inside the water tank as well as the Froude number are analyzed. The experimental visualizations are performed at intervals of five seconds for all different cases. The simulated results are compared with the visualized results, and both of them show the stratification phenomena and buoyancy force effects due to temperature difference and density variation. After certain times, depending on the case condition, the flow tends to reach a steady state.

Compressible Turbulent Boundary Layers on a Strongly Heated Wall

This paper concerns the theoretical and experimental modelling of the flat wall,highly heated,compressible turbulent boundary layer.Its final objective is to develop a numerical Navier-Stokes solver and to conclude on its capability to correctly represent complex aerothermic viscous flows near the wall.The paper presents a constructed numerical method with particular attention given to the turbulence modelling at low Reynolds number and comparisons with supersonic and transonic experimental data.For the transonic experiment,very high wall temperature(Tw=1100K)is realized.The method of this difficult experimental set up is discussed.The comparison between experimental and computational data conducts to the first conclusion and gives some indications for the future work.