Structural analysis of human CCR2b and primate CCR2b by molecular modeling and molecular dynamics simulation

CCR2b, a chemokine receptor for MCP-1, -2, -3, -4, plays an important role in a variety of diseases involving infection, inflammation, and/or injury, as well as being a coreceptor for HIV-1 infection. Two models of human CCR2b (hCCR2b) were generated by h

Centrifuge modeling of suction bucket foundations for platforms under ice-sheet-induced cyclic lateral loadings

This paper presents the results of a series of centrifuge model tests performed to study the behavior of suction bucket foundations for a tension leg platform in the Bohai Bay, China. The target lateral loadings were from ice-sheet-induced structural vibrations at a frequency of 0.8-1.0 Hz. The results indicate that excess pore water pressures reach the highest values within a depth of 1.0-1.5 in below the mud line. The pore pressures and the induced settlement and lateral displacement increase with the amplitude of the cyclic loading. Two failure modes were observed: liquefaction in early excitations and settlement-induced problems after long-term excitations. (c) 2006 Elsevier Ltd. All rights reserved.

De novo RNA synthesis and homology modeling of the classical swine fever virus RNA polymerase

Classical swine fever virus (CSFV) non-structural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp), a key enzyme which initiates RNA replication by a de novo mechanism without a primer and is a potential target for anti-virus therapy. We expressed the NS5B protein in Escherichia coli. The rGTP can stimulate de novo initiation of RNA synthesis and mutation of the GDD motif to Gly-Asp-Asp (GAA) abolishes the RNA synthesis. To better understand the mechanism of viral RNA synthesis in CSFV, a three-dimensional model was built by homology modeling based on the alignment with several virus RdRps. The model contains 605 residues folded in the characteristic fingers, palm and thumb domains. The fingers domain contains an N-terminal region that plays an important role in conformational change. We propose that the experimentally observed promotion of polymerase efficiency by rGTP is probably due to the conformational changes of the polymerase caused by binding the rGTP. Mutation of the GDD to GAA interferes with the interaction between the residues at the polymerase active site and metal ions, and thus renders the polymerase inactive. (c) 2005 Elsevier B.V. All rights reserved.

Structural determinants of steroids for cytochrome P450 3A4-mediated metabolism

Cytochrome P450 3A4 (CYP3A4), a major member of cytochrome P450 isoenzymes, metabolizes the majority of steroids in 6beta-position. For the purpose of determining requisite structural features of a series of structurally related steroids for CYP3A4-mediated metabolism, three-dimensional pharmacophore modeling as well as electrotopological state map were conducted for 15 steroids. Though prior studies speculated that the chemical reactivity of the allylic 6beta-position might have a greater influence on CYP3A4 selective 6-hydroxylation than steric constraints in the enzyme, our results reveal that for CYP3A4 steroidal substrates, it is not the chemical reactivity of atoms at 6beta-site, but the pharmacophoric features, i.e. the two hydrophobic rings together with two H-bond donors, that act as the key factors responsible for detemining the CYP3A4 selective 6-hydroxylation of steroids. (C) 2004 Elsevier B.V. All rights reserved.

Three-Dimensional Modeling of Heat Transfer and Fluid Flow in Laminar-Plasma Material Re-Melting Processing

Modeling study is performed concerning the heat transfer and fluid flow for a laminar argon plasma jet impinging normally upon a flat workpiece exposed to the ambient air. The diffusion of the air into the plasma jet is handled by using the combined-diffusion-coefficient approach. The heat flux density and jet shear stress distributions at the workpiece surface obtained from the plasma jet modeling are then used to study the re-melting process of a carbon steel workpiece. Besides the heat conduction within the workpiece, the effects of the plasma-jet inlet parameters (temperature and velocity), workpiece moving speed, Marangoni convection, natural convection etc. on the re-melting process are considered. The modeling results demonstrate that the shapes and sizes of the molten pool in the workpiece are influenced appreciably by the plasma-jet inlet parameters, workpiece moving speed and Marangoni convection. The jet shear stress manifests its effect at higher plasma-jet inlet velocities, while the natural convection effect can be ignored. The modeling results of the molten pool sizes agree reasonably with available experimental data.

Mathematical Modeling of Near-Wall Flows of Two-Phase Mixture with Evaporating Droplets

In the framework of the two-continuum approach, using the matched asymptotic expansion method, the equations of a laminar boundary layer in mist flows with evaporating droplets were derived and solved. The similarity criteria controlling the mist flows were determined. For the flow along a curvilinear surface, the forms of the boundary layer equations differ from the regimes of presence and absence of the droplet inertia deposition. The numerical results were presented for the vapor-droplet boundary layer in the neighborhood of a stagnation point of a hot blunt body. It is demonstrated that, due to evaporation, a droplet-free region develops near the wall inside the boundary layer. On the upper edge of this region, the droplet radius tends to zero and the droplet number density becomes much higher than that in the free stream. The combined effect of the droplet evaporation and accumulation results in a significant enhancement of the heat transfer on the surface even for small mass concentration of the droplets in the free stream. 在双连续介质理论框架下,采用匹配渐进展开方法导出并求解了具有蒸发液滴的汽雾流中层流边界层方程,给出了控制汽雾流的相似判据。对于沿曲面的流动,边界层方程的形式取决于是否存在液滴的惯性沉积。给出了热钝体验点附近蒸汽。液滴边界层的数值计算结果。它们表明：由于蒸发,在边界层内近壁处形成了一个无液滴区域；在该区上边界处,液滴半径趋于零而液滴数密度急剧增高。液滴蒸发及聚集的联合效应造成了表面热流的显著增加,甚至在自由来流中液滴质量浓度很低时此效应依然存在。

Molecular Dynamics Modeling of Diffusion Bonding

Molecular dynamics simulations on diffusion bonding of Cu-Ag showed that the thickness of the interfacial region depended on the stress. The interfacial region became amorphous during diffusion bonding, and it would normally transform from amorphous into crystalline structure when the structure was cooled to the room temperature.

Stochastic Structural Model of Rock and Soil Aggregates by Continuum-Based Discrete Element Method

This paper first presents a stochastic structural model to describe the random geometrical features of rock and soil aggregates. The stochastic structural model uses mixture ratio, rock size and rock shape to construct the microstructures of aggregates,and introduces two types of structural elements (block element and jointed element) and three types of material elements (rock element, soil element, and weaker jointed element)for this microstructure. Then, continuum-based discrete element method is used to study the deformation and failure mechanism of rock and soil aggregate through a series of loading tests. It is found that the stress-strain curve of rock and soil aggregates is nonlinear, and the failure is usually initialized from weaker jointed elements. Finally, some factors such as mixture ratio, rock size and rock shape are studied in detail. The numerical results are in good agreement with in situ test. Therefore, current model is effective for simulating the mechanical behaviors of rock and soil aggregates.

Modeling of Ammonothermal Growth of Nitrides

Bulk single crystals of GaN and AlN can be grown from supercritical fluids using the ammonothermal method, which utilizes ammonia as fluid rather than water as in the hydrothermal process. In this process, a mineralizer such as amide, imide or nitride is used to attack a bulk nitride feedstock at temperatures from 200°C to 500°C and pressures from 1 to 4 kbar. Ammonothermal systems have been modeled here using fluid dynamics, thermodynamics and heat transfer models. The nutrient is considered as a porous media bed and the fluid flow is simulated using the Darcy-Brinkman-Forchheimer model. The resulting governing equations are solved using the finite volume method. The effects of particle size on flow pattern and temperature distribution in an autoclave are analyzed.

Turbulent Modeling of ABL over Wavy Water Surface

A new model accounting for both turbulence and sea state effects has been proposed in this paper to describe momentum, heat and moisture exchanges through air-sea interface. While long wave components mainly change air flow profile, short wave components

Physical modeling of untrenched submarine pipeline instability

Wave-induced instability of untrenched pipeline on sandy seabed is a `wave-soil-pipeline' coupling dynamic problem. To explore the mechanism of the pipeline instability, the hydrodynamic loading with U-shaped oscillatory flow tunnel is adopted, which is quite different from the previous experiment system. Based on dimensional analysis, the critical conditions for pipeline instability are investigated by altering pipeline submerged weight, diameter, soil parameters, etc. Based on the experimental results, different linear relationships between Froude number (Fr) and non-dimensional pipeline weight (G) are obtained for two constraint conditions. Moreover, the effects of loading history on the pipeline stability are also studied. Unlike previous experiments, sand scouring during the process of pipe's losing stability is detected in the present experiments. In addition, the experiment results are compared with the previous experiments, based on Wake II model for the calculation of wave-induced forces upon pipeline. It shows that the results of two kinds of experiments are comparable, but the present experiments provide better physical insight of the wave-soil-pipeline coupling effects.

Probabilistic Modeling of Rosette Formation

英文摘要: Rosetting, or forming a cell aggregate between a single target nucleated cell and a number of red blood cells (RBCs), is a simple assay for cell adhesion-mediated by specific receptor-ligand interaction. For example, rosette formation between sheep RBC and human lymphocytes has been used to differentiate T cells from B cells. Rosetting assay is commonly used to determine the interaction of Fc gamma-receptors (Fc gamma R) expressed on inflammatory cells and IgG-coated on RBCs. Despite its wide use in measuring cell adhesion, the biophysical parameters of rosette formation have not been well characterized. Here we developed a probabilistic model to describe the distribution of rosette sizes, which is Poissonian. The average rosette size is predicted to be proportional to the apparent two-dimensional binding affinity of the interacting receptor-ligand pair and their site densities. The model has been supported by experiments of rosettes mediated by four molecular interactions: Fc gamma RIII interacting with IgG, T cell receptor and coreceptor CD8 interacting with antigen peptide presented by major histocompatibility molecule, P-selectin interacting with P-selectin glycoprotein ligand 1 (PSGL-1), and L-selectin interacting with PSGL-1. The latter two are structurally similar and are different from the former two. Fitting the model to data enabled us to evaluate the apparent effective two-dimensional binding affinity of the interacting molecular pairs: 7.19x10(-5) mu m(4) for Fc gamma RIII-IgG interaction, 4.66x10(-3) mu m(4) for P-selectin-PSGL-1 interaction, and 0.94x10(-3) mu m(4) for L-selectin-PSGL-1 interaction. These results elucidate the biophysical mechanism of rosette formation and enable it to become a semiquantitative assay that relates the rosette size to the effective affinity for receptor-ligand binding.

Progress In Modeling Of Fluid Flows In Crystal Growth Processes

Modeling of fluid flows in crystal growth processes has become an important research area in theoretical and applied mechanics. Most crystal growth processes involve fluid flows, such as flows in the melt, solution or vapor. Theoretical modeling has played an important role in developing technologies used for growing semiconductor crystals for high performance electronic and optoelectronic devices. The application of devices requires large diameter crystals with a high degree of crystallographic perfection, low defect density and uniform dopant distribution. In this article, the flow models developed in modeling of the crystal growth processes such as Czochralski, ammonothermal and physical vapor transport methods are reviewed. In the Czochralski growth modeling, the flow models for thermocapillary flow, turbulent flow and MHD flow have been developed. In the ammonothermal growth modeling, the buoyancy and porous media flow models have been developed based on a single-domain and continuum approach for the composite fluid-porous layer systems. In the physical vapor transport growth modeling, the Stefan flow model has been proposed based on the flow-kinetics theory for the vapor growth. In addition, perspectives for future studies on crystal growth modeling are proposed. (c) 2008 National Natural Science Foundation of China and Chinese Academy of Sciences. Published by Elsevier Limited and Science in China Press. All rights reserved.

Micromechanics Modeling Of Strength For Nanocrystalline Copper

We present a model in this paper for predicting the inverse Hall-Petch phenomenon in nanocrystalline (NC) materials which are assumed to consist of two phases: grain phase of spherical or spheroidal shapes and grain boundary phase. The deformation of the grain phase has an elasto-viscoplastic behavior, which includes dislocation glide mechanism, Coble creep and Nabarro-Herring creep. However the deformation of grain boundary phase is assumed to be the mechanism of grain boundary diffusion. A Hill self-consistent method is used to describe the behavior of nanocrystalline pure copper subjected to uniaxial tension. Finally, the effects of grain size and its distribution, grain shape and strain rate on the yield strength and stress-strain curve of the pure copper are investigated. The obtained results are compared with relevant experimental data in the literature.

Nonlinear Mechanical Modeling Of Cell Adhesion

Cell adhesion, which is mediated by the receptor-ligand bonds, plays an essential role in various biological processes. Previous studies often described the force-extension relationship of receptor-ligand bond with linear assumption. However, the force-extension relationship of the bond is intrinsically nonlinear, which should have significant influence on the mechanical behavior of cell adhesion. In this work, a nonlinear mechanical model for cell adhesion is developed, and the adhesive strength was studied at various bond distributions. We find that the nonlinear mechanical behavior of the receptor-ligand bonds is crucial to the adhesive strength and stability. This nonlinear behavior allows more bonds to achieve large bond force simultaneously, and therefore the adhesive strength becomes less sensitive to the change of bond density at the outmost periphery of the adhesive area. In this way, the strength and stability of cell adhesion are soundly enhanced. The nonlinear model describes the cell detachment behavior better than the linear model. (C) 2007 Elsevier Ltd. All rights reserved.