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601.
    
The dynamic interplay of post-translational modifications (PTMs) in chromatin provides a communication system for the regulation of gene expression. An increasing number of studies have highlighted the role that such crosstalk between PTMs plays in chromatin recognition. In this study, (bio)chemical and structural approaches were applied to specifically probe the impact of acetylation of Lys18 in the histone H3 tail peptide on peptide recognition by the protein methyltransferase coactivator-associated arginine methyltransferase 1 (CARM1). Peptidomimetics that recapitulate the transition state of protein arginine N-methyltransferases, were designed based on the H3 peptide wherein the target Arg17 was flanked by either a free or an acetylated lysine. Structural studies with these peptidomimetics and the catalytic domain of CARM1 provide new insights into the binding of the H3 peptide within the enzyme active site. While the co-crystal structures reveal that lysine acetylation results in minor conformational differences for both CARM1 and the H3 peptide, acetylation of Lys18 does lead to additional interactions (Van der Waals and hydrogen bonding) and likely reduces the cost of desolvation upon binding, resulting in increased affinity. Informed by these findings a series of smaller peptidomimetics were also prepared and found to maintain potent and selective CARM1 inhibition. These findings provide new insights both into the mechanism of crosstalk between arginine methylation and lysine acetylation as well as towards the development of peptidomimetic CARM1 inhibitors.  相似文献   
602.
The traditional hard disk drive (HDD) is often a bottleneck in the overall performance of modern computer systems. With the development of solid state drives (SSD) based on flash memory, new possibilities are available to improve secondary storage performance. In this work, we propose a new hybrid SSD–HDD storage system and a selection of algorithms designed to assign pages across an HDD and an SSD to optimise I/O performance. The hybrid system combines the advantages of the SSD’s fast random seek speed with the sequential access speed and large storage capacity of the HDD to produce significantly improved performance in a variety of situations. We further improve performance by allowing concurrent access across the two types of storage devices. We show the drive assignment problem is NP-complete and accordingly propose effective heuristic solutions. Extensive experiments using both synthetic and real data sets show our system with a small SSD can outperform a striped dual HDD and remain competitive with a dual SSD.  相似文献   
603.
Various rotating components of a gas turbine engine are subjected to high temperatures as well as high centrifugal forces. Abrupt temperature variations often introduce thermal stresses. These must of course be considered when the designer is faced with the problem of predicting the low cycle fatigue life of the relevant component.Particularly at higher temperatures the material behaviour is non-linear and may influence the accuracy of the computed results. Both the thermal conductivity- and the heat capacity properties become more and more temperature-dependent in higher temperature regions. In addition, convective heat transfer at heat exposed surfaces are temperature-dependent.This paper describes a linear- and two non-linear three-dimensional temperature field analyses of a radial gas turbine wheel. In one of the non-linear analyses the material properties were made temperature-dependent, whereas the second non-linear analysis had constant material properties but temperature-dependent heat transfer coefficients.The results obtained show that for the analyzed gas turbine wheel, a linear analysis will produce results which deviate insignificantly from the results obtained in a much costlier non-linear analysis. This is true for material properties and convective heat transfer coefficients that are non-linear only to a moderate extent. It is also fair to assume that this may be concluded for heat conduction problems of the same category, e.g. analysis of other machinery components, nuclear reactor design problems, etc.  相似文献   
604.
Journal of Scheduling - Single machine scheduling with sequence-dependent setup times is one of the classical problems of production planning with widespread applications in many industries....  相似文献   
605.
A 3D computational fluid dynamics program was used to calculate the wind-induced accumulation of phytoplankton in Eglwys Nynydd, a water supply reservoir in Wales. The computational fluid dynamics model solved the Navier-Stokes equations for the water velocities using the SIMPLE method to calculate the pressure. Two turbulence models were tested: a zero-equation model and the k-ε model. An unstructured nonorthogonal 3D grid with hexahedral cells was used. The distribution of the blue-green algae Microcystis was calculated by solving the transient convection-diffusion equation for phytoplankton concentration, based on the modeled flow field. The numerical model included algorithms for calculating the growth rate of phytoplankton and simulating the response of the algae to changes in underwater light intensity. The model was validated by comparing the horizontal distribution patterns produced by simulation with those recorded during a field survey of surface concentrations. The results demonstrated reasonable agreement, particularly when using the k-ε turbulence model. The main parameter affecting the results was the effective diameter of the Microcystis colonies.  相似文献   
606.
Measurements have been made of the compositional changes of fluxes and weld metal during submerged arc flux welding with a series of synthetic MnO-FeO-SiO2 model fluxes containing 40 wt pct SiO2 and different ratios of MnO to FeO. Mechanisms for the transfer of Mn, O, Si, C, S, and P are discussed in terms of the thermodynamic driving forces and kinetic factors such as diffusion, nucleation, and segregation. One unique deduction is that interfacial, not bulk activities of components (such as FeO) govern transfer into (or out of) the metal phase. The concentrations of C, P, S, and possibly Si tend to be larger in the molten weld metal than in the base plate.  相似文献   
607.
608.
This paper proposes a new data‐driven approach to model detailed splashes for liquid simulations with neural networks. Our model learns to generate small‐scale splash detail for the fluid‐implicit‐particle method using training data acquired from physically parametrized, high resolution simulations. We use neural networks to model the regression of splash formation using a classifier together with a velocity modifier. For the velocity modification, we employ a heteroscedastic model. We evaluate our method for different spatial scales, simulation setups, and solvers. Our simulation results demonstrate that our model significantly improves visual fidelity with a large amount of realistic droplet formation and yields splash detail much more efficiently than finer discretizations.  相似文献   
609.
A surface electromyogram (sEMG) contains information about physiological and morphological characteristics of the active muscle and its neural strategies. Because the electrodes are situated on the skin above the muscle, the sEMG is an easily obtainable source of information. However, different combinations of physiological and morphological characteristics can lead to similar sEMG signals and sEMG recordings contain noise and other artefacts. Therefore, many sEMG signal processing methods have been developed and applied to allow insight into neuromuscular physiology. This paper gives an overview of important advances in the development and applications of sEMG signal processing methods, including spectral estimation, higher order statistics and spatio-temporal processing. These methods provide information about muscle activation dynamics and muscle fatigue, as well as characteristics and control of single motor units (conduction velocity, firing rate, amplitude distribution and synchronization).  相似文献   
610.
The fracture toughness of a layered composite material is analyzed employing a combined two dimensional dislocation dynamics (DD)-cohesive zone (CZ) model. The fracture mechanism of an elastic-plastic (ductile) material sandwiched within purely elastic layers approaches ideally brittle behaviour with decreasing layer thickness. We investigate the influence of different constitutive parameters concerning dislocation plasticity as well as the effect of cohesive strength of the ductile material on the scaling of fracture toughness with layer thickness. For a constant layer thickness, the results of the numerical model are consistent with the expectation that fracture toughness decreases with increasing yield strength, but increases with the cohesive strength of the material. The scaling behaviour of the fracture toughness with layer thickness depends on these material parameters, but also on the dislocation microstructure in the vicinity of the crack tip. Strain localization due to easy dislocation generation right at the crack tip improves toughness in thin layers and leads to a jump-like increase of fracture toughness with layer thickness. However, the fracture toughness for films that are thick enough to exhibit bulk behaviour proves to be higher when the distribution of dislocations is more homogeneous, because in this case the crack grows in a stable fashion over some distance.  相似文献   
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