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51.
Software and Systems Modeling - Model-driven engineering (MDE) has proved to be a useful approach to cope with today’s ever-growing complexity in the development of software systems;...  相似文献   
52.
Software and Systems Modeling - Despite good results in several industrial projects, model-driven engineering (MDE) has not been widely adopted in industry. Although MDE has existed for more than a...  相似文献   
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Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC50 value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity.  相似文献   
55.
The loading of a wind turbine decreases towards the blade tip because of the velocities induced by the tip vortex. This tip loss effect has to be taken into account when performing actuator disc simulations, where the single blades of the turbine are not modeled. A widely used method applies a factor on the axial and tangential loading of the turbine. This factor decreases when approaching the blade tip. It has been shown that the factor should be different for the axial and tangential loading of the turbine to model the rotation of the resulting force vector at the airfoil sections caused by the induced velocity. The present article contains the derivation of a simple correction for the tangential load factor that takes this rotation into account. The correction does not need any additional curve fitting but just depends on the local airfoil characteristics and angle of attack. Actuator disc computations with the modified tip loss correction show improved agreement with results from actuator line, free wake lifting line, and blade element momentum simulations.  相似文献   
56.
Oxylipins constitute a family of oxidized fatty acids, that are well known as tissue hormones in mammals. They contribute to inflammation and its resolution. The major classes of these lipid mediators are inflammatory prostaglandins (PGs) and leukotrienes (LTs) as well as pro-resolving resolvins (Rvs). Understanding their biosynthetic pathways and modes of action is important for anti-inflammatory interventions. Besides mammals, marine algae also biosynthesize mammalian-like oxylipins and thus offer new opportunities for oxylipin research. They provide prolific sources for these compounds and offer unique opportunities to study alternative biosynthetic pathways to the well-known lipid mediators. Herein, we discuss recent findings on the biosynthesis of oxylipins in mammals and algae including an alternative pathway to prostaglandin E2, a novel pathway to a precursor of leukotriene B4, and the production of resolvins in algae. We evaluate the pharmacological potential of the algal metabolites with implications in health and disease.  相似文献   
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Mine Water and the Environment - Mine water hydraulics and geothermal potential of a deep shaft of the flooded Wolf mine in the Siegerland ore district of the Rhenish Massif in Germany were...  相似文献   
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Forschung im Ingenieurwesen - Die mechanischen Verluste von Verbrennungsmotoren hängen maßgeblich von den auftretenden Reibkräften innerhalb der Kolbengruppe ab. Da die Kolbengruppe...  相似文献   
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Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.  相似文献   
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