Product Integration Rules at Clenshaw-Curtis and Related Points: A Robust Implementation

Product integration rules generalizing the Fej?r, Clenshaw-Curtis,and Filippi quadrature rules respectively are derived for integralswith trigonometric and hyperbolic weight factors. The Chebyshevmoments of the weight functions are found to be given by well-conditionedexpressions, in terms of hypergeometric functions ₀F₁. An a priori error estimator is discussed which is shown bothto avoid wasteful invocation of the integration rule and toincrease significantly the robustness of the automatic quadratureprocedure. Then, specializing to extended Clenshaw-Curtis (ECC) rules,three types of a posteriori error estimates are considered andthe existence of a great risk of their failure is demonstratedby large scale validation tests. An empirical error estimator,superseding them for slowly varying integrands, is found toresult in a spectacular increase in the output reliability. Finally, enhancements in the control of the interval subdivisionstrategy aiming at increasing code robustness is discussed.Comparison with the code DQAWO of QUADPACK, with about a hundredthousand solved integrals, is illustrative of the increasedrobustness and error estimate reliability of our computer codeimplementation of the ECC rules.     

Biotransformation-mediated synthesis of (1S)-1-(2,6-dichloro-3-fluorophenyl)ethanol in enantiomerically pure form

An efficient four-step biotransformation-mediated synthesis of (1S)-1-(2,6-dichloro-3-fluorophenyl)ethanol in enantiomerically pure form is described. This compound is a key intermediate required for the preparation of PF-2341066, a potent inhibitor of c-Met/ALK that is currently in clinical development. The described synthesis was used to manufacture 6 kg of the title compound and can also be employed to produce the corresponding (1R)-enantiomer.     

Surface-charge-governed ion transport in nanofluidic channels

A study of ion transport in aqueous-filled silica channels as thin as 70 nm reveals a remarkable degree of conduction at low salt concentrations that departs strongly from bulk behavior: In the dilute limit, the electrical conductances of channels saturate at a value that is independent of both the salt concentration and the channel height. Our data are well described by an electrokinetic model parametrized only by the surface-charge density. Using chemical surface modifications, we further demonstrate that at low salt concentrations, ion transport in nanochannels is governed by the surface charge.     

Thermodynamic Complexation of Dopamine with Zinc(II) in Media with Different Dielectric Constants

The complexation of zinc(II) with dopamine has been investigated by spectrophotometric measurements in mixed solvent system at an ionic strength of 0.2 mol•dm－3 sodium chloride, employed at at (15±0.1), (25±0.1), (35±0.1) ℃ at inin a pH range of ca. 6 to ca. 7 with a high ratio of ligand to metal. The effect of solvent systems on protonation and complexation are was was discussed. Linear relationships are werewere observed by plotting lg K versus 1/D, where K and D show stability and dielectric constants, respectively.     

Selective and diagnostic labelling of serine hydrolases with reactive phosphonate inhibitors

Reactive phosphonates are important probes to target the active site of serine hydrolases, one of the largest and most diverse family of enzymes. Developing such inhibitory probes is of special importance in activity based protein profiling, a strategy that is increasingly used to gain information about a certain class of enzymes in complex proteosomes. Therefore, gaining detailed information about these inhibition events on the individual protein level is important since it affords information that can be used to fine-tune the probe for a specific task. Here, we report a novel and versatile synthesis protocol to access a variety of functionalised p-nitrophenyl phosphonate (PNPP) inhibitors from a common azide functionalised precursor using click chemistry. The obtained PNPPs were successfully used to covalently label serine hydrolases in their active sites with molecular tags. Furthermore, a model study is described in which we developed straightforward protocols that can be used to study protein inhibition events. Kinetic studies using UV-Vis and fluorescence spectroscopy techniques revealed that these PNPPs possess different inhibition rates for various proteins and were shown to be suitable probes to discriminate between various lipases. Additionally, we demonstrate that PNPPs are highly selective for serine hydrolases, making these probes very interesting as diagnostic or affinity probes for studying proteins in complex proteosomes.     

Lattice Boltzmann simulation of natural convection in nanofluid-filled 2D long enclosures at presence of magnetic field

In this paper, the effects of a magnetic field on natural convection flow in filled long enclosures with Cu/water nanofluid have been analyzed by lattice Boltzmann method. This study has been carried out for the pertinent parameters in the following ranges: the Rayleigh number of base fluid, Ra = 10³–10⁵, the volumetric fraction of nanoparticles between 0 and 6 %, the aspect ratio of the enclosure between A = 0.5 and 2. The Hartmann number has been varied from Ha = 0 to 90 with interval 30 while the magnetic field is considered at inclination angles of θ = 0°, 30°, 60° and 90°. Results show that the heat transfer decreases by the increment of Hartmann number for various Rayleigh numbers and the aspect ratios. Heat transfer decreases with the growth of the aspect ratio but this growth causes the effect of the nanoparticles to increase. The magnetic field augments the effect of the nanoparticles at high Rayleigh numbers (Ra = 10⁵). The effect of the nanoparticles rises for high Hartmann numbers when the aspect ratio increases. The rise in the magnetic field inclination improves heat transfer at aspect ratio of A = 0.5.