The microINR portable coagulometer: analytical quality and user-friendliness of a PT (INR) point-of-care instrument.

Regular measurement of prothrombin time as an international normalized ratio PT (INR) is mandatory for optimal and safe use of warfarin. Scandinavian evaluation of laboratory equipment for primary health care (SKUP) evaluated the microINR portable coagulometer (microINR®) (iLine Microsystems S.L., Spain) for measurement of PT (INR). Analytical quality and user-friendliness were evaluated under optimal conditions at an accredited hospital laboratory and at two primary health care centres (PHCCs). Patients were recruited at the outpatient clinic of the Laboratory of Medical Biochemistry, St Olav's University Hospital, Trondheim, Norway (n = 98) and from two PHCCs (n = 88). Venous blood samples were analyzed under optimal conditions on the STA-R®Evolution with STA-SPA + reagent (Stago, France) (Owren method), and the results were compared to capillary measurements on the microINR®. The imprecision of the microINR® was 6% (90% CI: 5.3-7.0%) and 6.3% (90% CI: 5.1-8.3) in the outpatient clinic and PHCC2, respectively for INR ≥2.5. The microINR® did not meet the SKUP quality requirement for imprecision ≤5.0%. For INR <2.5 at PHCC2 and at both levels in PHCC1, CV% was ≤5.0. The accuracy fulfilled the SKUP quality goal in both outpatient clinic and PHCCs. User-friendliness of the operation manual was rated as intermediate, defined by SKUP as neutral ratings assessed as neither good nor bad. Operation facilities was rated unsatisfactory, and time factors satisfactory. In conclusion, quality requirements for imprecision were not met. The SKUP criteria for accuracy was fulfilled both at the hospital and at the PHCCs. The user-friendliness was rated intermediate.

Molecular docking with ligand attached water molecules.

A novel approach to incorporate water molecules in protein-ligand docking is proposed. In this method, the water molecules display the same flexibility during the docking simulation as the ligand. The method solvates the ligand with the maximum number of water molecules, and these are then retained or displaced depending on energy contributions during the docking simulation. Instead of being a static part of the receptor, each water molecule is a flexible on/off part of the ligand and is treated with the same flexibility as the ligand itself. To favor exclusion of the water molecules, a constant entropy penalty is added for each included water molecule. The method was evaluated using 12 structurally diverse protein-ligand complexes from the PDB, where several water molecules bridge the ligand and the protein. A considerable improvement in successful docking simulations was found when including flexible water molecules solvating hydrogen bonding groups of the ligand. The method has been implemented in the docking program Molegro Virtual Docker (MVD).

Ab initio calculations for industrial materials engineering: successes and challenges.

Computational materials science based on ab initio calculations has become an important partner to experiment. This is demonstrated here for the effect of impurities and alloying elements on the strength of a Zr twist grain boundary, the dissociative adsorption and diffusion of iodine on a zirconium surface, the diffusion of oxygen atoms in a Ni twist grain boundary and in bulk Ni, and the dependence of the work function of a TiN-HfO(2) junction on the replacement of N by O atoms. In all of these cases, computations provide atomic-scale understanding as well as quantitative materials property data of value to industrial research and development. There are two key challenges in applying ab initio calculations, namely a higher accuracy in the electronic energy and the efficient exploration of large parts of the configurational space. While progress in these areas is fueled by advances in computer hardware, innovative theoretical concepts combined with systematic large-scale computations will be needed to realize the full potential of ab initio calculations for industrial applications.

MolDock: a new technique for high-accuracy molecular docking.

In this article we introduce a molecular docking algorithm called MolDock. MolDock is based on a new heuristic search algorithm that combines differential evolution with a cavity prediction algorithm. The docking scoring function of MolDock is an extension of the piecewise linear potential (PLP) including new hydrogen bonding and electrostatic terms. To further improve docking accuracy, a re-ranking scoring function is introduced, which identifies the most promising docking solution from the solutions obtained by the docking algorithm. The docking accuracy of MolDock has been evaluated by docking flexible ligands to 77 protein targets. MolDock was able to identify the correct binding mode of 87% of the complexes. In comparison, the accuracy of Glide and Surflex is 82% and 75%, respectively. FlexX obtained 58% and GOLD 78% on subsets containing 76 and 55 cases, respectively.

Interface energy of semicoherent metal-ceramic interfaces.

An ab initio based approach to determine energies and structures for semicoherent interfaces is developed and applied to the Fe(001)/VN(001) system. To account for elastic displacements resulting from the lattice misfit, we compare an atomistic approach using a model potential (embedded-atom method) with a continuum approach using the Peierls-Nabarro model. The total interface energy of the atomistic modeling is found to be well reproduced by the Peierls-Nabarro model, demonstrating that accurate interface energies of semicoherent interfaces can be obtained by combining first principles for the chemical part of the energy and a Peierls-Nabarro model to account for the elasticity of the media.

Quantitative analysis of WC grain shape in sintered WC-Co cemented carbides.

The morphology of WC grains is examined by ab initio calculations, and by transmission electron microscopy in a WC-Co cemented carbide. Two compositions are studied to determine the effect of carbon chemical potential on the shape development. The WC grains are found to be truncated triangles, and the grain morphology is adequately reproduced by the ab initio calculations. The energy difference between the two types of grain facets is shown to be due to the formation of stronger bonds with more covalent character between low coordinated W and Co atoms at one type of facet.