FeSiCr Alloy Powder to Carbonyl Iron Powder Mixing Ratio Effects on the Magnetic Properties of the Iron-Based Alloy Powder Cores Prepared Using Screen Printing.

A screen printing process was used to substitute dry molding to solve the uneven compaction problem in the coil center column during molding in this study. FeSiCr alloy powders (FSC) with a large particle size were mixed with fine spherical carbonyl iron powder to increase the compaction density. FSC to carbonyl iron powder (CIP) mixing ratio effects on magnetic paste rheological behaviors and magnetic properties of the molding coil prepared using screen printing were investigated. A magnetic paste with the lowest viscosity can be obtained using 3C7F (30% CIP + 70% FSC) due to the small-sized CIP adsorbed onto the FSC surface. This process reduces the interlocked network formation resulting from the CIP. The toroidal core with 3C7F exhibited the highest relative density and highest inductance. The coils with pure CIP and higher CIP content exhibited the better DC superposition characteristic. The toroidal core loss increased rapidly as the FSC content was increased. A proper trade-off between the inductance, DC-bias superposition characteristic, and magnetic core loss can be reached by choosing a suitable powder mixing ratio.

Open innovation in neuroscience research and drug discovery.

The pressures on the pharmaceutical industry have incentivised a number of new collaborative models of research and development which can be categorised as open innovation. Examples of the different types of models employed are discussed and some, but not all, of these have been used to promote research and drug discovery for central nervous system disorders. Some are completely open access, while others have some intellectual property restrictions. Going forward, more ways of promoting open innovation and the sharing of best practice, especially in the neurosciences, will stimulate research and hopefully accelerate new medicines development.

The Kaposi's sarcoma-associated herpesvirus complement control protein (KCP) binds to heparin and cell surfaces via positively charged amino acids in CCP1-2.

The Kaposi's sarcoma-associated herpesvirus (KSHV) complement control protein (KCP) inhibits the human complement system, and is similar in structure and function to endogenous complement inhibitors. Other inhibitors such as C4b-binding protein and factor H, as well as the viral homologue vaccinia virus complement control protein are known to bind heparin and, for the two latter, also to glycosaminoglycans at the surface of cells. We report here that KCP also binds to heparin at physiological ionic strength. With help of site directed mutagenesis, positively charged amino acids in the two N-terminal complement control protein (CCP) domains 1-2 were found to be necessary for heparin binding. In silico molecular docking of heparin to KCP confirmed the experimental data, and further explored the heparin binding site, enabling us to present a model of the KCP-heparin interaction. Furthermore, the docking analysis also yielded insights of the KCP structure, by indicating that the angle between CCP domains 1-2 during the initial binding of heparin is more extended than in the model we have previously presented. We also found that KCP binds to heparan sulfate and weakly to glycosaminoglycans at the surface of cells. This might indicate that KCP at the surface of viral particles aids in the primary attachment to the target cells, which is known to involve binding to heparan sulfate. Therefore, the present study contributes to the knowledge of heparin-protein interactions in general as well as to the understanding of the biology of KSHV.

Fast structure-based virtual ligand screening combining FRED, DOCK, and Surflex.

A protocol was devised in which FRED, DOCK, and Surflex were combined in a multistep virtual ligand screening (VLS) procedure to screen the pocket of four different proteins. One goal was to evaluate the impact of chaining "freely available packages to academic users" on docking/scoring accuracy and CPU time consumption. A bank of 65 660 compounds including 49 known actives was generated. Our procedure is successful because docking/scoring parameters are tuned according to the nature of the binding pocket and because a shape-based filtering tool is applied prior to flexible docking. The obtained enrichment factors are in line with those reported in recent studies. We suggest that consensus docking/scoring could be valuable to some drug discovery projects. The present protocol could process the entire bank for one receptor in less than a week on one processor, suggesting that VLS experiments could be performed even without large computer resources.

The Kaposi's sarcoma-associated herpesvirus complement control protein mimics human molecular mechanisms for inhibition of the complement system.

Kaposi's sarcoma-associated human herpesvirus (KSHV) is thought to cause Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Previously, we reported that the KSHV complement control protein (KCP) encoded within the viral genome is a potent regulator of the complement system; it acts both as a cofactor for factor I and accelerates decay of the C3 convertases (Spiller, O. B., Blackbourn, D. J., Mark, L., Proctor, D. G., and Blom, A. M. (2003) J. Biol. Chem. 278, 9283-9289). KCP is a homologue to human complement regulators, being comprised of four complement control protein (CCP) domains. In this, the first study to identify the functional sites of a viral homologue at the amino acid level, we created a three-dimensional homology-based model followed by site-directed mutagenesis to locate complement regulatory sites. Classical pathway regulation, both through decay acceleration and factor I cleavage of C4b, required a cluster of positively charged amino acids in CCP1 stretching into CCP2 (Arg-20, Arg-33, Arg-35, Lys-64, Lys-65, and Lys-88) as well as positively (Lys-131, Lys-133, and His-135) and negatively (Glu-99, Glu-152, and Asp-155) charged areas at opposing faces of the border region between CCPs 2 and 3. The regulation of the alternative pathway (via factor I-mediated C3b cleavage) was found to both overlap with classical pathway regulatory sites (Lys-64, Lys-65, Lys-88 and Lys-131, Lys-133, His-135) as well as require unique, more C-terminal residues in CCPs 3 and 4 (His-158, His-171, and His-213) and CCP 4 (Phe-195, Phe-207, and Leu-209). We show here that KCP has evolved to maintain the spatial structure of its functional sites, especially the positively charged patches, compared with host complement regulators.