WDX Analysis of Rapidly Quenched Nd-Fe-B Alloys with Ti + C Additives

 Quenched stoichiometric Nd-Fe-B alloys with Ti + C additives, which improve the hard magnetic properties, were investigated by EPMA technique. The exact quantitative wavelength dispersive analysis meets with two problems: the carbon blank value and the C-Kα line coincidence with Nd-Mγ, Nd-Mα and Nd-Mζ of higher diffraction orders. The carbon blank value depends on the special residual gas pressure in the recipient and was determined by repeated measurements of a carbon free iron reference specimen e.g. with subsequent corrections of the carbon content. The second problem can be solved by blanking out the Nd induced contribution to the C-Kα region by a differential detection mode. In this case an energy discriminator was used to set a lower and an upper level in order to suppress the neighbouring coincident lines. The optimized analysis allowed an exact determination of carbon content in all investigated phases.     

First-principle calculations of the Berry curvature of Bloch states for charge and spin transport of electrons

Recent progress in wave packet dynamics based on the insight of Berry pertaining to adiabatic evolution of quantum systems has led to the need for a new property of a Bloch state, the Berry curvature, to be calculated from first principles. We report here on the response to this challenge by the ab initio community during the past decade. First we give a tutorial introduction of the conceptual developments we mentioned above. Then we describe four methodologies which have been developed for first-principle calculations of the Berry curvature. Finally, to illustrate the significance of the new developments, we report some results of calculations of interesting physical properties such as the anomalous and spin Hall conductivity as well as the anomalous Nernst conductivity and discuss the influence of the Berry curvature on the de Haas-van Alphen oscillation.     

Picomolar FKBP inhibitors enabled by a single water-displacing methyl group in bicyclic [4.3.1] aza-amides

Methyl groups can have profound effects in drug discovery but the underlying mechanisms are diverse and incompletely understood. Here we report the stereospecific effect of a single, solvent-exposed methyl group in bicyclic [4.3.1] aza-amides, robustly leading to a 2 to 10-fold increase in binding affinity for FK506-binding proteins (FKBPs). This resulted in the most potent and efficient FKBP ligands known to date. By a combination of co-crystal structures, isothermal titration calorimetry (ITC), density-functional theory (DFT), and 3D reference interaction site model (3D-RISM) calculations we elucidated the origin of the observed affinity boost, which was purely entropically driven and relied on the displacement of a water molecule at the protein–ligand–bulk solvent interface. The best compounds potently occupied FKBPs in cells and enhanced bone morphogenic protein (BMP) signaling. Our results show how subtle manipulation of the solvent network can be used to design atom-efficient ligands for difficult, solvent-exposed binding pockets.

Enhancement by displacement. A single methyl group displaces a water molecule from the binding site of FKBPs, resulting in the most potent binders known, outperforming the natural products FK506 and rapamycin in biochemical and cellular assays.     

Codimension-two border collision bifurcation in a two-class growth model with optimal saving and switch in behavior

Nonlinear Dynamics - We consider a two-class growth model with optimal saving and switch in behavior. The dynamics of this model is described by a two-dimensional (2D) discontinuous map. We obtain...     

Tablet of Spondias mombin L. Developed from Nebulized Extract Prevents Gastric Ulcers in Mice via Cytoprotective and Antisecretory Effects

Spondias mombin L. (Anacardiaceae) has a worldwide distribution and is present in all regions of Brazil. Its leaves, flowers and bark are used as teas in folk medicine to treat diseases of the digestive system. This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity, and the related mechanisms of action of nebulized extract and tablets based on dried Spondias mombin (SmNE). SmNE screening showed the presence of flavonoids (0.65%), polyphenols (25.50%), where the major compound is gallic acid. In the acute oral toxicity assay, a dose of 2000 mg/kg of SmNE administered orally in Swiss mice did not induce any behavioral changes. SmNE (250 or 500 mg/kg p.o) significantly reduced the ulcerative lesion area when compared to the control group in ethanol and non-steroidal anti-inflammatory drug (NSAIDs) models. Results showed that treatment with SmNE (250 mg/kg) reduced acid secretion and gastric content, accompanied with an increase in pH. Previous administration of indomethacin and glibenclamide reversed the protection provided by SmNE, confirming the participation of prostaglandins (PGs) and ATP-sensitive potassium channels (KATP) in its gastroprotective effect. The SmNE tablets met the pharmacopeial quality requirements with gastroprotective activity and similar protection in comparison to the isolated extract administrated. In conclusion, SmNe has a gastroprotective activity related to cytoprotective mechanisms, such as the participation of endogenous prostaglandins and KATP channels, having an anti-secretory effect with systemic action. The formulation obtained presented gastroprotective effects similar to the administration of the extract, the tablets showed favorable compression characteristics by the direct route and met the pharmacopeial quality requirements.     

An efficient and highly flexible synthesis of (α),β-unsaturated γ-oxoesters

Siloxy substituted methyl cyclopropanecar?ylates are cleaved by bromine to afford α-bromo-γ-oxoester and, after treatment with triethylamine, good yields of α,β-unsaturated γ-oxoesters.