Continuous flow synthesis and scale-up of glycine- and taurine-conjugated bile salts

A multi-gram scale protocol for the N-acyl amidation of bile acids with glycine and taurine has been successfully developed under continuous flow processing conditions. Selecting ursodeoxycholic acid (UDCA) as the model compound and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) as the condensing agent, a modular mesoreactor assisted flow set-up was employed to significantly speed up the optimization of the reaction conditions and the flow scale-up synthesis. The results in terms of yield, in line purification, analysis, and implemented flow set-up for the reaction optimization and large scale production are reported and discussed.     

The influence of track modelling options on the simulation of rail vehicle dynamics

This paper investigates the effect of different models for track flexibility on the simulation of railway vehicle running dynamics on tangent and curved track. To this end, a multi-body model of the rail vehicle is defined including track flexibility effects on three levels of detail: a perfectly rigid pair of rails, a sectional track model and a three-dimensional finite element track model. The influence of the track model on the calculation of the nonlinear critical speed is pointed out and it is shown that neglecting the effect of track flexibility results in an overestimation of the critical speed by more than 10%. Vehicle response to stochastic excitation from track irregularity is also investigated, analysing the effect of track flexibility models on the vertical and lateral wheel–rail contact forces. Finally, the effect of the track model on the calculation of dynamic forces produced by wheel out-of-roundness is analysed, showing that peak dynamic loads are very sensitive to the track model used in the simulation.     

Effects of shear stiffness,rotatory and axial inertia,and interface stiffness on free vibrations of a two-layer beam

The linear dynamics of a two-layer beam is considered. Each beam is modelled by the Timoshenko kinematics, and all inertia terms are considered. The interface allows normal and tangential detachments, which are linearly proportional to the transmitted stresses. The eigenvalue problem providing the natural frequencies is solved exactly.An extensive study of the natural frequencies and of the normal modes is performed with the aim of understanding how the mechanical parameters of the composite influence the vibration behaviour.The study of the convergence of the solution toward that of a simplified problem obtained by neglecting axial and rotational inertia, shear deformations and by considering interface perfect adherence in the normal direction, constitutes the second objective of the work. This permits to consciously assess when these mechanical terms can actually be neglected, contrarily to what is usually done in practice, where they are disregarded ‘a priori’, without adequate care.     

The effects of electronic polarization on water adsorption in metal-organic frameworks: H(2)O in MIL-53(Cr)

The effects of electronic polarization on the adsorption of water in the MIL-53(Cr) metal-organic framework are investigated using molecular dynamics simulations. For this purpose a fully polarizable force field for MIL-53(Cr) was developed which is compatible with the ab initio-based TTM3-F water model. The analysis of the spatial distributions of the water molecules within the MIL-53(Cr) nanopores calculated as a function of loading indicates that polarization effects play an important role in the formation of hydrogen bonds between the water molecules and the hydroxyl groups of the framework. As a result, large qualitative differences are found between the radial distribution functions calculated with non-polarizable and polarizable force fields. The present analysis suggests that polarization effects can significantly impact molecular adsorption in metal-organic frameworks under hydrated conditions.     

Pair of Diastereomeric Uranyl Salen Cavitands Displaying Opposite Enantiodiscrimination of α-Amino Acid Ammonium Salts

A pair of diastereomeric salen cavitands and their uranyl complexes combine a chiral (R,R) salen bridge and an inherent chiral tris-bridged quinoxaline cup within the same molecule. Whereas the free ligands show a preference for the same enantiomer of an α-amino acid pair, the corresponding UO(2) complexes display opposite enantiodiscrimination and exceptionally high enantioselectivities (K(D)/K(L) = 26.4).     

A simple protocol for Matrix Assisted Laser Desorption Ionization- time of flight-mass spectrometry (MALDI-TOF-MS) analysis of lipids and proteins in single microsamples of paintings

A simple protocol, based on Bligh–Dyer (BD) extraction followed by MALDI-TOF-MS analysis, for fast identification of paint binders in single microsamples is proposed. For the first time it is demonstrated that the BD method is effective for the simultaneous extraction of lipids and proteins from complex, and atypical matrices, such as pigmented paint layers. The protocol makes use of an alternative denaturing anionic detergent (RapiGest™) in order to improve efficiency of protein digestion and purification step. Detection of various lipid classes, such as triacylglycerols (TAGs) and phospholipids (PLs), and their oxidation by-products was accomplished, whereas proteins could be identified by peptide mass fingerprinting. The effect of pigments on ageing of lipids and proteins was also investigated.     

Toward a fragment-based approach to MMPs inhibitors: an expedite and efficient synthesis of N-hydroxylactams

Matrix metalloproteinases (MMPs), a class of zinc-enzymes over-activated in many pathologies, such as arthritis and cancer, can be efficiently inhibited by a variety of molecules bearing zinc-binding groups (ZBGs). The hydroxamic acid moiety represents one of the most potent and widely exploited ZBG but the poor target selectivity and in vivo toxicity have tempered the initial enthusiasm for this class of potential therapeutics. These drawbacks might be circumvented, at least in part, by increasing the structural constraints around the hydroxamic moiety. Following this strategy we designed and prepared N-hydroxylactam molecules of different size through a synthetic protocol based on a ring closing metathesis amenable to a fragment-based approach potentially leading to a large molecular diversity.     

A Bayesian approach to vectorization of object boundaries from digital images and to geometrical uncertainty assessment

A new Bayesian approach is presented for extracting 2D object boundaries with measures of uncertainty. The boundaries are described by minimal closed sequences of segments and arcs, called mixed polygons. The sequence is minimal in the sense that it is able to describe all the geometrical properties of the boundary without being redundant. Based on geometrical measures evaluated on the object boundary model, a prior distribution is introduced in order to favor a mixed polygon with good geometrical properties, avoiding short sides, collinearity between segments, and so on. The estimation process is based on a two‐stage procedure that combines reversible‐jump MCMC (RJMCMC) and classic MCMC methods. The RJMCMC method is viewed as a model selection technique, and it is used to estimate the correct number of sides of the mixed polygon. The MCMC algorithm provides a sample of mixed polygons through which to evaluate the mixed polygon that best approximates the object boundary and its geometrical uncertainty. A convergence criterion for the RJMCMC method is provided. Copyright © 2011 John Wiley & Sons, Ltd.     

A new theoretical approach for structural modelling of riveted and spot welded multi-spot structures

A general theoretical approach based on theory of elasticity is presented in order to define the structural behaviour of riveted and spot welded joints. The new closed form solutions lead to the definition of a joint element useful to FE models of riveted or spot welded multi-spot structures. The objective is an accurate evaluation of the local elastic stiffness of spot joints in FE analysis, which is fundamental to perform a reliable simulation of multi-joint structures and, consequently, a good estimate of loads acting on spots; this makes it possible to introduce structural stress or new general criteria allowing, for example, to predict fatigue behaviour. On the other hand, a low entry of degrees of freedom is needed when several spot joints are present in a complex structure. The goal is to reach a reliable spot region model which can be used as the basis to develop a spot element in FE analysis. In the present paper, based on new closed form solutions, a spot element is introduced, so as to precisely evaluate both local and overall stiffness both of spot welded joints and riveted joints. Based on the stress function approach and the Kirchhoff plate theory in linear elastic hypotheses, closed-form in-plane stress, displacement, moment and transverse shear force solutions are derived for a new bidimensional model, subjected to various types of loads. The capability to simulate spot welds or rivets depends on the definition of two elastic parameters intrinsic in closed form solutions, that tunes the theoretical model according to actual joint behaviour.The proposed joint element combines the precision in the simulation with a very limited number degrees of freedom in the overall finite element model of an actual multi-spot structure.The results obtained using the introduced theoretical framework and spot element approach perfectly match those obtained using very refined FE models and experimental data.