Combinatorial synthesis of substituted biaryls and heterocyclic arylamines

In this paper, we report very general conditions that enable palladium-mediated coupling reactions on the solid support. A wide variety of biaryls and arylamines (including pyrimidines) have been synthesized using this protocol. The chemistry facilitates a combinatorial approach to the production of large numbers of medicinally relevant heterocyclic structures.     

Intermediate 16+16 multiplets inN=1 supergravity

Using the formalism developed by Ogievetsky and Sokatchev forN=1 Supergravity, we analyse the intermediate 16+16 sets (with one auxiliary spinor).     

Some features of the spectra and electric dipole transitions of (tt) and (tu) states

In this short note, with the help of a variational method, we show heavy quarkonia and open flavour states can be used to test the short and long range behaviour of the interquark forces.     

Quarkonia with a variational method

A variational method, based in independent minimization of energy levels, is applied to quantum mechanical quarkonium systems. A discussion is presented of the method, with emphasis on quark mass dependence of energy levels (Feynman-Hellman theorem), on the behaviour of wave functions at the origin (Martin's theorem) and on the ordering of energy levels. The potential used in the applications is the Coulomb (4-vector) + Linear (4-scalar) potentials, the fine and hyperfine splittings being included by means of the Fermi-Breit hamiltonian. An attempt is made for an overall treatment of the known splittings (radials-wave, hyperfine and fine splittings) for all quarkonium systems, using an approximately flavour independent potential. Thep-wave splittings, as well as the hyperfine splittings, are shown to be particularly sensitive to the nature and mass dependence of the potential. In particular, asymptotic freedom can be more easily tested there. On the other hand, radial excitations provide the place where the set up of short range potential effects should be first detected. Some results concerning the ordinary mesons are presented, and it is specifically pointed out that strong restrictions exist for the masses of the ρ′ and theA ₁. Predictions for the toponium family are also presented.     

A study of the charmonium,upsilon and strangeonium systems

We study the charmonium, upsilon and strangeonium systems with a linear+Coulomb potential, in the high α _s regime. Our approach is based on the Bethe-Salpeter equation, in ladder approximation, and the most interesting conclusion of our work seems to be that it is not possible to fit these three families of mesons using the same set of values for the parameters defining the potential.     

A rational method for probing macromolecules dissociation: the antibody-hapten system

The unbinding process of a protein-ligand complex of major biological interest was investigated by means of a computational approach at atomistic classical mechanical level. An energy minimisation-based technique was used to determine the dissociation paths of the system by probing only a relevant set of generalized coordinates. The complex problem was reduced to a low-dimensional scanning along a selected distance between the protein and the ligand. Orientational coordinates of the escaping fragment (the ligand) were also assessed in order to further characterise the unbinding. Solvent effects were accounted for by means of the Poisson–Boltzmann continuum model. The corresponding dissociation time was derived from the calculated barrier height, in compliance with the experimentally reported Arrhenius-like behaviour. The computed results are in good agreement with the available experimental data.     

A decomposition approach for the integrated vehicle-crew-roster problem with days-off pattern

The integrated vehicle-crew-roster problem with days-off pattern aims to simultaneously determine minimum cost vehicle and daily crew schedules that cover all timetabled trips and a minimum cost roster covering all daily crew duties according to a pre-defined days-off pattern. This problem is formulated as a new integer linear programming model and is solved by a heuristic approach based on Benders decomposition that iterates between the solution of an integrated vehicle-crew scheduling problem and the solution of a rostering problem. Computational experience with data from two bus companies in Portugal and data from benchmark vehicle scheduling instances shows the ability of the approach for producing a variety of solutions within reasonable computing times as well as the advantages of integrating the three problems.     

Inter-laboratory comparison of elemental analysis and gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS). Part I: delta13C measurements of selected compounds for the development of an isotopic Grob-test

This study was directed towards investigating suitable compounds to be used as stable isotope reference materials for gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) calibration. Several compounds were selected from those used in the 'Grob-test' mixture. Oxygen- and nitrogen-containing substances were added to these compounds to allow the mixture to be used as a possible multi-isotopic calibration tool for 2H/1H, 13C/12C, 15N/14N and 18O/16O ratio determinations. In this paper we present the results of delta13C measurements performed by the consortium of the five laboratories taking part in this inter-calibration exercise. All the compounds were individually assessed for homogeneity, short-term stability and long-term stability by means of EA-IRMS, as required by the bureau communitaire de reference (BCR) Guide for Production of Certified Reference Materials. The results were compared then with the GC-C-IRMS measurements using both polar and non-polar columns, and the final mixture of selected compounds underwent a further certification exercise assessing limits of accuracy and reproducibility under specified GC-C-IRMS conditions.     

Pathways to folding, nucleation events, and native geometry

We perform extensive Monte Carlo simulations of a lattice model and the Gō potential [N. Gō and H. Taketomi, Proc. Natl. Acad. Sci. U.S.A. 75, 559563 (1978)] to investigate the existence of folding pathways at the level of contact cluster formation for two native structures with markedly different geometries. Our analysis of folding pathways revealed a common underlying folding mechanism, based on nucleation phenomena, for both protein models. However, folding to the more complex geometry (i.e., that with more nonlocal contacts) is driven by a folding nucleus whose geometric traits more closely resemble those of the native fold. For this geometry folding is clearly a more cooperative process.