News & views: New Scientific Opportunities at the European Synchrotron Radiation Facility

Approximately 400 participants learned about the latest scientific capabilities at the Stanford Synchrotron Radiation Lightsource (SSRL) and Linac Coherent Light Source (LCLS) during the 2013 Users' Meeting at the SLAC National Accelerator Laboratory, October 1–4, 2013. The Users' Meeting included more than a dozen workshops as well as scientific awards, poster presentations, and talks on the latest scientific trends, challenges, and opportunities.     

An improved method to predict second cross virial coefficients

A previous method of the author to calculate the second cross virial coefficients is re-considered to improve the reliability of the predictions and to reduce the number of empirical rules. The method is based on the reduced second cross coefficient at the normal boiling temperature, , whose value is always assumed equal to unity. This value is then extrapolated to the experimental temperatures using only two empirical constants: K₁, a corrective multiplying factor of and K, in an exponential term as a multiplying factor of temperature. To improve the reliability of the method, literature experimental data are grouped in three binary classes:

- non-polar or slightly polar fluids;

- at least one strongly polar fluid;

- strong interactions of the acid–base type.

Only the critical constants and the normal boiling temperature are required as input parameters.

Deviations of calculated results from experimental one are in the range 25–40 cm³ mol⁻¹ for the first and the second class and below 300 cm³ mol⁻¹ for the third class.     

A Constraint-Based Method for Project Scheduling with Time Windows

This paper presents a heuristic algorithm for solving RCPSP/max, the resource constrained project scheduling problem with generalized precedence relations. The algorithm relies, at its core, on a constraint satisfaction problem solving (CSP) search procedure, which generates a consistent set of activity start times by incrementally removing resource conflicts from an otherwise temporally feasible solution. Key to the effectiveness of the CSP search procedure is its heuristic strategy for conflict selection. A conflict sampling method biased toward selection of minimal conflict sets that involve activities with higher-capacity requests is introduced, and coupled with a non-deterministic choice heuristic to guide the base conflict resolution process. This CSP search is then embedded within a larger iterative-sampling search framework to broaden search space coverage and promote solution optimization. The efficacy of the overall heuristic algorithm is demonstrated empirically on a large set of previously studied RCPSP/max benchmark problems.     

Full configuration interaction study of the metal-insulator transition in model systems: LiN linear chains (N=2,4,6,8)

The precursor of the metal-insulator transition is studied at ab initio level in linear chains of equally spaced lithium atoms. In particular, full configuration interaction calculations (up to 1 x 10(9) determinants) are performed, in order to take into account the different nature of the wave function at different internuclear distances. Several indicators of the Metal-Insulator transition (minimum of the energy gap, maximum of the localization tensor or of the polarizability) are considered and discussed. It is shown that the different indicators give concordant results, showing a rapid change in the nature of the wave function at an internuclear distance of about 7 bohrs.     

Fragment-based de novo ligand design by multiobjective evolutionary optimization

GANDI (Genetic Algorithm-based de Novo Design of Inhibitors) is a computational tool for automatic fragment-based design of molecules within a protein binding site of known structure. A genetic algorithm and a tabu search act in concert to join predocked fragments with a user-supplied list of fragments. A novel feature of GANDI is the simultaneous optimization of force field energy and a term enforcing 2D-similarity to known inhibitor(s) or 3D-overlap to known binding mode(s). Scaffold hopping can be promoted by tuning the relative weights of these terms. The performance of GANDI is tested on cyclin-dependent kinase 2 (CDK2) using a library of about 14 000 fragments and the binding mode of a known oxindole inhibitor to bias the design. Top ranking GANDI molecules are involved in one to three hydrogen bonds with the backbone polar groups in the hinge region of CDK2, an interaction pattern observed in potent kinase inhibitors. Notably, a GANDI molecule with very favorable predicted binding affinity shares a 2-N-phenyl-1,3-thiazole-2,4-diamine moiety with a known nanomolar inhibitor of CDK2. Importantly, molecules with a favorable GANDI score are synthetic accessible. In fact, eight of the 1809 molecules designed by GANDI for CDK2 are found in the ZINC database of commercially available compounds which also contains about 600 compounds with identical scaffolds as those in the top ranking GANDI molecules.     

Quasi-one-dimensional K-O chain in PTCDA thin films: evidence from first-principles calculations

Using density functional theory calculations we have found that K atoms in a PTCDA (3,4:9,10-perylenetetracarboxylic dianhydride) crystal form a quasi-one-dimensional (1D) K-O chain interacting with carboxylic oxygen of the terminal anhydride groups of PTCDA. The K-K distance in the chain (3.72 Angstrom) is commensurate to the periodicity of the organic semiconductor. We obtain that the K-O structure is stabilized by charge transfer from K to PTCDA molecules, forming prevalently ionic bonds: the electronic density of the chemistry induced gap states is essentially delocalized on the perylene core of PTCDA, while potassium appears spoiled of its charge. Band dispersion along the direction of molecular stack is evaluated to be 0.2 eV in pure PTCDA crystal and 0.5 eV in the K-doped system, confirming that the interaction occurs between different molecular planes.     

Separation of O- and C-allyl glycoside anomeric mixtures by capillary electrophoresis and high-performance liquid chromatography

Rapid and reliable methods for the analysis of O- and C-allyl galactopyranosides and glucopyranosides are presented, based on capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC). In MEKC, the formation of chromophoric and charged complexes between the saccharides and borate as well as the hydrophobic interactions with micelles jointly contributed to the selective separation and sensitive detection of all the investigated anomeric couples. Some non-purified synthesis mixtures of C-allyl glycosides were successfully characterised without pre-treatment. MEKC buffer conditions for which glycosides separation was successfully achieved were then exported and applied to reverse-phase liquid chromatography (RP-HPLC), for the quantitative isolation of each allyl glycoside anomer. Identification of the obtained anomeric products was performed by electrospray mass spectrometry and (13)C NMR spectroscopy. Glycoside-solvent interactions driving the selective anomeric separation were shortly addressed and discussed on the basis of sugar derivatives structural differences.     

Developments in network location with mobile and congested facilities

We review four facility location problems which are motivated by urban service applications and which can be thought of as extensions of the classic Q-median problem on networks. In problems P1 and P2 it is assumed that travel times on network links change over time in a probabilistic way. In P2 it is further assumed that the facilities (servers) are movable so that they can be relocated in response to new network travel times. Problems P3 and P4 examine the Q-median problem for the case when the service capacity of the facilities is finite and, consequently, some or all of the facilities can be unavailable part of the time. In P3 the facilities have stationary home locations but in P4 they have movable locations and thus can be relocated to compensate for the unavailability of the busy facilities. We summarize our main results to date on these problems.     

1H dynamic nuclear magnetic resonance study of hindered internal rotation in N-aroyl- and N-thioaroyl-N′- piperonylpiperazines

The NMR variable temperature behaviour of N-aroyl- and N-thioaroyl-N′-piperonylpiperazines was investigated. The largest chemical shift separation between the exchanging methylene groups, and the highest energy barrier, is found for the thioamide compounds. Results from semi-empirical calculations are qualitatively in line with the experimental findings, revealing that the higher barrier in the thiocarbonyl compounds compared with the carbonyl compounds is mainly connected with differences in the energies of ground states, rather than in those of transition states, of these molecules. The effect of the nature of the heterocyclic ring containing the amidic nitrogen atom on the barrier height is also discussed.