Speeding up European Reform: A Master Plan for the Lisbon Process -Dinner Speech

Entwicklung, EU-Staaten, Economic development, EU countries

The influence of geometry, surface character and flexibility on the permeation of ions and water through biological pores

A hydrophobic constriction site can act as an efficient barrier to ion and water permeation if its diameter is less than the diameter of an ion's first hydration shell. This hydrophobic gating mechanism is thought to operate in a number of ion channels, e.g. the nicotinic receptor, bacterial mechanosensitive channels (MscL and MscS) and perhaps in some potassium channels (e.g. KcsA, MthK, and KvAP). Simplified pore models allow one to investigate the primary characteristics of a conduction pathway, namely its geometry (shape, pore length, and radius), the chemical character of the pore wall surface, and its local flexibility and surface roughness. Our extended (ca. 0.1 \mu s) molecular dynamic simulations show that a short hydrophobic pore is closed to water for radii smaller than 0.45 nm. By increasing the polarity of the pore wall (and thus reducing its hydrophobicity) the transition radius can be decreased until for hydrophilic pores liquid water is stable down to a radius comparable to a water molecule's radius. Ions behave similarly but the transition from conducting to non-conducting pores is even steeper and occurs at a radius of 0.65 nm for hydrophobic pores. The presence of water vapour in a constriction zone indicates a barrier for ion permeation. A thermodynamic model can explain the behaviour of water in nanopores in terms of the surface tensions, which leads to a simple measure of "hydrophobicity" in this context. Furthermore, increased local flexibility decreases the permeability of polar species. An increase in temperature has the same effect, and we hypothesise that both effects can be explained by a decrease in the effective solvent-surface attraction which in turn leads to an increase in the solvent-wall surface free energy.Comment: Peer reviewed article appeared in Physical Biology http://www.iop.org/EJ/abstract/1478-3975/1/1/005

Efficient solution of 3D electromagnetic eddy-current problems within the finite volume framework of OpenFOAM

Eddy-current problems occur in a wide range of industrial and metallurgical applications where conducting material is processed inductively. Motivated by realising coupled multi-physics simulations, we present a new method for the solution of such problems in the finite volume framework of foam-extend, an extended version of the very popular OpenFOAM software. The numerical procedure involves a semi-coupled multi-mesh approach to solve Maxwell's equations for non-magnetic materials by means of the Coulomb gauged magnetic vector potential and the electric scalar potential. The concept is further extended on the basis of the impressed and reduced magnetic vector potential and its usage in accordance with Biot-Savart's law to achieve a very efficient overall modelling even for complex three-dimensional geometries. Moreover, we present a special discretisation scheme to account for possible discontinuities in the electrical conductivity. To complement our numerical method, an extensive validation is completing the paper, which provides insight into the behaviour and the potential of our approach.Comment: 47 pages, improved figures, updated references, fixed typos, reverse phase shift, consistent use of inner produc

Path Similarity Analysis: a Method for Quantifying Macromolecular Pathways

Diverse classes of proteins function through large-scale conformational changes; sophisticated enhanced sampling methods have been proposed to generate these macromolecular transition paths. As such paths are curves in a high-dimensional space, they have been difficult to compare quantitatively, a prerequisite to, for instance, assess the quality of different sampling algorithms. The Path Similarity Analysis (PSA) approach alleviates these difficulties by utilizing the full information in 3N-dimensional trajectories in configuration space. PSA employs the Hausdorff or Fr\'echet path metrics---adopted from computational geometry---enabling us to quantify path (dis)similarity, while the new concept of a Hausdorff-pair map permits the extraction of atomic-scale determinants responsible for path differences. Combined with clustering techniques, PSA facilitates the comparison of many paths, including collections of transition ensembles. We use the closed-to-open transition of the enzyme adenylate kinase (AdK)---a commonly used testbed for the assessment enhanced sampling algorithms---to examine multiple microsecond equilibrium molecular dynamics (MD) transitions of AdK in its substrate-free form alongside transition ensembles from the MD-based dynamic importance sampling (DIMS-MD) and targeted MD (TMD) methods, and a geometrical targeting algorithm (FRODA). A Hausdorff pairs analysis of these ensembles revealed, for instance, that differences in DIMS-MD and FRODA paths were mediated by a set of conserved salt bridges whose charge-charge interactions are fully modeled in DIMS-MD but not in FRODA. We also demonstrate how existing trajectory analysis methods relying on pre-defined collective variables, such as native contacts or geometric quantities, can be used synergistically with PSA, as well as the application of PSA to more complex systems such as membrane transporter proteins.Comment: 9 figures, 3 tables in the main manuscript; supplementary information includes 7 texts (S1 Text - S7 Text) and 11 figures (S1 Fig - S11 Fig) (also available from journal site

Erotic positions for two consenting males : considerations for a gay painting practise : an exegesis presented with exhibition as fulfillment of the requirements for thesis Master of Fine Arts at Massey University, Wellington, New Zealand

This exegesis is an exploration into painting and gay visual culture, and investigates what might constitute a "gay painting practise". It discusses my focus on the work of American photographer Bob Mizer and Physique Pictorial as source material for painting and the questions it raises regarding queer histories, gay sexuality and camp sensibilities. It considers the idea of queer utopian memory as a framework of looking back to moments of "sexual possibility" in order to transmit and receive utopian visions across intergenerational divides. It also considers gay sexuality, its ability to reimagine and restructure notions of intimacy, and its role in resisting gay assimilationist narratives. Drawing on the writings of various queer theorists, this exegesis considers how colour, form and content may contribute to a queer aesthetic. Making the argument for camp as a style of relating to things, I aim to situate my painting practise as a "gay painting practise" through a network of gay associations, affiliations and references

Prediction of hydration free energies for aliphatic and aromatic chloro derivatives using molecular dynamics simulations with the OPLS-AA force field

International audienceAll-atom molecular dynamics computer simulations were used to blindly predict the hydration free energies of a range of chloro-organic compounds as part of the SAMPL3 challenge. All compounds were parameterized within the framework of the OPLS-AA force field, using an established protocol to compute the absolute hydration free energy via a windowed free energy perturbation approach and thermodynamic integration. Three different approaches to deriving partial charge parameters were pursued: (1) using existing OPLS-AA atom types and charges with minor adjustments of partial charges on equivalent connecting atoms; (2) calculation of quantum mechanical charges via geometry optimization, followed by electrostatic potential (ESP) fitting, using Jaguar at the LMP2/cc-pVTZ(-F) level; and (3) via geometry optimization and CHelpG charges (Gaussian03 at the HF/6-31G* level), followed by two-stage RESP fitting. Protocol 3 generated the most accurate predictions with a root mean square (RMS) error of 1.2 kcal·mol −1 for the entire data set. It was found that the deficiency of the standard OPLS-AA parameters, protocol 1 (RMS error 2.4 kcal·mol −1 overall), was mostly due to compounds with more than three chlorine substituents on an aromatic ring. For this latter subset, the RMS errors were 1.4 kcal·mol −1 (protocol 3) and 4.3 kcal·mol −1 (protocol 1), respectively. We propose new OPLS-AA atom types for aromatic carbon and chlorine atoms in rings with ≥ 4 Cl-substituents that perform better than the best QM-based approach, resulting in an RMS error of 1.2 kcal·mol −1 for these difficult compounds