A possible model of benzimidazole binding to beta-tubulin disclosed by invoking an inter-domain movement.

Although it is well established that benzimidazole (BZMs) compounds exert their therapeutic effects through binding to helminth beta-tubulin and thus disrupting microtubule-based processes in the parasites, the precise location of the benzimidazole-binding site on the beta-tubulin molecule has yet to be determined. In the present study, we have used previous experimental data as cues to help identify this site. Firstly, benzimidazole resistance has been correlated with a phenylalanine-to-tyrosine substitution at position 200 of Haemonchus contortus beta-tubulin isotype-I. Secondly, site-directed mutagenesis studies, using fungi, have shown that other residues in this region of the protein can influence the interaction of benzimidazoles with beta-tubulin. However, the atomic structure of the alphabeta-tubulin dimer shows that residue 200 and the other implicated residues are buried within the protein. This poses the question: how might benzimidazoles interact with these apparently inaccessible residues? In the present study, we present a mechanism by which those residues generally believed to interact with benzimidazoles may become accessible to the drugs. Furthermore, by docking albendazole-sulphoxide into a modelled H. contortus beta-tubulin molecule we offer a structural explanation for how the mutation conferring benzimidazole resistance in nematodes may act, as well as a possible explanation for the species-specificity of benzimidazole anthelmintics.

Electron-impact fragmentation of Cl2-

merged beam technique has been used to investigate the fragmentation of the Cl ion in collisions with electrons over an energy range of 0–200 eV. We have measured absolute cross sections for detachment, detachment plus dissociation and dissociation processes. Over the energy range studied, the dominant breakup mechanism is dissociation. Dissociation is relatively enhanced in the e–+Cl collision system due to the suppression of the normally dominant detachment process, as a result of the large difference between the equilibrium internuclear distances of the Cl2 and Cl ground state potential curves. A prominent structure is observed just above the threshold in the Cl–+Cl+e– dissociation channel. It is proposed that the structure is a resonance associated with production and rapid decay of an excited state of the doubly charged Cl ion. A plausible mechanism for production of the di-anionic state based on an excitation plus capture process is suggested.

Radiative lifetimes of metastable states of negative ions

We present a technique for measuring the radiative lifetimes of metastable states of negative ions that involves the use of a heavy-ion storage ring. The method has been applied to investigate the radiative decay of the np3 2P1/2 levels of Te–(n=5) and Se–(n=4) and the 3p3 2D state of Si– for which the J=3/2 and 5/2 levels were unresolved. All of these states are metastable and decay primarily by emission of E2 and M1 radiation. Multi Configuration Dirac-Hartree-Fock calculations of rates for the transitions in Te– and Se– yielded lifetimes of 0.45 s and 4.7 s, respectively. The measured values agree well with these predicted values. In the case of the 2D state of Si–, however, our measurement was only able to set a lower limit on the lifetime. The upper limit of the lifetime that can be measured with our apparatus is set by how long the ions can be stored in the ring, a limit determined by the rate of collisional detachment. Our lower limit of 1 min for the lifetime of the 2D state is consistent with both the calculated lifetimes of 162 s for the 2D3/2 level and 27.3 h for the 2D5/2 level reported by O'Malley and Beck and 14.5 h and 12.5 h, respectively, from our Breit-Pauli calculations.

Predicting physical properties of ionic liquids

A simple method to predict the densities of a range of ionic liquids from their surface tensions, and vice versa, using a surface-tension-weighted molar volume, the parachor, is reported. The parachors of ionic liquids containing 1-alkyl-3-methylimidazolium cations were determined experimentally, but were also calculated directly from their structural compositions using existing parachor contribution data for neutral compounds. The calculated and experimentally determined parachors were remarkably similar, and the latter data were subsequently employed to predict the densities and surface tensions of the investigated ionic liquids. Using a similar approach, the molar refractions of ionic liquids were determined experimentally, as well as calculated using existing molar refraction contribution data for uncharged compounds. The calculated molar refraction data were employed to predict the refractive indices of the ionic liquids from their surface tensions. The errors involved in the refractive index predictions were much higher than the analogous predictions employing the parachor, but nevertheless demonstrated the potential for developing parachor and molar refraction contribution data for ions as tools to predict ionic liquid physical properties.

Analytically continued generalized continuum distorted waves

The continuum distorted-wave eikonal-initial-state (CDW-EIS) theory of Crothers and McCann (Crothers DSF and McCann JF, 1983 J. Phys. B: At. Mol. Opt. Phys. 16 3229 ) used to describe ionization in ion-atom collisions is generalized (G) to GCDW-EIS, to incorporate the azimuthal ange dependence into the final-state wavefunction. This is accomplished by the analytic continuation of hydrogenic-like wavefunctions from below to above threshold, using parabolic coordinates and quantum numbers including magnetic quantum numbers, thus providing a more complete set of states. At impact energies lower than 25 ke V u^{-1}, the total CDW-EIS ionization cross section falls off, with decreasing energy, too quickly in comparison with experimental data by Crothers and McCann. The idea behind and motivation for the GCDW-EIS model is to improve the theory with respect to experiment, by including contributions from non-zero magnetic quantum numbers. We also therefore incidentally provide a new derivation of the theory of continuum distorted waves for zero magnetic quantum numbers while simultaneously generalizing it.

Enhanced transmission in microwave arrays of periodic sub-wavelength apertures

In this paper we have conclusively proven that the "enhanced" optical transmission through a periodic array of sub-wavelength holes in metal films (Ebbessen's experiment) is the result of the array periodicity. This work has overturned the commonly accepted theory that the surface plasmons were responsible for the transmission enhancement. It was demonstrated that the reflectance, transmittance and frequency selectivity of the multilayered arrays can be efficiently modified by the aperture shapes.

Investigation of precision grinding process for production of silicon diaphragms

The application of precision grinding for the formation of a silicon diaphragm is investigated. The test structures involved 2-6 mm diam diaphragms with thicknesses in the range of 25-150 //m. When grinding is performed without supporting the diaphragm, bending occurs due to nonuniform removal of the silicon material over the diaphragm region. The magnitude of bending depends on the µNal thickness of the diaphragm. The results demonstrate that the use of a porous silicon support can significantly reduce the amount of bending, by a factor of up to 300 in the case of 50 m thick diaphragms. The use of silicon on insulator (SOI) technology can also suppress or eliminate bending although this may be a less economical process. Stress measurements in the diaphragms were performed using x-ray and Raman spectroscopies. The results show stress of the order of 1 X107-! X108 Pa in unsupported and supported by porous silicon diaphragms while SOI technology provides stress-free diaphragms. Results obtained from finite element method analysis to determine deterioration in the performance of a 6 mm diaphragm due to bending are presented. These results show a 10% reduction in performance for a 75 µm thick diaphragm with bending amplitude of 30 fim, but negligible reduction if the bending is reduced to

Theory of the near K-edge structure in electron energy loss spectroscopy

Arguments are given that lead to a formalism for calculating near K-edge structure in electron energy loss spectroscopy (EELS). This is essentially a one electron picture, while many body effects may be introduced at different levels, such as the local density approximation to density functional theory or the GW approximation to the electron self-energy. Calculations are made within the all electron LMTO scheme in crystals with complex atomic and electronic structures, and these are compared with experiment. (c) 2004 Elsevier B.V. All rights reserved.

On the solvation of L-aspartic acid

We use molecular statics and dynamics to study the stability of L-aspartic acid both in vacuo and solvated by polar and non-polar molecules using density functional theory in the generalized gradient approximation. We find that structures stable in vacuo are unstable in aqueous solution and vice versa. From our simulations we are able to come to some conclusions about the mechanism of stabilisation of zwitterions by polar protic solvents, water and methanol.

Importance of the H- channel in Ps-H scattering

It is shown that virtual H- formation has a profound effect upon low-energy Ps(1s)-H(1s) scattering, yet H- formation only accounts for about 10% of the total cross section just above threshold. Infinite series of Rydberg resonances converging on to the H- formation threshold are seen.

Second-order distorted wave calculation for electron impact ionization of hydrogen

The triple differential cross sections for ionization of atomic hydrogen by electron impact are analysed in the case of coplanar, asymmetric geometry within the framework of second- order distorted wave theory. Detailed calculations are performed without making any approximations (other than numerical) in the evaluation of the second-order amplitude. The present results are compared with experimental measurements and other theoretical calculations for incident energies of 250, 150 and 54.4 eV. It is found that the second-order calculations represent a marked improvement over the results obtained from first-order theories for impact energies of 150 eV and higher. The close agreement between the present second-order plane wave calculation and those of Byron et al calculated using the closure approximation at an incident energy of 250 eV implies that the closure approximation is valid for this energy. The large difference between the present second-order distorted wave calculations and experiment at an incident energy of 54.4 eV suggests that higher order effects are important for incident energies less than 100 eV.

Fully differential cross sections for transfer ionization - a sensitive probe of high level correlation effects in atoms

The transfer ionization process offers a unique opportunity to study radial and angular electron correlations in the helium atom. We report calculations for the multiple differential cross sections of the transfer ionization process p + He --> H + He++ + e(-). The results of these calculations demonstrate the strong sensitivity of the fully differential cross sections to fine details of electron correlation in the target atom. Specifically, angular electron correlation in the ground state of helium results in a broad peak in the electron emission spectra in the backward direction, relative to the incoming beam. Our model explains some of the key effects observed in measurements of multiple differential cross sections using the COLTRIMS technique.