Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target

Synthetic C peptides, corresponding to the C helix of the HIV type 1 (HIV-1) gp41 envelope protein, are potent inhibitors of HIV-1 membrane fusion. One such peptide is in clinical trials. The crystal structure of the gp41 core, in its proposed fusion-active conformation, is a trimer of helical hairpins in which three C helices pack against a central coiled coil. Each C helix shows especially prominent contacts with one of three symmetry-related, hydrophobic cavities on the surface of the coiled coil. We show that the inhibitory activity of the C peptide C34 depends on its ability to bind to this coiled-coil cavity. Moreover, examining a series of C34 peptide variants with modified cavity-binding residues, we find a linear relationship between the logarithm of the inhibitory potency and the stability of the corresponding helical-hairpin complexes. Our results provide strong evidence that this coiled-coil cavity is a good drug target and clarify the mechanism of C peptide inhibition. They also suggest simple, quantitative assays for the identification and evaluation of analogous inhibitors of HIV-1 entry.

The US Labour Immigration Scheme – All about being attractive? EU Perceptions and Stakeholders’ Perspectives Reviewed. Liberty and Security in Europe No. 67/September 2014

Labour immigration schemes that effectively attract qualified immigrant workers are a policy priority for many governments. But what are ‘attractive’ labour immigration schemes and policies? To whom are (or should) such policies (be) attractive? In Europe, the US is often portrayed as one of the most ‘attractive’ countries of immigration – if not the most ‘attractive’. This paper aims to analyse and provide a better understanding of the elements of the US immigration system that are supposedly attractive to foreign workers, by examining key features of the current and prospective US labour immigration rules. The paper finds that ‘attractiveness’ in this policy context is a highly malleable and flexible concept: What might be ‘attractive’ to one key stakeholder might not be to another.

Wild flowers worth notice : a selection of some of our native plants which are most attractive from their beauty, uses, or associations /

Mode of access: Internet.

Capital investments in Canada; some facts and figures respecting one of the most attractive investment fields in the world.

Mode of access: Internet.

Safer construction workplaces evident during the early 1990s.

Mode of access: Internet.

The singer's ladder, revealing the necessity of a serious approach to the most attractive and most difficult study in the world of art.

Mode of access: Internet.

The crown book of the beautiful, the wonderful, and the wise : presenting in attractive forms some of the most notable things in poetic literature, in science and in art, in history and biography, in earth, sea and sky, in philosophy and music /

Title within ornamental border, title in red and black.

Illustrated Cincinnati; a pictorial hand-book of the Queen city, comprising its architecture, manufacture, trade; its social, literary, scientific, and charitable institutions; its churches, schools and colleges; and all other principal points of interest to the visitor and resident, together with an account of the most attractive suburbs,

"Advertisements": p. 347-368.

Meatless menus, for lunch, dinner, and supper : being a series of attractive menus arranged to give adequate nourishment, with over 300 recipes drawn up specially for this book /

Includes indexes.

Creating--safe neighborhoods, safe streets, safe schools, safe workplaces using Illinois' drug laws.

Cover title.

Easy French cookery, containing over 300 economical and attractive recipes from a celebrated chef's note-book,

Mode of access: Internet.

Burritt, our alma mater : an attractive little book of facts and fiction, bringing up memories that cluster round Spencer's hills [with] letters from abroad by the late president, W. N. Billingsley /

Mode of access: Internet.

What works : workplaces without drugs.

Mode of access: Internet.

Non-additivity of attractive potentials in modeling of N-2 and Ar adsorption isotherms on graphitized carbon black and porous carbon by means of density functional theory

We present a new approach accounting for the nonadditivity of attractive parts of solid-fluid and fluidfluid potentials to improve the quality of the description of nitrogen and argon adsorption isotherms on graphitized carbon black in the framework of non-local density functional theory. We show that the strong solid-fluid interaction in the first monolayer decreases the fluid-fluid interaction, which prevents the twodimensional phase transition to occur. This results in smoother isotherm, which agrees much better with experimental data. In the region of multi-layer coverage the conventional non-local density functional theory and grand canonical Monte Carlo simulations are known to over-predict the amount adsorbed against experimental isotherms. Accounting for the non-additivity factor decreases the solid-fluid interaction with the increase of intermolecular interactions in the dense adsorbed fluid, preventing the over-prediction of loading in the region of multi-layer adsorption. Such an improvement of the non-local density functional theory allows us to describe experimental nitrogen and argon isotherms on carbon black quite accurately with mean error of 2.5 to 5.8% instead of 17 to 26% in the conventional technique. With this approach, the local isotherms of model pores can be derived, and consequently a more reliab * le pore size distribution can be obtained. We illustrate this by applying our theory against nitrogen and argon isotherms on a number of activated carbons. The fitting between our model and the data is much better than the conventional NLDFT, suggesting the more reliable PSD obtained with our approach.