“Efforts to Reprioritise the Agenda” in China: British American Tobacco's Efforts to Influence Public Policy on Secondhand Smoke in China

Monique Muggli and colleagues study British American Tobacco (BAT) internal documents and find that from the mid 1990s BAT pursued a strategy aimed at influencing the public debate on secondhand smoke in China

New Binding Mode to TNF-Alpha Revealed by Ubiquitin-Based Artificial Binding Protein

A variety of approaches have been employed to generate binding proteins from non-antibody scaffolds. Utilizing a beta-sheet of the human ubiquitin for paratope creation we obtained binding proteins against tumor necrosis factor (TNF)-alpha. The bioactive form of this validated pharmacological target protein is a non-covalently linked homo-trimer. This structural feature leads to the observation of a certain heterogeneity concerning the binding mode of TNF-alpha binding molecules, for instance in terms of monomer/trimer specificity. We analyzed a ubiquitin-based TNF-alpha binder, selected by ribosome display, with a particular focus on its mode of interaction. Using enzyme-linked immunosorbent assays, specific binding to TNF-alpha with nanomolar affinity was observed. In isothermal titration calorimetry we obtained comparable results regarding the affinity and detected an exothermic reaction with one ubiquitin-derived binding molecule binding one TNF-alpha trimer. Using NMR spectroscopy and other analytical methods the 1∶3 stoichiometry could be confirmed. Detailed binding analysis showed that the interaction is affected by the detergent Tween-20. Previously, this phenomenon was reported only for one other type of alternative scaffold-derived binding proteins – designed ankyrin repeat proteins – without further investigation. As demonstrated by size exclusion chromatography and NMR spectroscopy, the presence of the detergent increases the association rate significantly. Since the special architecture of TNF-alpha is known to be modulated by detergents, the access to the recognized epitope is indicated to be restricted by conformational transitions within the target protein. Our results suggest that the ubiquitin-derived binding protein targets a new epitope on TNF-alpha, which differs from the epitopes recognized by TNF-alpha neutralizing antibodies

Towards a Pharmacophore for Amyloid

Diagnosing and treating Alzheimer's and other diseases associated with amyloid fibers remains a great challenge despite intensive research. To aid in this effort, we present atomic structures of fiber-forming segments of proteins involved in Alzheimer's disease in complex with small molecule binders, determined by X-ray microcrystallography. The fiber-like complexes consist of pairs of β-sheets, with small molecules binding between the sheets, roughly parallel to the fiber axis. The structures suggest that apolar molecules drift along the fiber, consistent with the observation of nonspecific binding to a variety of amyloid proteins. In contrast, negatively charged orange-G binds specifically to lysine side chains of adjacent sheets. These structures provide molecular frameworks for the design of diagnostics and drugs for protein aggregation diseases

Results from the GPS Experiment on Equator-S

An encouraging concept for position determination of geostationary satellites is the use of the Global Positioning System (GPS). Although the geostationary orbit is well beyond the orbits of the GPS Navstar satellites (i.e. 20 000 km), it is possible to use GPS - as demonstrated with the GPS experiment on board of the German Small Satellite Equator-S. The experiment data have significant impact for the future use of GPS receivers on-board geostationary satellites. In the past, GPS receivers have only been used well below the orbital altitude of the GPS satellites. The reception of GPS signals at greater altitudes has been demonstrated within the Equator-S GPS experiment. As part of this, GPS signals have also been received from the antenna side lobes of the GPS satellites. The maximum altitude where the GPS receiver provided measurements was about 61 000 km

GPS Performance for GEO`s - the Equator-S Spacecraft Mission

The successfully usage of spaceborne GPS receivers for orbit- and attitude determination has in the past mainly been applied for spacecraft in near-circular Low Earth Orbits (LEO), e.g. TOPEX/POSEIDON, RADCAL. However, no experience exists of using GPS signals for Spacecraft navigation in altitudes above the GPS (20.000 km), such as the Geostationary Orbit (GTO). In this context, EQUATOR-S with it`s highly ellipitcal orbit offers a unique possibility in order to increases significantly the experience concerning GPS visibility, signal reception and GPS based navigation. The application of GPS based spacecraft navigation in GEO`s and GEO`s will bring advantages in many aspects. Besides orbit/attitude determination, GPS offers a potential for increasing command capabilities and decreasing ground station support. This will lead to a reduction of mission cost especially for LEOP phase of geostationary satellites. This paper describes first experiences in operating a GPS receiver in a highly elliptical orbit and presents first results of GPS visibilty and signal reception conditions within this orbit