Domain swapping in G-protein coupled receptor dimers

Computer simulations were performed on models of the beta2-adrenergicreceptor dimer, including 5,6-domain swapped dimers which have beenproposed as the active, high affinity form (here the dimer interface liesbetween helices 5 and 6). The calculations suggest that the domain swappeddimer is a high energy structure in both the apo dimer and in the presenceof propranolol. In the presence of agonist the energy of the domain swappeddimer is significantly lowered. Analysis of the dimer structure suggeststhat the agonist-induced conformational change optimizes the helix-helixinteractions at the 5-6 interface. An antagonist on the other hand haslittle effect on these interactions. These observations are consistent withthe hypothesis that the agonist functions by shifting the equilibrium infavour of the domain swapped dimer. Indirect support for the domainswapping hypothesis was obtained from the correlated mutations amongst theexternal residues of the known beta2-adrenergic receptors. These occurmainly at the 5-6 interface at precisely the locations predicted by thesimulations; site- directed mutagenesis data in support of a functionalrole for these lipid-facing correlated residues is presented. The articleincludes a review of the experimental evidence for G-protein coupledreceptor dimerization. Many other aspects of G-protein coupled receptoractivation are discussed in terms of this domain swapping hypothesis     

E-ARK Knowledge Center: Supporting the Definition and Assessment of Information Governance Practices

This article presents the knowledge center service, an aggregator of services developed under the scope of the E-ARK Project. This aims to provide a comprehensive set of services that will allow users to understand, contribute to, and validate information governance good practices. The knowledge center comprises two main services. The resources center is where users can learn more about information governance terms, requirements, and practice. It is composed of the vocabulary manager service and the reference requirements management service. The assessment services allow users to assess their information governance practices. It is comprised of the MoReq schemas validator service, the MoReq assessment, and the information governance maturity assessment.     

Investigation of impact ionization in thin GaAs diodes

The electron and hole multiplication coefficients, M_e and M_h, respectively, have been measured in thin GaAs homojunction PIN and NIP diodes and from conventional ionization analysis the effective electron and hole ionization coefficients, α and β, respectively, have been determined. The nominal intrinsic region thickness w of these structures ranges from 1.0 μm down to 25 nm. In the thicker structures, bulk-like behavior is observed; however, in the thinner structures, significant differences are found. As the i-regions become thinner and the electric fields increase, the M_e/M_h ratio is seen to approach unity. The experimental results are modeled and interpreted using a semianalytical solution of the Boltzmann equation. In thin (w⩽0.1 μm) devices the dead space effect reduces effective ionization coefficients below their bulk values at low values of carrier multiplication. However, overshoot effects compensate for this at extremely high fields (⩾1×10³ kV/cm)     

Adaptive-optics compensation in a Raman amplifier configuration

An experimental study of real-time adaptive compensation through a high-gain Raman amplifier is discussed. Atmospheric turbulence was simulated by selectively aberrated quartz plates designed to produce a turbulence-like phasefront distortion on a transmitted beacon. A 69-channel wavefront sensor measured the beacon's phasefront and commanded a deformable mirror to impose the conjugate phasefront on the Stokes seed to a high-gain, large-Fresnel-number Raman amplifier. After amplification, the output Stokes beam was made to retrace the path of the beacon back through the simulated turbulence. Measurements of the Stokes beam quality indicate a dramatic improvement to near-diffraction-limited performance. The experimental results are in good agreement with theory     

Review of the role of geographical information systems in housing: Potential areas for future research

The last decade has witnessed profound changes in the nature and function of local government in the British Isles. This has had major implications for the provision, management and control of housing. Decision‐making will require up‐to‐date information and the use of modern methods of analysis and display. This paper draws on a review of the published literature to demonstrate the potential for Geographical Information Systems (GIS) to aid this process especially in relation to the functions of local housing authorities. It is argued that GIS presents a technology whereby a great deal of data held by departments, much of which is spatially referenced, can be integrated in a corporate database to address housing management, maintenance and development issues. One area where GIS is perceived to have major benefits is in assisting housing needs assessment in local areas which, it is suggested, can have major benefits for local authorities in carrying out their ‘enabling’ functions.     

Relationship between composition and physical properties of a three-component sugar system

The relationship between composition and certain physical properties of water-sucrose-invert sugar solutions have been determined and means whereby the composition of any such solution may be derived from its refractive index and optical rotation are proposed.     

Use of terrestrial based lipids in aquaculture feeds and the effects on flesh organohalogen and fatty acid concentrations in farmed Atlantic salmon

Consumption of salmon, wild or farmed, has been encouraged by many scientists and by national and international health organizations due to the potential health benefits associated with their high contents of omega-3 (n-3) highly unsaturated fatty acids (n-3 HUFAs). In 2004, there was increased public concern regarding the safety of farmed Atlantic salmon following the publication of several studies that indicated higher levels of organohalogens in their flesh relative to those noted in the flesh of wild Pacific salmon. Farmed salmon obtain most of these contaminants from the consumption of marine fish oil (MFO) present in salmon feed. In both a laboratory feeding trial and an on-farm field study, partial replacement of MFO in aquaculture feeds with economical and abundant lipids of terrestrial origin resulted in farmed Atlantic salmon with reduced flesh polychlorinated biphenyl and polychlorinated dibenzodioxin and furan concentrations. Flesh levels of n-3 HUFAs (g/(100 g serving)) were lower in farmed Atlantic salmon fed diets with alternative lipids relative to farmed salmon fed more traditional MFO-based diets. However, the former salmon were found to have higher flesh levels of n-3 HUFAs and also similar or lower flesh levels of organic contaminants than some species of market-size wild Pacific salmon. These findings showthat consumption of either farmed Atlantic salmon or wild Pacific salmon can meet recommended weekly n-3 HUFA levels with minimal concurrent intake of flesh organohalogens.     

Effects of the benzodiazepine receptor inverse agonist Ro 15-4513 on the ingestion of sucrose and sodium saccharin solutions: A microstructural analysis of licking behavior.

The effects of the benzodiazepine receptor partial inverse agonist Ro 15-4513 on consumption of either a 1% sucrose solution or a 0.1% sodium saccharin solution in nondeprived male rats was examined. A video-recording approach was adopted in which licks were counted in a frame-by-frame analysis. Ro 15-4513 (1–10 mg/kg) caused a significant decrease in the intake of both sucrose and saccharin solutions that was associated with a reduction in the initial rate of licking. There was a decrease in the total duration of drinking, total licks, and number of bouts for both sucrose and saccharin. For sucrose, mean bout duration was significantly reduced, although this was not so for saccharin. Intrabout lick rate, the latency to engage in drinking, and the postdrinking time were not affected for either sucrose or saccharin. These data are consistent with previous evidence that strongly suggests that benzodiazepines influence palatability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The use of spatial analytical techniques to explore patterns of fire incidence: A South Wales case study

The application of mapping and spatial analytical techniques to explore geographical patterns of crime incidence is well established. In contrast, the analysis of operational incident data routinely collected by fire brigades has received relatively less research attention, certainly in the UK academic literature. The aim of this paper is to redress this balance through the application of spatial analytical techniques that permit an exploration of the spatial dynamics of fire incidents and their relationships with socio-economic variables. By examining patterns for different fire incident types, including household fires, vehicle fires, secondary fires and malicious false alarms in relation to 2001 Census of Population data for an area of South Wales, we demonstrate the potential of such techniques to reveal spatial patterns that may be worthy of further contextual study. Further research is needed to establish how transferable these findings are to other geographical settings and how replicable the findings are at different geographical scales. The paper concludes by drawing attention to the current gaps in knowledge in analysing trends in fire incidence and proposes an agenda to advance such research using spatial analytical techniques.