beta-arrestin binding to the beta(2)-adrenergic receptor requires both receptor phosphorylation and receptor activation

Homologous desensitization of beta(2)-adrenergic receptors has been shown to be mediated by phosphorylation of the agonist-stimulated receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by binding of beta-arrestins to the phosphorylated receptor. Binding of beta-arrestin to the receptor is a prerequisite for subsequent receptor desensitization, internalization via clathrin-coated pits, and the initiation of alternative signaling pathways. In this study we have investigated the interactions between receptors and beta-arrestin2 in living cells using fluorescence resonance energy transfer. We show that (a) the initial kinetics of beta-arrestin2 binding to the receptor is limited by the kinetics of GRK2-mediated receptor phosphorylation; (b) repeated stimulation leads to the accumulation of GRK2-phosphorylated receptor, which can bind beta-arrestin2 very rapidly; and (c) the interaction of beta-arrestin2 with the receptor depends on the activation of the receptor by agonist because agonist withdrawal leads to swift dissociation of the receptor-beta-arrestin2 complex. This fast agonist-controlled association and dissociation of beta-arrestins from prephosphorylated receptors should permit rapid control of receptor sensitivity in repeatedly stimulated cells such as neurons.

Design, implementation and testing of an intelligent knowledge-based system for the supervisory control of a hot rolling mill

This paper describes the design, implementation and testing of an intelligent knowledge-based supervisory control (IKBSC) system for a hot rolling mill process. A novel architecture is used to integrate an expert system with an existing supervisory control system and a new optimization methodology for scheduling the soaking pits in which the material is heated prior to rolling. The resulting IKBSC system was applied to an aluminium hot rolling mill process to improve the shape quality of low-gauge plate and to optimise the use of the soaking pits to reduce energy consumption. The results from the trials demonstrate the advantages to be gained from the IKBSC system that integrates knowledge contained within data, plant and human resources with existing model-based systems. (c) 2005 Elsevier Ltd. All rights reserved.

10,000 years in the life of the river Wandle: excavations at the former Vinamul site, Butter Hill, Wallington

Archaeological excavations alongside the river Wandle in Wallington produced evidence of the environmental history and human exploitation of the area. The recovery of a large assemblage of struck flint provided information on the nature of the prehistoric activities represented, while a detailed environmental archaeological programme permitted an examination of both the local sediment successions and thus an opportunity to reconstruct the environmental history of the site. The site revealed a complex sedimentary sequence deposited in riverine conditions, commencing during the early Holocene (from c 10,000 years before present) and continuing through the late Holocene (c last 3000 years). Large flint nodules were washed by the river onto the site where they were procured and worked by Mesolithic and Bronze Age communities. Potentially usable nodules had been tested, and suitable pieces completely reduced, while the majority of useful flakes and blades had been removed for use elsewhere. Small numbers of retouched pieces, such as scrapers and piercers, indicate that domestic activities took place nearby. By the Saxon period the site had begun to stabilise, although it remained marshy and probably peripheral to habitation. Two pits from this period were excavated, one of which contained an antler pick. A small quantity of cereal grain also suggests that cultivated land lay in the vicinity of the site. During the 19th century a mill race was dug across the site, redirecting water from the river Wandle, which resulted in episodic flooding.

The impact of buy to let residential investment on local housing markets: evidence from Glasgow, Scotland

The advent of the 'buy to let' (BTL) phenomenon in the UK. apart from producing a new wave of individualized rental market investment, has been widely judged to be a speculative and destabilizing force in the housing market. This paper provides a detailed empirical investigation of new residential investment in one city (Glasgow) where BTL has made a relatively large impact. In seeking to overcome data problems, the study employed qualitative (expert interviews and a landlord survey) and quantitative methods (census, the Register of Sasines, standardized house price information and modelling thereof) in order to assess the nature and scale of BTL, the motivations of investors and its impact on the private housing market. The evidence suggests that white Glasgow is in many re.spects different to rental markets elsewhere in the UK and although the investment has thus far largely occurred in a benign environment, the context for future investment, on balance, looks sustainable (i.e.favourable changes to pension planning law and the maturing market for BTL}. Long-term market impact is an empirical question that depends on the specific interactions of market niches or segments (i.e. the first-time buyer market for apartments} with potential buy to let investment. Our conclusion, to borrow a Scottish legal term, is that BTL induced volatility is 'not proven'.

Integrated palaeoecology and archaeology: a powerful approach for understanding pre-Columbian Amazonia

The old paradigm that Amazonia's tropical ecosystems prevented cultural development beyond small-scale shifting agricultural economies, that had little environmental impact, no longer holds true for much of Amazonia. A diversity of archaeological evidence, including terra preta soils, raised fields, causeways, large habitation mounds, geometric earthworks, and megalithic monuments, all point to considerable cultural complexity and environmental impacts. However, uncertainty remains over the chronology of these cultures, their diet and economy, and the scale of environmental impact and land use associated with them. Here, we argue that a cross-disciplinary approach, closely coupling palaeoecology and archaeology, can potentially resolve these uncertainties. We show how, with careful site selection (pairing small and large lakes, close proximity to archaeological sites, transects of soil pits) and choice of techniques (e.g., pollen, phytoliths, starch grains, charcoal, stable isotopes), these two disciplines can be successfully integrated to provide a powerful tool for investigating the relationship between pre-Columbian cultures and their environment.

WCSC 2013: the 3rd World Chess Software Championship

The 3rd World Chess Software Championship took place in Yokohama, Japan during August 2013. It pits chess engines against each other on a common hardware platform - in this instance, the Intel i7 2740 Ivy Bridge with 16GB RAM supporting a potential eight processing threads. It was narrowly won by HIARCS from JUNIOR and PANDIX with JONNY, SHREDDER and MERLIN taking the remaining places. Games, occasionally annotated, are available here.

Pit clusters and the temporality of occupation: an earlier Neolithic site at Kilverstone, Thetford, Norfolk

This paper discusses 226 earlier Neolithic pits found at Kilverstone in Norfolk. In particular, it focuses on the dynamics involved in the site's creation, investigating what had happened to the material found in the pits prior to deposition, and exploring the material connections (refitting sherds and flints) across the site. As a result of these material insights, it proved possible to shed important light on the character of that place in particular, and on the temporality of Neolithic deposition and occupation in general.

The concentration of creditors: evidence from small businesses

This article examines the determinants of concentration of creditors. The empirical evidence drawn from this article supports the proposition of Bolton and Scharfstein (1996) that for negotiation reasons, high-quality borrowers tend to borrow from multiple sources and is contrary to the theoretical prediction of Bris and Welch (2005). This finding implies the existence of hold-up problems in financing small businesses where information conveyance is difficult between lenders. It is further supported by the evidence that dispersed bank relationships are associated with relationships of a longer history and a closer physical distance to lenders.

Mediated action and sexual risk: Searching for 'culture' in discourses of homosexuality and AIDS prevention in China

This paper examines the concept of ‘culture’ and its relationship to HIV prevention. Culture is here seen as the interaction between human beings and the various ‘cultural tools’ they appropriate when taking action. Among these tools are ways of speaking which encode certain meanings, ideologies and social practices. When individuals take action with regard to AIDS, what they do is mediated through voices which they borrow strategically from their environ- ment. The textual tools that are available and the ways individuals adapt and combine them work to either limit or amplify their participation in HIV prevention. What are traditionally seen as ‘cultures’ or ‘sub-cultures’, or worse, ‘risk groups’, are, in this perspective, viewed as ‘communities of practice’, groups of individuals who share particular cultural tools and ways of using them. This conceptual framework is applied to recent discourses of homosexuality and AIDS prevention in China. An instance of ‘of� cial’ discourse in the form of an AIDS education pamphlet for ‘gays’ is analysed for the voices it contains and how these voices are strategically marshalled by the authors and mixed with other voices in ways which amplify participation in AIDS prevention for some and limit it for others. This ‘offical’ discourse is then compared to the discourse of homosexually active Chinese men recently interviewed in Beijing and Fuzhou to examine which of these of� cial voices and other voices they appropriate, and how they adapt these voices in responding to HIV.