G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein.

The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits of heterotrimeric G proteins (G beta gamma), p21ras activation, and an as-yet-unidentified tyrosine kinase. To investigate the mechanism of G beta gamma-stimulated p21ras activation, G beta gamma-mediated tyrosine phosphorylation was examined by overexpressing G beta gamma or alpha 2-C10 adrenergic receptors (ARs) that couple to Gi in COS-7 cells. Immunoprecipitation of phosphotyrosine-containing proteins revealed a 2- to 3-fold increase in the phosphorylation of two proteins of approximately 50 kDa (designated as p52) in G beta gamma-transfected cells or in alpha 2-C10 AR-transfected cells stimulated with the agonist UK-14304. The latter response was pertussis toxin sensitive. These proteins (p52) were also specifically immunoprecipitated with anti-Shc antibodies and comigrated with two Shc proteins, 46 and 52 kDa. The G beta gamma- or alpha 2-C10 AR-stimulated p52 (Shc) phosphorylation was inhibited by coexpression of the carboxyl terminus of beta-adrenergic receptor kinase (a G beta gamma-binding pleckstrin homology domain peptide) or by the tyrosine kinase inhibitors genistein and herbimycin A, but not by a dominant negative mutant of p21ras. Worthmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) inhibited phosphorylation of p52 (Shc), implying involvement of PI3K. These results suggest that G beta gamma-stimulated Shc phosphorylation represents an early step in the pathway leading to p21ras activation, similar to the mechanism utilized by growth factor tyrosine kinase receptors.

Effects of central imidazolinergic and alpha2-adrenergic activation on water intake

Non-adrenergic ligands that bind to imidazoline receptors (I-R), a selective ligand that binds to alpha2-adrenoceptors (alpha2-AR) and mixed ligands that bind to both receptors were tested for their action on water intake behavior of 24-h water-deprived rats. All drugs were injected into the third cerebral ventricle. Except for agmatine (80 nmol), mixed ligands binding to I-R/alpha2-AR such as guanabenz (40 nmol) and UK 14304 (20 nmol) inhibited water intake by 65% and up to 95%, respectively. The selective non-imidazoline alpha2-AR agonist, alpha-methylnoradrenaline, produced inhibition of water intake similar to that obtained with guanabenz, but at higher doses (80 nmol). The non-adrenergic I-R ligands histamine (160 nmol, mixed histaminergic and imidazoline ligand) and imidazole-4-acetic acid (80 nmol, imidazoline ligand) did not alter water intake. The results show that selective, non-imidazoline alpha2-AR activation suppresses water intake, and suggest that the action on imidazoline sites by non-adrenergic ligands is not sufficient to inhibit water intake.

G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein.

The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits of heterotrimeric G proteins (G beta gamma), p21ras activation, and an as-yet-unidentified tyrosine kinase. To investigate the mechanism of G beta gamma-stimulated p21ras activation, G beta gamma-mediated tyrosine phosphorylation was examined by overexpressing G beta gamma or alpha 2-C10 adrenergic receptors (ARs) that couple to Gi in COS-7 cells. Immunoprecipitation of phosphotyrosine-containing proteins revealed a 2- to 3-fold increase in the phosphorylation of two proteins of approximately 50 kDa (designated as p52) in G beta gamma-transfected cells or in alpha 2-C10 AR-transfected cells stimulated with the agonist UK-14304. The latter response was pertussis toxin sensitive. These proteins (p52) were also specifically immunoprecipitated with anti-Shc antibodies and comigrated with two Shc proteins, 46 and 52 kDa. The G beta gamma- or alpha 2-C10 AR-stimulated p52 (Shc) phosphorylation was inhibited by coexpression of the carboxyl terminus of beta-adrenergic receptor kinase (a G beta gamma-binding pleckstrin homology domain peptide) or by the tyrosine kinase inhibitors genistein and herbimycin A, but not by a dominant negative mutant of p21ras. Worthmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) inhibited phosphorylation of p52 (Shc), implying involvement of PI3K. These results suggest that G beta gamma-stimulated Shc phosphorylation represents an early step in the pathway leading to p21ras activation, similar to the mechanism utilized by growth factor tyrosine kinase receptors.

Parametric study of the behaviour of reinforced concrete columns in fire

The research is concerned with the application of the computer simulation technique to study the performance of reinforced concrete columns in a fire environment. The effect of three different concrete constitutive models incorporated in the computer simulation on the structural response of reinforced concrete columns exposed to fire is investigated. The material models differed mainly in respect to the formulation of the mechanical properties of concrete. The results from the simulation have clearly illustrated that a more realistic response of a reinforced concrete column exposed to fire is given by a constitutive model with transient creep or appropriate strain effect The assessment of the relative effect of the three concrete material models is considered from the analysis by adopting the approach of a parametric study, carried out using the results from a series of analyses on columns heated on three sides which produce substantial thermal gradients. Three different loading conditions were used on the column; axial loading and eccentric loading both to induce moments in the same sense and opposite sense to those induced by the thermal gradient. An axially loaded column heated on four sides was also considered. The computer modelling technique adopted separated the thermal and structural responses into two distinct computer programs. A finite element heat transfer analysis was used to determine the thermal response of the reinforced concrete columns when exposed to the ISO 834 furnace environment. The temperature distribution histories obtained were then used in conjunction with a structural response program. The effect of the occurrence of spalling on the structural behaviour of reinforced concrete column is also investigated. There is general recognition of the potential problems of spalling but no real investigation into what effect spalling has on the fire resistance of reinforced concrete members. In an attempt to address the situation, a method has been developed to model concrete columns exposed to fire which incorporates the effect of spalling. A total of 224 computer simulations were undertaken by varying the amounts of concrete lost during a specified period of exposure to fire. An array of six percentages of spalling were chosen for one range of simulation while a two stage progressive spalling regime was used for a second range. The quantification of the reduction in fire resistance of the columns against the amount of spalling, heating and loading patterns, and the time at which the concrete spalls appears to indicate that it is the amount of spalling which is the most significant variable in the reduction of fire resistance.

Union strategies in representing ‘new workers’ : the case of UK retail union

The purpose of this paper is to explore the changing nature of employee voice through trade union representation in the retail industry. The retail industry is a major employer in the UK and is one of the few private sector service industries with union representation (Griffin et al 2003). The requisite union: the Distributive and Allied Workers (USDAW) union is one of the biggest unions in the country. However, the characteristics of the industry provide unique challenges for employee voice and representation including: high labour turnover; high use of casual, female and student labour; and, variable levels of union recognition (Reynolds et al 2005). Irrespective of these challenges, any extension of representation and organisation by unions in the retail sector is inherently valuable, socially and politically, given that retail workers are often categorised as vulnerable, due to the fact that they are among the lowest paid in the economy, sourced from disadvantages labour markets and increasingly subject to atypical employment arrangements (Broadbridge 2002; Henley 2006; Lynch 2005; Roan 2003).

The legality of tissue transplants for the benefit of family members in the UK and Australia : implications for saviour siblings

The ethics of creating ‘saviour siblings’ for the benefit of another has received much attention, but little consideration has been given to the legal position of those saviours born who may be asked to provide tissue for transplantation to another during childhood. This article examines the ethical issues surrounding minor donation as well as the existing legal framework in the UK and Australia that regulates minors providing tissue for the benefit of another. Against this background the position of minor saviours, who are called upon to donate bone marrow or peripheral blood stem cells, is examined. This analysis suggests that the law does not provide sufficient protection for minor saviours who are called upon to donate to another. It is argued that specific ethical obligations are owed to saviours—that ought to be reflected in the law—in order to protect them from exploitation while they remain minors.

Union strategies in representing ‘new’ workers : the comparative case of UK and Australian retail unions

This paper is a comparative exploratory study of the changing nature of employee voice through trade union representation in the retail industry in the UK and Australia. In both countries, the retail industry is a major employer and is one of the few private sector service industries with significant union membership (Griffin et al 2003). The relevant unions, the Distributive and Allied Workers Union (USDAW) and the Shop, Distributive and Allied Union (SDA), are the fourth largest and largest unions in the UK and Australia respectively. However, despite this seeming numerical strength in membership, the characteristics of the industry provide unique challenges for employee voice and representation. The significance of the study is that any extension of representation and organisation by unions in the retail sector is valuable socially and politically, given that retail workers are often categorised a s vulnerable, due to their low pay, the predominance of disadvantaged labour market groups such a s women and young people, workers’ atypical employment arrangements and, in the case of the UK, variable levels of union recognition which inhibit representation (Broadbridge 2002; Henley 2006; Lynch 2005; Roan & Diamond 2003; Reynolds et al 2005). In addition, specifically comparative projects have value in that they allow some variables relating to the ‘industry’ to be held constant, thus reducing the range of potential explanations of differences in union strategy. They also have value in that the research partners may be more likely to notice and problematise taken-for-granted aspects of practices in another country, thus bringing to the fore key features and potentially leading to theoretical innovation. Finally, such projects may assist in transnational diffusion of union strategy.

The role of timber plantations in UK Investment portfolios

Although timber plantations and forests are classified as forms of agricultural production, the ownership of this land classification is not limited to rural producers. Timber plantations and forests are now regarded as a long-term investment with both institutional and absentee owners. While the NCREIF property indices have been the benchmarks for the measurement of the performance of the commercial property market in the UK, for many years the IPD timberland index has recently emerged as the U.K. forest and timberland performance indicator. The IPD Forest index incorporates 126 properties over five regions in the U.K. This paper will utilise the IPD Forestry Index to examine the performance of U.K. timber plantations and forests over the period 1981-2004. In particular, issues to be critically assessed include plantation and forest performance analysis, comparative investment analysis, and the role of plantations and forests in investment portfolios, the risk reduction and portfolio benefits of plantations and forests in mixed-asset portfolios and the strategic investment significance of U.K. timberlands.

An Analysis of UK Farmland : 1981-2004

The importance of agriculture in many countries has tended to reduce as their economies move from a resource base to a manufacturing industry base. Although the level of agricultural production in first world countries has increased over the past two decades, this increase has generally been at a less significant rate compared to other sectors of the economies. Despite this increase in secondary and high technology industries, developed countries have continued to encourage and support their agricultural industries. This support has been through both tariffs and price support. Although the average farm production property may require this support to maintain long-term production, the better farms can actually achieve production levels and commodity prices that result in these units being competitive on a free market basis. This paper will analyse the total return performance of UK farmland over the period 1981-2004. This analysis will compare the total return from rural properties in the UK and compare this performance to commercial property returns (total, office, retail, industrial), equities and gilts over this 24-year period. The analysis will be based on the IPD UK let land index and the IPD property index. The portfolio diversification and risk-reduction benefits of UK farmland will be highlighted. The analysis shows that rural property has negative correlations with equities and gilts, as well as insignificant positive correlations with retail, industrial and office property. Rural property also provides portfolio diversification benefits.

How current pedagogy methods in games teaching in the UK, Australia and the US have been shaped by historical, socio cultural, environmental and political constraints

Crucial to enhancing the status and quality of games teaching in schools is a developed understanding of the teaching strategies adopted by practitioners. In this paper, we will demonstrate that contemporary games‟ teaching is a product of individual, task and environmental constraints (Newell, 1986). More specifically, we will show that current pedagogy in the U.K., Australia and the United States is strongly influenced by historical, socio-cultural environmental and political constraints. In summary, we will aim to answer the question „why do teachers teach games the way they do.‟ In answering this question, we conclude that teacher educators, who are trying to influence pedagogical practice, must understand these potential constraints and provide appropriate pre-service experiences to give future physical education teachers the knowledge, confidence and ability to adopt a range of teaching styles when they become fully fledged teachers. Essential to this process is the need to enable future practitioners to base their pedagogical practice on a sound understanding of contemporary learning theories of skill acquisition.

Practitioner influence on contact lens prescribing in the UK

Contact lenses are mainly fitted by registered optometrists and contact lens opticians in the UK. Data we have gathered from annual contact lens fitting surveys over the past 12 years indicate that, on average, registered optometrists and contact lens opticians undertake 3.2 and 7.1 contact lens fits per week (p < 0.0001). More experienced practitioners tend to fit older patients. Practitioners fitting more lenses per year tend to fit a higher proportion of soft lenses. Contact lens opticians tend to fit a higher proportion of patients with planned replacement and daily disposable lenses compared with optometrists.

Prosecution history estoppel in the UK?

The doctrine of 'prosecution history estoppel' (PH estoppel) as developed in the United States has strong intuitive appeal, especially when applied to counterbalance a related patent law principle, the doctrine of equivalents. The doctrines are receiving increasing attention in US patent decisions, to the point where one patent litigator recently compared them to "two cars that keep bumping fenders. They are frequently returned to the shop for repairs". Could PH estoppel find its way into UK patent law? This article briefly examines the doctrine, its evolution in the US and the problems associated with importing the doctrine into the UK. As the EU legislation stands, Article 69 and the Protocol to the European Patent Convention (EPC) pose serious obstacles to using the doctrine directly in claim construction. However there appears to be some scope to apply the doctrine as a limited form of defence in infringement actions.

Artful determination : "state of the art" and PCME Ltd v. Goyen COntrols Co. UK Ltd

In a recent decision by Mr Justice Laddie, a patent was held anticipated by, inter alia, prior use of a device which fell within the claims of the patent in suit, even though its circuitry was enclosed in resin. The anticipating invention had been "made available to the public" within the terms of section 2 (2) of the Patents Act 1977 because its essential integers would have been revealed by an interesting character, the "skilled forensic engineer".

Digital scenography for "Markus the Sadist" : UK National Tour

How does a digitally mediated environment work towards the ongoing support of the Hip Hop landscape present in the work of Jonzi D productions UK National Tour of "Markus the Sadist"