The regulation of integrin-linked kinase in human platelets: evidence for involvement in the regulation of integrin alpha(2)beta(1)

Background: Activation of the platelet integrin alpha(2)beta(1) is closely regulated due to the high thrombogenicity of its ligand. As a beta(1) interacting kinase, ILK represents a candidate intracellular regulator of alpha(2)beta(1) in human platelets. Objectives We investigated the regulation of ILK in human platelets and the role of ILK in regulating alpha(2)beta(1) activation in HEL cells, a megakaryocytic cell line. Methods: An in-vitro kinase assay was used to determine the effect of platelet agonists on ILK kinase activity together with the contribution of PI3K and PKC on ILK activation. Interaction of ILK with beta(1)-integrin subunits was investigated by coimmunoprecipitation and the role of ILK in regulating alpha(2)beta(1) function assessed by overexpression studies in HEL cells. Results: We report that collagen and thrombin modulate ILK kinase activity in human platelets in an aggregation-independent manner. Furthermore, ILK activity is dually regulated by PI3K and PKC in thrombin-stimulated platelets and regulated by PI3K in collagen-stimulated cells. ILK associates with the beta(1)-integrin subunits immunoprecipitated from platelet cell lysates, an association which increased upon collagen stimulation. Overexpression of ILK in HEL cells enhanced alpha(2)beta(1)-mediated adhesion whereas overexpression of kinase-dead ILK reduced adhesion, indicating a role for this kinase in the positive regulation of alpha(2)beta(1). Conclusions: Our findings that ILK regulates alpha(2)beta(1) in HEL cells, is activated in platelets and associates with beta(1)-integrins, raise the possibility that it may play a key role in adhesion events upon agonist stimulation of platelets.

An fMRI study of parietal cortex involvement in the visual guidance of locomotion

Locomoting through the environment typically involves anticipating impending changes in heading trajectory in addition to maintaining the current direction of travel. We explored the neural systems involved in the “far road” and “near road” mechanisms proposed by Land and Horwood (1995) using simulated forward or backward travel where participants were required to gauge their current direction of travel (rather than directly control it). During forward egomotion, the distant road edges provided future path information, which participants used to improve their heading judgments. During backward egomotion, the road edges did not enhance performance because they no longer provided prospective information. This behavioral dissociation was reflected at the neural level, where only simulated forward travel increased activation in a region of the superior parietal lobe and the medial intraparietal sulcus. Providing only near road information during a forward heading judgment task resulted in activation in the motion complex. We propose a complementary role for the posterior parietal cortex and motion complex in detecting future path information and maintaining current lane positioning, respectively. (PsycINFO Database Record (c) 2010 APA, all rights reserved)

Community involvement in urban design: help or hindrance?

This paper examines the realities of community involvement in urban design in the context of a study of the West Itchen Neighbourhood of Southampton, a diverse inner city area accommodating some 7,000 households and 18,000 people. The findings are based on a literature review of community involvement in urban design and case study research into three government supported regeneration projects all located within the study area: a Neighbourhood Renewal Area - designated in 1994; an Estate Action Scheme - implemented between 1993 and 1996; and a Single Regeneration Budget programme - following a successful bid in 1995. The research was undertaken by Helen Gregory in 1997/8 as the basis of a dissertation, supervised by Alan Rowley, submitted for the award of an MPhil in Environmental Planning and Development from The University of Reading.

Causal evidence for frontal involvement in memory target maintenance by posterior brain areas during distracter interference of visual working memory

Dorsolateral prefrontal cortex (DLPFC) is recruited during visual working memory (WM) when relevant information must be maintained in the presence of distracting information. The mechanism by which DLPFC might ensure successful maintenance of the contents of WM is, however, unclear; it might enhance neural maintenance of memory targets or suppress processing of distracters. To adjudicate between these possibilities, we applied time-locked transcranial magnetic stimulation (TMS) during functional MRI, an approach that permits causal assessment of a stimulated brain region's influence on connected brain regions, and evaluated how this influence may change under different task conditions. Participants performed a visual WM task requiring retention of visual stimuli (faces or houses) across a delay during which visual distracters could be present or absent. When distracters were present, they were always from the opposite stimulus category, so that targets and distracters were represented in distinct posterior cortical areas. We then measured whether DLPFC-TMS, administered in the delay at the time point when distracters could appear, would modulate posterior regions representing memory targets or distracters. We found that DLPFC-TMS influenced posterior areas only when distracters were present and, critically, that this influence consisted of increased activity in regions representing the current memory targets. DLPFC-TMS did not affect regions representing current distracters. These results provide a new line of causal evidence for a top-down DLPFC-based control mechanism that promotes successful maintenance of relevant information in WM in the presence of distraction.

The use of public participation and economic appraisal for public involvement in large-scale hydropower projects: Case study of the Nam Theun 2 Hydropower Project

Gaining public acceptance is one of the main issues with large-scale low-carbon projects such as hydropower development. It has been recommended by the World Commission on Dams that to gain public acceptance, publicinvolvement is necessary in the decision-making process (WCD, 2000). As financially-significant actors in the planning and implementation of large-scale hydropowerprojects in developing country contexts, the paper examines the ways in which publicinvolvement may be influenced by international financial institutions. Using the casestudy of the NamTheun2HydropowerProject in Laos, the paper analyses how publicinvolvement facilitated by the Asian Development Bank had a bearing on procedural and distributional justice. The paper analyses the extent of publicparticipation and the assessment of full social and environmental costs of the project in the Cost-Benefit Analysis conducted during the projectappraisal stage. It is argued that while efforts were made to involve the public, there were several factors that influenced procedural and distributional justice: the late contribution of the Asian Development Bank in the projectappraisal stage; and the issue of non-market values and discount rate to calculate the full social and environmental costs.

Patient and public involvement in healthcare quality improvement: how organizations can help patients and professionals to collaborate

Citizens across the world are increasingly called upon to participate in healthcare improvement. It is often unclear how this can be made to work in practice. This 4- year ethnography of a UK healthcare improvement initiative showed that patients used elements of organizational culture as resources to help them collaborate with healthcare professionals. The four elements were: (1) organizational emphasis on nonhierarchical, multidisciplinary collaboration; (2) organizational staff ability to model desired behaviours of recognition and respect; (3) commitment to rapid action, including quick translation of research into practice; and (4) the constant data collection and reflection process facilitated by improvement methods.

English teachers in the digital age – a case study of policy and expert practice from England

This article is a case study of how English teachers in England have coped with the paradigm shift from print to digital literacy. It reviews a large scale national initiative that was intended to upskill all teachers, considers its weak impact and explores the author’s involvement in the evaluation of the project’s direct value to English teachers. It explores how this latter evaluation revealed how best practice in English using ICT was developing in a variable manner. It then reports on a recent small scale research project that investigated how very good teachers have adapted ICT successfully into their teaching. It focuses on how the English teachers studied in the project are developing a powerful new pedagogy situated in the life worlds of their students and suggests that this model may be of benefit to many teachers. The issues this article reports on have resonance in all English speaking countries. This article is also a personal story of the author’s close involvement with ICT and English over 20 years, and provides evidence for his conviction that digital technologies will eventually transform English teaching.

Evaluation of biospheric components in Earth system models using modern and palaeo-observations: the state-of-the-art

Earth system models (ESMs) are increasing in complexity by incorporating more processes than their predecessors, making them potentially important tools for studying the evolution of climate and associated biogeochemical cycles. However, their coupled behaviour has only recently been examined in any detail, and has yielded a very wide range of outcomes. For example, coupled climate–carbon cycle models that represent land-use change simulate total land carbon stores at 2100 that vary by as much as 600 Pg C, given the same emissions scenario. This large uncertainty is associated with differences in how key processes are simulated in different models, and illustrates the necessity of determining which models are most realistic using rigorous methods of model evaluation. Here we assess the state-of-the-art in evaluation of ESMs, with a particular emphasis on the simulation of the carbon cycle and associated biospheric processes. We examine some of the new advances and remaining uncertainties relating to (i) modern and palaeodata and (ii) metrics for evaluation. We note that the practice of averaging results from many models is unreliable and no substitute for proper evaluation of individual models. We discuss a range of strategies, such as the inclusion of pre-calibration, combined process- and system-level evaluation, and the use of emergent constraints, that can contribute to the development of more robust evaluation schemes. An increasingly data-rich environment offers more opportunities for model evaluation, but also presents a challenge. Improved knowledge of data uncertainties is still necessary to move the field of ESM evaluation away from a "beauty contest" towards the development of useful constraints on model outcomes.

Reflections on practical approaches to involving children and young people in the data analysis process

This article reflects on key methodological issues emerging from children and young people's involvement in data analysis processes. We outline a pragmatic framework illustrating different approaches to engaging children, using two case studies of children's experiences of participating in data analysis. The article highlights methods of engagement and important issues such as the balance of power between adults and children, training, support, ethical considerations, time and resources. We argue that involving children in data analysis processes can have several benefits, including enabling a greater understanding of children's perspectives and helping to prioritise children's agendas in policy and practice. (C) 2007 The Author(s). Journal compilation (C) 2007 National Children's Bureau.

The social relations of business representation and devolved governance in the United Kingdom

The reform of regional governance in the United Kingdom has been, in part, premised on the notion that regions provide new territories of action in which cooperative networks between business communities and state-agencies can be established. Promoting business interests is seen as one mechanism for enhancing the economic competitiveness and performance of 'laggard' regions. Yet, within this context of change, business agendas and capacities are often assumed to exist 'out there, as a resource waiting to be tapped by state institutions. There is little recognition that business organisations' involvement in networks of governance owes much to historical patterns and practices of business representation, to the types of activities that exist within the business sector, and to interpretations of their own role and position within wider policymaking and implementation networks. This paper, drawing on a study of business agendas in post-devolution Scotland, demonstrates that in practice business agendas are highly complex. Their formation in any particular place depends on the actions of reflexive agents, whose perspectives and capacities are shaped by the social, economic, and political contexts within which they are operating. As such, any understanding of business agendas needs to identify the social relations of business as a whole, rather than assuming away such complexities.