Analysis of second messenger pathways stimulated by different chemokines acting at the chemokine receptor

The chemokine receptor, CCR5, responds to several chemokines leading to changes in activity in several signalling pathways. Here, we investigated the ability of different chemokines to provide differential activation of pathways. The effects of five CC chemokines acting at CCR5 were investigated for their ability to inhibit forskolin- stimulated 3'-5'-cyclic adenosine monophosphate (cAMP) accumulation and to stimulate Ca2+ mobilisation. in Chinese hamster ovary (CHO) cells expressing CCR5. Macrophage inflammatory protein 1 alpha (D26A) (MIP-1 alpha (D26A), CCL3 (D26A)), regulated on activation, normal T-cell expressed and secreted (RANTES, CCLS), MIP-1 beta (CCL4) and monocyte chemoattractant protein 2 (MCP-2, CCL8) were able to inhibit forskolin -stimulated CAMP accumulation, whilst MCP-4 (CCL13) could not elicit a response. CCL3 (D26A), CCL4, CCLS, CCL8 and CCL13 were able to stimulate Ca2+ mobilisation. through CCRS, although CCL3 (D26A) and CCL5 exhibited biphasic concentration-response curves. The Ca2+ responses induced by CCL4, CCL5, CCL8 and CCL13 were abolished by pertussis toxin, whereas the response to CCL3 (D26A) was only partially inhibited by pertussis toxin, indicating G(i/o)-independent signalling induced by this chemokine. Although the rank order of potency of chemokines was similar between the two assays, certain chemokines displayed different pharmacological profiles in cAMP inhibition and Ca2+ mobilisation assays. For instance, whilst CCL13 could not inhibit forskolin-stimulated cAMP accumulation, this chemokine was able to induce Ca2+ mobilisation via CCR5. It is concluded that different chemokines acting at CCR5 can induce different pharmacological responses, which may account for the broad spectrum of chemokines that can act at CCRS. (C) 2007 Elsevier Inc. All rights reserved.

A design of e-procurement infrastructure model for public service sector

Procurement is one of major business operations in public service sector. The advance of information and communication technology (ICT) pushes this business operation to increase its efficiency and foster collaborations between the organization and its suppliers. This leads to a shift from the traditional procurement transactions to an e-procurement paradigm. Such change impacts on business process, information management and decision making. E-procurement involves various stakeholders who engage in activities based on different social and cultural practices. Therefore, a design of e-procurement system may involve complex situations analysis. This paper describes an approach of using the problem articulation method to support such analysis. This approach is applied to a case study from UAE.

Evolution in software systems: foundations of the SPE classification scheme

The SPE taxonomy of evolving software systems, first proposed by Lehman in 1980, is re-examined in this work. The primary concepts of software evolution are related to generic theories of evolution, particularly Dawkins' concept of a replicator, to the hermeneutic tradition in philosophy and to Kuhn's concept of paradigm. These concepts provide the foundations that are needed for understanding the phenomenon of software evolution and for refining the definitions of the SPE categories. In particular, this work argues that a software system should be defined as of type P if its controlling stakeholders have made a strategic decision that the system must comply with a single paradigm in its representation of domain knowledge. The proposed refinement of SPE is expected to provide a more productive basis for developing testable hypotheses and models about possible differences in the evolution of E- and P-type systems than is provided by the original scheme. Copyright (C) 2005 John Wiley & Sons, Ltd.

Adapting to the effects of climate change on water supply reliability

This paper presents preliminary results from an assessment of the barriers to adaptation to water supply shortage in a case study catchment in south east England with multiple supply companies. The investigation applies a conceptual framework, which distinguishes between generic barriers affecting the ability of supply companies to make adaptation decisions, and specific barriers to the implementation of each option. The preliminary analysis suggests that whilst there is a widespread awareness of the challenge of climate change, and a conceptual understanding of the need for adaptation, some of the generic barriers that will affect detailed evaluations and actual adaptation decisions have yet to be approached. The analysis also shows that different individual adaptation options are assessed differently by different stakeholders, and that there are differences in the barriers to adoption between supply-side and demand-side measures. First, however, the paper develops the general conceptual framework for the characterisation of the barriers to adaptation used in the study.

Goal-refinement appraisal of soft projects (GRASP)

Industrial projects are often complex and burdened with time pressures and a lack of information. The term 'soft-project' used here stands for projects where the ‘what’ and/or the ‘how’ is uncertain, which is often the experience in projects involving software intensive systems developments. This thesis intertwines the disciplines of project management and requirements engineering in a goal-oriented application of the maxim ‘keep all objectives satisfied’. It thus proposes a method for appraising projects. In this method, a goal-oriented analysis establishes a framework with which expert judgements are collected so as to construct a confidence profile in regard to the feasibility and adequacy of the project's planned outputs. It is hoped that this appraisal method will contribute to the activities of project ‘shaping’ and aligning stakeholders’ expectations whilst helping project managers appreciate what parts of their project can be progressed and what parts should be held pending further analysis. This thesis offers the following original contribution: an appreciation of appraisal in the project context; a goal-oriented confidence profiling technique; and: a technique to produce goal-refinement diagrams – referred to as Goal Sketching. Collectively these amount to a method for the ‘Goal Refinement Appraisal of Soft-Projects’ (GRASP). The validity of the GRASP method is shown for two projects. In the first it is used for shaping a business investigation project. This is done in real-time in the project. The second case is a retrospective study of an enterprise IT project. This case tests the effectiveness of forecasting project difficulty from an initial confidence profile.

Normative, systemic and procedural aspects: a review of indicator‐based sustainability assessments in agriculture

Several methods for assessing the sustainability of agricultural systems have been developed. These methods do not fully: (i) take into account the multi‐functionality of agriculture; (ii) include multidimensionality; (iii) utilize and implement the assessment knowledge; and (iv) identify conflicting goals and trade‐offs. This paper reviews seven recently developed multidisciplinary indicator‐based assessment methods with respect to their contribution to these shortcomings. All approaches include (1) normative aspects such as goal setting, (2) systemic aspects such as a specification of scale of analysis, (3) a reproducible structure of the approach. The approaches can be categorized into three typologies. The top‐down farm assessments focus on field or farm assessment. They have a clear procedure for measuring the indicators and assessing the sustainability of the system, which allows for benchmarking across farms. The degree of participation is low, potentially affecting the implementation of the results negatively. The top‐down regional assessment assesses the on‐farm and the regional effects. They include some participation to increase acceptance of the results. However, they miss the analysis of potential trade‐offs. The bottom‐up, integrated participatory or transdisciplinary approaches focus on a regional scale. Stakeholders are included throughout the whole process assuring the acceptance of the results and increasing the probability of implementation of developed measures. As they include the interaction between the indicators in their system representation, they allow for performing a trade‐off analysis. The bottom‐up, integrated participatory or transdisciplinary approaches seem to better overcome the four shortcomings mentioned above.

Community based ecotourism as a panacea for protected areas: the use of common property theory in its analysis and development

Tourism is the worlds largest employer, accounting for 10% of jobs worldwide (WTO, 1999). There are over 30,000 protected areas around the world, covering about 10% of the land surface(IUCN, 2002). Protected area management is moving towards a more integrated form of management, which recognises the social and economic needs of the worlds finest areas and seeks to provide long term income streams and support social cohesion through active but sustainable use of resources. Ecotourism - 'responsible travel to natural areas that conserves the environment and improves the well- being of local people' (The Ecotourism Society, 1991) - is often cited as a panacea for incorporating the principles of sustainable development in protected area management. However, few examples exist worldwide to substantiate this claim. In reality, ecotourism struggles to provide social and economic empowerment locally and fails to secure proper protection of the local and global environment. Current analysis of ecotourism provides a useful checklist of interconnected principles for more successful initiatives, but no overall framework of analysis or theory. This paper argues that applying common property theory to the application of ecotourism can help to establish more rigorous, multi-layered analysis that identifies the institutional demands of community based ecotourism (CBE). The paper draws on existing literature on ecotourism and several new case studies from developed and developing countries around the world. It focuses on the governance of CBE initiatives, particularly the interaction between local stakeholders and government and the role that third party non-governmental organisations can play in brokering appropriate institutional arrangements. The paper concludes by offering future research directions."

Understanding stakeholder requirements on an NHS hospital project: application of semiotics-rooted theories.

Hospitals represent complex and difficult contexts for AEC (architecture, engineering and construction) professionals to engage with due to their functional complexity and diversity of stakeholder interests (i.e. patient, visitor, medical specialist). Hospital designers need to take note of changing NHS policy contexts (e.g. the possible empowerment of general practitioners to shape services), technological advances in medical equipment design and the potential health needs of future generations. It is imperative for hospital designers and architects to align their processes and methodologies (e.g. briefing and requirements capture) to the needs and desires of their clients so that a medical facility design is produced which is truly aligned to the requirements of the hospital stakeholders. Semiotics, the “study” or “discipline” of signs aims to investigate the nature of signs (their inception, representation and meaning), whilst semiotics-rooted theories are concerned with investigating how meaning and understanding is mobilized between persons and between organisations. This paper details a semiotics-rooted research approach for investigating the interactions between hospital designers and stakeholders on a forthcoming NHS hospital project in the UK. A semiotics grounded study will potentially provide a deeper understanding of how meaning and understanding is established between hospital project stakeholders and construction professionals.

Diaspora return of transnational migrants to Trinidad and Tobago: the additional contributions of social remittances

Current enthusiasm among development stakeholders for the enticement and recruitment ‘back home’ of skilled Diaspora migrants has predominantly revolved around how human capital gains and transfers of capital, knowledge, technical skills and workplace entrepreneurialism and innovation can be facilitated. In this article, we widen the conceptual basis of this dimension of the migration–development nexus, by bringing the additional contributions of the social remittances that return migrants offer, and practice, into the mix. As evidence, the article examines how and why a sample of ‘middling’1 Trinidadian transnational professionals engage in social development activities and why experiences vary widely on their return. Their views are appraised through the verbal optic of their narratives, which they shared with us during in-depth interviews. Several among these Diaspora returnees appear to be agents for the diffusion and infusion of social capital and non-monetary, social remittances in the homeland to which they have returned in mid-life and mid-career. Others are disappointed, or frustrated, and have their hopes dashed, leading to thoughts of re-migration, or re-return. Despite such difficulties, we find that family belonging and national pride strengthens many of these return migrants’ development potential through their deeply felt commitments to local ‘capacity-building’.

Enterprise intelligence: searching for a single version of the truth

Multiple versions of information and associated problems are well documented in both academic research and industry best practices. Many solutions have proposed a single version of the truth, with Business intelligence being adopted by many organizations. Business Intelligence (BI), however, is largely based on the collection of data, processing and presentation of information to meet different stakeholders’ requirement. This paper reviews the promise of Enterprise Intelligence, which promises to support decision-making based on a defined strategic understanding of the organizations goals and a unified version of the truth.

Construction management strategies : a theory of construction management

The construction industry has become a truly global network of interconnected stakeholders making demands which require the involvement of skilled workforces from all over the world. Construction Management Strategies sets the foundations for understanding and managing construction’s inherent complexity and uniqueness. It establishes clear definitions of commonly accepted terms like built environment, construction, civil engineering, etc. which are often given confusing and conflicting interpretations. It cuts through the plethora of overlapping role titles currently used in the construction sector that make it difficult to establish how projects are actually managed.

Evaluating the likelihood of the adoption of an animal welfare assessment system in European agri-food supply chains

Purpose – The purpose of this paper is to analyse the likelihood of adoption of a recently designed Welfare Assessment System in agri-food supply chains and the factors affecting the adoption decision. The application is carried out for pig and poultry chains. Design/methodology/approach – This research consisted of two main components: interviews with retailers in pig and poultry supply chains in eight different EU countries to explore their perceptions towards the adoption possibilities of the welfare assessment system; and a conjoint analysis designed to evaluate the perceived adoption likelihood of the assessment system by different Standards Formulating Organisations (SFOs). Findings – Stakeholders were found to be especially concerned about the costs of implementation of the system and how it could, or should, be merged with existing assurance schemes. Another conclusion of the study is that the presence of a strong third independent party supporting the implementation of the welfare assessment system would be the most important influence on the decision whether, or not, to adopt it. Originality/value – This research evaluates the adoption possibilities of a novel Welfare Assessment System and presents the views of different supply chain stakeholders on an adoption of such a system. The main factors affecting the adoption decision are identified and analysed. Contrary to expectations, the costs of adoption of a new welfare assessment system were not considered to be the most important factor affecting the decision of supply chain stakeholders about the adoption of this new welfare system.

The challenge of self-regulation in commercial property leasing: a study of lease codes in the UK.

Purpose – UK Government policy to address perceived market failure in commercial property leasing has largely been pursued through industry self-regulation. Yet, it is proving difficult to assess whether self-regulation on leasing has been a “success”, or even to determine how to evaluate this. The purpose of this paper is to provide a framework for this and a clearer understanding of self-regulation in commercial leasing. Design/methodology/approach – A literature review suggests key criteria to explain the (in)effectiveness of self-regulation. UK lease codes are analysed in the light of this literature, drawing on previous research carried out by the authors on the operation of these codes. Findings – Lease codes appear to be failing as an effective system of self-regulation. While there are influential market actors championing them, the fragmentation of the leasing process lessens this influence. The structures are not there to ensure implementation, monitor compliance and record views of affected stakeholders. Research limitations/implications – This work adds to the literature on self-regulation in general, and provides an insight into its operation in a previously unexplored industry. Research is needed into the experience of other countries in regulating the property industry by voluntary means. Social implications – There are institutional limitations to self-regulation within the property industry. This has implications for policy makers in considering the advantages and limitation of using a voluntary solution to achieve policy aims within the commercial leasing market. Originality/value – This paper provides a first step in considering the lease codes in the wider context of industry self-regulation and is relevant to policy makers and industry bodies.

Traditional Chinese medicine research in the post-genomic era: good practice, priorities, challenges and opportunities

Background and aims: GP-TCM is the 1st EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. This paper aims to summarise the objectives, structure and activities of the consortium and introduces the position of the consortium regarding good practice, priorities, challenges and opportunities in TCM research. Serving as the introductory paper for the GPTCM Journal of Ethnopharmacology special issue, this paper describes the roadmap of this special issue and reports how the main outputs of the ten GP-TCM work packages are integrated, and have led to consortium-wide conclusions. Materials and methods: Literature studies, opinion polls and discussions among consortium members and stakeholders. Results: By January 2012, through 3 years of team building, the GP-TCM consortium had grown into a large collaborative network involving ∼200 scientists from 24 countries and 107 institutions. Consortium members had worked closely to address good practice issues related to various aspects of Chinese herbal medicine (CHM) and acupuncture research, the focus of this Journal of Ethnopharmacology special issue, leading to state-of-the-art reports, guidelines and consensus on the application of omics technologies in TCM research. In addition, through an online survey open to GP-TCM members and non-members, we polled opinions on grand priorities, challenges and opportunities in TCM research. Based on the poll, although consortium members and non-members had diverse opinions on the major challenges in the field, both groups agreed that high-quality efficacy/effectiveness and mechanistic studies are grand priorities and that the TCM legacy in general and its management of chronic diseases in particular represent grand opportunities. Consortium members cast their votes of confidence in omics and systems biology approaches to TCM research and believed that quality and pharmacovigilance of TCM products are not only grand priorities, but also grand challenges. Non-members, however, gave priority to integrative medicine, concerned on the impact of regulation of TCM practitioners and emphasised intersectoral collaborations in funding TCM research, especially clinical trials. Conclusions: The GP-TCM consortium made great efforts to address some fundamental issues in TCM research, including developing guidelines, as well as identifying priorities, challenges and opportunities. These consortium guidelines and consensus will need dissemination, validation and further development through continued interregional, interdisciplinary and intersectoral collaborations. To promote this, a new consortium, known as the GP-TCM Research Association, is being established to succeed the 3-year fixed term FP7 GP-TCM consortium and will be officially launched at the Final GP-TCM Congress in Leiden, the Netherlands, in April 2012.