Which authorities are alike?

This article describes the first results from the recent revision to The ONS classification of local and health authorities of Great Britain to allow for boundary changes. For each local and health authority of Great Britain as at April 1999 it presents 'most similar' authorities as measured by a selection of 37 socioeconomic and demographic variables from the 1991 Census. These results will assist local and health authorities in identifying other appropriate authorities for comparative studies. A second article, to be published in Population Trends 99, will present the results of the analysis to identify groups of authorities in a hierarchy of new Clusters, Groups and Families for the revised classification.     

Population review of 1999: England and Wales

This article outlines the main features of the population of England and Wales in 1999. Where 1999 figures have not yet been produced, data for the latest available year are given.     

INFORMATION CHARACTERIZATION OF COMMUNICATION CHANNELS FOR SYSTEM IDENTIFICATION

This paper studies identification of systems in which the system output is quantized, transmitted through a digital communication channel, and observed afterwards. The concept of the CR Ratio is introduced to characterize impact of communication channels on identification. The relationship between the CR Ratio and Shannon channel capacity is discussed. Identification algorithms are further developed when the channel error probability is unknown.     

Collaborative Project Management: A Systemic Approach to Heavy Equipment Manufacturing Project Management

Quite often over the last decade, heavy equipment manufacturers are trying to improve their project management performance with the use of effective project management methods. However, the challenges encountered aren’t isolated problems and a systemic approach is required. This paper exemplifies how a systemic approach can be applied to heavy equipment manufacturing project (HEMP) management, through of a multifaceted vision. The findings present in the paper are based on a two-year case study in a metallurgic equipment manufacturing enterprise in China. Based on the analysis of HEMP management problems and the contributions on systemic approach application in project management, the paper enriches existing theory by: (1) interpreting the HEMP management system with the top-down disassembly method; (2) developing the collaborative project management approach with a systems view highlighting the project characteristics management and inter-departmental collaboration; (3) making suggestions for systemic approach application in project management. For practitioners and researchers, the findings are particularly meaningful for manufacturing project management and systemic approach application.     

Cellular responses to mild heat stress

Since its discovery in 1962 by Ritossa, the heat shock response has been extensively studied by a number of investigators to understand the molecular mechanism underlying the cellular response to heat stress. The most well characterized heat shock response is induction of the heat shock proteins that function as molecular chaperones and exert cell cycle regulatory and anti-apoptotic activities. While most investigators have focused their studies on the toxic effects of heat stress in organisms such as severe heat stress-induced cell cycle arrest and apoptosis, the cellular response to fever-ranged mild heat stress has been rather underestimated. However, the cellular response to mild heat stress is likely to be more important in a physiological sense than that to severe heat stress because the body temperature of homeothermic animals increases by only 1–2°C during febrile diseases. Here we provide information that mild heat stress does have some beneficial role in organisms via positively regulating cell proliferation and differentiation, and immune response in mammalian cells.Received 14 May 2004; received after revision 2 August 2004; accepted 16 August 2004     

Human peripheral blood monuclear cells transfected with messenger RNA stimulate antigen-specific cytotoxic T-lymphocytes in vitro

The efficiency of test vaccines needs to be evaluated by quantification of the triggered cellular immune response. Usually, for these assays, autologous target cells expressing the vaccine antigen are required. In the context of messenger RNA (mRNA)-based vaccinations, the target cells used for the read-out are mRNA-transfected monocyte-derived dendritic cells (Mo-DCs). Their production typically requires samples of 100 ml blood from the patients, and limits the number of assays that can be performed. We show here that fresh peripheral blood mononuclear cells (PBMCs) can be transfected with mRNA by electroporation. Such cells are as efficient as mRNA-transfected Mo-DCs for their ability to activate memory T cells in vitro. Thus, mRNA-transfected PBMCs are a convenient replacement of mRNA-transfected Mo-DCs for the in vitro monitoring of natural or vaccine-induced immune responses.Received 17 February 2005; received after revision 1 May 2005; accepted 7 Juni 2005     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005     

Marrow mesenchymal stem cells transduced with TPO/FL genes as support for ex vivo expansion of hematopoietic stem/progenitor cells

A new marrow-derived mesenchymal stem cell (hMSC) line that could support expansion of hematopoietic stem/progenitor cells (HSPCs) was developed. Primary hMSCs were infected with retrovirus containing Flt-3 ligand and thrombopoietin genes. CD34+ cells from cord blood were expanded with primary hMSCs or transduced hMSCs. The expansion of total nucleated cells, CD34+ cells and mixed colonies containing erythroid and myeloid cells and megakaryocytes for 2 weeks coculture with transduced hMSCs was remarkably increased. The outputs of long-term culture-initiating cells for 2 and 4 weeks coculture with transduced hMSCs were also largely increased. The expansion rates of HSPCs with transduced hMSCs were unchanged for 6 weeks. In contrast, the expansion rates of HSPCs with primary hMSCs declined drastically through 6 weeks. SCID-repopulating cell expansion with transduced hMSCs for 4 weeks was significantly higher than that of uncultured CD34+ cells and HSPCs expanded with primary hMSCs. Received 21 June 2005; received after revision 30 July 2005; accepted 24 August 2005     

Leptin receptor action and mechanisms of leptin resistance

The adipose tissue-derived hormone leptin regulates energy balance and neuroendocrine function. Resistance to the appetite-suppressing effects of leptin is associated with common forms of obesity. Here, we review the mechanisms by which leptin activates intracellular signals and the roles that these signals play in leptin action in vivo. Furthermore, we discuss potential mechanisms of leptin resistance, specifically focusing on data regarding the neuroanatomical locus of leptin resistance and potential mechanisms by which expression of the suppressor of cytokine signaling-3 may impair leptin action.Received 30 September 2004; received after revision 12 November 2004; accepted 23 November 2004