The masses and radii of HD 186753B and TYC7096-222-1B: the discovery of two M-dwarfs that eclipse A-type stars

We present observations of two new single-lined eclipsing binaries, both consisting of an Am star and an M-dwarf, discovered by the Wide Angle Search for Planets transit photometry survey. Using WASP photometry and spectroscopic measurements we find that HD 186753B has an orbital period of P=1.9194 days, a mass of M=0.24±0.02~M? and radius of R=0.31+0.06-0.06~R?; and that TCY7096-222-1B has an orbital period of P=8.9582 days, a mass of between 0.29 and 0.54 M? depending on eccentricity and radius of R=0.263+0.02-0.07~R?. We find that the Am stars have relatively low rotational velocities that closely match the orbital velocities of the M-dwarfs, suggesting that they have been “spun-down” by the M-dwarfs.

Pulmonary rehabilitation and follow-on services: a Northern Ireland survey

There should be a clear pathway through pulmonary rehabilitation and follow-on services. The aim of this survey was to determine the characteristics of the different components of the patient pathway, that is, pulmonary rehabilitation programs, ongoing exercise facilities, and support networks in Northern Ireland. Questionnaires were sent to current providers of pulmonary rehabilitation, providers of ongoing exercise, and support groups in Northern Ireland. Findings relating to the current status of pulmonary rehabilitation in Northern Ireland up to January 2007 are reported. There are currently 23 pulmonary rehabilitation programs in Northern Ireland. There appears to be a pathway through the short-term pulmonary rehabilitation program (6-8 weeks). Programs met standards for structure and format, except for the frequency of supervised exercise. Not all programs have links for the provision of ongoing exercise, but a range of exercise programs are available in leisure centers in Northern Ireland that include people with respiratory disease. There are 13 support groups for patients with respiratory disease in Northern Ireland and their function is diverse. Pulmonary rehabilitation is established in Northern Ireland, although not all patients are able to access these. Facilities for ongoing exercise and support groups are less developed. Improvements could be facilitated by better communication within the patient pathway and a strategic coordinated approach.

Do environmental and task characteristics matter in the control of externalized local public services? Unveiling the relevance of party characteristics and citizens’ offstage voice

Purpose: The purpose of this paper is to investigate the mechanisms adopted by cities to control the provision of externalized public services and to explore the determinants of such control choices.

Design/methodology/approach: The paper presents the results of a multiple case study based on the experiences of three cities and three public services (transport, solid waste collection and home care services for the elderly), where control mechanisms and their possible antecedents were analyzed.

Findings: The results show that the control models found in the cases analyzed do not correspond to the "pure" patterns described in the private sector literature and that the factors identified by management control contributions do not seem to be exhaustive in explaining the configuration of control systems in the public sector. While environmental and task characteristics only partially explain the adoption of certain configurations of control, the features of the control systems seem to be rather influenced by variables that are related to party characteristics.

Originality/value: The paper shows that the combinations of control mechanisms are more multifaceted than those presented in the literature, and that the factors identified in the private sector literature do not seem to explain comprehensively the configuration of control systems in the public sector. © Emerald Group Publishing Limited.

Discovery of multiple neuropeptide families in the phylum Platyhelminthes

Available evidence shows that short amidated neuropeptides are widespread and have important functions within the nervous systems of all flatworms (phylum Platyhelminthes) examined, and could therefore represent a starting point for new lead drug compounds with which to combat parasitic helminth infections. However, only a handful of these peptides have been characterised, the rigorous exploration of the flatworm peptide signalling repertoire having been hindered by the dearth of flatworm genomic data. Through searches of both expressed sequence tags and genomic resources using the basic local alignment search tool (BLAST), we describe 96 neuropeptides on 60 precursors from 10 flatworm species. Most of these (51 predicted peptides on 14 precursors) are novel and are apparently restricted to flatworms; the remainder comprise nine recognised peptide families including FMRFamide-like (FLPs), neuropeptide F (NPF)-like, myomodulin-like, buccalin-like and neuropeptide FF (NPFF)-like peptides; notably, the latter have only previously been reported in vertebrates. Selected peptides were localised immunocytochemically to the Schistosoma mansoni nervous system. We also describe several novel flatworm NPFs with structural features characteristic of the vertebrate neuropeptide Y (NPY) superfamily, previously unreported characteristics which support the common ancestry of flatworm NPFs with the NPY-superfamily. Our dataset provides a springboard for investigation of the functional biology and therapeutic potential of neuropeptides in flatworms, simultaneously launching flatworm neurobiology into the post-genomic era. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Discovery of novel Agonists and antagonists of the free fatty acid receptor 1 (FFAR1) using virtual screening

The G-protein-coupled receptor free fatty acid receptor 1 (FFAR1), previously named GPR40, is a possible novel target for the treatment of type 2 diabetes. In an attempt to identify new ligands for this receptor, we performed virtual screening (VS) based on two-dimensional (2D) similarity, three-dimensional (3D) pharmacophore searches, and docking studies by using the structure of known agonists and our model of the ligand binding site, which was validated by mutagenesis. VS of a database of 2.6 million compounds followed by extraction of structural neighbors of functionally confirmed hits resulted in identification of 15 compounds active at FFAR1 either as full agonists, partial agonists, or pure antagonists. Site-directed mutagenesis and docking studies revealed different patterns of ligand-receptor interactions and provided important information on the role of specific amino acids in binding and activation of FFAR1.

Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable gamma-Secretase Inhibitor

During the course of our research efforts to develop a potent and selective gamma-secretase inhibitor for the treatment of Alzheimer's disease, we investigated a series of carboxamide-substituted sulfonamides. Optimization based on potency, Notch/amyloid-beta precursor protein selectivity, and brain efficacy after oral dosing led to the discovery of 4 (BMS-708163). Compound 4 is a potent inhibitor of gamma-secretase (A beta 40 IC50 = 0.30 nM), demonstrating a 193-fold selectivity against Notch. Oral administration of 4 significantly reduced A beta 40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs.

Recruitment and Retention in Front-line Services: The case of childcare

This article highlights how problems of recruitment and retention in front-line services create a particular challenge to traditional HRM models and solutions. Private day nurseries make an interesting example of the challenges facing managers in the service sector as the combination of a feminised workforce, a price-sensitive service, public-private competition and state regulation create particular difficulties. We report on a study of 33 day nurseries involving interviews with managers and employees over an eight-month period. Our findings show that childcare providers have to cope with recruitment and retention problems associated with high-end interactive service provision compounded by gender segregation and small business characteristics. Our analysis of employer and employee perspectives examines labour market issues affecting recruitment, and categorises the reasons for staff turnover into internal 'push' factors, external 'pull' factors, outside factors and functional turnover.

Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure

Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high throughput screen as inducers of human ATP binding cassette transporter A1 expression. Mechanism of action studies led to the identification of GSK3987 (4) as an LXR ligand. 4 recruits the steroid receptor coactivator-1 to human LXR alpha and LXRP with EC(50)s of 40 nM, profiles as an LXR agonist in functional assays, and activates LXR though a mechanism that is similar to first generation LXR agonists.

Families with multiple problems: Some challenges in identifying and providing services to those experiencing adversities across the life course

Summary A concern amongst policy makers to identify high cost and low productivity populations has created a new interest in identifying those who experience adversities across the life-course. This paper outlines the development of conceptual understandings of families whose children experience multiple adversities and links this with later poor outcomes in adult life and examines some of the research challenges in establishing such linkages. Findings It is argued that current thinking with regard to these issues reflects historical domains within which services to children and to adults are located. The challenge to domain thinking is both horizontal and vertical. Policy being required to address the horizontal axis by co-ordinating planned approaches to multiple needs across services. And policy being necessary to address the vertical cleavage between children’s and adult services in ways which join up services across the life path; conceptually and practically acknowledging the links between child and adult experiences. Application Such policy developments will inevitably require social work to develop alternative paradigms for understanding the needs of children and adults and designing services to effectively meet these.