Characterization of recombinant influenza B viruses with key neuraminidase inhibitor resistance mutations

Objectives and methods: An influenza B virus plasmid-based rescue system was used to introduce site-specific mutations, previously observed in neuraminidase (NA) inhibitor-resistant viruses, into the NA protein of six recombinant viruses. Three mutations observed only among in vitro selected zanamivir-resistant influenza A mutants were introduced into the B/Beijing/1/87 virus NA protein, to change residue E116 to glycine, alanine or aspartic acid. Residue E116 was also mutated to valine, a mutation found in the clinic among oseltamivir-resistant viruses. An arginine to lysine change at position 291 (292 N2 numbering) mimicked that seen frequently in influenza A N2 clinical isolates resistant to oseltamivir. Similarly, an arginine to lysine change at position 149 (152 in N2 numbering) was made to reproduce the change found in the only reported zanamivir-resistant clinical isolate of influenza B virus. In vitro selection and prolonged treatment in the clinic leads to resistance pathways that require compensatory mutations in the haemagglutinin gene, but these appear not to be important for mutants isolated from immunocompetent patients. The reverse genetics system was therefore used to generate mutants containing only the NA mutation. Results and conclusions: With the exception of a virus containing the E116G mutation, mutant viruses were attenuated to different levels in comparison with wild-type virus. This attenuation was a result of altered NA activity or stability depending on the introduced mutation. Mutant viruses displayed increased resistance to zanamivir, oseltamivir and peramivir, with certain viruses displaying cross-resistance to all three drugs.

A new species of Myosotis L. (Boraginaceae) from Cameroon, with a key to the Tropical African species of the genus

Myosotic cameroonensis Cheek & R Becker (Boraginacene) is described from Cameroon. Its conservation status and taxonomic affinities are assessed and an updated key to the Tropical African species of the genus is presented.

Insights into the effects on metal binding of the systematic substitution of five key glutamate ligands in the ferritin of Escherichia coli

Ferritins are nearly ubiquitous iron storage proteins playing a fundamental role in iron metabolism. They are composed of 24 subunits forming a spherical protein shell encompassing a central iron storage cavity. The iron storage mechanism involves the initial binding and subsequent O-2-dependent oxidation of two Fe2+ ions located at sites A and B within the highly conserved dinuclear "ferroxidase center" in individual subunits. Unlike animal ferritins and the heme-containing bacterioferritins, the Escherichia coli ferritin possesses an additional iron-binding site (site C) located on the inner surface of the protein shell close to the ferroxidase center. We report the structures of five E. coli ferritin variants and their Fe3+ and Zn2+ (a redox-stable alternative for Fe2+) derivatives. Single carboxyl ligand replacements in sites A, B, and C gave unique effects on metal binding, which explain the observed changes in Fe2+ oxidation rates. Binding of Fe2+ at both A and B sites is clearly essential for rapid Fe2+ oxidation, and the linking of Fe-B(2+) to Fe-C(2+) enables the oxidation of three Fe2+ ions. The transient binding of Fe2+ at one of three newly observed Zn2+ sites may allow the oxidation of four Fe2+ by one dioxygen molecule.

Key performance indicators (KPIs) and priority setting in using the multi-attribute approach for assessing sustainable intelligent buildings

The main objectives of this paper are to: firstly, identify key issues related to sustainable intelligent buildings (environmental, social, economic and technological factors); develop a conceptual model for the selection of the appropriate KPIs; secondly, test critically stakeholder's perceptions and values of selected KPIs intelligent buildings; and thirdly develop a new model for measuring the level of sustainability for sustainable intelligent buildings. This paper uses a consensus-based model (Sustainable Built Environment Tool- SuBETool), which is analysed using the analytical hierarchical process (AHP) for multi-criteria decision-making. The use of the multi-attribute model for priority setting in the sustainability assessment of intelligent buildings is introduced. The paper commences by reviewing the literature on sustainable intelligent buildings research and presents a pilot-study investigating the problems of complexity and subjectivity. This study is based upon a survey perceptions held by selected stakeholders and the value they attribute to selected KPIs. It is argued that the benefit of the new proposed model (SuBETool) is a ‘tool’ for ‘comparative’ rather than an absolute measurement. It has the potential to provide useful lessons from current sustainability assessment methods for strategic future of sustainable intelligent buildings in order to improve a building's performance and to deliver objective outcomes. Findings of this survey enrich the field of intelligent buildings in two ways. Firstly, it gives a detailed insight into the selection of sustainable building indicators, as well as their degree of importance. Secondly, it tesst critically stakeholder's perceptions and values of selected KPIs intelligent buildings. It is concluded that the priority levels for selected criteria is largely dependent on the integrated design team, which includes the client, architects, engineers and facilities managers.

Contractor key competitiveness indicators: A China study

A proper method to assess contractor competitiveness is important both for assisting clients in the selection of proper contractors and for assisting contractors in the development of more competitive bidding strategies. Previous studies have identified various indicators for assessing contractor competitiveness, and several assessment methods have been introduced. Nevertheless, these studies are limited because they are unable to tell which indicators are more important in different market environments. This paper identifies the key competitiveness indicators �KCIs� for assessing contractor competitiveness in the Chinese construction market. An index value is used to indicate the relative significance of various competitiveness indicators based on which KCIs are identified. The data applied in this study are from a survey of the construction industry in mainland China. The research findings provide valuable information for both existing businesses and the construction professionals who plan to compete for construction works in the Chinese market. The study provides useful references for further studies that compare the KCIs used in the Chinese construction industry and those used in other construction industries.

Assessing reading at Key Stage 2: SATs as measures of children's inferential abilities

This article describes two studies. The first study was designed to investigate the ways in which the statutory assessments of reading for 11-year-old children in England assess inferential abilities. The second study was designed to investigate the levels of performance achieved in these tests in 2001 and 2002 by 11-year-old children attending state-funded local authority schools in one London borough. In the first study, content and questions used in the reading papers for the Standard Assessment Tasks (SATs) in the years 2001 and 2002 were analysed to see what types of inference were being assessed. This analysis suggested that the complexity involved in inference making and the variety of inference types that are made during the reading process are not adequately sampled in the SATs. Similar inadequacies are evident in the ways in which the programmes of study for literacy recommended by central government deal with inference. In the second study, scripts of completed SATs reading papers for 2001 and 2002 were analysed to investigate the levels of inferential ability evident in scripts of children achieving different SATs levels. The analysis in this article suggests that children who only just achieve the 'target' Level 4 do so with minimal use of inference skills. They are particularly weak in making inferences that require the application of background knowledge. Thus, many children who achieve the reading level (Level 4) expected of 11-year-olds are entering secondary education with insecure inference-making skills that have not been recognised.

The Namib Sand Sea digital database of aeolian dunes and key forcing variables

A new digital atlas of the geomorphology of the Namib Sand Sea in southern Africa has been developed. This atlas incorporates a number of databases including a digital elevation model (ASTER and SRTM) and other remote sensing databases that cover climate (ERA-40) and vegetation (PAL and GIMMS). A map of dune types in the Namib Sand Sea has been derived from Landsat and CNES/SPOT imagery. The atlas also includes a collation of geochronometric dates, largely derived from luminescence techniques, and a bibliographic survey of the research literature on the geomorphology of the Namib dune system. Together these databases provide valuable information that can be used as a starting point for tackling important questions about the development of the Namib and other sand seas in the past, present and future.