Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy

Here, we analyze the complete coding sequences of all recognized tick-borne flavivirus species, including Gadgets Gully, Royal Farm and Karshi virus, seabird-associated flaviviruses, Kadam virus and previously uncharacterized isolates of Kyasanur Forest disease virus and Omsk hemorrhagic fever virus. Significant taxonomic improvements are proposed, e.g. the identification of three major groups (mammalian, seabird and Kadam tick-borne flavivirus groups), the creation of a new species (Karshi virus) and the assignment of Tick-borne encephalitis and Louping ill viruses to a unique species (Tick-borne encephalitis virus) including four viral types (i.e. Western Tick-borne encephalitis virus, Eastern Tick-borne encephalitis virus, Turkish sheep Tick-borne encephalitis virus and Louping ill Tick-borne encephalitis virus). The analyses also suggest a complex relationship between viruses infecting birds and those infecting mammals. Ticks that feed on both categories of vertebrates may constitute the evolutionary bridge between the three distinct identified lineages.

Analysis of molecular determinants of affinity and relative efficacy of a series of R- and S-2-(dipropylamino)tetralins at the 5-HT1A serotonin receptor

1 Factors influencing agonist affinity and relative efficacy have been studied for the 5-HT1A serotonin receptor using membranes of CHO cells expressing the human form of the receptor and a series of R-and S-2-(dipropylamino)tetralins (nonhydroxylated and monohydroxylated (5-OH, 6-OH, 7-OH, 8-OH) species). 2 Ligand binding studies were used to determine dissociation constants for agonist binding to the 5HT(1A) receptor: (a) K-i values for agonists were determined in competition versus the binding of the agonist [H-3]-8-OH DPAT. Competition data were all fitted best by a one-binding site model. (b) K-i values for agonists were also determined in competition versus the binding of the antagonist [H-3]-NAD-199. Competition data were all fitted best by a two-binding site model, and agonist affinities for the higher (K-h) and lower affinity (K-1) sites were determined. 3 The ability of the agonists to activate the 5-HT1A receptor was determined using stimulation of [S-35]-GTPgammaS binding. Maximal effects of agonists (E-max) and their potencies (EC50) were determined from concentration/response curves for stimulation of [S-35]-GTPgammaS binding. 4 K-1/K-h determined from ligand binding assays correlated with the relative efficacy (relative Em) of agonists determined in [S-35]-GTPgammaS binding assays. There was also a correlation between K-1/K-h and K-1/EC50 for agonists determined from ligand binding and [S-35]-GTPgammaS binding assays. 5 Simulations of agonist binding and effect data were performed using the Ternary Complex Model in order to assess the use of K-1/K-h for predicting the relative efficacy of agonists. British Journal of Pharmacology (2003) 138, 1129-1139. doi: 10. 1038/sj.bjp.705085.

Criticial determinants of construction tendering costs: Quantity surveyors' standpoint

Identification of cost-determinant variables and evaluation of their degree of influence play an essential role in building reliable cost models and enhance the competitive edge of quantity surveyors as well as contracting organisations. Sixty-seven variables affecting pre-tender construction cost estimates are identified through literature and interviews. These factors are grouped into six categories and a comparison analysis of their impact is conducted. Priority ranking of cost-influencing factors is carried out using a questionnaire survey commissioned amongst quantity surveyors based in the UK. Findings of this survey indicate that there is a strong agreement between quantity surveyors in ranking cost-influencing factors of construction projects. Comparisons between the outcomes of this research and other related studies are presented.

Designing dietary interventions: a reappraisal of the demographic and socio-economic determinants of dietary choice in the UK

The facilitation of healthier dietary choices by consumers is one of the key elements of the UK Government’s food strategy. Designing and targeting dietary interventions requires a clear understanding of the determinants of dietary choice. Conventional analysis of the determinants of dietary choice has focused on mean response functions which may mask significant differences in the dietary behaviour of different segments of the population. In this paper we use a quantile regression approach to investigate how food consumption behaviour varies amongst UK households in different segments of the population, especially in the upper and lower quantiles characterised by healthy or unhealthy consumption patterns. We find that the effect of demographic determinants of dietary choice on households that exhibit less healthy consumption patterns differs significantly from that on households that make healthier consumption choices. A more nuanced understanding of the differences in the behavioural responses of households making less-healthy eating choices provides useful insights for the design and targeting of measures to promote healthier diets.

On the determinants of optimal border enforcement

We extend the current immigration-enforcement literature by incorporating both the practice of people smuggling and a role for non-wage income into a two-country, dynamic general equilibrium model. We use the model economy to examine three questions. First, how does technological progress in the smuggling industry affect the level of migration and capital accumulation for a given level of enforcement? Second, do changes in border enforcement affect the level of migration, capital accumulation, and smuggling activity? Third, is the optimal level of enforcement sensitive to technological progress in the smuggling industry? We show that the government chooses to devote resources to border enforcement only if the deterrent effect on smugglers is large enough. Otherwise, it is not worth taxing host-country natives as the taxes paid will more than offset any income gain resulting from fewer migrants.