Repertoire of HLA-DR1-restricted CD4 T cell responses to capsular Caf1 antigen of Y. pestis HLA-transgenic mice

Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under development as a recombinant vaccine. However, little is known about the specificity of human T cell responses for Caf1. We characterized CD4 T cell epitopes of Caf1 in 'humanized'-HLA-DR1 transgenic mice lacking endogenous MHC class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T cell immunity was measured with respect to proliferative and IFNgamma T cell responses and recognition by a panel of T cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased towards a single immunodominant epitope near the C-terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.

Output Additionality of Public Support for Innovation: Evidence for Irish Manufacturing Plants

Public support for private R&D and innovation is part of most national and regional innovation support regimes. In this article, we estimate the effect of public innovation support on innovation outputs in Ireland and Northern Ireland. Three dimensions of output additionality are considered: extensive additionality, in which public support encourages a larger proportion of the population of firms to innovate; improved product additionality, in which there is an increase in the average importance of incremental innovation; new product additionality, in which there is an increase in the average importance of more radical innovation. Using an instrumental variable approach, our results are generally positive, with public support for innovation having positive, and generally significant, extensive, improved and new product additionality effects. These results hold both for all plants and indigenously owned plants, a specific target of policy in both jurisdictions. The suggestion is that grant aid to firms can be effective in both encouraging firms to initiate new innovation and improve the quality and sophistication of their innovation activity. Our results also emphasize the importance for innovation of in-house R&D, supply-chain linkages, skill levels and capital investment, all of which may be the focus of complementary policy initiatives.

Agricultural intensification and biodiversity partitioning in European landscapes comparing plants, carabids, and birds

Effects of agricultural intensification (AI) on biodiversity are often assessed on the plot scale, although processes determining diversity also operate on larger spatial scales. Here, we analyzed the diversity of vascular plants, carabid beetles, and birds in agricultural landscapes in cereal crop fields at the field (n = 1350), farm (n = 270), and European-region (n = 9) scale. We partitioned diversity into its additive components alpha, beta, and gamma, and assessed the relative contribution of beta diversity to total species richness at each spatial scale. AI was determined using pesticide and fertilizer inputs, as well as tillage operations and categorized into low, medium, and high levels. As AI was not significantly related to landscape complexity, we could disentangle potential AI effects on local vs. landscape community homogenization. AI negatively affected the species richness of plants and birds, but not carabid beetles, at all spatial scales. Hence, local AI was closely correlated to beta diversity on larger scales up to the farm and region level, and thereby was an indicator of farm-and region-wide biodiversity losses. At the scale of farms (12.83-20.52%) and regions (68.34-80.18%), beta diversity accounted for the major part of the total species richness for all three taxa, indicating great dissimilarity in environmental conditions on larger spatial scales. For plants, relative importance of alpha diversity decreased with AI, while relative importance of beta diversity on the farm scale increased with AI for carabids and birds. Hence, and in contrast to our expectations, AI does not necessarily homogenize local communities, presumably due to the heterogeneity of farming practices. In conclusion, a more detailed understanding of AI effects on diversity patterns of various taxa and at multiple spatial scales would contribute to more efficient agri-environmental schemes in agroecosystems.

Tobacco smoking increases the risk of high-grade dysplasia and cancer among patients with Barrett's esophagus

Background & Aims: Esophageal adenocarcinoma arises from Barrett's esophagus (BE); patients with this cancer have a poor prognosis. Identification of modifiable lifestyle factors that affect the risk of progression from BE to esophageal adenocarcinoma might prevent its development. We investigated associations among body size, smoking, and alcohol use with progression of BE to neoplasia. Methods: We analyzed data from patients with BE identified from the population-based Northern Ireland BE register, diagnosed between 1993 and 2005 with specialized intestinal metaplasia (n = 3167). Data on clinical, demographic, and lifestyle factors related to diagnosis of BE were collected from hospital case notes. We used the Northern Ireland Cancer Registry to identify which of these patients later developed esophageal adenocarcinoma, adenocarcinomas of the gastric cardia, or esophageal high-grade dysplasia. Cox proportional hazards models were used to associate lifestyle factors with risk of progression.
Results: By December 31, 2008, 117 of the patients with BE developed esophageal high-grade dysplasia or adenocarcinomas of the esophagus or gastric cardia. Current tobacco smoking was significantly associated with an increased risk of progression (hazard ratio = 2.03; 95% confidence interval, 1.29-3.17) compared with never smoking, and across all strata of smoking intensity. Alcohol consumption was not related to risk of progression. Measures of body size were infrequently reported in endoscopy reports, and body size was not associated with risk of progression.
Conclusions: Smoking tobacco increases the risk of progression to cancer or high-grade dysplasia 2-fold among patients with BE, compared with patients with BE that have never smoked. Smoking cessation strategies should be considered for patients with BE.