Beschreibung: Background: Patients with chronic hepatitis B virus infection (CHB) usually mount a modest T cell response against HBV epitopes. In order to determine immunogenic epitopes of HBV recognized by HBV-specific T cells, previous studies focused on previously confirmed HBV epitopes and assessed the T cell response by the number of HBV-specific T cells by IFN-γ ELISPOT. Methods: We studied T cell functionality by combined in silico methods predicting HBV-specific epitopes and experimental investigations on the recognition of these epitopes. 30 chronic CHB patients and 10 patients with resolved HBV (RHB) were included in the study. We identified epitopes from the literature and by in silico analysis. These were evaluated for immunogenicity by use of synthetic peptides representing the epitopes through exposure to PBMCs from patients with CHB or RHB by IFN-γ ELISPOT. The number of IFN-γ producing cells (SFC), mean spot size (MSS) and stimulation index (SI) were recorded. Results: The frequency of HBV-specific T cells producing IFN-γ after stimulation with HBV epitopes was similar in CHB and RHB patients. CHB patients had a higher MSS SI than RHB patients. Patients not carrying the HLA-A2 genotype had higher SFC SI and MSS SI. Patients with HLA-A11 had higher MSS SI compared to non- HLA-A11 allele patients. HBeAg-positive patients had a lower MSS SI, and none of the HBeAg positive patients had the HLA-A11 genotype. We found 3 immunogenic epitopes not described previously. Conclusion: IFN-γ ELISPOT-determined MSS is an efficient marker for T cell recognition of epitopes. This experimental measure showed the in silico analysis for epitope prediction to be a valuable tool in future studies on HLA genotypes and HBV epitopes. This way our study now points to previously unappreciated consequences of carrying the HLA-A11 allele in terms of stronger immunity to HBV.

Beschreibung: Background: Lung cancer stage at diagnosis predicts possible curative treatment. In Denmark and the UK, lung cancer patients have lower survival rates than citizens in most other European countries, which may partly be explained by a comparatively longer diagnostic interval in these two countries. In Denmark, a pathway was introduced in 2008 allowing general practitioners (GPs) to refer patients suspected of having lung cancer directly to fast-track diagnostics. However, symptom presentation of lung cancer in general practice is known to be diverse and complex, and systematic knowledge of the routes to diagnosis is needed to enable earlier lung cancer diagnosis in Denmark. This study aims to describe the routes to diagnosis, the diagnostic activity preceding diagnosis and the diagnostic intervals for lung cancer in the Danish setting. Methods: We conducted a national registry-based cohort study on 971 consecutive incident lung cancer patients in 2010 using data from national registries and GP questionnaires. Results: GPs were involved in 68.3% of cancer patients’ diagnostic pathways, and 27.4% of lung cancer patients were referred from the GP to fast-track diagnostic work-up. A minimum of one X-ray was performed in 85.6% of all cases before diagnosis. Patients referred through a fast-track route more often had diagnostic X-rays (66.0%) than patients who did not go through fast-track (49.4%). Overall, 33.6% of all patients had two or more X-rays performed during the 90 days before diagnosis. Patients whose symptoms were interpreted as non-alarm symptoms or who were not referred to fast-track were more likely to experience a long diagnostic interval than patients whose symptoms were interpreted as alarm symptoms or who were referred to fast-track. Conclusions: Lung cancer patients followed several diagnostic pathways. The existing fast-track pathway must be supplemented to ensure earlier detection of lung cancer. The high incidence of multiple X-rays warrants a continued effort to develop more accurate lung cancer tests for use in primary care.

Beschreibung: Coupling picolinic acid (pyridine-2-carboxylic acid) and pyridine-2,6-dicarboxylic acid with N-alkylanilines affords a range of mono- and bis-amides in good to moderate yields. These amides are of interest for potential applications in catalysis, coordination chemistry and molecular devices. The reaction of picolinic acid with thionyl chloride to generate the acid chloride in situ leads not only to the N-alkyl-N-phenylpicolinamides as expected but also the corresponding 4-chloro-N-alkyl-N-phenylpicolinamides in the one pot. The two products are readily separated by column chromatography. Chlorinated products are not observed from the corresponding reactions of pyridine-2,6-dicarboxylic acid. X-Ray crystal structures for six of these compounds are described. These structures reveal a general preference for cis amide geometry in which the aromatic groups (N-phenyl and pyridyl) are cis to each other and the pyridine nitrogen anti to the carbonyl oxygen. Variable temperature 1H NMR experiments provide a window on amide bond isomerisation in solution. Scientific Reports 5 doi: 10.1038/srep09950

Beschreibung: Article Comprehensive elucidation of metal-support interactions is important for controlling and improving their performances in a range of pertinent technologies. Here, the authors reveal how subsurface defects influence the adhesion and wetting of a metal on the surface of a metal oxide. Nature Communications doi: 10.1038/ncomms9845 Authors: Igor Beinik, Matti Hellström, Thomas N. Jensen, Peter Broqvist, Jeppe V. Lauritsen