Five minutes with Mats Persson: “National parliaments are the solution to the EU’s democratic deficit”

European Parliament elections are due to be held in May 2014. Ahead of the elections, EUROPP’s Managing Editor Stuart Brown spoke to Mats Persson, the Director of Open Europe, about his views on the European Parliament, the role of national parliaments in the integration process, and whether the efforts to reform the European Union advocated by British Prime Minister David Cameron are likely to be successful

Quantum size effect in Pb(100) films: the role of symmetry and implication for film growth

We show from density-functional calculations that Pb(100) thin films exhibit quantum size effect with a bilayer periodicity in film energies, film relaxations, and work functions, which originate from different symmetry of the stacking geometry of odd and even layer films. The bilayer periodicity of the film energy is argued to survive on a semiconductor substrate, which should allow the growth of ``magically'' thick even-layer Pb(100) films. Furthermore, it is found that the quantum well states in a simple metal film can be classified into $\sigma$-bonded and $\pi$-bonded states, which quantize independently

Carbon and nitrogen pools and fluxes above and below ground in spruce, pine and birch stands in southern Sweden

We synthesised results on soil carbon (C) and nitrogen (N) fluxes and the accumulation of soil organic C and N under adjacent 50-year-old Norway spruce, Scots pine and silver birch stands growing on similar soils and evaluated the different processes involved. C and N budgets were calculated. Spruce stands had larger stocks of C and N in biomass and soil than birch stands, with pine intermediate. The differences in soil stocks were mainly found in the organic layer, whereas differences in the mineral soil were small. The study showed that there is no simple answer to what is causing the differences in soil C and N stocks, because several processes are interacting. Spruce and pine trees had higher biomass and litter production than birch trees, but total litter inputs showed no significant difference between stands, because the rich ground vegetation under pine and birch contributed with substantial litter inputs, in contrast to the poor ground vegetation under spruce. Decomposition rate (per g of C) was markedly higher under birch than under spruce and pine resulting in lower C and N stocks in the organic layer. This effect was amplified by higher abundance and biomass of earthworms, favoured by higher pH and palatable litter under birch. Earthworm bioturbation probably both increased decomposition rate and damaged the ectomycorrhizal network with negative consequences for the formation of mycorrhizal litter and C storage. In conclusion, the direct effects of spruce, pine and birch litter on C and N pools and fluxes were modified by indirect effects of understorey structure, pH and earthworm responses

STM fingerprint of molecule–adatom interactions in a self-assembled metal–organic surface coordination network on Cu(111)

7 páginas, 5 figuras, 3 tablas.-- El pdf del artículo es la versión pre-print.A novel approach of identifying metal atoms within a metal–organic surface coordination network using scanning tunnelling microscopy (STM) is presented. The Cu adatoms coordinated in the porous surface network of 1,3,8,10-tetraazaperopyrene (TAPP) molecules on a Cu(111) surface give rise to a characteristic electronic resonance in STM experiments. Using density functional theory calculations, we provide strong evidence that this resonance is a fingerprint of the interaction between the molecules and the Cu adatoms. We also show that the bonding of the Cu adatoms to the organic exodentate ligands is characterised by both the mixing of the nitrogen lone-pair orbitals of TAPP with states on the Cu adatoms and the partial filling of the lowest unoccupied molecular orbital (LUMO) of the TAPP molecule. Furthermore, the key interactions determining the surface unit cell of the network are discussed.This work was financially supported by the European Union through the Marie Curie Research Training Network PRAIRIES (MRTN-CT-2006-035810). Support from the Swiss National Science Foundation, the National Center of Competence in Research (NCCR) ‘‘Nanoscale Science’’ and the Wolfermann Naegeli Stiftung is also acknowledged. MP is also grateful for support from the Swedish Research Council (VR).Peer reviewe

A diverse panel of hepatitis C virus glycoproteins for use in vaccine research reveals extremes of monoclonal antibody neutralization resistance

Despite significant advances in the treatment of hepatitis C virus (HCV) infection, the need to develop preventative vaccines remains. Identification of the best vaccine candidates and evaluation of their performance in preclinical and clinical development will require appropriate neutralization assays utilizing diverse HCV isolates. We aimed to generate and characterize a panel of HCVE1E2 glycoproteins suitable for subsequent use in vaccine and therapeutic antibody testing. Full-length E1E2 clones were PCR amplified from patient- derived serum samples, cloned into an expression vector, and used to generate viral pseudoparticles (HCVpp). In addition, some of these clones were used to generate cell culture infectious (HCVcc) clones. The infectivity and neutralization sensitivity of these viruses were then determined. Bioinformatic and HCVpp infectivity screening of approximately 900 E1E2 clones resulted in the assembly of a panel of 78 functional E1E2 proteins representing distinct HCV genotypes and different stages of infection. These HCV glycoproteins differed markedly in their sensitivity to neutralizing antibodies. We used this panel to predict antibody efficacy against circulating HCV strains, highlighting the likely reason why some monoclonal antibodies failed in previous clinical trials. This study provides the first objective categorization of cross-genotype patient-derived HCVE1E2 clones according to their sensitivity to antibody neutralization. It has shown that HCV isolates have clearly distinguishable neutralization-sensitive, -resistant, or -intermediate phenotypes, which are independent of genotype. The panel provides a systematic means for characterization of the neutralizing response elicited by candidate vaccines and for defining the therapeutic potential of monoclonal antibodies

'A hidden disorder until the pieces fall into place' - a qualitative study of vaginal prolapse

<p>Abstract</p> <p>Background</p> <p>Vaginal prolapse affects quality of life negatively and is associated with urinary, bowel, and sexual symptoms. Few qualitative studies have explored women's experiences of vaginal prolapse. The objective of the study was to elucidate the experiences of living with prolapse and its impact on daily life, prior to surgical intervention.</p> <p>Methods</p> <p>In-depth interviews were conducted with 14 women with vaginal prolapse, prior to surgical treatment. Recruitment of the informants was according to 'purposive sampling'. An interview guide was developed, including open-ended questions addressing different themes, which was processed and revised during the data collection and constituted part of a study-emergent design. Data were collected until 'saturation' was achieved, that is, when no significant new information was obtained by conducting further interviews. Interviews were audiotaped, transcribed verbatim, and analyzed according to manifest and latent content analysis.</p> <p>Results</p> <p>The theme defining the process of living with prolapse and women's experiences was labelled 'process of comprehension and action'. The findings constitute two categories: obstacles and facilitators to seeking health care. The category <it>obstacles </it>comprises six subcategories that define the factors restraining women from seeking health care: absence of information, blaming oneself, feeling ignored by the doctor, having a covert condition, adapting to successive impairment, and trivializing the symptoms and de-prioritizing own health. The category <it>facilitators </it>include five subcategories that define the factors promoting the seeking of health care: confirmation and support by others, difficulty in accepting an ageing body, feeling sexually unattractive, having an unnatural body, and reaching the point of action.</p> <p>Conclusion</p> <p>The main theme identified was the 'process of comprehension and action'. This process consisted of factors functioning as either obstacles or facilitators to seeking health care. The main obstacles described by the participants were lack of information and confirmation. The main facilitators constituted feeling sexually unattractive and impaired physical ability due to prolapse. Information on prolapse should be easily accessible, to improve the possibility for women to gain knowledge about the condition and overcome obstacles to seeking health care. Health care professionals have a significant role in facilitating the process by confirming and informing women about available treatment.</p

High-level secretion of recombinant monomeric murine and human single-chain Fv antibodies from Drosophila S2 cells

Single-chain variable fragment (scFvs) antibodies are small polypeptides (∼26 kD) containing the heavy (VH) and light (VL) immunoglobulin domains of a parent antibody connected by a flexible linker. In addition to being frequently used in diagnostics and therapy for an increasing number of human diseases, scFvs are important tools for structural biology as crystallization chaperones. Although scFvs can be expressed in many different organisms, the expression level of an scFv strongly depends on its particular amino acid sequence. We report here a system allowing for easy and efficient cloning of (i) scFvs selected by phage display and (ii) individual heavy and light chain sequences from hybridoma cDNA into expression plasmids engineered for secretion of the recombinant fragment produced in Drosophila S2 cells. We validated the method by producing five scFvs derived from human and murine parent antibodies directed against various antigens. The production yields varied between 5 and 12 mg monomeric scFv per liter of supernatant, indicating a relative independence on the individual sequences. The recombinant scFvs bound their cognate antigen with high affinity, comparable with the parent antibodies. The suitability of the produced recombinant fragments for structural studies was demonstrated by crystallization and structure determination of one of the produced scFvs, derived from a broadly neutralizing antibody against the major glycoprotein E2 of the hepatitis C virus. Structural comparison with the Protein Data Bank revealed the typical spatial organization of VH and VL domains, further validating the here-reported expression system

Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Stereopure Lactam-Based HIV-1 Protease Inhibitors

In an effort to identify a new class of druglike HIV-1 protease inhibitors, four different stereopure beta-hydroxy gamma-lactam-containing inhibitors have been synthesized, biologically evaluated, and cocrystallized. The impact of the tether length of the central spacer (two or three carbons) was also investigated. A compound with a shorter tether and (3R,4S) absolute configuration exhibited high activity with a K-i of 2.1 nM and an EC50 of 0.64 mu M. Further optimization by decoration of the P1' side chain furnished an even more potent HIV-1 protease inhibitor (K-i = 0.8 nM, EC50 = 0.04 mu M). According to X-ray analysis, the new class of inhibitors did not fully succeed in forming two symmetric hydrogen bonds to the catalytic aspartates. The crystal structures of the complexes further explain the difference in potency between the shorter inhibitors (two-carbon spacer) and the longer inhibitors (three-carbon spacer)

Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research

A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase