Small angle neutron scattering observation of chain retraction after a large step deformation

The process of retraction in entangled linear chains after a fast nonlinear stretch was detected from time-resolved but quenched small angle neutron scattering (SANS) experiments on long, well-entangled polyisoprene chains. The statically obtained SANS data cover the relevant time regime for retraction, and they provide a direct, microscopic verification of this nonlinear process as predicted by the tube model. Clear, quantitative agreement is found with recent theories of contour length fluctuations and convective constraint release, using parameters obtained mainly from linear rheology. The theory captures the full range of scattering vectors once the crossover to fluctuations on length scales below the tube diameter is accounted for

A collaborative approach to mapping value of fisheries resources in the North Sea (Part 1: Methodology)

IMARES and LEI are both contracted on occasion to perform VMS-analyses to produce maps of fishing activity or economic value of fisheries in particular area(s) in the North Sea. Until present, IMARES and LEI use their own methodology which is inspired mostly on their own unique data availabilities which may lead to different results. This in turn may lead to questioning of these methodologies and results, especially in relation to estimations of economic value. The aim of the current study is to compare both methodologies by IMARES and LEI en decide upon a common (unique) methodology for producing fishing activity and value maps and estimating economic value of specific areas. The current report describes the jointly agreed methodology between scientists from IMARES and LEI, using input from the fishing industry. This methodology can be readily applied in future projects aimed at describing the value of particular areas in the North Sea in terms of fishing activity. A secondary aim - included on request of the Dutch Fish Product Board (PVIS) - is to address the question of how IMARES and/or LEI can make use of knowledge of the fishing industry in VMS mapping projects

Substrate-derived Sortase A inhibitors: targeting an essential virulence factor of Gram-positive pathogenic bacteria

The bacterial transpeptidase Sortase A (SrtA) is a surface enzyme of Gram-positive pathogenic bacteria. It has been shown to be an essential virulence factor for the establishment of various bacterial infections, including septic arthritis. However, the development of potent Sortase A inhibitors remains an unmet challenge. Sortase A relies on a five amino acid sorting signal (LPXTG), by which it recognizes its natural target. We report the synthesis of a series of peptidomimetic inhibitors of Sortase A based on the sorting signal, supported by computational binding analysis. By employing a FRET-compatible substrate, our inhibitors were assayed in vitro. Among our panel, we identified several promising inhibitors with IC50 values below 200 mu M, with our strongest inhibitor - LPRDSar - having an IC50 of 18.9 mu M. Furthermore, it was discovered that three of our compounds show an effect on growth and biofilm inhibition of pathogenic Staphylococcus aureus, with the inclusion of a phenyl ring seemingly key to this effect. The most promising compound in our panel, BzLPRDSar, could inhibit biofilm formation at concentrations as low as 32 mu g mL(-1), manifesting it as a potential future drug lead. This could lead to treatments for MRSA infections in clinics and diseases such as septic arthritis, which has been directly linked with SrtA

Identification of rare earth elements in synthetic and natural monazite and xenotime by visible-to-shortwave infrared reflectance spectroscopy

To support the role of proximal and remote sensing in geological rare earth element (REE) resource exploration, we studied the reflectance spectroscopy of synthetic single- and mixed-REE phosphate phases. Synthesis yielded monazite for the elements La to Gd, and xenotime for Dy to Lu and Y. Visible-to-shortwave infrared (350–2500 nm) reflectance spectra of synthetic single-REE monazites and xenotimes can be used to identify the ions responsible for the absorption features in natural monazites and xenotimes. Nd3+, Pr3+ and Sm3+ produce the main absorption features in monazites. In natural xenotime, Dy3+, Er3+, Ho3+ and Tb3+ ions cause the prevalent absorptions. The majority of the REE-related absorption features are due to photons exciting electrons within the 4f subshell of the trivalent lanthanide ions to elevated energy levels resulting from spin-orbit coupling. There are small (&lt; 20 nm) shifts in the wavelengths of these absorptions depending on the nature of the ligands. The energy levels are further split by crystal field effects, manifested in the reflectance spectra as closely spaced (∼ 5–20 nm) multiplets within the larger absorption features. Superimposed on the electronic absorptions are vibrational absorptions in the H2O molecule or within [OH]−, [CO3]2− and [PO4]3− functional groups, but so far only the carbonate-related spectral features seem usable as a diagnostic tool in REE-bearing minerals. Altogether, our study creates a strengthened knowledge base for detection of REE using reflectance spectroscopy and provides a starting point for the identification of REE and their host minerals in mineral resources by means of hyperspectral methods.</p

Moderate-Resolution Spectroscopy of the Lensed Quasar 2237+0305: A search for Ca ii Absorption Due to the Interstellar Medium in the Foreground Lensing Galaxy

The gravitational lens system 2237 + 0305 consists of a low-redshift barred spiral galaxy (z = 0.0394) centered on a more distant quasar (z = 1.695). Because the lensing galaxy is nearly face on, spectroscopy of the background quasar affords a unique opportunity to study the interstellar medium in the galaxy\u27s center and buW:. We report moderate-resolution spectroscopy of QS02237 + 0305 yielding a 3u upper limit of 72 rnA forthe rest equivalent width of Ca II K absorption d);le to gas in the intervening galaxy. Since gas in the Milky Way thick disk typically produces 220 mA Ca II lines along lines of sight at high galactic latitude, while our line of sight to QSO 2237 + 0305 is effectively the weighted mean of four lines of sight, each of which transects an entire halo diameter in the lensing galaxy rather than just a radius, our Ca II upper limit argues against the presence. of such a thick disk near the center of the lensing galaxy. Also, published studies indicate that at 8200 A, QSO 2237 + 0305 suffers roughly 0.5 mag of extinction due to the lensing galaxy. Assuming a normal gas-to-dust ratio and allowing for various sources of uncertainty, this absorption estimate combined with our Ca II Kupper limit implies that calcium is depleted with respect to hydrogen by at least 2.7-3.7 dex, compared to solar abundances. This depletion is similar to the more extreme cases seen in our own galaxy, and higher-dispersion observations may further decrease the upper limit on Ca II absorption

Linkage analysis and whole exome sequencing identify a novel candidate gene in a Dutch multiple sclerosis family

Background: Multiple sclerosis (MS) is a complex disease resulting from the joint effect of many genes. It has been speculated that rare variants might explain part of the missing heritability of MS. Objective: To identify rare coding genetic variants by analyzing a large MS pedigree with 11 affected individuals in several generations. Methods: Genome-wide linkage screen and whole exome sequencing (WES) were performed to identify novel coding variants in the shared region(s) and in the known 110 MS risk loci. The candidate variants were then assessed in 591 MS patients and 3169 controls. Results: Suggestive evidence for linkage was obtained to 7q11.22-q11.23. In WES data, a rare missense variant p.R183C in FKBP6 was identified that segregated with the disease in this family. The minor allele frequency was higher in an independent cohort of MS patients than in healthy controls (1.27% vs 0.95%), but not significant (odds ratio (OR) = 1.33 (95% confidence interval (CI): 0.8–2.4), p = 0.31). Conclusion: The rare missense variant in FKBP6 was identified in a large Dutch MS family segregating with the disease. This association to MS was not found in an independent MS cohort. Overall, genome-wide studies in larger cohorts are needed to adequately investigate the role of rare variants in MS risk

Spatial and seasonal fleet activity and cod distribution in Flemish Cap

The aim of this analysis is to describe the spatial and seasonal fleet activity and cod distribution in the Flemish Cap area in the period 2008-2013. Especial attention is paid to the relative distribution of mature and immature sub-stocks, as well as individuals bellow 41 cm size (Minimum Landing Size, MLS). The following data sources were analyzed for different periods depending on the data availability and the aim followed: Daily Catch Reports (DCR), Vessel Monitoring System (VMS), Spanish Scientific Observers, EU Flemish Cap surveys.Framework Contract MARE/2012/21 - "Scientific advice for Fisheries beyond EU Waters" - Specific Contract No 2 (SI2.681887

Vitality, perceived social support and disease activity determine the performance of social roles in recently diagnosed multiple sclerosis: a longitudinal analysis.

Objective: The aim of this study was to identify the principal determinants that are longitudinally associated with the performance of social roles in the first 3 years following a diagnosis of multiple sclerosis. Design: Inception cohort with 5 measurements over 3 years. Patients: A total of 156 patients recently diagnosed with multiple sclerosis. Method: Performance of social roles was measured using the 2 role functioning and the social sub-scales of the Medical Outcome Study Short Form 36. Potential determinants (n = 43) were divided into the following clusters: patient and disease characteristics (n = 12), psychosocial characteristics (n= 10), basic functions (n= 18) and basic activities (n= 3). Multivariate longitudinal regression analyses were performed with generalized estimating equations. A backwards selection procedure for every cluster per outcome reduced the large number of potential determinants. In order to determine whether longitudinal associations are present the selected determinants were entered into an overall regression model. Results: Twenty-three candidate determinants were selected. Vitality, measured with the SF36 sub-scale vitality, the T2-weighted supratentorial lesion load and the perceived amount of social support, measured with the Social Support List Discrepancies, were longitudinally associated with the performance of social roles in 2 or 3 of the models. Conclusion: Vitality, the perceived amount of social support, and disease activity, i.e. the T2-weighted supratentorial lesion load, determine the performance of social roles in the early stages of multiple sclerosis. © 2007 The Authors. Journal Compilation © 2007 Foundation of Rehabilitation Information

Perspectives on the Use of Multiple Sclerosis Risk Genes for Prediction

Objective: A recent collaborative genome-wide association study replicated a large number of susceptibility loci and identified novel loci. This increase in known multiple sclerosis (MS) risk genes raises questions about clinical applicability of genotyping. In an empirical set we assessed the predictive power of typing multiple genes. Next, in a modelling study we explored current and potential predictive performance of genetic MS risk models. Materials and Methods: Genotype data on 6 MS risk genes in 591 MS patients and 600 controls were used to investigate the predictive value of combining risk alleles. Next, the replicated and novel MS risk loci from the recent and largest international genome-wide association study were used to construct genetic risk models simulating a population of 100,000 individuals. Finally, we assessed the required numbers, frequencies, and ORs of risk SNPs for higher discriminative accuracy in the future. Results: Individuals with 10 to 12 risk alleles had a significantly increased risk compared to individuals with the average population risk for developing MS (OR 2.76 (95% CI 2.02-3.77)). In the simulation study we showed that the area under the receiver operating characteristic curve (AUC) for a risk score based on the 6 SNPs was 0.64. The AUC increases to 0.66 using the well replicated 24 SNPs and to 0.69 when including all replicated and novel SNPs (n = 53) in the risk model. An additional 20 SNPs with allele frequency 0.30 and ORs 1.1 would be needed to increase the AUC to a slightly higher level of 0.70, and at least 50 novel variants with allele frequency 0.30 and ORs 1.4 would be needed to obtain an AUC of 0.85. Conclusion: Although new MS risk SNPs emerge rapidly, the discriminatory ability in a clinical setting will be limited