Reply to Comment on "Reevaluation of the parton distribution of strange quarks in the nucleon"

A Comment on the recently published reevaluation of the polarization-averaged parton distribution of strange quarks in the nucleon using final data on the multiplicities of charged kaons in semi-inclusive deep-inelastic scattering is reviewed. Important features of the comparison of one-dimensional projections of the multidimensional HERMES data are pointed out. A test of the leading-order extraction of xS(x) using the difference between charged-kaon multiplicities is repeated. The results are consistent with leading-order predictions within the uncertainties in the input data, and do not invalidate the earlier extraction of xS(x).Comment: Reply Comment to arXiv:1407.372

A comparison of TCAR, CIR and LAMBDA GNSS ambiguity resolution

With the envisioned introduction of three-carrier GNSS's (modernized GPS, Galileo), new methods of ambiguity resolution have been developed. In this contribution we will compare two important candidate methods for triple-frequency ambiguity resolution with the already existing LAMBDA (Least-squares Ambiguity Decorrelation Adjustment) method; the TCAR (Three-Carrier Ambiguity Resolution) method; and the CIR (Cascading Integer Resolution) method. It will be shown that for their estimation principle, both TCAR and CIR rely on integer bootstrapping, whereas LAMBDA is based on integer least-squares, of which optimality has been proven, that is, highest probability of success. In TCAR and CIR pre-defined ambiguity transformation are used, whereas LAMBDA exploits the information content of the full ambiguity variance-covariance matrix, with statistical decorrelation the objective in constructing the ambiguity transformation. For the aspect of resolving the ambiguities, TCAR and CIR are designed for use with the geometry-free model. LAMBDA can intrinsically handle any GNSS model with integer ambiguities and thereby utilize satellite geometry to its benefit in geometry-based models

Towards Reliable Concurrent Software

As the use of concurrent software is increasing, we urgently need techniques to establish the correctness of such applications. Over the last years, significant progress has been made in the area of software verification, making verification techniques usable for realistic applications. However, much of this work concentrates on sequential software, and a next step is necessary to apply these results also on realistic concurrent software. In this paper, we outline a research agenda to realise this goal. We argue that current techniques for verification of concurrent software need to be further developed in multiple directions: extending the class of properties that can be established, improving the level of automation that is available for this kind of verification, and enlarging the class of concurrent programs that can be verified

A cohesive network approach for modelling fibre and matrix damage in composite laminates

In the current study a high fidelity analysis approach is used to predict the failure process of notched composite structures. Discrete cracking is explicitly modelled by incorporating cohesive interface elements along potential failure paths. These elements form an interconnected network to account for the interaction between interlaminar and intralaminar failure modes. Finite element models of these configurations were created in the commercial analysis software ABAQUS and a user defined material subroutine (UMAT) was used to describe the behaviour of the cohesive elements. The material subroutine ensured that the model remained stable despite significant damage, which is a significant challenge for implicit damage simulations. Two analysis approaches were adopted using either the as-measured or modified (in-situ) ply strengths. Both approaches were capable of closely predicting the mean ultimate strength for a range of hole diameters. However, using the measured ply properties resulted in extensive matrix cracking in the surface ply which caused a deviation from the experimentally measured surface strain. The results demonstrate that high fidelity physically based modelling approaches have the ability to complement or replace certain experimental programs focussed on the design and certification of composite structures

Functional consequences of sphingomyelinase-induced changes in erythrocyte membrane structure.

Inflammation enhances the secretion of sphingomyelinases (SMases). SMases catalyze the hydrolysis of sphingomyelin into phosphocholine and ceramide. In erythrocytes, ceramide formation leads to exposure of the removal signal phosphatidylserine (PS), creating a potential link between SMase activity and anemia of inflammation. Therefore, we studied the effects of SMase on various pathophysiologically relevant parameters of erythrocyte homeostasis. Time-lapse confocal microscopy revealed a SMase-induced transition from the discoid to a spherical shape, followed by PS exposure, and finally loss of cytoplasmic content. Also, SMase treatment resulted in ceramide-associated alterations in membrane-cytoskeleton interactions and membrane organization, including microdomain formation. Furthermore, we observed increases in membrane fragility, vesiculation and invagination, and large protein clusters. These changes were associated with enhanced erythrocyte retention in a spleen-mimicking model. Erythrocyte storage under blood bank conditions and during physiological aging increased the sensitivity to SMase. A low SMase activity already induced morphological and structural changes, demonstrating the potential of SMase to disturb erythrocyte homeostasis. Our analyses provide a comprehensive picture in which ceramide-induced changes in membrane microdomain organization disrupt the membrane-cytoskeleton interaction and membrane integrity, leading to vesiculation, reduced deformability, and finally loss of erythrocyte content. Understanding these processes is highly relevant for understanding anemia during chronic inflammation, especially in critically ill patients receiving blood transfusions

Improved labelling of DTPA- and DOTA-conjugated peptides and antibodies with 111In in HEPES and MES buffer

Contains fulltext : 108269.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: In single photon emission computed tomography [SPECT], high specific activity of 111In-labelled tracers will allow administration of low amounts of tracer to prevent receptor saturation and/or side effects. To increase the specific activity, we studied the effect of the buffer used during the labelling procedure: NaAc, NH4Ac, HEPES and MES buffer. The effect of the ageing of the 111InCl3 stock and cadmium contamination, the decay product of 111In, was also examined in these buffers. METHODS: Escalating amounts of 111InCl3 were added to 1 mug of the diethylene triamine pentaacetic acid [DTPA]- and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA]-conjugated compounds (exendin-3, octreotide and anti-carbonic anhydrase IX [CAIX] antibody). Five volumes of 2-(N-morpholino)ethanesulfonic acid [MES], 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid [HEPES], NH4Ac or NaAc (0.1 M, pH 5.5) were added. After 20 min at 20 degrees C (DTPA-conjugated compounds), at 95 degrees C (DOTA-exendin-3 and DOTA-octreotide) or at 45 degrees C (DOTA-anti-CAIX antibody), the labelling efficiency was determined by instant thin layer chromatography. The effect of the ageing of the 111InCl3 stock on the labelling efficiency of DTPA-exendin-3 as well as the effect of increasing concentrations of Cd2+ (the decay product of 111In) were also examined. RESULTS: Specific activities obtained for DTPA-octreotide and DOTA-anti-CAIX antibody were five times higher in MES and HEPES buffer. Radiolabelling of DTPA-exendin-3, DOTA-exendin-3 and DTPA-anti-CAIX antibody in MES and HEPES buffer resulted in twofold higher specific activities than that in NaAc and NH4Ac. Labelling of DTPA-exendin-3 decreased with 66% and 73% for NaAc and NH4Ac, respectively, at day 11 after the production date of 111InCl3, while for MES and HEPES, the maximal decrease in the specific activity was 10% and 4% at day 11, respectively. The presence of 1 pM Cd2+ in the labelling mixture of DTPA-exendin-3 in NaAc and NH4Ac markedly reduced the labelling efficiency, whereas Cd2+ concentrations up to 0.1 nM did not affect the labelling efficiency in MES and HEPES buffer. CONCLUSIONS: We showed improved labelling of DTPA- and DOTA-conjugated compounds with 111In in HEPES and MES buffer. The enhanced labelling efficiency appears to be due to the reduced competitive chelation of cadmium. The enhanced labelling efficiency will allow more sensitive imaging of the biomarkers with SPECT

A hybrid embedded cohesive element method for predicting matrix cracking in composites

The complex architecture of many fibre-reinforced composites makes the generation of finite element meshes a labour-intensive process. The embedded element method, which allows the matrix and fibre reinforcement to be meshed separately, offers a computationally efficient approach to reduce the time and cost of meshing. In this paper we present a new approach of introducing cohesive elements into the matrix domain to enable the prediction of matrix cracking using the embedded element method. To validate this approach, experiments were carried out using a modified Double Cantilever Beam with ply drops, with the results being compared with model predictions. Crack deflection was observed at the ply drop region, due to the differences in stiffness, strength and toughness at the bi-material interface. The new modelling technique yields accurate predictions of the failure process in composites, including fracture loads and crack deflection path

Trained immunity or tolerance : opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors

Article Accepted Date: 29 January 2014. ACKNOWLEDGMENTS D.C.I. received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-2010-260338 (“Fungi in the setting of inflammation, allergy and autoimmune diseases: translating basic science into clinical practices” [ALLFUN]) (awarded to M.G.N.). M.G.N. and J.Q. were supported by a Vici grant of the Netherlands Organization of Scientific Research (awarded to M.G.N.). This work was supported, in part, by National Institutes of Health grant GM53522 to D.L.W. N.A.R.G. was supported by the Wellcome Trust.Peer reviewedPublisher PD

68Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET

Contains fulltext : 89596.pdf (publisher's version ) (Closed access)PURPOSE: Insulinomas are neuroendocrine tumours derived from pancreatic beta-cells. The glucagon-like peptide 1 receptor (GLP-1R) is expressed with a high incidence (>90%) and high density in insulinomas. Glucagon-like peptide 1 (GLP-1), the natural ligand of GLP-1R, is rapidly degraded in vivo. A more stable agonist of GLP-1R is exendin-3. We investigated imaging of insulinomas with DOTA-conjugated exendin-3 labelled with (68)Ga. METHODS: Targeting of insulinomas with [Lys(40)(DOTA)]exendin-3 labelled with either (111)In or (68)Ga was investigated in vitro using insulinoma tumour cells (INS-1). [Lys(40)((111)In-DTPA)]Exendin-3 was used as a reference in this study. In vivo targeting was investigated in BALB/c nude mice with subcutaneous INS-1 tumours. PET imaging was performed using a preclinical PET/CT scanner. RESULTS: In vitro exendin-3 specifically bound and was internalized by GLP-1R-positive cells. In BALB/c nude mice with subcutaneous INS-1 tumours a high uptake of [Lys(40)((111)In-DTPA)]exendin-3 in the tumour was observed (33.5 +/- 11.6%ID/g at 4 h after injection). Uptake was specific, as determined by coinjection of an excess of unlabelled [Lys(40)]exendin-3 (1.8 +/- 0.1%ID/g). The pancreas also exhibited high and specific uptake (11.3 +/- 1.0%ID/g). High uptake was also found in the kidneys (144 +/- 24%ID/g) and this uptake was not receptor-mediated. In this murine tumour model optimal targeting of the GLP-1R expressing tumour was obtained at exendin doses < or =0.1 microg. Remarkably, tumour uptake of (68)Ga-labelled [Lys(40)(DOTA)]exendin-3 was lower (8.9 +/- 3.1%ID/g) than tumour uptake of (111)In-labelled [Lys(40)(DTPA)]exendin-3 (25.4 +/- 7.2%ID/g). The subcutaneous tumours were clearly visualized by small-animal PET imaging after injection of 3 MBq of [Lys(40)((68)Ga-DOTA)]exendin-3. CONCLUSION: [Lys(40)((68)Ga-DOTA)]Exendin-3 specifically accumulates in insulinomas, although the uptake is lower than that of [Lys(40)((111)In-DTPA)]exendin-3. Therefore, [Lys(40)((68)Ga-DOTA)]exendin-3 is a promising tracer to visualize insulinomas with PET.01 juli 201