A Real-time Impedance-Based Screening Assay for Drug-Induced Vascular Leakage

Vascular leakage is a serious side effect of therapies based on monoclonal antibodies or cytokines which may lead to life-threatening situations. With the steady increase of new drug development programs for large molecules, there is an urgent need for reliable tools to assess this potential liability of new medicines in a rapid and cost-effective manner. Using human umbilical vein endothelial cells (HUVECs) as a model for endothelium, we established an impedance-based assay measuring the integrity of the endothelial cell monolayer in real time. We could demonstrate that the HUVEC monolayer in our system was a relevant model as cells expressed major junctional proteins known to be responsible for maintaining tightness as well as receptors targeted by molecules known to induce vascular leakage in vivo. We assessed the time-dependent loss of barrier function using impedance and confirmed that signals obtained corresponded well to those from standard transwell assays. We assayed a series of reference molecules which led to the expected change of barrier integrity. A nonspecific cytotoxic effect could be excluded by using human fibroblasts as a nonresponder cell line. Finally, we could show reversibility of vascular permeability induced by histamine, IL-1β, or TNF-α by coincubation with established antagonists, further demonstrating relevance of this new model. Taken together, our results suggest that impedance in combination with HUVECs as a specific model can be applied to assess clinically relevant vascular leakage on an in vitro leve

Evaluation of seven European aerosol optical depth retrieval algorithms for climate analysis

Satellite data are increasingly used to provide observation-based estimates of the effects of aerosols on climate. The Aerosol-cci project, part of the European Space Agency's Climate Change Initiative (CCI), was designed to provide essential climate variables for aerosols from satellite data. Eight algorithms, developed for the retrieval of aerosol properties using data from AATSR (4), MERIS (3) and POLDER, were evaluated to determine their suitability for climate studies. The primary result from each of these algorithms is the aerosol optical depth (AOD) at several wavelengths, together with the Ångström exponent (AE) which describes the spectral variation of the AOD for a given wavelength pair. Other aerosol parameters which are possibly retrieved from satellite observations are not considered in this paper. The AOD and AE (AE only for Level 2) were evaluated against independent collocated observations from the ground-based AERONET sun photometer network and against “reference” satellite data provided by MODIS and MISR. Tools used for the evaluation were developed for daily products as produced by the retrieval with a spatial resolution of 10 × 10 km2 (Level 2) and daily or monthly aggregates (Level 3). These tools include statistics for L2 and L3 products compared with AERONET, as well as scoring based on spatial and temporal correlations. In this paper we describe their use in a round robin (RR) evaluation of four months of data, one month for each season in 2008. The amount of data was restricted to only four months because of the large effort made to improve the algorithms, and to evaluate the improvement and current status, before larger data sets will be processed. Evaluation criteria are discussed. Results presented show the current status of the European aerosol algorithms in comparison to both AERONET and MODIS and MISR data. The comparison leads to a preliminary conclusion that the scores are similar, including those for the references, but the coverage of AATSR needs to be enhanced and further improvements are possible for most algorithms. None of the algorithms, including the references, outperforms all others everywhere. AATSR data can be used for the retrieval of AOD and AE over land and ocean. PARASOL and one of the MERIS algorithms have been evaluated over ocean only and both algorithms provide good results

Geographical Distribution and Genetic Diversity of Bank Vole Hepaciviruses in Europe

The development of new diagnostic methods resulted in the discovery of novel hepaciviruses in wild populations of the bank vole (Myodes glareolus, syn. Clethrionomys glareolus). The naturally infected voles demonstrate signs of hepatitis similar to those induced by hepatitis C virus (HCV) in humans. The aim of the present research was to investigate the geographical distribution of bank vole-associated hepaciviruses (BvHVs) and their genetic diversity in Europe. Real-time reverse transcription polymerase chain reaction (RT-qPCR) screening revealed BvHV RNA in 442 out of 1838 (24.0%) bank voles from nine European countries and in one of seven northern red-backed voles (Myodes rutilus, syn. Clethrionomys rutilus). BvHV RNA was not found in any other small mammal species (n = 23) tested here. Phylogenetic and isolation-by-distance analyses confirmed the occurrence of both BvHV species (Hepacivirus F and Hepacivirus J) and their sympatric occurrence at several trapping sites in two countries. The broad geographical distribution of BvHVs across Europe was associated with their presence in bank voles of different evolutionary lineages. The extensive geographical distribution and high levels of genetic diversity of BvHVs, as well as the high population fluctuations of bank voles and occasional commensalism in some parts of Europe warrant future studies on the zoonotic potential of BvHVs.Peer reviewe

Development, Production and Evaluation of Aerosol Climate Data Records from European Satellite Observations (Aerosol_cci)

Producing a global and comprehensive description of atmospheric aerosols requires integration of ground-based, airborne, satellite and model datasets. Due to its complexity, aerosol monitoring requires the use of several data records with complementary information content. This paper describes the lessons learned while developing and qualifying algorithms to generate aerosol Climate Data Records (CDR) within the European Space Agency (ESA) Aerosol_cci project. An iterative algorithm development and evaluation cycle involving core users is applied. It begins with the application-specific refinement of user requirements, leading to algorithm development, dataset processing and independent validation followed by user evaluation. This cycle is demonstrated for a CDR of total Aerosol Optical Depth (AOD) from two subsequent dual-view radiometers. Specific aspects of its applicability to other aerosol algorithms are illustrated with four complementary aerosol datasets. An important element in the development of aerosol CDRs is the inclusion of several algorithms evaluating the same data to benefit from various solutions to the ill-determined retrieval problem. The iterative approach has produced a 17-year AOD CDR, a 10-year stratospheric extinction profile CDR and a 35-year Absorbing Aerosol Index record. Further evolution cycles have been initiated for complementary datasets to provide insight into aerosol properties (i.e., dust aerosol, aerosol absorption).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

The 2018 GaN power electronics roadmap

Gallium nitride (GaN) is a compound semiconductor that has tremendous potential to facilitate economic growth in a semiconductor industry that is silicon-based and currently faced with diminishing returns of performance versus cost of investment. At a material level, its high electric field strength and electron mobility have already shown tremendous potential for high frequency communications and photonic applications. Advances in growth on commercially viable large area substrates are now at the point where power conversion applications of GaN are at the cusp of commercialisation. The future for building on the work described here in ways driven by specific challenges emerging from entirely new markets and applications is very exciting. This collection of GaN technology developments is therefore not itself a road map but a valuable collection of global state-of-the-art GaN research that will inform the next phase of the technology as market driven requirements evolve. First generation production devices are igniting large new markets and applications that can only be achieved using the advantages of higher speed, low specific resistivity and low saturation switching transistors. Major investments are being made by industrial companies in a wide variety of markets exploring the use of the technology in new circuit topologies, packaging solutions and system architectures that are required to achieve and optimise the system advantages offered by GaN transistors. It is this momentum that will drive priorities for the next stages of device research gathered here