Seasonal speedup of a Greenland marine-terminating outlet glacier forced by surface melt–induced changes in subglacial hydrology

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Extensive retreat of Greenland tidewater glaciers 2000-2010

Overall mass loss from the Greenland ice sheet nearly doubled during the early 2000s resulting in an increased contribution to sea-level rise, with this step-change being mainly attributed to the widespread frontal retreat and accompanying dynamic thinning of tidewater glaciers. Changes in glacier calving-front positions are easily derived from remotely sensed imagery and provide a record of dynamic change. However, ice-sheet-wide studies of calving fronts have been either spatially or temporally limited. In this study multiple calving-front positions were derived for 199 Greenland marine-terminating outlet glaciers with width greater than 1 km using Landsat imagery for the 11-year period 2000–2010 in order to identify regional seasonal and inter-annual variations. During this period, outlet glaciers were characterized by sustained and substantial retreat summing to more than 267 km, with only 11 glaciers showing overall advance. In general, the pattern of mass loss detected by GRACE (Gravity Recovery and Climate Experiment) and other measurements is reflected in the calving record of Greenland glaciers. Our results suggest several regions in the south and east of the ice sheet likely share controls on their dynamic changes, but no simple single control is apparent

Winter mass balance of Drangajökull ice cap (NW Iceland) derived from satellite sub-meter stereo images

Sub-meter resolution, stereoscopic satellite images allow for the generation of accurate and high-resolution digital elevation models (DEMs) over glaciers and ice caps. Here, repeated stereo images of Drangajökull ice cap (NW Iceland) from Pléiades and WorldView2 (WV2) are combined with in situ estimates of snow density and densification of firn and fresh snow to provide the first estimates of the glacier-wide geodetic winter mass balance obtained from satellite imagery. Statistics in snow- and ice-free areas reveal similar vertical relative accuracy (<  0.5 m) with and without ground control points (GCPs), demonstrating the capability for measuring seasonal snow accumulation. The calculated winter (14 October 2014 to 22 May 2015) mass balance of Drangajökull was 3.33 ± 0.23 m w.e. (meter water equivalent), with ∼ 60 % of the accumulation occurring by February, which is in good agreement with nearby ground observations. On average, the repeated DEMs yield 22 % less elevation change than the length of eight winter snow cores due to (1) the time difference between in situ and satellite observations, (2) firn densification and (3) elevation changes due to ice dynamics. The contributions of these three factors were of similar magnitude. This study demonstrates that seasonal geodetic mass balance can, in many areas, be estimated from sub-meter resolution satellite stereo images.This study was funded by the University of Iceland (UI) Research Fund. Pleiades images were acquired at research price thanks to the CNES ISIS program (http://www.isis-cnes.fr). The WV2 DEM was obtained through the ArcticDEM project. This work is a contribution to the Rannis grant of excellence project, ANATILS. Collaboration and travels between IES and LEGOS were funded by the Jules Verne research fund and the TOSCA program from the French Space Agency, CNES. This study used the recent lidar mapping of the glaciers in Iceland that was funded by the Icelandic Research Fund, the Landsvirkjun research fund, the Icelandic Road Administration, the Reykjavik Energy Environmental and Energy Research Fund, the Klima-og Luftgruppen (KoL) research fund of the Nordic Council of Ministers, the Vatnajokull National Park, the organization Friends of Vatnajokull, the National Land Survey of Iceland, the Icelandic Meteorological Office and the UI research fund. The ground-based mass balance measurements on Drangajokull have been jointly funded by Orkubu Vestfjarda (Westfjord Power Company), the National Energy Authority (2004-2009) and the Icelandic Meteorological Office (2009-2015).Peer Reviewe

SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice.

DESIGN: Pharmacokinetic and pharmacodynamic parameters of cremophor-paclitaxel, nab-paclitaxel (human-albumin-bound paclitaxel, Abraxane) and a novel mouse-albumin-bound paclitaxel (m-nab-paclitaxel) were evaluated in genetically engineered mouse models (GEMMs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS), histological and biochemical analysis. Preclinical evaluation of m-nab-paclitaxel included assessment by three-dimensional high-resolution ultrasound and molecular analysis in a novel secreted protein acidic and rich in cysteine (SPARC)-deficient GEMM of pancreatic ductal adenocarcinoma (PDA). RESULTS: nab-Paclitaxel exerted its antitumoural effects in a dose-dependent manner and was associated with less toxicity compared with cremophor-paclitaxel. SPARC nullizygosity in a GEMM of PDA, Kras(G12D);p53(flox/-);p48Cre (KPfC), resulted in desmoplastic ductal pancreas tumours with impaired collagen maturation. Paclitaxel concentrations were significantly decreased in SPARC null plasma samples and tissues when administered as low-dose m-nab-paclitaxel. At the maximally tolerated dose, SPARC deficiency did not affect the intratumoural paclitaxel concentration, stromal deposition and the immediate therapeutic response. CONCLUSIONS: nab-Paclitaxel accumulates and acts in a dose-dependent manner. The interaction of plasma SPARC and albumin-bound drugs is observed at low doses of nab-paclitaxel but is saturated at therapeutic doses in murine tumours. Thus, this study provides important information for future preclinical and clinical trials in PDA using nab-paclitaxel in combination with novel experimental and targeted agents

Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays

Background: Academic pathology suffers from an acute and growing lack of workforce resource. This especially impacts on translational elements of clinical trials, which can require detailed analysis of thousands of tissue samples. We tested whether crowdsourcing – enlisting help from the public – is a sufficiently accurate method to score such samples. Methods: We developed a novel online interface to train and test lay participants on cancer detection and immunohistochemistry scoring in tissue microarrays. Lay participants initially performed cancer detection on lung cancer images stained for CD8, and we measured how extending a basic tutorial by annotated example images and feedback-based training affected cancer detection accuracy. We then applied this tutorial to additional cancer types and immunohistochemistry markers – bladder/ki67, lung/EGFR, and oesophageal/CD8 – to establish accuracy compared with experts. Using this optimised tutorial, we then tested lay participants’ accuracy on immunohistochemistry scoring of lung/EGFR and bladder/p53 samples. Results: We observed that for cancer detection, annotated example images and feedback-based training both improved accuracy compared with a basic tutorial only. Using this optimised tutorial, we demonstrate highly accurate (>0.90 area under curve) detection of cancer in samples stained with nuclear, cytoplasmic and membrane cell markers. We also observed high Spearman correlations between lay participants and experts for immunohistochemistry scoring (0.91 (0.78, 0.96) and 0.97 (0.91, 0.99) for lung/EGFR and bladder/p53 samples, respectively). Conclusions: These results establish crowdsourcing as a promising method to screen large data sets for biomarkers in cancer pathology research across a range of cancers and immunohistochemical stains

Levodopa does not affect expression of reinforcement learning in older adults

Dopamine has been implicated in learning from rewards and punishment, and in the expression of this learning. However, many studies do not fully separate retrieval and decision mechanisms from learning and consolidation. Here, we investigated the effects of levodopa (dopamine precursor) on choice performance (isolated from learning or consolidation). We gave 31 healthy older adults 150 mg of levodopa or placebo (double-blinded, randomised) 1 hour before testing them on stimuli they had learned the value of the previous day. We found that levodopa did not affect the overall accuracy of choices, nor the relative expression of positively or negatively reinforced values. This contradicts several studies and suggests that overall dopamine levels may not play a role in the choice performance for values learned through reinforcement learning in older adults

Application of phage display to high throughput antibody generation and characterization.

We have created a high quality phage display library containing over 1010 human antibodies and describe its use in the generation of antibodies on an unprecedented scale. We have selected, screened and sequenced over 38,000 recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400 antibodies were characterized by specificity testing and detailed sequence analysis and the data/clones are available online. Sensitive detection was demonstrated in a bead based flow cytometry assay. Furthermore, positive staining by immunohistochemistry on tissue microarrays was found for 37% (143/381) of antibodies. Thus, we have demonstrated the potential of and illuminated the issues associated with genome-wide monoclonal antibody generation.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are