Temperature

KEY HEADLINES: • The first MCCIP ARC in 2006 reported following what was then the warmest year globally in 2005 (0.26°C higher than the 1981-2010 average). • Since 2005, new global record temperatures have been set in 2010 and then in each successive year 2014, 2015 and 2016. In these last three record years the global average temperature anomaly was 0.31,0.44, 0.56°C higher than the 1981-2010 average. • 2014 was a record warm year for coastal air and sea temperatures around the UK. Between 1984 and 2014 coastal water temperatures rose around the UK at an average rate of 0.28 °C/decade. The rate varies between regions, the slowest warming was in the Celtic Sea at 0.17 °C/decade and the maximum rate was in the Southern North Sea at 0.45 °C/decade. • There is also variability over shorter time periods. In all regions of UK seas there was a negative trend in the 10-year period between 2003 and 2013. This is due to variability within the ocean /atmosphere system which is natural. • There is a trend towards fewer in-situ observations, and this will ultimately influence the confidence in future assessments. • Some gridded datasets can offer alternatives to single point observations, but to understand the patterns of ocean variability, the quality information from ocean timeseries cannot yet be replaced by surface observations or autonomous data collection. • The first MCCIP report card in 2006 used the UKCIP projections from 2002 which had a very limited representation of the SST. • The latest updates to the UK Climate Projections shelf seas models were published in 2016 and projected increases in sea surface temperature for 2069-89 relative to 1960-89 of over 3 °C for most of the North Sea, English Channel, Irish and Celtic Seas. For the deeper areas to the north and west of Scotland out towards Rockall and in the Faroe Shetland Channel the increase in temperature is projected to be closer to 2 °C. • Over the last 10 years there has been a steady improvement in the scientific basis underlying centennial sea temperature projections for the seas around the UK, and significant progress in the field of seasonal and decadal projections. • The scientific basis to such projections and predictions will continue to improve over the next 10 years, with increasing resolution, treatment of climate uncertainties, and methodology. Over the centennial scale the difference between emissions scenarios are still the source of the largest uncertainties. • Development of North West European Shelf (NWS) modelling systems driven by seasonal forecasting systems may allow NWS temperature prediction over the monthly to decadal period

The 4q12 Amplicon in Malignant Peripheral Nerve Sheath Tumors: Consequences on Gene Expression and Implications for Sunitinib Treatment

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive tumors which originate from Schwann cells and develop in about 10% of neurofibromatosis type 1 (NF1) patients. The five year survival rate is poor and more effective therapies are needed. Sunitinib is a drug targeting receptor tyrosine kinases (RTK) like PDGFRα, c-Kit and VEGFR-2. These genes are structurally related and cluster on chromosomal segment 4q12.) was present in MPNST cell lines suggesting an autocrine loop. We show that VEGF triggered signal transduction via the MAPK pathway, which could be blocked by sunitinib. might serve as predictive markers for efficacy of sunitinib

Decadal prediction of the North Atlantic subpolar gyre in the HiGEM high-resolution climate model

This paper presents an analysis of initialised decadal hindcasts of the North Atlantic subpolar gyre (SPG) using the HiGEM model, which has a nominal grid-spacing of 90 km in the atmosphere, and 1/3 ∘∘ in the ocean. HiGEM decadal predictions (HiGEM-DP) exhibit significant skill at capturing 0–500 m ocean heat content in the SPG, and outperform historically forced transient integrations and persistence for up to a decade ahead. An analysis of case-studies of North Atlantic decadal change, including the 1960s cooling, the mid-1990s warming, and the post-2005 cooling, show that changes in ocean circulation and heat transport dominate the predictions of the SPG. However, different processes are found to dominate heat content changes in different regions of the SPG. Specifically, ocean advection dominates in the east, but surface fluxes dominate in the west. Furthermore, compared to previous studies, we find a smaller role for ocean heat transport changes due to ocean circulation anomalies at the latitudes of the SPG, and, for the 1960s cooling, a greater role for surface fluxes. Finally, HiGEM-DP predicts the observed positive state of the North Atlantic Oscillation in the early 1990s. These results support an important role for the ocean in driving past changes in the North Atlantic region, and suggest that these changes were predictable

Impact of Immunization Technology and Assay Application on Antibody Performance – A Systematic Comparative Evaluation

Antibodies are quintessential affinity reagents for the investigation and determination of a protein's expression patterns, localization, quantitation, modifications, purification, and functional understanding. Antibodies are typically used in techniques such as Western blot, immunohistochemistry (IHC), and enzyme-linked immunosorbent assays (ELISA), among others. The methods employed to generate antibodies can have a profound impact on their success in any of these applications. We raised antibodies against 10 serum proteins using 3 immunization methods: peptide antigens (3 per protein), DNA prime/protein fragment-boost (“DNA immunization”; 3 per protein), and full length protein. Antibodies thus generated were systematically evaluated using several different assay technologies (ELISA, IHC, and Western blot). Antibodies raised against peptides worked predominantly in applications where the target protein was denatured (57% success in Western blot, 66% success in immunohistochemistry), although 37% of the antibodies thus generated did not work in any of these applications. In contrast, antibodies produced by DNA immunization performed well against both denatured and native targets with a high level of success: 93% success in Western blots, 100% success in immunohistochemistry, and 79% success in ELISA. Importantly, success in one assay method was not predictive of success in another. Immunization with full length protein consistently yielded the best results; however, this method is not typically available for new targets, due to the difficulty of generating full length protein. We conclude that DNA immunization strategies which are not encumbered by the limitations of efficacy (peptides) or requirements for full length proteins can be quite successful, particularly when multiple constructs for each protein are used

Surfing the spectrum - what is on the horizon?

Diagnostic imaging techniques have evolved with technological advancements - but how far? The objective of this article was to explore the electromagnetic spectrum to find imaging techniques which may deliver diagnostic information of equal, or improved, standing to conventional radiographs and to explore any developments within radiography which may yield improved diagnostic data. A comprehensive literature search was performed using Medline, Web of Knowledge, Science Direct and PubMed Databases. Boolean Operators were used and key-terms included (not exclusively): terahertz, X-ray, ultraviolet, visible, infra-red, magnetic resonance, dental, diagnostic, caries and periodontal. Radiographic techniques are primarily used for diagnostic imaging in dentistry, and continued developments in X-ray imaging include: phase contrast, darkfield and spectral imaging. Other modalities have potential application, for example, terahertz, laser doppler and optical techniques, but require further development. In particular, infra-red imaging has regenerated interest with caries detection in vitro, due to improved quality and accessibility of cameras. Non-ionising imaging techniques, for example, infra-red, are becoming more commensurate with traditional radiographic techniques for caries detection. Nevertheless, X-rays continue to be the leading diagnostic image for dentists, with improved diagnostic potential for lower radiation dose becoming a reality

Utilizing chimeric antigen receptors to direct natural killer cell activity.

Natural killer (NK) cells represent an attractive lymphocyte population for cancer immunotherapy due to their ability to lyse tumor targets without prior sensitization and without need for human leukocyte antigens-matching. Chimeric antigen receptors (CARs) are able to enhance lymphocyte targeting and activation toward diverse malignancies. CARs consist of an external recognition domain (typically a small chain variable fragment) directed at a specific tumor antigen that is linked with one or more intracellular signaling domains that mediate lymphocyte activation. Most CAR studies have focused on their expression in T cells. However, use of CARs in NK cells is starting to gain traction because they provide a method to redirect these cells more specifically to target refractory cancers. CAR-mediated anti-tumor activity has been demonstrated using NK cell lines, as well as NK cells isolated from peripheral blood, and NK cells produced from human pluripotent stem cells. This review will outline the CAR constructs that have been reported in NK cells with a focus on comparing the use of different signaling domains in combination with other co-activating domains