Genetic regulation of the tissue specific expression of Pyruvate kinase

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Spatial positioning of EB family proteins at microtubule tips involves distinct nucleotide-dependent binding properties

EB proteins track the ends of growing microtubules and regulate microtubule dynamics both directly and by acting as the hub of the tip-tracking network. Mammalian cells express cell type-specific combinations of three EB proteins with different cellular roles. Here we reconstitute EB1, EB2 and EB3 tip tracking in vitro. We find that all three EBs show rapid exchange at the microtubule tip and that their signal correlates to the microtubule assembly rate. However, the three signals differ in their maxima and the position from the microtubule tip. Using microtubules built with nucleotide analogues and site-directed mutagenesis, we show that EB2 prefers binding to microtubule lattices containing a 1:1 mixture of different nucleotides and its distinct binding specificity is conferred by amino acid substitutions at the right-hand side interface of the EB microtubule-binding domain with tubulin. Our data are consistent with the model that all three EB paralogs sense the nucleotide state of both β-tubulins flanking their binding site. Their different profile of preferred binding sites contributes to occupying spatially distinct domains at the temporally evolving microtubule tip structure

Small CCI – Exploring App Evaluation with Preschoolers

Child-Computer Interaction (CCI) is predominantly studied with school aged children. Working with preschool children, generally unable to read or write, involves addressing many challenges around planning, recruitment, and interpretation of findings. There are few examples in the literature of the challenges faced when conducting evaluations of technology with preschool children and very few evaluations conducted for commercial software companies. Our case study paper describes a six-week, twelve session, evaluation study of a commercial app (Lingokids) with children aged three and four in two nursery (preschool / kindergarten) schools. We describe challenges we met and describe how we adapted our plans to fit the context. We show how we were able to explore engagement and learning without gathering any personal data. With our practical tips and reflections, we hope our work will encourage others to work with young children in ways that respect their limited ability to understand assent and participation

Capturing cropland and grassland management impacts on soil carbon in the UK LULUCF inventory

This project aimed to identify the extent to which emissions due to changes in Soil Organic Carbon (SOC) stocks arising from Cropland and Grassland/Grazing Land management can be incorporated into the UK’s Land Use, Land Use Change and Forestry (LULUCF) inventory. Key management activities were identified which might affect SOC stocks. A literature review carried out as part of the project concluded that tillage reduction cannot be considered a reliable management option to increase the SOC content of UK soils. However increasing crop residue returns and increasing inputs of manure and fertiliser could increase SOC stock although the SOC stock increases resulting from manure and fertiliser inputs could be outweighed by increases nitrous oxide emissions and the risk of nitrate run-off. The review found that increasing crop yields through increased fertilisation and improved crop rotation could increase the annual input of crop residues and root exudate to soils and hence increase SOC on low fertility soils. Manure additions resulted in greater C sequestration than the addition of equivalent amounts of N as mineral fertiliser and the effect lasted longer. However, increasing inputs of nitrogen from fertiliser or manure risk increasing N2O emissions which could negate any increases in SOC stock. IPCC default stock change factors were judged to be inappropriate to the UK, based on expert opinion and the literature review findings. Therefore the project used the Daily DayCent and Landscape DNDC models to attempt to estimate stock change factors for Cropland management activities under UK conditions. Although based on a very limited dataset this suggested that the effect of Cropland management activities under UK conditions might be less than implied by the IPCC stock change factors. Tillage reduction was found to have little effect on SOC stocks. Increasing manure and crop residue inputs increased SOC stocks, with manure inputs being particularly effective. A framework for reporting SOC stock changes resulting from Cropland management was developed, and used to assess mitigation options. Overall the impact of Cropland Management on SOC is likely to be very small compared to other activities in the LULUCF inventory such as land use change. The most effective mitigation option was using Cropland from annual tillage crops to perennial crops, fallow and set aside. However given the need for food production there is limited scope for such change. Increasing manure, fertiliser and crop residue inputs gave smaller increases in SOC stocks, but practical considerations limit the scope of these actions. Lack of field data on the effect of Grassland improvement on SOC stocks was identified as a knowledge gap. The literature review suggested that intensification could increase SOC stocks under pasture on mineral soils. However, expert opinion suggested that this might not be the case for rough grazing on organo-mineral soils, where intensification might lead to SOC loss. This lack of data meant that it was not possible to calibrate or validate models to estimate UK specific stock change factors for Grassland. As the IPCC stock change factors were judged to be inappropriate to UK conditions assessment of the mitigation potential of Grassland management using these factors was not carried out to avoid presenting potentially misleading results. Suggested strategies for filling these knowledge gaps are outlined in the report. Attempts to assess grass/crop rotation patterns across the UK using data from the Integrated Administration and Control System (IACS) used to handle Common Agricultural Policy (CAP) payments were hampered by difficulties in obtaining access to the data. However land use change matrices were generated for England and Wales, and used to map areas of change. Subject to data availability, this approach could be used in future inventories to give a better representation the effect of rotation patterns on SOC stocks

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

The effect of systemic insecticides on aphids

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