Crystallization and preliminary crystallographic analysis of the DNA gyrase B protein from B-stearothermophilus

DNA gyrase B (GyrB) from B. stearothermophilus has been crystallized in the presence of the non-hydrolyzable ATP analogue, 5'-adenylpl-beta-gamma-imidodiphosphate (ADPNP), by the dialysis method. A complete native data set to 3.7 Angstrom has been collected from crystals which belonged to the cubic space group I23 with unit-cell dimension a = 250.6 Angstrom. Self-rotation function analysis indicates the position of a molecular twofold axis. Low-resolution data sets of a thimerosal and a selenomethionine derivative have also been analysed. The heavy-atom positions are consistent with one dimer in the asymmetric unit

Improving the effectiveness of virtual schools

This is the final version. Available from the University of Exeter via the DOI in this record. This report seeks to address the question of why children in care get markedly different educational outcomes depending on which local authority has responsibility for them. This is an important issue of fairness and the effectiveness of social policy. We explore this question through the lens of the ‘virtual school’ – the team within each local authority tasked with supporting learning and held accountable for progress and attainment. Virtual schools have existed across England since 2014 and play a key role in advocating for young people, liaising with schools and delivering learning opportunities. The report draws on expert interviews with key stakeholders, focus groups of virtual school heads and analysis of secondary data about local authorities and their virtual schools. It focuses on the concept of effectiveness as it relates to virtual schools and how this might be improved.KPMG Foundatio

Ongoing transients in carbonate compensation

Uptake of anthropogenic CO2 is acidifying the oceans. Over the next 2000 years, this will modify the dissolution and preservation of sedimentary carbonate. By coupling new formulas for the positions of the calcite saturation horizon, zsat, the compensation depth, zcc, and the snowline, zsnow, to a biogeochemical model of the oceanic carbonate system, we evaluate how these horizons will change with ongoing ocean acidification. Our model is an extended Havardton-Bear-type box model, which includes novel kinetic descriptions for carbonate dissolution above, between, and below these critical depths. In the preindustrial ocean, zsat and zcc are at 3939 and 4750 m, respectively. When forced with the IS92a CO2 emission scenario, the model forecasts (1) that zsat will rise rapidly (“runaway” conditions) so that all deep water becomes undersaturated, (2) that zcc will also rise and over 1000 years will pass before it will be stabilized by the dissolution of previously deposited CaCO3, and (3) that zsnow will respond slowly to acidification, rising by ∼1150 m during a 2000 year timeframe. A further simplified model that equates the compensation and saturation depths produces quantitatively different results. Finally, additional feedbacks due to acidification on calcification and increased atmospheric CO2 on organic matter productivity strongly affect the positions of the compensation horizons and their dynamics.

OxyCAP UK: Oxyfuel Combustion - academic Programme for the UK

The OxyCAP-UK (Oxyfuel Combustion - Academic Programme for the UK) programme was a £2 M collaboration involving researchers from seven UK universities, supported by E.On and the Engineering and Physical Sciences Research Council. The programme, which ran from November 2009 to July 2014, has successfully completed a broad range of activities related to development of oxyfuel power plants. This paper provides an overview of key findings arising from the programme. It covers development of UK research pilot test facilities for oxyfuel applications; 2-D and 3-D flame imaging systems for monitoring, analysis and diagnostics; fuel characterisation of biomass and coal for oxyfuel combustion applications; ash transformation/deposition in oxyfuel combustion systems; materials and corrosion in oxyfuel combustion systems; and development of advanced simulation based on CFD modelling

Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database.

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987-2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ± 13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ≤50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort.Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry

Inhibition of NF-kB 1 (NF-kBp50) by RNA interference in chicken macrophage HD11 cell line challenged with Salmonellaenteritidis

The NF-kB pathway plays an important role in regulating the immunity response in animals. In this study, small interfering RNAs (siRNA) were used to specifically inhibit NF-kB 1 expression and to elucidate the role of NF-kB in the signal transduction pathway of the Salmonella challenge in the chicken HD11 cell line. The cells were transfected with either NF-kB 1 siRNA, glyceraldehyde 3-phosphate dehydrogenase siRNA (positive control) or the negative control siRNA for 24 h, followed by Salmonella enteritidis (SE) challenge or non-challenge for 1 h and 4 h. Eight candidate genes related to the signal pathway of SE challenge were selected to examine the effect of NF-kB 1 inhibition on their expressions by mRNA quantification. The results showed that, with a 36% inhibition of NF-kB 1 expression, gene expression of both Toll-like receptor (TLR) 4 and interleukin (IL)-6 was consistently and significantly increased at both 1 h and 4 h following SE challenge, whereas the gene expression of MyD88 and IL-1β was increased at 1 h and 4 h, respectively. These findings suggest a likely inhibitory regulation by NF-kB 1, and could lay the foundation for studying the gene network of the innate immune response of SE infection in chickens

A methodology for the risk assessment of climate variability and change under uncertainty

Existing methods for the assessment of the potential impacts of climate change in productive activities and sectors are usually limited to point estimates that do not consider the inherent variability and uncertainty of climatic and socioeconomic variables. This is a major drawback given that only a limited and potentially misleading estimation of risk can be expected when ignoring such determinant factors. In this paper, a new methodology is introduced that is capable of integrating the agent's beliefs and expert judgment into the assessment of the potential impacts of climate change in a quantitative manner by means of an objective procedure. The goal is to produce tailor-made information to assist decision-making under uncertainty in a way that is consistent with the current state of knowledge and the available subjective "expert" information. Time-charts of the evolution of different risk measures, that can be relevant for assisting decision-making and planning, can be constructed using this new methodology. This methodology is illustrated with a case study of coffee production in Mexico. Time-dependent probabilistic scenarios for coffee production and income, conditional on the agent's beliefs and expert judgment, are developed for the average producer under uncertain future conditions. It is shown that variability in production and income, generated by introducing climate variability and uncertainty are important factors affecting decision-making and the assessment of economic viability that are frequently ignored. The concept of Value at Risk, commonly applied in financial risk management, is introduced as a means for estimating the maximum expected loss for a previously chosen confidence level. Results are tailor-made for agents that have incomplete information and different beliefs. In this case study, the costs of climate change for coffee production in Veracruz are estimated to have a present value representing from 3 to 14 times the current annual value of coffee production in the state. © 2011 The Author(s)

The effects of CO2, climate and land-use on terrestrial carbon balance, 1920-1992: An analysis with four process-based ecosystem models

The concurrent effects of increasing atmospheric CO2 concentration, climate variability, and cropland establishment and abandonment on terrestrial carbon storage between 1920 and 1992 were assessed using a standard simulation protocol with four process-based terrestrial biosphere models. Over the long-term(1920–1992), the simulations yielded a time history of terrestrial uptake that is consistent (within the uncertainty) with a long-term analysis based on ice core and atmospheric CO2 data. Up to 1958, three of four analyses indicated a net release of carbon from terrestrial ecosystems to the atmosphere caused by cropland establishment. After 1958, all analyses indicate a net uptake of carbon by terrestrial ecosystems, primarily because of the physiological effects of rapidly rising atmospheric CO2. During the 1980s the simulations indicate that terrestrial ecosystems stored between 0.3 and 1.5 Pg C yr−1, which is within the uncertainty of analysis based on CO2 and O2 budgets. Three of the four models indicated (in accordance with O2 evidence) that the tropics were approximately neutral while a net sink existed in ecosystems north of the tropics. Although all of the models agree that the long-term effect of climate on carbon storage has been small relative to the effects of increasing atmospheric CO2 and land use, the models disagree as to whether climate variability and change in the twentieth century has promoted carbon storage or release. Simulated interannual variability from 1958 generally reproduced the El Niño/Southern Oscillation (ENSO)-scale variability in the atmospheric CO2 increase, but there were substantial differences in the magnitude of interannual variability simulated by the models. The analysis of the ability of the models to simulate the changing amplitude of the seasonal cycle of atmospheric CO2 suggested that the observed trend may be a consequence of CO2 effects, climate variability, land use changes, or a combination of these effects. The next steps for improving the process-based simulation of historical terrestrial carbon include (1) the transfer of insight gained from stand-level process studies to improve the sensitivity of simulated carbon storage responses to changes in CO2 and climate, (2) improvements in the data sets used to drive the models so that they incorporate the timing, extent, and types of major disturbances, (3) the enhancement of the models so that they consider major crop types and management schemes, (4) development of data sets that identify the spatial extent of major crop types and management schemes through time, and (5) the consideration of the effects of anthropogenic nitrogen deposition. The evaluation of the performance of the models in the context of a more complete consideration of the factors influencing historical terrestrial carbon dynamics is important for reducing uncertainties in representing the role of terrestrial ecosystems in future projections of the Earth system

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis