97 resultados para Immuno-diagnostics
Resumo:
Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE−/− mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane β-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events.
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The parameterisation of diabatic processes in numerical models is critical for the accuracy of weather forecasts and for climate projections. A novel approach to the evaluation of these processes in models is introduced in this contribution. The approach combines a suite of on-line tracer diagnostics with off-line trajectory calculations. Each tracer tracks accumulative changes in potential temperature associated with a particular parameterised diabatic process in the model. A comparison of tracers therefore allows the identification of the most active diabatic processes and their downstream impacts. The tracers are combined with trajectories computed using model-resolved winds, allowing the various diabatic contributions to be tracked back to their time and location of occurrence. We have used this approach to investigate diabatic processes within a simulated extratropical cyclone. We focus on the warm conveyor belt, in which the dominant diabatic contributions come from large-scale latent heating and parameterised convection. By contrasting two simulations, one with standard convection parameterisation settings and another with reduced parameterised convection, the effects of parameterised convection on the structure of the cyclone have been determined. Under reduced parameterised convection conditions, the large-scale latent heating is forced to release convective instability that would otherwise have been released by the convection parameterisation. Although the spatial distribution of precipitation depends on the details of the split between parameterised convection and large-scale latent heating, the total precipitation amount associated with the cyclone remains largely unchanged. For reduced parameterised convection, a more rapid and stronger latent heating episode takes place as air ascends within the warm conveyor belt.
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BACKGROUND Methyl benzimidazole carbamate (MBC) fungicides are used to control the oilseed rape pathogen Pyrenopeziza brassicae. Resistance to MBCs has been reported in P. brassicae, but the molecular mechanism(s) associated with reductions in sensitivity have not been verified in this species. Elucidation of the genetic changes responsible for resistance, hypothesised to be target-site mutations in β-tubulin, will enable resistance diagnostics and thereby inform resistance management strategies. RESULTS P. brassicae isolates were classified as sensitive, moderately resistant or resistant to MBCs. Crossing P. brassicae isolates of different MBC sensitivities indicated that resistance was conferred by a single gene. The MBC-target encoding gene β-tubulin was cloned and sequenced. Reduced MBC sensitivity of field isolates correlated with β-tubulin amino acid substitutions L240F and E198A. The highest level of MBC resistance was measured for isolates carrying E198A. Negative cross-resistance between MBCs and the fungicides diethofencarb and zoxamide was only measured in E198A isolates. PCR-RFLP was used to screen isolates for the presence of L240F and E198A. The substitutions E198G and F200Y were also detected in DNA samples from P. brassicae populations after cloning and sequencing of PCR products. The frequencies of L240F and E198A in different P. brassicae populations were quantified by pyrosequencing. There were no differences in the frequencies of these alleles between P. brassicae populations sampled from different locations or after fungicide treatment regimes. CONCLUSIONS The molecular mechanisms affecting sensitivity to MBCs in P. brassicae have been identified. Pyrosequencing assays are a powerful tool for quantifying fungicide-resistant alleles in pathogen populations.
Resumo:
The warm conveyor belt (WCB) of an extratropical cyclone generally splits into two branches. One branch (WCB1) turns anticyclonically into the downstream upper-level tropospheric ridge, while the second branch (WCB2) wraps cyclonically around the cyclone centre. Here, the WCB split in a typical North Atlantic cold-season cyclone is analysed using two numerical models: the Met Office Unified Model and the COSMO model. The WCB flow is defined using off-line trajectory analysis. The two models represent the WCB split consistently. The split occurs early in the evolution of the WCB with WCB1 experiencing maximum ascent at lower latitudes and with higher moisture content than WCB2. WCB1 ascends abruptly along the cold front where the resolved ascent rates are greatest and there is also line convection. In contrast, WCB2 remains at lower levels for longer before undergoing saturated large-scale ascent over the system's warm front. The greater moisture in WCB1 inflow results in greater net potential temperature change from latent heat release, which determines the final isentropic level of each branch. WCB1 also exhibits lower outflow potential vorticity values than WCB2. Complementary diagnostics in the two models are utilised to study the influence of individual diabatic processes on the WCB. Total diabatic heating rates along the WCB branches are comparable in the two models with microphysical processes in the large-scale cloud schemes being the major contributor to this heating. However, the different convective parameterisation schemes used by the models cause significantly different contributions to the total heating. These results have implications for studies on the influence of the WCB outflow in Rossby wave evolution and breaking. Key aspects are the net potential temperature change and the isentropic level of the outflow which together will influence the relative mass going into each WCB branch and the associated negative PV anomalies at the tropopause-level flow.
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A primitive equation model is used to study the sensitivity of baroclinic wave life cycles to the initial latitude-height distribution of humidity. Diabatic heating is parametrized only as a consequence of condensation in regions of large-scale ascent. Experiments are performed in which the initial relative humidity is a simple function of model level, and in some cases latitude bands are specified which are initially relatively dry. It is found that the presence of moisture can either increase or decrease the peak eddy kinetic energy of the developing wave, depending on the initial moisture distribution. A relative abundance of moisture at mid-latitudes tends to weaken the wave, while a relative abundance at low latitudes tends to strengthen it. This sensitivity exists because competing processes are at work. These processes are described in terms of energy box diagnostics. The most realistic case lies on the cusp of this sensitivity. Further physical parametrizations are then added, including surface fluxes and upright moist convection. These have the effect of increasing wave amplitude, but the sensitivity to initial conditions of relative humidity remains. Finally, 'control' and 'doubled CO2' life cycles are performed, with initial conditions taken from the time-mean zonal-mean output of equilibrium GCM experiments. The attenuation of the wave resulting from reduced baroclinicity is more pronounced than any effect due to changes in initial moisture.
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A novel analytical model for mixed-phase, unblocked and unseeded orographic precipitation with embedded convection is developed and evaluated. The model takes an idealised background flow and terrain geometry, and calculates the area-averaged precipitation rate and other microphysical quantities. The results provide insight into key physical processes, including cloud condensation, vapour deposition, evaporation, sublimation, as well as precipitation formation and sedimentation (fallout). To account for embedded convection in nominally stratiform clouds, diagnostics for purely convective and purely stratiform clouds are calculated independently and combined using weighting functions based on relevant dynamical and microphysical time scales. An in-depth description of the model is presented, as well as a quantitative assessment of its performance against idealised, convection-permitting numerical simulations with a sophisticated microphysics parameterisation. The model is found to accurately reproduce the simulation diagnostics over most of the parameter space considered.
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A number of recent papers have employed the BDS test as a general test for mis-specification for linear and nonlinear models. We show that for a particular class of conditionally heteroscedastic models, the BDS test is unable to detect a common mis-specification. Our results also demonstrate that specific rather than portmanteau diagnostics are required to detect neglected asymmetry in volatility. However for both classes of tests reasonable power is only obtained using very large sample sizes.
Resumo:
Diabatic processes can alter Rossby wave structure; consequently errors arising from model processes propagate downstream. However, the chaotic spread of forecasts from initial condition uncertainty renders it difficult to trace back from root mean square forecast errors to model errors. Here diagnostics unaffected by phase errors are used, enabling investigation of systematic errors in Rossby waves in winter-season forecasts from three operational centers. Tropopause sharpness adjacent to ridges decreases with forecast lead time. It depends strongly on model resolution, even though models are examined on a common grid. Rossby wave amplitude reduces with lead time up to about five days, consistent with under-representation of diabatic modification and transport of air from the lower troposphere into upper-tropospheric ridges, and with too weak humidity gradients across the tropopause. However, amplitude also decreases when resolution is decreased. Further work is necessary to isolate the contribution from errors in the representation of diabatic processes.
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Within the SPARC Data Initiative, the first comprehensive assessment of the quality of 13 water vapor products from 11 limb-viewing satellite instruments (LIMS, SAGE II, UARS-MLS, HALOE, POAM III, SMR, SAGE III, MIPAS, SCIAMACHY, ACE-FTS, and Aura-MLS) obtained within the time period 1978-2010 has been performed. Each instrument's water vapor profile measurements were compiled into monthly zonal mean time series on a common latitude-pressure grid. These time series serve as basis for the "climatological" validation approach used within the project. The evaluations include comparisons of monthly or annual zonal mean cross sections and seasonal cycles in the tropical and extratropical upper troposphere and lower stratosphere averaged over one or more years, comparisons of interannual variability, and a study of the time evolution of physical features in water vapor such as the tropical tape recorder and polar vortex dehydration. Our knowledge of the atmospheric mean state in water vapor is best in the lower and middle stratosphere of the tropics and midlatitudes, with a relative uncertainty of. 2-6% (as quantified by the standard deviation of the instruments' multiannual means). The uncertainty increases toward the polar regions (+/- 10-15%), the mesosphere (+/- 15%), and the upper troposphere/lower stratosphere below 100 hPa (+/- 30-50%), where sampling issues add uncertainty due to large gradients and high natural variability in water vapor. The minimum found in multiannual (1998-2008) mean water vapor in the tropical lower stratosphere is 3.5 ppmv (+/- 14%), with slightly larger uncertainties for monthly mean values. The frequently used HALOE water vapor data set shows consistently lower values than most other data sets throughout the atmosphere, with increasing deviations from the multi-instrument mean below 100 hPa in both the tropics and extratropics. The knowledge gained from these comparisons and regarding the quality of the individual data sets in different regions of the atmosphere will help to improve model-measurement comparisons (e.g., for diagnostics such as the tropical tape recorder or seasonal cycles), data merging activities, and studies of climate variability.
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A comprehensive quality assessment of the ozone products from 18 limb-viewing satellite instruments is provided by means of a detailed intercomparison. The ozone climatologies in form of monthly zonal mean time series covering the upper troposphere to lower mesosphere are obtained from LIMS, SAGE I/II/III, UARS-MLS, HALOE, POAM II/III, SMR, OSIRIS, MIPAS, GOMOS, SCIAMACHY, ACE-FTS, ACE-MAESTRO, Aura-MLS, HIRDLS, and SMILES within 1978–2010. The intercomparisons focus on mean biases of annual zonal mean fields, interannual variability, and seasonal cycles. Additionally, the physical consistency of the data is tested through diagnostics of the quasi-biennial oscillation and Antarctic ozone hole. The comprehensive evaluations reveal that the uncertainty in our knowledge of the atmospheric ozone mean state is smallest in the tropical and midlatitude middle stratosphere with a 1σ multi-instrument spread of less than ±5%. While the overall agreement among the climatological data sets is very good for large parts of the stratosphere, individual discrepancies have been identified, including unrealistic month-to-month fluctuations, large biases in particular atmospheric regions, or inconsistencies in the seasonal cycle. Notable differences between the data sets exist in the tropical lower stratosphere (with a spread of ±30%) and at high latitudes (±15%). In particular, large relative differences are identified in the Antarctic during the time of the ozone hole, with a spread between the monthly zonal mean fields of ±50%. The evaluations provide guidance on what data sets are the most reliable for applications such as studies of ozone variability, model-measurement comparisons, detection of long-term trends, and data-merging activities.
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We utilize energy budget diagnostics from the Coupled Model Intercomparison Project phase 5 (CMIP5) to evaluate the models' climate forcing since preindustrial times employing an established regression technique. The climate forcing evaluated this way, termed the adjusted forcing (AF), includes a rapid adjustment term associated with cloud changes and other tropospheric and land-surface changes. We estimate a 2010 total anthropogenic and natural AF from CMIP5 models of 1.9 ± 0.9 W m−2 (5–95% range). The projected AF of the Representative Concentration Pathway simulations are lower than their expected radiative forcing (RF) in 2095 but agree well with efficacy weighted forcings from integrated assessment models. The smaller AF, compared to RF, is likely due to cloud adjustment. Multimodel time series of temperature change and AF from 1850 to 2100 have large intermodel spreads throughout the period. The intermodel spread of temperature change is principally driven by forcing differences in the present day and climate feedback differences in 2095, although forcing differences are still important for model spread at 2095. We find no significant relationship between the equilibrium climate sensitivity (ECS) of a model and its 2003 AF, in contrast to that found in older models where higher ECS models generally had less forcing. Given the large present-day model spread, there is no indication of any tendency by modelling groups to adjust their aerosol forcing in order to produce observed trends. Instead, some CMIP5 models have a relatively large positive forcing and overestimate the observed temperature change.
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A new frontier in weather forecasting is emerging by operational forecast models now being run at convection-permitting resolutions at many national weather services. However, this is not a panacea; significant systematic errors remain in the character of convective storms and rainfall distributions. The DYMECS project (Dynamical and Microphysical Evolution of Convective Storms) is taking a fundamentally new approach to evaluate and improve such models: rather than relying on a limited number of cases, which may not be representative, we have gathered a large database of 3D storm structures on 40 convective days using the Chilbolton radar in southern England. We have related these structures to storm life-cycles derived by tracking features in the rainfall from the UK radar network, and compared them statistically to storm structures in the Met Office model, which we ran at horizontal grid length between 1.5 km and 100 m, including simulations with different subgrid mixing length. We also evaluated the scale and intensity of convective updrafts using a new radar technique. We find that the horizontal size of simulated convective storms and the updrafts within them is much too large at 1.5-km resolution, such that the convective mass flux of individual updrafts can be too large by an order of magnitude. The scale of precipitation cores and updrafts decreases steadily with decreasing grid lengths, as does the typical storm lifetime. The 200-m grid-length simulation with standard mixing length performs best over all diagnostics, although a greater mixing length improves the representation of deep convective storms.
Resumo:
The Madden–Julian Oscillation (MJO) is the chief source of tropical intra-seasonal variability, but is simulated poorly by most state-of-the-art GCMs. Common errors include a lack of eastward propagation at the correct frequency and zonal extent, and too small a ratio of eastward- to westward-propagating variability. Here it is shown that HiGEM, a high-resolution GCM, simulates a very realistic MJO with approximately the correct spatial and temporal scale. Many MJO studies in GCMs are limited to diagnostics which average over a latitude band around the equator, allowing an analysis of the MJO’s structure in time and longitude only. In this study a wider range of diagnostics is applied. It is argued that such an approach is necessary for a comprehensive analysis of a model’s MJO. The standard analysis of Wheeler and Hendon (Mon Wea Rev 132(8):1917–1932, 2004; WH04) is applied to produce composites, which show a realistic spatial structure in the MJO envelopes but for the timing of the peak precipitation in the inter-tropical convergence zone, which bifurcates the MJO signal. Further diagnostics are developed to analyse the MJO’s episodic nature and the “MJO inertia” (the tendency to remain in the same WH04 phase from one day to the next). HiGEM favours phases 2, 3, 6 and 7; has too much MJO inertia; and dies out too frequently in phase 3. Recent research has shown that a key feature of the MJO is its interaction with the diurnal cycle over the Maritime Continent. This interaction is present in HiGEM but is unrealistically weak.
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The classic vertical advection-diffusion (VAD) balance is a central concept in studying the ocean heat budget, in particular in simple climate models (SCMs). Here we present a new framework to calibrate the parameters of the VAD equation to the vertical ocean heat balance of two fully-coupled climate models that is traceable to the models’ circulation as well as to vertical mixing and diffusion processes. Based on temperature diagnostics, we derive an effective vertical velocity w∗ and turbulent diffusivity k∗ for each individual physical process. In steady-state, we find that the residual vertical velocity and diffusivity change sign in mid-depth, highlighting the different regional contributions of isopycnal and diapycnal diffusion in balancing the models’ residual advection and vertical mixing. We quantify the impacts of the time-evolution of the effective quantities under a transient 1%CO2 simulation and make the link to the parameters of currently employed SCMs.
Resumo:
An evidence-based review of the potential impact that the introduction of genetically-modified (GM) cereal and oilseed crops could have for the UK was carried out. The inter-disciplinary research project addressed the key research questions using scenarios for the uptake, or not, of GM technologies. This was followed by an extensive literature review, stakeholder consultation and financial modelling. The world area of canola, oilseed rape (OSR) low in both erucic acid in the oil and glucosinolates in the meal, was 34M ha in 2012 of which 27% was GM; Canada is the lead producer but it is also grown in the USA, Australia and Chile. Farm level effects of adopting GM OSR include: lower production costs; higher yields and profits; and ease of farm management. Growing GM OSR instead of conventional OSR reduces both herbicide usage and environmental impact. Some 170M ha of maize was grown in the world in 2011 of which 28% was GM; the main producers are the USA, China and Brazil. Spain is the main EU producer of GM maize although it is also grown widely in Portugal. Insect resistant (IR) and herbicide tolerant (HT) are the GM maize traits currently available commercially. Farm level benefits of adopting GM maize are lower costs of production through reduced use of pesticides and higher profits. GM maize adoption results in less pesticide usage than on conventional counterpart crops leading to less residues in food and animal feed and allowing increasing diversity of bees and other pollinators. In the EU, well-tried coexistence measures for growing GM crops in the proximity of conventional crops have avoided gene flow issues. Scientific evidence so far seems to indicate that there has been no environmental damage from growing GM crops. They may possibly even be beneficial to the environment as they result in less pesticides and herbicides being applied and improved carbon sequestration from less tillage. A review of work on GM cereals relevant for the UK found input trait work on: herbicide and pathogen tolerance; abiotic stress such as from drought or salinity; and yield traits under different field conditions. For output traits, work has mainly focussed on modifying the nutritional components of cereals and in connection with various enzymes, diagnostics and vaccines. Scrutiny of applications submitted for field trial testing of GM cereals found around 9000 applications in the USA, 15 in Australia and 10 in the EU since 1996. There have also been many patent applications and granted patents for GM cereals in the USA for both input and output traits;an indication of the scale of such work is the fact that in a 6 week period in the spring of 2013, 12 patents were granted relating to GM cereals. A dynamic financial model has enabled us to better understand and examine the likely performance of Bt maize and HT OSR for the south of the UK, if cultivation is permitted in the future. It was found that for continuous growing of Bt maize and HT OSR, unless there was pest pressure for the former and weed pressure for the latter, the seed premia and likely coexistence costs for a buffer zone between other crops would reduce the financial returns for the GM crops compared with their conventional counterparts. When modelling HT OSR in a four crop rotation, it was found that gross margins increased significantly at the higher levels of such pest or weed pressure, particularly for farm businesses with larger fields where coexistence costs would be scaled down. The impact of the supply of UK-produced GM crops on the wider supply chain was examined through an extensive literature review and widespread stakeholder consultation with the feed supply chain. The animal feed sector would benefit from cheaper supplies of raw materials if GM crops were grown and, in the future, they might also benefit from crops with enhanced nutritional profile (such as having higher protein levels) becoming available. This would also be beneficial to livestock producers enabling lower production costs and higher margins. Whilst coexistence measures would result in increased costs, it is unlikely that these would cause substantial changes in the feed chain structure. Retailers were not concerned about a future increase in the amount of animal feed coming from GM crops. To conclude, we (the project team) feel that the adoption of currently available and appropriate GM crops in the UK in the years ahead would benefit farmers, consumers and the feed chain without causing environmental damage. Furthermore, unless British farmers are allowed to grow GM crops in the future, the competitiveness of farming in the UK is likely to decline relative to that globally.