Immune Responses to Homocitrullinated Protein/Peptide in Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease which causes joint destruction. RA pathogenesis involves citrullinated peptides binding to the shared epitope (SE) during autoantigen presentation, and subsequent Anti-Citrulline Antibody (ACA) production. Their target, citrulline, is very similar to homocitrulline. The main objective of this study was to investigate anti-homocitrulline immune responses in RA. Specifically, it investigated if: i) Anti-Homocitrulline Antibodies (AHA) were RA specific by screening patients with various inflammatory rheumatic diseases and healthy individuals. ii) ACA also bound homocitrulline by affinity purification and characterization. iii) anti-homocitrulline immune responses involved the SE by computer modelling and immunization of mice. Results showed that AHA were common in RA only, some ACA also bound homocitrulline, and the SE could accommodate homocitrulline but did not restrict anti-homocitrulline responses in mice. In conclusion, AHA are specific to RA and some ACA cross-react with homocitrullinated targets. The SE is not essential for anti-homocitrulline responses

Uncertainty quantification for computer models with spatial output using calibration-optimal bases

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this recordThe calibration of complex computer codes using uncertainty quantification (UQ) methods is a rich area of statistical methodological development. When applying these techniques to simulators with spatial output, it is now standard to use principal component decomposition to reduce the dimensions of the outputs in order to allow Gaussian process emulators to predict the output for calibration. We introduce the ‘terminal case’, in which the model cannot reproduce observations to within model discrepancy, and for which standard calibration methods in UQ fail to give sensible results. We show that even when there is no such issue with the model, the standard decomposition on the outputs can and usually does lead to a terminal case analysis. We present a simple test to allow a practitioner to establish whether their experiment will result in a terminal case analysis, and a methodology for defining calibrationoptimal bases that avoid this whenever it is not inevitable. We present the optimal rotation algorithm for doing this, and demonstrate its efficacy for an idealised example for which the usual principal component methods fail. We apply these ideas to the CanAM4 model to demonstrate the terminal case issue arising for climate models. We discuss climate model tuning and the estimation of model discrepancy within this context, and show how the optimal rotation algorithm can be used in developing practical climate model tuning tools

Multi-Model Assessment of the Factors Driving the Ozone Evolution Over the 21st Century

The evolution of ozone from 1960 to 2100 is examined in simulations from fourteen chemistry-climate models. There is general agreement among the models at the broadest levels, with all showing column ozone decreasing at all latitudes from 1960 to around 2000, then increasing at all latitudes over the first half of the 21 st century (21 C), and latitudinal variations in the rate of increase and date of return to historical values. In the second half of the century, ozone is projected to carry on increasing, level off or even decrease depending on the latitude, resulting in variable dates of return to historical values at latitudes where column ozone has declined below those levels. Separation into partial column above and below 20 hPa reveals that these latitudinal differences are almost completely due to differences in the lower stratosphere. At all latitudes, upper stratospheric ozone increases throughout the 21 C and returns to 1960 levels before the end of the century, although there is a spread among the models in dates that ozone returns to historical values. Using multiple linear regression the upper stratospheric ozone increase comes from almost equal contributions due to decrease in halogens and cooling from increased greenhouse gas concentrations. The evolution of lower stratospheric ozone differs with latitude. In the tropical lower stratosphere an increase in tropical upwelling causes a steady decrease in ozone through the 21C, and total column ozone does not return to 1960 levels in all models. In contrast, lower stratospheric and total column ozone in middle and high latitudes increases during the 21 C and returns to 1960 levels. For all models there is an earlier return for ozone to historical levels in the northern hemisphere. This is thought to be due to interhemispheric differences in transport

The modulation of stationary waves, and their response to climate change, by parameterized orographic drag

The parameterization of orographic drag processes in atmospheric models remains uncertain due to a lack of observational and theoretical constraints on their formulation and free parameters. While previous studies have demonstrated that parameterized orographic drag acting near the surface has a significant impact on the atmospheric circulation, this work follows a more systematic approach to investigate its impacts on the large scale circulation and the circulation response to climate change. A set of experiments with a comprehensive atmospheric general circulation model is used to ascertain the range of climatological circulations that may arise from parameter uncertainty. It is found that the Northern Hemisphere (NH) wintertime stationary wave field is strongly damped over the North Pacific (NP) and amplified over the North Atlantic (NA) as a result of increased low-level parameterized orographic drag, both of which are shown to be conducive to higher-latitude westerlies. A comparison with the stationary wave field presented in other studies suggests that the too zonal NA jet and equatorward NP jet biases that are prevalent in climate models may be at least partly due to their representation of orographic drag. The amplitude of the stationary wave response to climate change across the experiments is shown to scale with the magnitude of low-level parameterized orographic drag through its influence on the present-day climatological stationary wave amplitudes over different sectors of the NH, which is consistent with linear stationary wave theory. This work highlights the importance of fidelity in a model's basic state for regional climate change projections

How does dynamical downscaling affect model biases and future projections of explosive extratropical cyclones along North America’s Atlantic coast?

Explosive extratropical cyclones (EETCs) are rapidly intensifying low pressure systems that generate severe weather along North America’s Atlantic coast. Global climate models (GCMs) tend to simulate too few EETCs, perhaps partly due to their coarse horizontal resolution and poorly resolved moist diabatic processes. This study explores whether dynamical downscaling can reduce EETC frequency biases, and whether this affects future projections of storms along North America’s Atlantic coast. A regional climate model (CanRCM4) is forced with the CanESM2 GCM for the periods 1981 to 2000 and 2081 to 2100. EETCs are tracked from relative vorticity using an objective feature tracking algorithm. CanESM2 simulates 38% fewer EETC tracks compared to reanalysis data, which is consistent with a negative Eady growth rate bias (−0.1 day−1). Downscaling CanESM2 with CanRCM4 increases EETC frequency by one third, which reduces the frequency bias to −22%, and increases maximum EETC precipitation by 22%. Anthropogenic greenhouse gas forcing is projected to decrease EETC frequency (−15%, −18%) and Eady growth rate (−0.2 day−1, −0.2 day−1), and increase maximum EETC precipitation (46%, 52%) in CanESM2 and CanRCM4, respectively. The limited effect of dynamical downscaling on EETC frequency projections is consistent with the lack of impact on the maximum Eady growth rate. The coarse spatial resolution of GCMs presents an important limitation for simulating extreme ETCs, but Eady growth rate biases are likely just as relevant. Further bias reductions could be achieved by addressing processes that lead to an underestimation of lower tropospheric meridional temperature gradients

Contributions to twentieth century total column ozone change from halocarbons, tropospheric ozone precursors, and climate change

We investigate ozone changes from preindustrial times to the present using a chemistry-climate model. The influence of changes in physical climate, ozone-depleting substances, N2O, and tropospheric ozone precursors is estimated using equilibrium simulations with these different factors set at either preindustrial or present-day values. When these effects are combined, the entire decrease in total column ozone from preindustrial to present day is very small (–1.8 DU) in the global annual average, though with significant decreases in total column ozone over large parts of the Southern Hemisphere during austral spring and widespread increases in column ozone over the Northern Hemisphere during boreal summer. A significant contribution to the total ozone column change is the increase in lower stratospheric ozone associated with the increase in ozone precursors (5.9 DU). Also noteworthy is the near cancellation of the global average climate change effect on ozone (3.5 DU) by the increase in N2O (–3.9 DU)

Nonlinear wave-activity conservation laws and Hamiltonian structure for the two-dimensional anelastic equations

Exact, finite-amplitude, local wave-activity conservation laws are derived for disturbances to steady flows in the context of the two-dimensional anelastic equations. The conservation laws are expressed entirely in terms of Eulerian quantities, and have the property that, in the limit of a small-amplitude, slowly varying, monochromatic wave train, the wave-activity density A and flux F, when averaged over phase, satisfy F = cgA where cg is the group velocity of the waves. For nonparallel steady flows, the only conserved wave activity is a form of disturbance pseudoenergy; when the steady flow is parallel, there is in addition a conservation law for the disturbance pseudomomentum. The above results are obtained not only for isentropic background states (which give the so-called “deep form” of the anelastic equations), but also for arbitrary background potential-temperature profiles θ0(z) so long as the variation in θ0(z) over the depth of the fluid is small compared with θ0 itself. The Hamiltonian structure of the equations is established in both cases, and its symmetry properties discussed. An expression for available potential energy is also derived that, for the case of a stably stratified background state (i.e., dθ0/dz > 0), is locally positive definite; the expression is valid for fully three-dimensional flow. The counterparts to results for the two-dimensional Boussinesq equations are also noted

Quantifying the contributions to stratospheric ozone changes from ozone depleting substances and greenhouse gases

A state-of-the-art chemistry climate model coupled to a three-dimensional ocean model is used to produce three experiments, all seamlessly covering the period 1950–2100, forced by different combinations of long-lived Greenhouse Gases (GHGs) and Ozone Depleting Substances (ODSs). The experiments are designed to quantify the separate effects of GHGs and ODSs on the evolution of ozone, as well as the extent to which these effects are independent of each other, by alternately holding one set of these two forcings constant in combination with a third experiment where both ODSs and GHGs vary. We estimate that up to the year 2000 the net decrease in the column amount of ozone above 20 hPa is approximately 75% of the decrease that can be attributed to ODSs due to the offsetting effects of cooling by increased CO2. Over the 21st century, as ODSs decrease, continued cooling from CO2 is projected to account for more than 50% of the projected increase in ozone above 20 hPa. Changes in ozone below 20 hPa show a redistribution of ozone from tropical to extra-tropical latitudes with an increase in the Brewer-Dobson circulation. In addition to a latitudinal redistribution of ozone, we find that the globally averaged column amount of ozone below 20 hPa decreases over the 21st century, which significantly mitigates the effect of upper stratospheric cooling on total column ozone. Analysis by linear regression shows that the recovery of ozone from the effects of ODSs generally follows the decline in reactive chlorine and bromine levels, with the exception of the lower polar stratosphere where recovery of ozone in the second half of the 21st century is slower than would be indicated by the decline in reactive chlorine and bromine concentrations. These results also reveal the degree to which GHGrelated effects mute the chemical effects of N2O on ozone in the standard future scenario used for the WMO Ozone Assessment. Increases in the residual circulation of the atmosphere and chemical effects from CO2 cooling more than halve the increase in reactive nitrogen in the mid to upper stratosphere that results from the specified increase in N2O between 1950 and 2100

Stratospheric variability and tropospheric annular‐mode timescales

Climate models tend to exhibit much too persistent Southern Annular Mode (SAM) circulation anomalies in summer, compared to observations. Theoretical arguments suggest this bias may lead to an overly strong model response to anthropogenic forcing during this season, which is of interest since the largest observed changes in Southern Hemisphere high‐latitude climate over the last few decades have occurred in summer, and are congruent with the SAM. The origin of this model bias is examined here in the case of the Canadian Middle Atmosphere Model, using a novel technique to quantify the influence of stratospheric variability on tropospheric annular‐mode timescales. Part of the model bias is shown to be attributable to the too‐late breakdown of the stratospheric polar vortex, which allows the tropospheric influence of stratospheric variability to extend into early summer. However, the analysis also reveals an enhanced summertime persistence of the model’s SAM that is unrelated to either stratospheric variability or the bias in model stratospheric climatology, and is thus of tropospheric origin. No such feature is evident in the Northern Hemisphere. The effect of stratospheric variability in lengthening tropospheric annular‐mode timescales is evident in both hemispheres. While in the Southern Hemisphere the effect is restricted to late‐spring/early summer, in the Northern Hemisphere it can occur throughout the winter‐spring season, with the seasonality of peak timescales exhibiting considerable variability between different 50 year sections of the same simulation