Abstract. This is the second of two papers that document the creation of the New European Wind Atlas (NEWA). In Part 1, we described the sensitivity experiments and accompanying evaluation done to arrive at the final mesoscale model setup used to produce the mesoscale wind atlas. In this paper, Part 2, we document how we made the final wind atlas product, covering both the production of the mesoscale climatology generated with the Weather Research and Forecasting (WRF) model and the microscale climatology generated with the Wind Atlas Analysis and Applications Program (WAsP). The paper includes a detailed description of the technical and practical aspects that went into running the mesoscale simulations and the downscaling using WAsP. We show the main results from the final wind atlas and present a comprehensive evaluation of each component of the NEWA model chain using observations from a large set of tall masts located all over Europe. The added value of the WRF and WAsP downscaling of wind climatologies is evaluated relative to the performance of the driving ERA5 reanalysis and shows that the WRF downscaling reduces the mean wind speed bias and spread relative to that of ERA5 from -1.50±1.30 to 0.02±0.78 m s−1. The WAsP downscaling has an added positive impact relative to that of the WRF model in simple terrain. In complex terrain, where the assumptions of the linearized flow model break down, both the mean bias and spread in wind speed are worse than those from the raw mesoscale results.

Abstract. This is the first of two papers that document the creation of the New European Wind Atlas (NEWA). It describes the sensitivity analysis and evaluation procedures that formed the basis for choosing the final setup of the mesoscale model simulations of the wind atlas. The suitable combination of model setup and parameterizations, bound by practical constraints, was found for simulating the climatology of the wind field at turbine-relevant heights with the Weather Research and Forecasting (WRF) model. Initial WRF model sensitivity experiments compared the wind climate generated by using two commonly used planetary boundary layer schemes and were carried out over several regions in Europe. They confirmed that the most significant differences in annual mean wind speed at 100 m a.g.l. (above ground level) mostly coincide with areas of high surface roughness length and not with the location of the domains or maximum wind speed. Then an ensemble of more than 50 simulations with different setups for a single year was carried out for one domain covering northern Europe for which tall mast observations were available. We varied many different parameters across the simulations, e.g. model version, forcing data, various physical parameterizations, and the size of the model domain. These simulations showed that although virtually every parameter change affects the results in some way, significant changes in the wind climate in the boundary layer are mostly due to using different physical parameterizations, especially the planetary boundary layer scheme, the representation of the land surface, and the prescribed surface roughness length. Also, the setup of the simulations, such as the integration length and the domain size, can considerably influence the results. We assessed the degree of similarity between winds simulated by the WRF ensemble members and the observations using a suite of metrics, including the Earth Mover's Distance (EMD), a statistic that measures the distance between two probability distributions. The EMD was used to diagnose the performance of each ensemble member using the full wind speed and direction distribution, which is essential for wind resource assessment. We identified the most realistic ensemble members to determine the most suitable configuration to be used in the final production run, which is fully described and evaluated in the second part of this study (Dörenkämper et al., 2020).

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BACKGROUND AND PURPOSEIL-13 is a pleiotropic Th2 cytokine considered likely to play a pivotal role in asthma. Here we describe the preclinical in vitro and in vivo characterization of CAT-354, an IL-13-neutralizing IgG4 monoclonal antibody (mAb), currently in clinical development.EXPERIMENTAL APPROACHIn vitro the potency, specificity and species selectivity of CAT-354 was assayed in TF-1 cells, human umbilical vein endothelial cells and HDLM-2 cells. The ability of CAT-354 to modulate disease-relevant mechanisms was tested in human cells measuring bronchial smooth muscle calcium flux induced by histamine, eotaxin generation by normal lung fibroblasts, CD23 upregulation in peripheral blood mononuclear cells and IgE production by B cells. In vivo CAT-354 was tested on human IL-13-induced air pouch inflammation in mice, ovalbumin-sensitization and challenge in IL-13 humanized mice and antigen challenge in cynomolgus monkeys.KEY RESULTSCAT-354 has a 165 pM affinity for human IL-13 and functionally neutralized human, human variant associated with asthma and atopy (R130Q) and cynomolgus monkey, but not mouse, IL-13. CAT-354 did not neutralize human IL-4. In vitro CAT-354 functionally inhibited IL-13-induced eotaxin production, an analogue of smooth muscle airways hyperresponsiveness, CD23 upregulation and IgE production. In vivo in humanized mouse and cynomolgus monkey antigen challenge models CAT-354 inhibited airways hyperresponsiveness and bronchoalveolar lavage eosinophilia.CONCLUSIONS AND IMPLICATIONSCAT-354 is a potent and selective IL-13-neutralizing IgG4 mAb. The preclinical data presented here support the trialling of this mAb in patients with moderate to severe uncontrolled asthma.

ObjectivePrevious work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)–GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue and investigated the effects of anti-GM-CSFRα antibody treatment in vitro and in vivo in a preclinical model of RA.MethodsWe compared GM-CSFRα expression on macrophages positive for CD68 or CD163 on synovial biopsy samples from patients with RA or psoriatic arthritis (PsA) to disease controls. In addition, we studied the effects of CAM-3003, an anti-GM-CSFR antibody in a collagen induced arthritis model of RA in DBA/1 mice. The pharmacokinetic profile of CAM-3003 was studied in naïve CD1(ICR) mice (see online supplement) and used to interpret the results of the pharmacodynamic studies in BALB/c mice.ResultsGM-CSFRα was expressed by CD68 positive and CD163 positive macrophages in the synovium, and there was a significant increase in GM-CSFRα positive cells in patients in patients with RA as well as patients with PsA compared with patients with osteoarthritis and healthy controls. In the collagen induced arthritis model there was a dose dependent reduction of clinical arthritis scores and the number of F4/80 positive macrophages in the inflamed synovium after CAM-3003 treatment. In BALB/c mice CAM-3003 inhibited recombinant GM-CSF mediated margination of peripheral blood monocytes and neutrophils.ConclusionsThe findings support the ongoing development of therapies aimed at interfering with GM-CSF or its receptor in various forms of arthritis, such as RA and PsA.