ALBERT

Description: Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras-driven mouse model of PDA (Ela-KrasG12Vp53−/−) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.

Description: The impact of aerosol–radiation and aerosol–cloud interactions on the radiative forcing is subject to large uncertainties. This is caused by the limited understanding of aerosol optical properties and the role of aerosols as cloud condensation/ice nuclei (CCN/IN). On the other hand, aerosol optical properties and vertical distribution are highly related, and their uncertainties come from different processes. This work attempts to quantify the sensitivity of aerosol optical properties (i.e. aerosol optical depth; AOD) and their vertical distribution (using the extinction coefficient, backscatter coefficient, and concentrations' species profiles) to key processes. In order to achieve this objective, sensitivity tests have been carried out, using the WRF-Chem regional fully coupled model by modifying the dry deposition, sub-grid convective transport, relative humidity, and wet scavenging. The 2010 Russian heatwave–wildfires episode has been selected as case study. Results indicate that AOD is sensitive to these key processes in the following order of importance: (1) modification of relative humidity, causing AOD differences of up to 0.6; (2) modification of vertical convection transport with AOD differences around −0.4; and (3) the dry deposition with AOD absolute differences of up to −0.35 and 0.3. Moreover, these AOD changes exhibit a nonlinear response. Both an increase and a decrease in the RH result in higher AOD values. On the other hand, both the increase and offset of the sub-grid convective transport lead to a reduction in the AOD over the fire area. In addition, a similar nonlinear response is found when reducing the dry deposition velocity; in particular, for the accumulation mode where the concentration of several species increases (while a decrease might be expected). These nonlinear responses are highly dependent on the equilibrium of the thermodynamics system sulfate–nitrate–SOA (secondary organic aerosol). In this sense, small changes in the concentration of one species can strongly affect others, finally affecting aerosol optical properties. Changes in this equilibrium could come from modifications in relative humidity, dry deposition, or vertical convective transport. By itself, dry deposition also presents a high uncertainty influencing the AOD representation.

Description: In the framework of the third phase of the Air Quality Model Evaluation International Initiative (AQMEII3), and as contribution to the second phase of the Hemispheric Transport of Air Pollution (HTAP2) activities for Europe and North America, the impacts of a 20 % decrease of global and regional anthropogenic emissions on surface air pollutant levels in 2010 are simulated by an international community of regional-scale air quality modeling groups, using different state-of-the-art chemistry and transport models (CTMs). The emission perturbations at the global level, as well as over the HTAP2-defined regions of Europe, North America and East Asia, are first simulated by the global Composition Integrated Forecasting System (C-IFS) model from European Centre for Medium-Range Weather Forecasts (ECMWF), which provides boundary conditions to the various regional CTMs participating in AQMEII3. On top of the perturbed boundary conditions, the regional CTMs used the same set of perturbed emissions within the regional domain for the different perturbation scenarios that introduce a 20 % reduction of anthropogenic emissions globally as well as over the HTAP2-defined regions of Europe, North America and East Asia. Results show that the largest impacts over both domains are simulated in response to the global emission perturbation, mainly due to the impact of domestic emission reductions. The responses of NO2, SO2 and PM concentrations to a 20 % anthropogenic emission reduction are almost linear (∼ 20 % decrease) within the global perturbation scenario with, however, large differences in the geographical distribution of the effect. NO2, CO and SO2 levels are strongly affected over the emission hot spots. O3 levels generally decrease in all scenarios by up to ∼ 1 % over Europe, with increases over the hot spot regions, in particular in the Benelux region, by an increase up to ∼ 6 % due to the reduced effect of NOx titration. O3 daily maximum of 8 h running average decreases in all scenarios over Europe, by up to ∼ 1 %. Over the North American domain, the central-to-eastern part and the western coast of the US experience the largest response to emission perturbations. Similar but slightly smaller responses are found when domestic emissions are reduced. The impact of intercontinental transport is relatively small over both domains, however, still noticeable particularly close to the boundaries. The impact is noticeable up to a few percent, for the western parts of the North American domain in response to the emission reductions over East Asia. O3 daily maximum of 8 h running average decreases in all scenarios over north Europe by up to ∼ 5 %. Much larger reductions are calculated over North America compared to Europe. In addition, values of the Response to Extra-Regional Emission Reductions (RERER) metric have been calculated in order to quantify the differences in the strengths of non-local source contributions to different species among the different models. We found large RERER values for O3 (∼ 0.8) over both Europe and North America, indicating a large contribution from non-local sources, while for other pollutants including particles, low RERER values reflect a predominant control by local sources. A distinct seasonal variation in the local vs. non-local contributions has been found for both O3 and PM2.5, particularly reflecting the springtime long-range transport to both continents.

Description: The climate effect of atmospheric aerosols is associated with their influence on the radiative budget of the Earth due to the direct aerosol–radiation interactions (ARIs) and indirect effects, resulting from aerosol–cloud–radiation interactions (ACIs). Online coupled meteorology–chemistry models permit the description of these effects on the basis of simulated atmospheric aerosol concentrations, although there is still some uncertainty associated with the use of these models. Thus, the objective of this work is to assess whether the inclusion of atmospheric aerosol radiative feedbacks of an ensemble of online coupled models improves the simulation results for maximum, mean and minimum temperature at 2 m over Europe. The evaluated models outputs originate from EuMetChem COST Action ES1004 simulations for Europe, differing in the inclusion (or omission) of ARI and ACI in the various models. The cases studies cover two important atmospheric aerosol episodes over Europe in the year 2010: (i) a heat wave event and a forest fire episode (July–August 2010) and (ii) a more humid episode including a Saharan desert dust outbreak in October 2010. The simulation results are evaluated against observational data from the E-OBS gridded database. The results indicate that, although there is only a slight improvement in the bias of the simulation results when including the radiative feedbacks, the spatiotemporal variability and correlation coefficients are improved for the cases under study when atmospheric aerosol radiative effects are included.

Description: Atmospheric aerosols modify the radiative budget of the Earth due to their optical, microphysical and chemical properties, and are considered one of the most uncertain climate forcing agents. In order to characterise the uncertainties associated with satellite and modelling approaches to represent aerosol optical properties, mainly aerosol optical depth (AOD) and Ångström exponent (AE), their representation by different remote-sensing sensors and regional online coupled chemistry–climate models over Europe are evaluated. This work also characterises whether the inclusion of aerosol–radiation (ARI) or/and aerosol–cloud interactions (ACI) help improve the skills of modelling outputs.Two case studies were selected within the EuMetChem COST Action ES1004 framework when important aerosol episodes in 2010 all over Europe took place: a Russian wildfire episode and a Saharan desert dust outbreak that covered most of the Mediterranean Sea. The model data came from different regional air-quality–climate simulations performed by working group 2 of EuMetChem, which differed according to whether ARI or ACI was included or not. The remote-sensing data came from three different sensors: MODIS, OMI and SeaWIFS. The evaluation used classical statistical metrics to first compare satellite data versus the ground-based instrument network (AERONET) and then to evaluate model versus the observational data (both satellite and ground-based data).Regarding the uncertainty in the satellite representation of AOD, MODIS presented the best agreement with the AERONET observations compared to other satellite AOD observations. The differences found between remote-sensing sensors highlighted the uncertainty in the observations, which have to be taken into account when evaluating models. When modelling results were considered, a common trend for underestimating high AOD levels was observed. For the AE, models tended to underestimate its variability, except when considering a sectional approach in the aerosol representation. The modelling results showed better skills when ARI+ACI interactions were included; hence this improvement in the representation of AOD (above 30 % in the model error) and AE (between 20 and 75 %) is important to provide a better description of aerosol–radiation–cloud interactions in regional climate models.

Description: Online coupled meteorology–chemistry models permit the description of the aerosol–radiation (ARI) and aerosol–cloud interactions (ACIs). The aim of this work is to assess the representation of several cloud properties in regional-scale coupled models when simulating the climate–chemistry–cloud–radiation system. The evaluated simulations are performed under the umbrella of the Air Quality Model Evaluation International Initiative (AQMEII) Phase 2 and include ARI+ACI interactions. Model simulations are evaluated against observational data from the European Space Agency (ESA) Cloud_cci project. The results show an underestimation (overestimation) of cloud fraction (CF) over land (sea) areas by the models. Lower bias values are found in the ensemble mean. Cloud optical depth (COD) and cloud ice water path (IWP) are generally underestimated over the whole European domain. The cloud liquid water path (LWP) is broadly overestimated. The temporal correlation suggests a generally positive correlation between models and satellite observations. Finally, CF gives the best spatial variability representation, whereas COD, IWP, and LWP show less capacity. The differences found can be attributed to differences in the microphysics schemes used; for instance, the number of ice hydrometeors and the prognostic/diagnostic treatment of the LWP are relevant.

Description: Through the comparison of several regional-scale chemistry transport modeling systems that simulate meteorology and air quality over the European and North American continents, this study aims at (i) apportioning error to the responsible processes using timescale analysis, (ii)  helping to detect causes of model error, and (iii) identifying the processes and temporal scales most urgently requiring dedicated investigations. The analysis is conducted within the framework of the third phase of the Air Quality Model Evaluation International Initiative (AQMEII) and tackles model performance gauging through measurement-to-model comparison, error decomposition, and time series analysis of the models biases for several fields (ozone, CO, SO2, NO, NO2, PM10, PM2. 5, wind speed, and temperature). The operational metrics (magnitude of the error, sign of the bias, associativity) provide an overall sense of model strengths and deficiencies, while apportioning the error to its constituent parts (bias, variance, and covariance) can help assess the nature and quality of the error. Each of the error components is analyzed independently and apportioned to specific processes based on the corresponding timescale (long scale, synoptic, diurnal, and intraday) using the error apportionment technique devised in the former phases of AQMEII. The application of the error apportionment method to the AQMEII Phase 3 simulations provides several key insights. In addition to reaffirming the strong impact of model inputs (emission and boundary conditions) and poor representation of the stable boundary layer on model bias, results also highlighted the high interdependencies among meteorological and chemical variables, as well as among their errors. This indicates that the evaluation of air quality model performance for individual pollutants needs to be supported by complementary analysis of meteorological fields and chemical precursors to provide results that are more insightful from a model development perspective. This will require evaluation methods that are able to frame the impact on error of processes, conditions, and fluxes at the surface. For example, error due to emission and boundary conditions is dominant for primary species (CO, particulate matter (PM)), while errors due to meteorology and chemistry are most relevant to secondary species, such as ozone. Some further aspects emerged whose interpretation requires additional consideration, such as the uniformity of the synoptic error being region- and model-independent, observed for several pollutants; the source of unexplained variance for the diurnal component; and the type of error caused by deposition and at which scale.

Description: In this study we introduce a hybrid ensemble consisting of air quality models operating at both the global and regional scale. The work is motivated by the fact that these different types of models treat specific portions of the atmospheric spectrum with different levels of detail, and it is hypothesized that their combination can generate an ensemble that performs better than mono-scale ensembles. A detailed analysis of the hybrid ensemble is carried out in the attempt to investigate this hypothesis and determine the real benefit it produces compared to ensembles constructed from only global-scale or only regional-scale models. The study utilizes 13 regional and 7 global models participating in the Hemispheric Transport of Air Pollutants phase 2 (HTAP2)–Air Quality Model Evaluation International Initiative phase 3 (AQMEII3) activity and focuses on surface ozone concentrations over Europe for the year 2010. Observations from 405 monitoring rural stations are used for the evaluation of the ensemble performance. The analysis first compares the modelled and measured power spectra of all models and then assesses the properties of the mono-scale ensembles, particularly their level of redundancy, in order to inform the process of constructing the hybrid ensemble. This study has been conducted in the attempt to identify that the improvements obtained by the hybrid ensemble relative to the mono-scale ensembles can be attributed to its hybrid nature. The improvements are visible in a slight increase of the diversity (4 % for the hourly time series, 10 % for the daily maximum time series) and a smaller improvement of the accuracy compared to diversity. Root mean square error (RMSE) improved by 13–16 % compared to G and by 2–3 % compared to R. Probability of detection (POD) and false-alarm rate (FAR) show a remarkable improvement, with a steep increase in the largest POD values and smallest values of FAR across the concentration ranges. The results show that the optimal set is constructed from an equal number of global and regional models at only 15 % of the stations. This implies that for the majority of the cases the regional-scale set of models governs the ensemble. However given the high degree of redundancy that characterizes the regional-scale models, no further improvement could be expected in the ensemble performance by adding yet more regional models to it. Therefore the improvement obtained with the hybrid set can confidently be attributed to the different nature of the global models. The study strongly reaffirms the importance of an in-depth inspection of any ensemble of opportunity in order to extract the maximum amount of information and to have full control over the data used in the construction of the ensemble.

Description: An accurate simulation of the absorption properties is key for assessing the radiative effects of aerosol on meteorology and climate. The representation of how chemical species are mixed inside the particles (the mixing state) is one of the major uncertainty factors in the assessment of these effects. Here we compare aerosol optical properties simulations over Europe and North America, coordinated in the framework of the third phase of the Air Quality Model Evaluation International Initiative (AQMEII), to 1 year of AERONET sunphotometer retrievals, in an attempt to identify a mixing state representation that better reproduces the observed single scattering albedo and its spectral variation. We use a single post-processing tool (FlexAOD) to derive aerosol optical properties from simulated aerosol speciation profiles, and focus on the absorption enhancement of black carbon when it is internally mixed with more scattering material, discarding from the analysis scenes dominated by dust. We found that the single scattering albedo at 440 nm (ω0,440) is on average overestimated (underestimated) by 3–5 % when external (core-shell internal) mixing of particles is assumed, a bias comparable in magnitude with the typical variability of the quantity. The (unphysical) homogeneous internal mixing assumption underestimates ω0,440 by ∼14 %. The combination of external and core-shell configurations (partial internal mixing), parameterized using a simplified function of air mass aging, reduces the ω0,440 bias to -1/-3 %. The black carbon absorption enhancement (Eabs) in core-shell with respect to the externally mixed state is in the range 1.8–2.5, which is above the currently most accepted upper limit of ∼1.5. The partial internal mixing reduces Eabs to values more consistent with this limit. However, the spectral dependence of the absorption is not well reproduced, and the absorption Ångström exponent AAE675440 is overestimated by 70–120 %. Further testing against more comprehensive campaign data, including a full characterization of the aerosol profile in terms of chemical speciation, mixing state, and related optical properties, would help in putting a better constraint on these calculations.

Description: The main uncertainties regarding the estimation of changes in the Earth's energy budget are related to the role of atmospheric aerosols. These changes are caused by aerosol–radiation (ARIs) and aerosol–cloud interactions (ACIs), which heavily depend on aerosol properties. Since the 1980s, many international modeling initiatives have studied atmospheric aerosols and their climate effects. Phase 3 of the Air Quality Modelling Evaluation International Initiative (AQMEII) focuses on evaluating and intercomparing regional and linked global/regional modeling systems by collaborating with the Task Force on the Hemispheric Transport of Air Pollution Phase 2 (HTAP2) initiative. Within this framework, the main aim of this work is the assessment of the representation of aerosol optical depth (AOD) and the Ångström exponent (AE) in AQMEII Phase 3 simulations over Europe. The evaluation was made using remote-sensing data from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensors aboard the Terra and Aqua platforms, and the instruments belonging to the ground-based Aerosol Robotic Network (AERONET) and the Maritime Aerosol Network (MAN). Overall, the skills of AQMEII simulations when representing AOD (mean absolute errors from 0.05 to 0.30) produced lower errors than for the AE (mean absolute errors from 0.30 to 1). Regardless of the models or the emissions used, models were skillful at representing the low and mean AOD values observed (below 0.5). However, high values (around 1.0) were overpredicted for biomass burning episodes, due to an underestimation in the common fires' emissions, and were overestimated for coarse particles – principally desert dust – related to the boundary conditions. Despite this behavior, the spatial and temporal variability of AOD was better represented by all the models than AE variability, which was strongly underestimated in all the simulations. Noticeably, the impact of the model selection when representing aerosol optical properties is higher than the use of different emission inventories. On the other hand, the influence of ARIs and ACIs has a little visible impact compared to the impact of the model used.