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The identification of the severe COVID-19 virus in December 2019 led the World Health Organization to declare a global pandemic by March 2020. Up till recently with the first available vaccines, the only prevention measures include strict social, travel, and working restrictions in a so-called lockdown period that lasted for several weeks (mid-March to the end of April 2020 for most of Europe). This abrupt change in social behavior is expected to impact local but also regional atmospheric composition, and the environmental impact is potentially of high interest to policy and decision-makers.The Aerosol, Clouds, and Trace Gases Research Infrastructure (ACTRIS) is a pan-European research infrastructure producing high-quality data and information on short-lived atmospheric constituents and on the processes leading to the variability of these constituents in natural and controlled atmospheres. Realizing the crucial scientific value of ACTRIS observations of atmospheric composition changes across Europe, the ACTRIS community promptly actioned internal communication [AD1] thread to organize and set-up COVID-19 related activities. Such reactive internal involvement of ACTRIS partners generated timely outcomes. In fact, during the lockdown period in spring 2020, most of the ACTRIS observational and exploratory platforms were operational providing continuous access to data on air quality and atmospheric composition and, as a tailored service arrangement, to reinvent ACTRIS simulation chambers for testing mask filtering efficiencies. [AD2] ACTRIS response to the COVID-19 pandemic showcases multiple benefits to policy- and decision-makers focused on environmental and societal impacts of COVID-19 and the closing down of several sectors of society (e.g. transport, industry, services). To boost the visibility of ACTRIS COVID-19 response at the European level, ACTRIS actively engaged and collaborated with the wider community of Research Infrastructures (ESFRI, ENVRI, and ERF-AISBL) in Europe to support joint activities for SARS-CoV-2. The Open Science Session on COVID-19 during the ACTRIS week event brought together a broad audience and key-note speaker from major European agencies and organizations (ESA, ECMWF, FMI, ICOS). The online format of the event created the opportunity to open ACTRIS science to a broader public. At the national level, atmospheric scientists were interviewed on COVID impacts raising awareness on the work undertaken in the research infrastructure to the general public.ACTRIS aims at establishing further engagement and direct communication with decision and policy-makers and, for that, envisage the implementation of ad-hoc efforts. This presentation will showcase the various efforts and success stories to capture society as well as policy- and decision-makers.

The identification of the severe COVID-19 virus in December 2019 led the World Health Organization to declare a global pandemic by March 2020. Up till recently with the first available vaccines, the only prevention measures include strict social, travel and working restrictions in a so-called lockdown period that lasted for several weeks (mid-March to the end of April 2020 for most of Europe). This abrupt change in social behaviour is expected to impact local but also regional atmospheric composition, and the environmental impact is highly interesting to study.The Aerosol, Clouds and Trace Gases Research Infrastructure (ACTRIS) is a pan-European research infrastructure producing high-quality data and information on short-lived atmospheric constituents and on the processes leading to the variability of these constituents in natural and controlled atmospheres. ACTRIS integrates, harmonizes, and distributes datasets, activities, and services provided by the Central Facilities and National Facilities, located in 22 European countries. During the lockdown period in spring 2020 most of the ACTRIS observational were operational. The National Facilities performing the ambient measurements are generally regional background sites, with the aim to detect changes on regional level. Within the context of the current COVID-19 outbreak, ACTRIS has been continuously providing access to data on air quality and atmospheric composition. This is of particular interest and importance as it provides unique information measured from the ground to assess the European air quality and atmospheric composition during the lockdown complementing, in a fundamental way, satellite observations and modelling analysis. ACTRIS released a comprehensive and quality assured set of atmospheric measurement data during the COVID-19 pandemic spring 2020 – January– May 2020. This includes:- 30 sites with aerosol in situ measurements providing mainly absorption and scattering coefficient, size and/or number distribution. A few sites with high time solution aerosol chemical composition;- 12 sites with trace gases in situ data providing VOCs and NOX measurements;24 sites with aerosol remote sensing data providing profiles with backscattering and extinction coefficient;- 11 cloud remote sensing sites providing profile information of 9 various cloud properties.To facilitate studies, ACTRIS has compiled the data and coined a DOI for the data sets measured during the COVID-19 spring lockdown period, including an intensive aerosol remote sensing campaign in May. This presentation will present the data set and the potential applications and benefits using ACTRIS COVID-19 dataset for studying atmospheric composition changes during COVID-19 lockdown periods.

Understanding long-term variations in aerosol loading is essential for evaluating the health and climate effects of airborne particulates as well as the effectiveness of pollution control policies. The expected satellite lifetime is about 10 to 15 years. Therefore, to study the variations of atmospheric constituents over longer periods information from different satellites must be utilized. Here we introduce a method to construct a combined annual and seasonal long time series of AOD at 550 nm using the Along-Track Scanning Radiometers (ATSR: ATSR-2 and AATSR combined) and the MODerate resolution Imaging Spectroradiometer on Terra (MODIS/Terra), which together cover the 1995–2017 period. The long-term (1995–2017) combined AOD time series are presented for all of mainland China, for southeastern (SE) China and for 10 selected regions in China. Linear regression was applied to the combined AOD time series constructed for individual L3 (1∘ × 1∘) pixels to estimate the AOD tendencies for two periods: 1995–2006 (P1) and 2011–2017 (P2), with respect to the changes in the emission reduction policies in China. During P1, the annually averaged AOD increased by 0.006 (or 2 % of the AOD averaged over the corresponding period) per year across all of mainland China, reflecting increasing emissions due to rapid economic development. In SE China, the annual AOD positive tendency in 1995–2006 was 0.014 (3 %) per year, reaching maxima (0.020, or 4 %, per year) in Shanghai and the Pearl River Delta regions. After 2011, during P2, AOD tendencies reversed across most of China with the annually averaged AOD decreasing by −0.015 (−6 %) per year in response to the effective reduction of the anthropogenic emissions of primary aerosols, SO2 and NOx. The strongest AOD decreases were observed in the Chengdu (−0.045, or −8 %, per year) and Zhengzhou (−0.046, or −9 %, per year) areas, while over the North China Plain and coastal areas the AOD decrease was lower than −0.03 (approximately −6 %) per year. In the less populated areas the AOD decrease was small. The AOD tendency varied by both season and region. The increase in the annually averaged AOD during P1 was mainly due to an increase in summer and autumn in SE China (0.020, or 4 %, and 0.016, or 4 %, per year, respectively), while during winter and spring the AOD actually decreased over most of China. The AOD negative tendencies during the 2011–2017 period were larger in summer than in other seasons over the whole of China (ca. −0.021, or −7 %, per year) and over SE China (ca. −0.048, or −9 %, per year). The long-term AOD variations presented here show a gradual decrease in the AOD after 2011 with an average reduction of 30 %–50 % between 2011 and 2017. The effect is more visible in the highly populated and industrialized regions in SE China, as expected.

Satellite-based aerosol products are routinely validated against ground-based reference data, usually obtained from sun photometer networks such as AERONET (AEROsol RObotic NETwork). In a typical validation exercise a spatial sample of the instantaneous satellite data is compared against a temporal sample of the point-like ground-based data. The observations do not correspond to exactly the same column of the atmosphere at the same time, and the representativeness of the reference data depends on the spatiotemporal variability of the aerosol properties in the samples. The associated uncertainty is known as the collocation mismatch uncertainty (CMU). The validation results depend on the sampling parameters. While small samples involve less variability, they are more sensitive to the inevitable noise in the measurement data. In this paper we study systematically the effect of the sampling parameters in the validation of AATSR (Advanced Along-Track Scanning Radiometer) aerosol optical depth (AOD) product against AERONET data and the associated collocation mismatch uncertainty. To this end, we study the spatial AOD variability in the satellite data, compare it against the corresponding values obtained from densely located AERONET sites, and assess the possible reasons for observed differences. We find that the spatial AOD variability in the satellite data is approximately 2 times larger than in the ground-based data, and the spatial variability correlates only weakly with that of AERONET for short distances. We interpreted that only half of the variability in the satellite data is due to the natural variability in the AOD, and the rest is noise due to retrieval errors. However, for larger distances (∼ 0.5∘) the correlation is improved as the noise is averaged out, and the day-to-day changes in regional AOD variability are well captured. Furthermore, we assess the usefulness of the spatial variability of the satellite AOD data as an estimate of CMU by comparing the retrieval errors to the total uncertainty estimates including the CMU in the validation. We find that accounting for CMU increases the fraction of consistent observations.

The evaluation of modelling diagnostics with appropriate observations is an important task that establishes the capabilities and reliability of models. In this study we compare aerosol and cloud properties obtained from three different climate models (ECHAM-HAM, ECHAM-HAM-SALSA, and NorESM) with satellite observations using Moderate Resolution Imaging Spectroradiometer (MODIS) data. The simulator MODIS-COSP version 1.4 was implemented into the climate models to obtain MODIS-like cloud diagnostics, thus enabling model-to-model and model-to-satellite comparisons. Cloud droplet number concentrations (CDNCs) are derived identically from MODIS-COSP-simulated and MODIS-retrieved values of cloud optical depth and effective radius. For CDNC, the models capture the observed spatial distribution of higher values typically found near the coasts, downwind of the major continents, and lower values over the remote ocean and land areas. However, the COSP-simulated CDNC values are higher than those observed, whilst the direct model CDNC output is significantly lower than the MODIS-COSP diagnostics. NorESM produces large spatial biases for ice cloud properties and thick clouds over land. Despite having identical cloud modules, ECHAM-HAM and ECHAM-HAM-SALSA diverge in their representation of spatial and vertical distributions of clouds. From the spatial distributions of aerosol optical depth (AOD) and aerosol index (AI), we find that NorESM shows large biases for AOD over bright land surfaces, while discrepancies between ECHAM-HAM and ECHAM-HAM-SALSA can be observed mainly over oceans. Overall, the AIs from the different models are in good agreement globally, with higher negative biases in the Northern Hemisphere. We evaluate the aerosol–cloud interactions by computing the sensitivity parameter ACICDNC=dln⁡(CDNC)/dln⁡(AI) on a global scale. However, 1 year of data may be considered not enough to assess the similarity or dissimilarities of the models due to large temporal variability in cloud properties. This study shows how simulators facilitate the evaluation of cloud properties and expose model deficiencies, which are necessary steps to further improve the parameterisation in climate models.

The evaluation of modeling diagnostics with appropriate observations is an important task that establishes the capabilities and reliability of models. In this study we compare aerosol and cloud properties obtained from three different climate models ECHAM-HAM, ECHAM-HAM-SALSA, and NorESM with satellite observations using MOderate Resolution Imaging Spectrometer (MODIS) data. The simulator MODIS-COSP version 1.4 was implemented into the climate models to obtain MODIS-like cloud diagnostics, thus enabling model to model and model to satellite comparisons. Cloud droplet number concentrations (CDNC) are derived identically from MODIS-COSP simulated and MODIS-retrieved values of cloud optical depth and effective radius. For CDNC, the models capture the observed spatial distribution of higher values typically found near the coasts, downwind of the major continents, and lower values over the remote ocean and land areas. However, the COSP-simulated CDNC values are higher than those observed, whilst the direct model CDNC output is significantly lower than the MODIS-COSP diagnostics. NorESM produces large spatial biases for ice cloud properties and thick clouds over land. Despite having identical cloud modules, ECHAM-HAM and ECHAM-HAM-SALSA diverge in their representation of spatial and vertical distribution of clouds. From the spatial distributions of aerosol optical depth (AOD) and aerosol index (AI), we find that NorESM shows large biases for AOD over bright land surfaces, while discrepancies between ECHAM-HAM and ECHAM-HAM-SALSA can be observed mainly over oceans. Overall, the AIs from the different models are in good agreement globally, with higher negative biases on the Northern Hemisphere. We computed the aerosol-cloud interactions as the sensitivity of dln(CDNC)/dln(AI) on a global scale. However, one year of data may be considered not enough to assess the similarity or dissimilarities of the models due to large temporal variability in cloud properties. This study shows how simulators facilitate the evaluation of cloud properties and expose model deficiencies which are necessary steps to further improve the parametrization in climate models.

Understanding long-term trends in aerosol loading is essential for evaluating the health and climate effects of airborne particulates as well as the effectiveness of pollution control policies. Here we introduce a method to construct a combined annual and seasonal AOD long time series using the Along-Track Scanning Radiometers (ATSR: ATSR-2 and AATSR) and MODerate resolution Imaging Spectroradiometer Terra (MODIS/Terra), which together cover the period of 1995–2017. The long-term (1995–2017) annual and seasonal combined AOD time series are presented for the all of mainland China, for southeastern (SE) China and for 10 selected regions in China and analyzed to reveal the AOD tendencies during the last 23 years. Linear regression has been applied to individual L3 (1°×1°) pixels of the annual and seasonal combined AOD time series to estimate the AOD tendencies for three periods: 1995–2006 (P1) and 2011–2017 (P2), as regarding the changes in the emission reduction policies, and the whole period 1995–2017 (WP), when combined AOD time series is available. Positive tendencies of annual AOD (0.006, or 2 % of AOD, per year) prevailed across all of mainland China before 2006 due to emission increases induced by rapid economic development. In southeastern China, the annual AOD positive tendency in 1995–2006 was 0.014, or 3 % of AOD, per year in SE China, reaching maxima (0.020, or 4 % of AOD, per year) in Shanghai and the Pearl River Delta regions. Negative AOD tendencies (−0.015, or −6 % of AOD, per year) were identified across most of China after 2011 in conjunction with effective emission reduction in anthropogenic primary aerosols, SO2 and NOx (Jin et al., 2016, van der A et al., 2017). The strongest AOD decrease is observed in Chengdu (−0.045, or −8 % of AOD, per year) and Zhengzhou (−0.046, or −9 % of AOD, per year) areas, while over the North China plane and coastal areas the AOD decrease was lower than −0.03, or ca. −6 % of AOD, per year. In the less populated areas, the AOD decrease was small. The AOD tendencies for the whole period 1995–2017 were much less pronounced compared to P1 and P2. The reason for that is that positive AOD tendency has been observed at the beginning of WP (in P1) and negative AOD tendency has been observed at the end of WP (in P2), which partly cancel each other during 1995–2017. In the WP, AOD was slightly increasing over the Beijing-Tianjin-Hebei area (0.008, or 1.3 % of AOD, per year) and the Pearl River Delta (0.004, or 0.6 % of AOD, per year). A slightly negative AOD tendency (−0.004, or −0.7 % per year) was observed in the Chengdu and Zhengzhou areas. Seasonal patterns in the AOD regional long-term trend are evident. The contribution of seasonal AOD tendencies in annual tendencies was not equal along the year. While the annual AOD tendency was positive in 1995–2006, the AOD tendencies in winter and spring were slightly negative (ca. −0.002, or −1 % of AOD, per year) over the most of China during that period. AOD tendencies were positive in summer (0.008, or 2 % of AOD, per year) and autumn (0.006, or 6 % of AOD, per year) over all mainland China and SE China (0.020, or 4 % of AOD, per year and 0.016, or 4 % of AOD, per year in summer and autumn, respectively). The AOD negative tendencies in 2011–2017 were higher compared to other seasons in summer over China (ca. −0.021, or −7 % of AOD, per year) and over SE China (ca. −0.048, or −9 % of AOD, per year). The results obtained in the current study show that the effect of the changes in the emission regulations policy in China during 1995–2017 is evident in AOD gradual decrease after 2011. The effect is more visible in the highly populated and industrialized regions in SE China.

In this paper we describe an extension SAR study of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine nucleus as A3AR antagonist. Our initial aim was to replace the phenylcarbamoyl moiety at the 5 position of PTP nucleus with a thiourea functionality to evaluate the contribution of new structural modification against the A3AR. The synthesized 12-25 were not characterized by the predicted side chain but by a 1,3-disubstituted guanidine and are shown to be interesting A3AR antagonists.

A series of 1,3,6-triphenylpyrazolo[3,4- b ]pyridin-4-one derivatives was designed, synthesized and evaluated for cytotoxic activity in A375 human melanoma and human erythroleukemia (HEL) cells. The new pyrazolopyridones displayed comparable activities to the antitumor compound etoposide. The inhibitory effect of compounds 17, 18, 27 and 32 against topoisomerase II-mediated cleavage activities was measured finding good correlation with the results obtained from MTS assay. Docking studies into bacterial topoisomerase II (DNA Gyrase), topoisomerase IIα and topoisomerase IIβ binding sites in the DNA binding interface were performed.

The discrimination of cloudy from cloud-free pixels is required in almost any estimate of a parameter retrieved from satellite data in the ultraviolet (UV), visible (VIS) or infrared (IR) parts of the electromagnetic spectrum. In this paper we report on the development of a neural network (NN) algorithm to estimate cloud fractions using radiances measured at the top of the atmosphere with the NASA-Aura Ozone Monitoring Instrument (OMI). We present and discuss the results obtained from the application of two different types of neural networks, i.e., extreme learning machine (ELM) and back propagation (BP). The NNs were trained with an OMI data sets existing of six orbits, tested with three other orbits and validated with another two orbits. The results were evaluated by comparison with cloud fractions available from the MODerate Resolution Imaging Spectrometer (MODIS) flying on Aqua in the same constellation as OMI, i.e., with minimal time difference between the OMI and MODIS observations. The results from the ELM and BP NNs are compared. They both deliver cloud fraction estimates in a fast and automated way, and they both performs generally well in the validation. However, over highly reflective surfaces, such as desert, or in the presence of dust layers in the atmosphere, the cloud fractions are not well predicted by the neural network. Over ocean the two NNs work equally well, but over land ELM performs better.

A Sonogashira coupling strategy was employed to synthesize a new series of allosteric modulators for the A1 adenosine receptor based on the 2-amino-3-(p-chlorobenzoyl)-4-substituted thiophene skeleton, with a two-carbon (rigid or flexible) linker between the 5-position of the thiophene ring and a (hetero)aryl or alkyl moiety. Among the compounds characterized by the presence of a common phenylacetylene moiety at the 5-position of the thiophene ring, the neopentyl substitution at the 4-position supported a strong activity. In the series of 4-neopentyl derivatives, the presence of an acetylene spacer at the 5-position of the thiophene is optimal for activity, whereas reduction of the acetylene to an ethyl moiety decreased activity, both in functional and binding assays. Derivatives 4e, 4g-h, 4j, 4l, and 4m were the most promising compounds in binding (saturation and competition) and functional cAMP studies, being able to potentiate agonist [(3)H]CCPA binding to the A1 receptor, with 4e as the best compound of the series. The latter compound also retarded the dissociation of another radiolabeled agonist, [(3)H]NECA, from the receptor.

2-Amino-3-benzoyl thiophenes have been widely reported to act as allosteric enhancers at the A1 adenosine receptor. Their activity can be increased considerably by appropriate substitutions at the 4- and 5-positions of the thiophene ring. Substituent size at the thiophene C-4 position seemed to be a factor closely related to activity, with the 4-neopentyl (2,2-dimethylpropyl) substitution showing the greatest enhanced activity. A wide series of 2-amino-3-aroyl-4-neopentylthiophene derivatives with general structure 3, characterized by the presence of different substituents (bromine, aryl and heteroaryl) at the 5-position of the thiophene ring, have been identified as potent AEs at the A1AR. With only one exception, all of the synthesized compounds proved to be superior to the reference compound PD 81,723 in a functional assay. Derivatives 3p, 3u, 3am, 3ap and 3ar were the most active compounds in binding (saturation and competition) and functional cAMP studies, being able to potentiate agonist [(3)H]CCPA binding to the A1 receptor.

Retrieved from the Moderate Resolution Imaging Spectroradiometer (MODIS) on-board the Aqua satellite, 12 years (2003–2014) of aerosol and cloud properties were used to statistically quantify aerosol–cloud interaction (ACI) over the Baltic Sea region, including the relatively clean Fennoscandia and the more polluted central–eastern Europe. These areas allowed us to study the effects of different aerosol types and concentrations on macro- and microphysical properties of clouds: cloud effective radius (CER), cloud fraction (CF), cloud optical thickness (COT), cloud liquid water path (LWP) and cloud-top height (CTH). Aerosol properties used are aerosol optical depth (AOD), Ångström exponent (AE) and aerosol index (AI). The study was limited to low-level water clouds in the summer. The vertical distributions of the relationships between cloud properties and aerosols show an effect of aerosols on low-level water clouds. CF, COT, LWP and CTH tend to increase with aerosol loading, indicating changes in the cloud structure, while the effective radius of cloud droplets decreases. The ACI is larger at relatively low cloud-top levels, between 900 and 700 hPa. Most of the studied cloud variables were unaffected by the lower-tropospheric stability (LTS), except for the cloud fraction. The spatial distribution of aerosol and cloud parameters and ACI, here defined as the change in CER as a function of aerosol concentration for a fixed LWP, shows positive and statistically significant ACI over the Baltic Sea and Fennoscandia, with the former having the largest values. Small negative ACI values are observed in central–eastern Europe, suggesting that large aerosol concentrations saturate the ACI.

Cloud misclassification is a serious problem in the retrieval of aerosol optical depth (AOD), which might considerably bias the AOD results. On the one hand, residual cloud contamination leads to AOD overestimation, whereas the removal of high-AOD pixels (due to their misclassification as clouds) leads to underestimation. To remove cloud-contaminated areas in AOD retrieved from reflectances measured with the (Advanced) Along Track Scanning Radiometers (ATSR-2 and AATSR), using the ATSR dual-view algorithm (ADV) over land or the ATSR single-view algorithm (ASV) over ocean, a cloud post-processing (CPP) scheme has been developed at the Finnish Meteorological Institute (FMI) as described in Kolmonen et al. (2016). The application of this scheme results in the removal of cloud-contaminated areas, providing spatially smoother AOD maps and favourable comparison with AOD obtained from the ground-based reference measurements from the AERONET sun photometer network. However, closer inspection shows that the CPP also removes areas with elevated AOD not due to cloud contamination, as shown in this paper. We present an improved CPP scheme which better discriminates between cloud-free and cloud-contaminated areas. The CPP thresholds have been further evaluated and adjusted according to the findings. The thresholds for the detection of high-AOD regions (> 60 % of the retrieved pixels should be high-AOD (> 0.6) pixels), and cloud contamination criteria for low-AOD regions have been accepted as the default for AOD global post-processing in the improved CPP. Retaining elevated AOD while effectively removing cloud-contaminated pixels affects the resulting global and regional mean AOD values as well as coverage. Effects of the CPP scheme on both spatial and temporal variation for the period 2002–2012 are discussed. With the improved CPP, the AOD coverage increases by 10–15 % with respect to the existing scheme. The validation versus AERONET shows an improvement of the correlation coefficient from 0.84 to 0.86 for the global data set for the period 2002–2012. The global aggregated AOD over land for the period 2003–2011 is 0.163 with the improved CPP compared to 0.144 with the existing scheme. The aggregated AOD over ocean and globally (land and ocean together) is 0.164 with the improved CPP scheme (compared to 0.152 and 0.150 with the existing scheme, for ocean and globally respectively). Effects of the improved CPP scheme on the 10-year time series are illustrated and seasonal and temporal changes are discussed. The improved CPP method introduced here is applicable to other aerosol retrieval algorithms. However, the thresholds for detecting the high-AOD regions, which were developed for AATSR, might have to be adjusted to the actual features of the instruments.

Recent developments indicate that CB(2) receptor ligands have the potential to become therapeutically important. To explore this potential, it is necessary to develop compounds with high affinity for the CB(2) receptor. Very recently, we have identified the oxazinoquinoline carboxamides as a novel class of CB(2) receptor full agonists. In this paper we describe the medicinal chemistry of a new series of heteroaryl-4-oxopyridine/7-oxopyrimidine derivatives. Some of the reported compounds showed high affinity and potency at the CB(2) receptor while showing only modest affinity for the centrally expressed CB(1) cannabinoid receptor. Moreover, we found that the functionality of these ligands is controlled by the nature of the heteroaryl function condensed with the pyridine ring. In 3,5-cyclic adenosine monophosphate (cAMP) assays, the novel series show dose-dependent effects on the modulation of forskolin-induced cAMP production, revealing different behaviors as full agonists, partial agonists, and inverse agonists.

Twelve years (2003–2014) of aerosol and cloud properties retrieved from the Moderate Resolution Imaging Spectroradiometer (MODIS) on-board the Aqua satellite were used to statistically quantify aerosol-cloud interaction (ACI) over the Baltic Sea region including the relatively clean Fennoscandia and the more polluted Central-Eastern Europe. These areas allowed us to study the effects of different aerosol types and concentrations on macro- and microphysical properties of clouds: cloud effective radius (CER), cloud fraction (CF), cloud optical thickness (COT), cloud liquid water path (LWP) and cloud top height (CTH). Aerosol properties used are aerosol optical depth (AOD), Ångström Exponent (AE) and aerosol index (AI). The study was limited to low level water clouds in the summer. The vertical distributions of the relationships between cloud properties and aerosols show an effect of aerosols on low-level water clouds. CF, COT, LWP and CTH tend to increase with aerosol loading, indicating changes in the cloud structure, while the effective radius of cloud droplets decreases. The ACI is larger at relatively low cloud top levels, between 900 hPa and 700 hPa. Most of the studied cloud variables were unaffected by the lower tropospheric stability (LTS) except for the cloud fraction. The spatial distribution of aerosol and cloud parameters and ACI, here defined as the change in CER as a function of aerosol concentration for a fixed liquid water path (LWP), shows positive and statistically significant ACI over the Baltic Sea and Fennoscandia, with the former having the largest values. Small negative ACI values are observed in Central-Eastern Europe, suggesting that large aerosol concentrations saturate the ACI.

We recently described the synthesis of 1-benzyl-3-propyl-1H,8H-imidazo[2,1-f]purine-2,4-diones, new potent and selective A3 adenosine receptor antagonists containing a xanthine core. The present work can be considered an extension of our SAR studies on related structures in which the effect of different kind of substitutions at the 1-, 3- and 8-positions has been evaluated in order to improve both the potency and the hydrophilicity of the originally synthesised molecules. The A3 binding disposition of these compounds was also investigated through docking and 3D-QSAR studies.

CB2 cannabinoid receptor ligands are known to be therapeutically important for the treatment of numerous diseases. Recently, we have identified the heteroaryl-4-oxopyridine/7-oxopyrimidine derivatives as highly potent and selective CB2 receptor ligands, showing that the pharmakodynamics of the new compounds was controlled by the nature of the heterocycle core. In this paper we describe the synthesis and biological evaluation of 7-oxo-4-pentyl-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide derivatives that led to the identification of novel CB2 receptor inverse agonists. Cyclic AMP experiments on CB2 receptors expressed in CHO cells revealed that introduction of structural modifications at position 2 of triazolopyrimidine template changes the functional activity from partial to inverse agonism. The molecular docking analysis of the novel structures is reported.

A new series of N(6)-[(hetero)aryl/(cyclo)alkyl-carbamoyl-methoxy-phenyl]-(2-chloro)-5'-N-ethylcarboxamido-adenosines (24-43) has been synthesised and tested in binding assays at hA(1), hA(2A) and hA(3) adenosine receptors, and in a functional assay at the hA(2B) subtype. The examined compounds displayed high potency in activating A(2B) receptors with good selectivity versus A(2A) subtypes. The introduction of an unsubstituted 4-[(phenylcarbamoyl)-methoxy]-phenyl chain at the N(6) position of 5'-N-ethylcarboxamido-adenosine led us to the recognition of compound 24 as a full agonist displaying the highest efficacy of the series (EC(50) hA(2B)=7.3 nM). These compounds represent the first report about adenosine-related structures capable of activating hA(2B) subtype in the low nanomolar range.

The transient receptor potential ankyrin 1 (TRPA1) channel is an irritant sensor highly expressed on nociceptive neurons. The clinical use of TRPA1 antagonists is based on the concept that TRPA1 is active during disease states like neuropathic pain. Indeed, in Phase 2a proof-of-concept studies the TRPA1 antagonist GRC17536 has shown efficacy in patients with painful diabetic neuropathy. Moreover, animal studies suggest that the therapeutic value of TRPA1 antagonists extends beyond pain to pruritus, asthma and cough with limited safety concerns. This review provides a comprehensive overview of the patent literature (since 2007) on small-molecule inhibitors of the TRPA1 channel. Despite the clear progress, many unanswered questions remain. Future advancement to Phase 3 studies will assess the real translational potential of this research field.

Stimulation of A(2A) adenosine receptors (AR) promotes anti-inflammatory responses in animal models of allergic rhinitis, asthma, chronic obstructive pulmonary disease, and rheumatic diseases. Herein we describe the results of a research program aimed at identifying potent and selective agonists of the A(2A)AR as potential anti-inflammatory agents. The recent crystallographic analysis of A(2A)AR agonists and antagonists in complex with the receptor provided key information on the structural determinants leading to receptor activation or blocking. In light of this, we designed a new series of 2-((4-aryl(alkyl)piperazin-1-yl)alkylamino)-5'-N-ethylcarboxamidoadenosines with high A(2A)AR affinity, activation potency and selectivity obtained by merging distinctive structural elements of known agonists and antagonists of the investigated target. Docking-based SAR optimization allowed us to identify compound 42 as one of the most potent and selective A(2A) agonist discovered so far (K-i hA(2A)AR = 4.8 nM, EC50 hA(2A)AR = 4.9 nM, K-i hA(1)AR > 10.000 nM, K-i hA(3)AR = 1487 nM, EC50 hA(2B)AR > 10 000 nM).

A series of 4-allyl/benzyl-7,8-dihydro-8-methyl/ethyl-2-[(substituted) isoxazol/pyrazol-3/5-yl]-1H-imidazo[2,1-i]purin-5(4H)-ones has been synthesized and evaluated in radioligand binding assays to determine their affinities at the human A 1, A 2A, and A 3 adenosine receptors. Efficacy at the hA 2B AR and antagonism of selected ligands at the hA 3 AR were also assessed through cAMP experiments. All of the synthesized molecules exhibited high affinity at the hA 3 AR (K i values ranging from 1.46 to 44.8 nM), as well as remarkable selectivity versus A 1, A 2A, and A 2B AR subtypes. Compound (R)-4-allyl-8-ethyl-7,8-dihydro-2-(3-methoxy-1-methyl-1H- pyrazol-5-yl)-1H-imidazo[2,1-i]purin-5(4H)-one (R-33) was found to be the most potent and selective ligand of the series (K i hA 3 = 1.46 nM, K i hA 2A/K i hA 3 > 3425; IC 50 hA 2B/K i hA 3 > 3425; K i hA 1/K i hA 3 = 1729). Molecular modeling studies were helpful in rationalizing the available structure-activity relationships along with the selectivity profiles of the new series of ligands. © 2011 American Chemical Society.

A total of 118 stratiform water clouds were observed by ground-based remote sensing instruments at the Mace Head Atmospheric Research Station on the West coast of Ireland from 2009 to 2015. Microphysical and optical characteristics of these clouds were studied as well as the impact of aerosols on these properties. Microphysical and optical cloud properties were derived using the algorithm SYRSOC (SYnergistic Remote Sensing Of Clouds). Ground-based in-situ measurements of aerosol concentrations and the transport path of air masses at cloud level were investigated as well. The cloud properties were studied in dependence of the prevailing air mass at cloud level, and season. We found higher cloud droplet number concentrations (CDNC) and smaller effective radii (reff) with greater pollution. Median CDNC ranged from 60 cm−3 in marine air masses to 160 cm−3 in continental air. Median reff ranged from 8 μm in polluted conditions to 10 μm in marine air. Effective droplet size distributions were broader in marine than in continental cases. Cloud optical thickness (COT) and albedo were lower in cleaner air masses and higher in more polluted conditions, with medians ranging from 2.1 to 4.9 and 0.22 to 0.39, respectively. However, calculation of COT and albedo was strongly affected by liquid water path (LWP) and departure from adiabatic conditions. A comparison of SYRSOC results with MODIS (Moderate-Resolution Imaging Spectroradiometer) observations showed large differences for LWP and COT, but good agreement for reff with a linear fit with slope near 1 and offset of -1 μm.

Fatty acid amide hydrolase (FAAH) inhibitors have gained attention as potential therapeutic targets in the management of neuropathic pain. Here, we report a series of pyrazole phenylcyclohexylcarbamate derivatives standing on the known carbamoyl FAAH inhibitor URB597. Structural modifications led to the recognition of compound 22 that inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 nM). The most active compounds of this series showed significant selectivity toward monoacylglycerol lipase (MAGL) enzyme. In addition, molecular modeling and reversibility behavior of the new class of FAAH inhibitors are presented in this article.

A series of 1,3,6-triphenylpyrazolo[3,4-b]pyridin-4-one derivatives was designed, synthesized and evaluated for cytotoxic activity in A375 human melanoma and human erythroleukemia (HEL) cells. The new pyrazolopyridones displayed comparable activities to the antitumor compound etoposide. The inhibitory effect of compounds 17, 18, 27 and 32 against topoisomerase II-mediated cleavage activities was measured finding good correlation with the results obtained from MTS assay. Docking studies into bacterial topoisomerase II (DNA Gyrase), topoisomerase IIα and topoisomerase IIβ binding sites in the DNA binding interface were performed.

2-Amino-3-benzoyl thiophenes have been widely reported to act as allosteric enhancers at the A1 adenosine receptor. Their activity can be increased considerably by appropriate substitutions at the 4- and 5-positions of the thiophene ring. Substituent size at the thiophene C-4 position seemed to be a factor closely related to activity, with the 4-neopentyl (2,2-dimethylpropyl) substitution showing the greatest enhanced activity. A wide series of 2-amino-3-aroyl-4-neopentylthiophene derivatives with general structure 3, characterized by the presence of different substituents (bromine, aryl and heteroaryl) at the 5-position of the thiophene ring, have been identified as potent AEs at the A1AR. With only one exception, all of the synthesized compounds proved to be superior to the reference compound PD 81,723 in a functional assay. Derivatives 3p, 3u, 3am, 3ap and 3ar were the most active compounds in binding (saturation and competition) and functional cAMP studies, being able to potentiate agonist [(3)H]CCPA binding to the A1 receptor.

The discrimination of cloudy pixels is required in almost any estimate of a parameter retrieved from a satellite image in the ultraviolet (UV), visual (VIS) or infra-red (IR) parts of the electromagnetic spectrum. Also, the distincion of clouds within satellite imagery and the distribution of their micro-physical properties is essential to the understanding of radiative transfer through the atmosphere. This paper reports the development of neural network algorithms for cloud detection for the NASA-Aura Ozone Monitoring Instrument (OMI). We present and discuss the results obtained by training mathematical neural networks with simultaneous application to OMI and Aqua-MODerate Resolution Imaging Spectrometer (MODIS) data. The neural network delivers cloud fraction estimates in a fast and automated way. The developed neural network approach performs generally well in the training. Highly reflective surfaces, such as ice, snow, sun glint and desert, or atmospheric dust mislead the neural network to a wrong predicted cloud fraction.

We recently described the medicinal chemistry of a new series of heteroaryl-4-oxopyridine/7-oxopyrimidines as CB2 receptor partial agonists, showing that the functionality of these ligands is controlled by the nature of the heteroaryl function condensed with the pyridine ring. We describe herein the design and synthesis of the 7-oxopyrazolo[1,5-a]pyrimidine-6-carboxamides, structural isomers of our previously reported pyrazolo[3,4-b]pyridines. All of the new compounds showed high affinity and selectivity for the CB2 receptor in the nanomolar range. In 3,5-cyclic adenosine monophosphate (cAMP) assays, the novel series shows stimulatory effects on forskolin-induced cAMP production acting as inverse agonists.

Cannabinoid CB(2) receptor activation by selective agonists has been shown to produce analgesic effects in preclinical models of inflammatory, neuropathic, and bone cancer pain. In this study the effect of a novel CB(2)agonist (MT178) was evaluated in different animal models of pain. First of all, in vitro competition binding experiments performed on rat, mouse, or human CB receptors revealed a high affinity, selectivity, and potency of MT178. The analgesic properties of the novel CB(2) agonist were evaluated in various in vivo experiments, such as writhing and formalin assays, showing a good efficacy comparable with that produced by the nonselective CB agonist WIN 55,212-2. A dose-dependent antiallodynic effect of the novel CB(2) compound in the streptozotocin-induced diabetic neuropathy was found. In a bone cancer pain model and in the acid-induced muscle pain model, MT178 was able to significantly reduce mechanical hyperalgesia in a dose-related manner. Notably, MT178 failed to provoke locomotor disturbance and catalepsy, which were observed following the administration of WIN 55,212-2. CB(2) receptor mechanism of action was investigated in dorsal root ganglia where MT178 mediated a reduction of [(3)H]-d-aspartate release. MT178 was also able to inhibit capsaicin-induced substance P release and NF-κB activation. These results demonstrate that systemic administration of MT178 produced a robust analgesia in different pain models via CB(2) receptors, providing an interesting approach to analgesic therapy in inflammatory and chronic pain without CB(1)-mediated central side effects.

Cannabinoid receptor agonists have gained attention as potential therapeutic targets of inflammatory and neuropathic pain. Here, we report the identification and optimization of a series of 7-oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide derivatives as a novel chemotype of selective cannabinoid CB(2) receptor agonists. Structural modifications led to the identification of several compounds as potent and selective cannabinoid receptor agonists (20, hCB(2)K(i) = 2.5 nM, SI = 166; 21, hCB(2)K(i) = 0.81 nM, SI = 383; 38, hCB(2)K(i) = 15.8 nM, SI633; 56, hCB(2)K(i) = 8.12 nM, SI1231; (R)-58, hCB(2)K(i) = 9.24 nM, SI1082). The effect of a chiral center on the biological activity was also investigated, and it was found that the (R)-enantiomers exhibited greater affinity at the CB(2) receptor than the (S)-enantiomers. In 3,5-cyclic adenosine monophosphate assays, the novel series behaved as agonists, exhibiting functional activity at the human CB(2) receptor.

A relevant problem of the pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine nucleus, an attractive scaffold for the preparation of adenosine receptor antagonists, is the low water solubility. We originally functionalized the C(5) position with a salifiable 4-pyridylcarbamoyl moiety that conferred good water solubility at low pH (4.0) but poor solubility at physiologic pH, indicative of the dissociation of the pyridinium species. Here we replaced the pyridin-4-yl moiety with a 1-(substituted)piperidin-4-yl ring to exploit the higher basicity of this nucleus and for the the possibility to generate stable, water-soluble salts. The hydrochloride salt of the 1-(cyclohexylmethyl)piperidin-4-yl derivative (10, K(i)(hA(3)) = 9.7 nM, IC(50)(hA(3)) = 30 nM, K(i)(hA(1)/hA(3)) = 351, K(i)(hA(2A)/hA(3))515, IC(50)(hA(2B))5 μM) showed a solubility of 8 mg/mL at physiological pH and gave a stable aqueous system suitable for intravenous infusion. Molecular modeling studies were helpful in rationalizing the available structure-activity relationships and the selectivity profile of the new ligands.

Molecular modeling studies, including the comparative molecular field analysis (CoMFA) method, on 52 antagonists of the A2B adenosine receptor with known biological activity were performed to identify the three-dimensional features responsible for A2B adenosine receptor antagonist activity. On the basis of these and previous results on the potent antagonist effect of 8-pyrazolyl-xanthines at human A2BAR, a new series of compounds was synthesized and evaluated in binding studies against the human A1, A2A, A3, and A2BARs. A remarkable improvement in selectivity with respect to the previous series, maintaining the potency at human A2B receptor, was achieved, as exemplified by the 8-[3-(4-chloro-6-trifluoromethyl-1H-benzoimidazol-2-yl-methoxy)-1-methyl-1H-pyrazol-5-yl]-1,3-dipropyl-3,7-dihydro-purine-2,6-dione derivative 66: Ki A2B = 9.4 nM, IC50 hA2B = 26 nM hA1/hA2B = 269, hA2A/hA2B > 106, hA3/hA2B >106. This study also led to the identification of a series of pyrazole-xanthine compounds with a simplified s...

The discovery and development of adenosine receptor antagonists have represented for years an attractive field of research from the perspective of identifying new drugs for the treatment of widespread disorders such as inflammation, asthma and Parkinson's disease. The present work can be considered as an extension of our structure-activity relationship studies on the pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine (PTP) nucleus, extensively investigated by us as a useful template, in particular, for the identification of A(2A) and A(3) adenosine receptor antagonists. In order to explore the role of the nitrogen at the 7-position, we performed a new synthetic strategy for the preparation of pyrrolo[3,4-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives which can be considered as 7-deaza analogues of the parent PTPs. We also synthesised a novel series of pyrazolo[3,4-e][1,2,4]triazolo[1,5-c]pyrimidines as junction isomers of the reference compounds. In both cases we obtained some examples of potent antagonists (K(i) in the low nanomolar range) with variable selectivity profiles in relation to the nature of substituents introduced at the C(5)-, N(8)- and/or N(9)-positions. The pyrrolo-triazolo-pyrimidine derivative 9b appeared to be a potent A(3) adenosine receptor antagonist (K(i)=10 nM) with good selectivity over hA(1) (74-fold) and hA(2A) (20-fold) adenosine receptors combined with low activity at the hA(2B) subtype (IC(50)=906 nM). Moreover, some examples of high-affinity A(1)/A(2A) dual antagonists have been identified in both series. This work constitutes a new and important contribution for the comprehension of the interaction between PTPs and adenosine receptors.

The transient receptor potential ankyrin 1 (TRPA1) channel is activated by a series of by-products of oxidative/nitrative stress, produced under inflammatory conditions or in the case of tissue damage, thus generating inflammatory and neuropathic pain and neurogenic inflammatory responses. These findings have identified TRPA1 as an emerging opportunity for the design and synthesis of selective inhibitors as potential analgesic and antiinflammatory agents. Herein we present the synthesis and functional evaluation of a new series of 7-substituted-1,3-dimethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives designed as TRPA1 antagonists. A small library of compounds has been built by the introduction of differently substituted N(7)-phenylacetamide or N(7)-[4-(substituted-phenyl)-thiazol-2-yl]-acetamide chains. All the synthesized compounds were assayed to evaluate their ability to block acrolein-mediated activation of native human and rat TRPA1 channels employing a fluorometric calcium imaging assay. Our study led us to the identification of compound 3h which showed considerably improved potency (IC(50)=400nM) against human TRPA1 with regard to some of the most representative antagonists previously reported and integrated in our screening program as reference compounds. In addition, 3h proved to maintain its efficacy toward rTRPA1, which designates it as a possible candidate for future evaluation of in vivo efficacy in rodent animal model of inflammatory and neuropathic pain.

The potential employment of selective A3 adenosine receptor (A3AR) antagonists in the therapeutic treatment of important pathologies, such as asthma, inflammation, neurodegeneration, glaucoma and cancer, is subject to intensive studies because of the considerable role of this receptor in a number of pathophysiological processes. A wide number of compounds exerting high potency and selectivity in antagonizing the hA3 AR has been so far recognized being generally characterized by a remarkable structural diversity: nitrogen-containing aromatic monocyclic (thiazoles, thiadiazoles, 1,4-dihydropyridines, pyridines, 2-mercaptopyrimidines), bicyclic (flavonoid, isoquinoline, quinozalines, (aza)adenines), tricyclic systems (pyrazoloquinolines, triazoloquinoxalines, pyrazolotriazolopyrimidines, triazolopurines, tricyclic xanthines). The latest identification of nucleoside-derived antagonists, structurally related to the endogenous ligand, opened new frontiers for the elucidation of the therapeutic potential of this kind of ligands. Probably as a result of the enigmatic physiological role of A3AR, whose activation seems related to opposite effects concerning tissues protection in inflammatory and cancer cells, a few molecules have till now reached the preclinical investigation phase.

Clouds play a vital role in Earth's energy balance by modulating atmospheric processes, thus it is crucial to have accurate information on their spatial and temporal variability. Furthermore, clouds are relevant in those processes involved in aerosol-cloud-radiation interactions. The work conducted and presented herein concentrates on the retrievals of cloud properties, as well as their application for climate studies. While remote sensing observation systems have been used to analyze the atmosphere and observe its changes for the last decades, climate models predict how climate will change in the future. Altogether, these sources of observations are needed to better understand cloud processes and their impact on climate. In this thesis aerosol and cloud properties from the three above mentioned sources are applied to evaluate their potential in representing cloud properties and applicability in climate studies on local, regional and global scales. One aim of this thesis focuses on evaluating cloud parameters from ground-based remote-sensing sensors and from climate models using the MODerate Imaging Spectroradiometer (MODIS) data as a reference dataset. It is found that ground-based measurements of liquid clouds are in good agreement with MODIS cloud droplet size while poor correlation is found in the amount of cloud liquid water due to the management of drizzle. The comparison of the cloud diagnostic from three climate models with MODIS data, enabled through the application of a satellite simulator, helped to understand discrepancies among models as well as discover deficiencies in their simulation processes. These findings are important to further improve the parametrization of atmospheric constituents in climate models, therefore enhancing the accuracy of climate projections. In this thesis it is also assessed the impact of aerosol particles on clouds. Satellite data can be used to derive climatically crucial quantities that are otherwise not directly retrieved (such as aerosol index and cloud droplet number concentration) which can be used to infer the sensitivity of clouds to aerosols changes. Results on the local and regional scales show that contrasting aerosol backgrounds indicate a higher sensitivity of clouds to aerosol changes in cleaner ambient air and a lower sensitivity in polluted areas, further corroborating the notion that anthropogenic emission modify clouds. On the global scale, the estimates of the aerosol-cloud interactions present, overall, a good agreement between the satellite- and model-based values which are in line with the results from other models. Abstract available only in English.