Application of remotely-sensed cloud properties for climate studies

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 interaction present, overall, a good agreement between the satellite- and model-based values which are in line with the results from other models

Design and Synthesis of New A2A and A3 Adenosine Receptors Antagonists

The aim of this work was the design and synthesis of new A2A and A3 adenosine receptors antagonists. Two different studies have been performed. The first one based on structural modifications of the pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pirimidine nucleus, reported in literature. In order to identify a new series of A2A or A3 AR antagonists and with the aim to better investigate the role of the nitrogen at the 7- position on the interaction with ARs, it was performed a synthetic strategy for the preparation of the pyrrolo[3,4-e][1,2,4]triazolo[1,5-c]pyrimidine nucleus which can be considered the 7-deaza-analogue of the pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine core. In order to complete the SAR studies on this class of compounds, it has been synthesised a novel series of pyrazolo[3,4-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives which can be considered the structural isomers of the parent pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives. From the biological data obtained, we can assert that the concomitant presence of the N7 and N8 is fundamental for the selectivity of these A2A/A3 ligands versus the remaining ARs subtype. Our results confirmed the importance of the presence of the NH at the 5- position of the PTPs nuclus, this could be due to the formation of an essential ligand-receptor hydrogen bond. Most of these compounds, revealed to be non selective ARs antagonists. Derivative 5-{[(4-methoxy-phenyl)carbamoyl]amino}-(2-furan-2-yl)-8-methyl-8H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-c]pyrimidine resulted to be the best compound of the series in term of both affinity (hA3Ki = 15nM) and selectivity. The aim of the second project was to obtain A3 antagonists with improve water-solubility. 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)-one derivatives have been synthesised and evaluated in radioligand binding assays to determine their affinities at the human A1, A2A, and A3 adenosine receptors. Efficacy at the hA2B AR and antagonism of selected ligands at the hA3 AR were also assessed through cAMP experiments. All the synthesised molecules exhibited high affinity at the hA3 AR (Ki values ranging from 1.46 to 44.8 nM) as well as remarkable selectivity versus A1, A2A and A2B AR subtypes. In view of the chirality of the tricycles, for selected compounds both the racemic mixtures and the pure enantiomers have been prepared with the purpose of determine a possible receptor stereoselectivity. 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 showed to be the most potent hA3 AR ligand of the series (hA3Ki = 1.46 nM), in addition with very high selectivity over all the other ARs (hA2AKi/ hA3Ki > 3425; hA2BIC50/ hA3Ki > 3425; hA1Ki/ hA3Ki = 1,729)

Estimates of the aerosol indirect effect over the Baltic Sea region derived from 12 years of MODIS observations

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), Angstrom 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.Peer reviewe

Post-processing to remove residual clouds from aerosol optical depth retrieved using the Advanced Along Track Scanning Radiometer

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 cloudcontaminated 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 cloudcontaminated 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 lowAOD 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.Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Transient receptor potential ankyrin 1 (TRPA1) antagonists

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

A3 adenosine receptor antagonists: History and future perspectives

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 hA 3 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. © 2010 Springer Science+Business Media B.V

Pyrazole phenylcyclohexylcarbamates as inhibitors of human fatty acid amide hydrolases (FAAH)

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 ¼ 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