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The replacement of toxic solvents with greener alternatives in Heck–Cassar–Sonogashira (HCS) cross-couplings was investigated. The fine-tuning of the HCS protocol allowed to achieve complete conversions and high speed under mild conditions. N-Hydroxyethylpyrrolidone (HEP) gave the best results. Moreover, the methodology was successfully applied to the synthesis of an intermediate of the anticancer drug Erlotinib, demonstrating the versatility of the new green protocol.

Ampicillin, discovered in 1958, was the first broad spectrum semisynthetic penicillin introduced into the market. Despite its wide use not all the impurities have been identified to date. Herein, the last unknown impurity present in commercially available medicines was isolated and identified. This impurity that accounts up to 0.8 in area % by HPLC (EP 10.0) in the Reference Listed Drugs (RLD) was characterized and identified to be the 16-keto penicillin G. The structure was confirmed by comparison with a chemically synthesized sample. The determination of the Relative Response Factor (RRF) of the impurity respect to the parent drug allowed to recalculate the real amount that is consistently below the reporting threshold.

11 pags., 4 figs., New particle formation in the Arctic atmosphere is an important source of aerosol particles. Understanding the processes of Arctic secondary aerosol formation is crucial due to their significant impact on cloud properties and therefore Arctic amplification. We observed the molecular formation of new particles from low-volatility vapors at two Arctic sites with differing surroundings. In Svalbard, sulfuric acid (SA) and methane sulfonic acid (MSA) contribute to the formation of secondary aerosol and to some extent to cloud condensation nuclei (CCN). This occurs via ion-induced nucleation of SA and NH and subsequent growth by mainly SA and MSA condensation during springtime and highly oxygenated organic molecules during summertime. By contrast, in an ice-covered region around Villum, we observed new particle formation driven by iodic acid but its concentration was insufficient to grow nucleated particles to CCN sizes. Our results provide new insight about sources and precursors of Arctic secondary aerosol particles., The authors acknowledge European Research Council (GASPARCON, Grant no. 714621 and COALA, Grant no. 638703), Academy of Finland (Project nos. 296628, 306853, 317380, 316114, and 320094), INTERACT, European Regional Development Fund (project MOBTT42), Austrian Science Fund (FWF, Project J3951-N36), the European Union's Horizon 2020 Research and Innovation Program (Grant no. 689443) via project iCUPE (Integrative and Comprehensive Understanding on Polar Environments) and Project ERC-2016- COG 726349 CLIMAHAL, National Research Foundation (NRF) of the Ministry of Science, ICT and Future Planning (NRF-2018R1A2A1A19019281), Knut-and-Alice-Wallenberg Foundation within the Arctic Climate Across Scales (Project No. \,2016.0024), the Swedish EPA's (Naturvårdsverket) Environmental monitoring program (Miljöövervakning), the Swedish Research Council FORMAS (Project "Interplay between water, clouds and Aerosols in the Arctic," \# 2016-01427), Climate Change Tower – Integrated Project of the National Research Council of Italy and the National Interest Project by the Italian Minister of Education, University and Research (PRIN2007 and PRIN2009). The authors thank Department of Earth System Sciences and Technologies for the Environment, Department of Earth Sciences and Technology of the Environment of CNR and the doctoral program in atmospheric sciences at the University of Helsinki for financial support. Aarhus University acknowledge financial support from Danish Ministry of Environment and food and Ministry of Climate, Energy and Utilities by means of DANCEA.

A growing interest in peptides as active pharmaceutical ingredients (APIs) requires the development of efficient strategies for their preparation. This is particularly challenging in the case of long peptides with a strong tendency for aggregation and folding. Here, we describe the pseudoproline-assisted convergent synthesis of GLP-1 receptor agonist lipopeptides liraglutide and semaglutide, which involves the stepwise condensation of three fragments in the solid phase. The insertion of a pseudoproline residue at the site of fragment coupling prevents aggregation and allows obtaining these peptides with excellent purity and high yield. In addition, for the synthesis of lipidated side chains, we developed a novel approach that involves copper(II) lysinate intermediates and can be particularly suitable for the industrial preparation of both liraglutide and semaglutide and other peptides with a similar branched structure.

The Arctic is an important natural laboratory that is extremely sensitive to climatic changes and its monitoring is, therefore, of great importance. Due to the environmental extremes it is often hard to deploy sensors and observations are limited to a few sparse observation points limiting the spatial and temporal coverage of the Arctic measurement. Given these constraints the possibility of deploying a rugged network of low-cost sensors remains an interesting and convenient option. The present work validates for the first time a low-cost sensor array (AIRQino) for monitoring basic meteorological parameters and atmospheric composition in the Arctic (air temperature, relative humidity, particulate matter, and CO2). AIRQino was deployed for one year in the Svalbard archipelago and its outputs compared with reference sensors. Results show good agreement with the reference meteorological parameters (air temperature (T) and relative humidity (RH)) with correlation coefficients above 0.8 and small absolute errors (&asymp, 1 &deg, C for temperature and &asymp, 6% for RH). Particulate matter (PM) low-cost sensors show a good linearity (r2 &asymp, 0.8) and small absolute errors for both PM2.5 and PM10 (&asymp, 1 &micro, g m&minus, 3 for PM2.5 and &asymp, 3 &micro, 3 for PM10), while overall accuracy is impacted both by the unknown composition of the local aerosol, and by high humidity conditions likely generating hygroscopic effects. CO2 exhibits a satisfying agreement with r2 around 0.70 and an absolute error of &asymp, 23 mg m&minus, 3. Overall these results, coupled with an excellent data coverage and scarce need of maintenance make the AIRQino or similar devices integrations an interesting tool for future extended sensor networks also in the Arctic environment.

The hydrolysis and rearrangement of the dihydroorotic (Hor) residue in the presence of bases, leading to the formation of the hydantoin (Hyd) impurity, represent one of the major problems in manufacturing of the gonadotropin-releasing hormone antagonist Degarelix. In an attempt to find efficient strategies to overcome this problem, we carried out a screening of organic bases in order to select those which afforded both the rapid Fmoc deprotection during the solid-phase synthesis and the absence of this peculiar rearrangement. Among the bases tested, only tert-butylamine did not affect the peptide molecule and was able to perform fast Fmoc removal. The use of tert-butylamine for the synthesis of Degarelix led to a product with excellent purity and yield without a detectable amount of the hydantoin impurity. Thus, we showed that tert-butylamine can be a suitable alternative to piperidine for industrial-scale production of Degarelix or other Hor-containing peptide pharmaceuticals.

The Arctic is one critical environment for monitoring climate change as well as variations in background concentrations of atmospheric components. The associated logistic difficulties, though, make hard to deploy an extensive monitoring network of sensors, limiting long time-series to only sparse and costly point observations. Low-cost sensors are experiencing a widespread employment in research and monitoring applications and could be an interesting tool to deploy spatialized monitoring networks even in extreme environments. In this context, two CNR Labs (IBE and ISAC) made a long-term deployment of a prototypal low-cost sensor for atmospheric composition monitoring in the polar research village of Ny-Ålesund (Svalbard, Norway). In about one year of measurements the low-cost sensor showed: i) a good consistency in the data series with minimal data loss, ii) no significant requirements for maintenance and iii) the capability of capturing the main atmospheric trends of the Arctic lower troposphere.

An innovative approach to characterize concentration of atmospheric aerosol particles and air mass layering along the elevation profile of glaciers is presented for the first time and validated, exploiting low weight and fast response sensors deployed on a snowmobile. Two micro-Aethalometers for black carbon measurements and a miniature Diffusion Size Classifier (miniDisc) for total aerosol concentration (airborne particles) in the 14–260 nm range were used. Test experiments were conducted in the Arctic (Svalbard) in Spring (2016). Three glaciers in the Spitsbergen region were considered for this exploratory study, the Austre Broggerbreen, the Edithbreen and the Kongsvegen. The Austre Broggerbreen and Edithbreen were considered as test sites to setup the experiment, to optimize the sampling strategy and to identify some basic experimental artefacts. Kongsvegen glacier was chosen for the main case study, extending from the Kongsfjorden coast to roughly 700 m above sea level for a total length of ca. 25 km and with a nearly constant elevation gradient. The obtained results were rather consistent for the three glaciers and show an increase of nanoparticles with altitude. Black carbon concentration show stationary to decreasing trends going from the bottom to the top of the glaciers. These observations indicate a very active secondary aerosol formation at the highest elevations, responsible for the increase concentration of ultrafine particles at the glacier top. On the other side, black carbon shows higher levels at the lower altitudes of the glacier. This is indicative that in absence of a long-range transport as demonstrated by calculated back trajectories, black carbon might have accumulated due to the effect of katabatic winds flow along the glacier profile. The results obtained were compared and are largely consistent with the observations from concurrent soundings with a tethered balloon experiment conducted in the nearby site of Ny-Alesund. The proposed experimental design opens new perspectives for future experiments, which may be of relevance for the understanding of black carbon and dry dust deposition on the glacier surface, which may impact the melting of ice and snow. The investigations also contribute to better understanding of the transport and surface exchange processes acting within the atmospheric layer over glacier surface.

The availability of 5-year time series of velocity and temperature data from two sonic anemometers installed at Jang Bogo Station, Antarctica, allowed a systematic investigation of the turbulence features in a stable layer affected by submeso motions and characterized by the vertical divergence of some second-order moments for a large fraction of time (quite a non-ideal surface layer). The investigation of the effect of the averaging time interval on the statistics of the second-order moments showed that this is greater for the variances of the velocity components with respect to that for the vertical fluxes. This corresponds to a greater contribution from low-frequency motions. The turbulence statistics were investigated and compared with current literature results in terms of vertical structure, share of energy between horizontal and vertical components, skewness of the vertical velocity and turbulent velocities. As a general result, all the normalized second-order moments show a clear change passing from neutral to stable conditions, passing through the range of bulk Richardson number equal to 0.1–1.

Water mass generation and mixing in the eastern Fram Strait are strongly influenced by the interaction between Atlantic and Arctic waters and by the local atmospheric forcing, which produce dense water that substantially contributes to maintaining the global thermohaline circulation. The West Spitsbergen margin is an ideal area to study such processes. Hence, in order to investigate the deep flow variability on short-term, seasonal, and multiannual timescales, two moorings were deployed at ~1040 m depth on the southwest Spitsbergen continental slope. We present and discuss time series data collected between June 2014 and June 2016. They reveal thermohaline and current fluctuations that were largest from October to April, when the deep layer, typically occupied by Norwegian Sea Deep Water, was perturbed by sporadic intrusions of warmer, saltier, and less dense water. Surprisingly, the observed anomalies occurred quasi-simultaneously at both sites, despite their distance (~170 km). We argue that these anomalies may arise mainly by the effect of topographically trapped waves excited and modulated by atmospheric forcing. Propagation of internal waves causes a change in the vertical distribution of the Atlantic water, which can reach deep layers. During such events, strong currents typically precede thermohaline variations without significant changes in turbidity. However, turbidity increases during April&ndash, June in concomitance with enhanced downslope currents. Since prolonged injections of warm water within the deep layer could lead to a progressive reduction of the density of the abyssal water moving toward the Arctic Ocean, understanding the interplay between shelf, slope, and deep waters along the west Spitsbergen margin could be crucial for making projections on future changes in the global thermohaline circulation.

We examine the dependence on wind speed of the share of the mean turbulent kinetic energy among the three velocity components in the near-neutral surface layer. To contrast the general behaviour and the local effects, four datasets are considered, corresponding to different surfaces and environmental conditions. For high wind speeds (i.e., wind speed $$\approx {10}\,{\hbox {ms}^{-1}}$$ ), the shares are well-defined and about the same for all sites. As wind speed decreases (becoming $$\approx {1}\,{\hbox { ms}^{-1}}$$ ), large record-to-record variability occurs giving, on average, an almost isotropic state for the horizontal velocity components. Through spectral analysis, we relate this behaviour to the low-frequency, submeso motions and to the lack of conditions required by Reynolds averaging. The implications for modelling are also discussed, showing that the wind speed, or a related quantity, must be accounted for, besides stability, in second-order closures.

To replace dimethylformamide (DMF) in fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis, we explored the application of mixtures of green solvents (green solvents mixtures for solid-phase peptide synthesis (GM-SPPS)) as combinations of Cyrene (dihydrolevoglucosenone), sulfolane, or anisole with dimethyl carbonate or diethyl carbonate, in different proportions. Their ability to swell differently functionalized polystyrene and polyethylene glycol resins was explored, and solubility of amino acids and coupling reagents was studied. Moreover, the synthesis of the model peptide Aib-enkephalin was performed in the new green mixtures, confirming the possibility to fully replace DMF all over SPPS. The two established best green protocols were then successfully applied to the synthesis of a longer peptide (Aib-ACP). Finally, the green solvent-based procedure was applied to the synthesis of the reduced form of the active pharmaceutical ingredient (API) Octreotide. After oxidative cyclization and a single high-pressure column chromatography, the pharmaceutical-grade compound was isolated in comparable high yield to that obtained with the standard procedures.

The highly potent, long-acting, gonadotropin-releasing hormone antagonist Degarelix is known to be very efficient for prostate cancer treatment. The synthesis of decapeptide Degarelix is complicated because of the presence in its sequence of several unnatural alpha-amino acids, which are prone to rearrangements and side reactions. In particular, the rearrangement of the dihydroorotic (Hor) moiety with following hydantoin formation in the presence of bases represents one of the major problems. In this study, we describe a novel chemical strategy to overcome this obstacle by the use of the corresponding p-nitrophenylalanine derivative, which is reduced on the solid support to p-aminophenylalanine and acylated with dihydroorotic acid at the end of the solid-phase synthesis. Thus, the contact of Hor with the bases required for Fmoc deprotection is completely avoided. This approach provides a superior purity of Degarelix when the synthesis is carried out in the industrial scale as well.

Alkylidene acetoacetamides are useful building blocks for the preparation of a number of biologically active derivatives, including dehydro-β-amino-acid-containing peptidomimetics. A one-pot two-step protocol for the preparation of amino-acid-derived unsaturated acetoacetamides has been optimized. The use of microwave activation avoids, or at least decreases, the need for catalysts in both steps. A leucine derivative was selected from the small collection of molecules obtained to be transformed into the corresponding dehydro-β-amino-acid-containing peptidomimetic. It is known that such fragments are able to induce β-turns into peptide sequences, and, due to the presence of the unsaturation, they may represent sites for selective modification and conjugation.

An extensive set of measurements (May–August 2012 and June–November 2013) taken at the Amundsen-Nobile Climate Change Tower located at Ny-Alesund, Svalbard, allowed investigation of some features of the vertical structure of the atmospheric stable boundary layer (SBL) at high latitudes. The main sensors are three sonic anemometers and four low-frequency thermo-hygrometers and anemometers. The momentum flux τ, the sensible heat flux Q and the turbulent kinetic energy K data at different levels demonstrated the occurrence of both the traditional and upside-down SBL cases, according to the classification proposed in the literature. Based on a linear approximation of the profiles, the vertical scales were found to be different for the different second-order moments. In the traditional case, the scales hτ , hQ and hK, defined as levels for which fluxes became zero, can be considered to approximate the boundary-layer depth. While the distributions of hτ and hQ were found to be similar, having the ratio hQ/hτ equally distributed around unity although with a positive skewness, those of hτ and hK look quite different, having the ratio hK/hτ >1 in about 90% of the cases and with a median value >2. In the upside-down case, the scales sτ, sQ and sK, defined as the height at which the value of the considered quantity doubles that at the surface, give a measure of the vertical variations of the moments. Comparing the distributions of these three scales, similar results to those for the traditional case were found, although with slightly different statistics. The values of the ratio between scales affect the vertical profile of the local Obukhov length in both the traditional and upside-down SBL cases.

The vertical features of the variations in the atmospheric ozone density, temperature and wind velocity observed at Ny-Alesund, Svalbard were studied by applying the principal component analysis to the ozonesounding data collected during the 1992–2016 period. Two data sets corresponding to intra-seasonal (IS) variations, which are composed by harmonics with lower than 1 year periods and inter-annual (IA) variations, characterised by larger periods, were extracted and analysed separately. The IS variations in all the three parameters were found to be composed mainly by harmonics typical for the Madden-Julian Oscillation (from 30- to 60-day periods) and, while the first four principal components (PCs) associated with the temperature and wind contributed about 90% to the IS variations, the ozone IS oscillations appeared to be a higher dimensional object for which the first 15 PCs presented almost the same extent of contribution. The IA variations in the three parameters were consisted of harmonics that correspond to widely registered over the globe Quasi-Biennial, El Nino-Southern, North Atlantic and Arctic Oscillations respectively, and the IA variations turned out to be negligible below the tropopause that characterises the Svalbard troposphere as comparatively closed system with respect to the long-period global variations. The behaviour of the first and second PCs associated with IS ozone variations in the time of particular events, like the strong ozone depletion over Arctic in the spring 2011 and solar eclipses was discussed and the changes in the amplitude-frequency features of these PCs were assumed as signs of the atmosphere response to the considered phenomena.

To characterize the local low-level circulation in the Tyrrhenian Sea coastal area near Rome, the wind velocity field observed by Doppler sodar operating in the Estate of Castelporziano, has been studied. The prevailing diurnal behavior of the wind speed and wind direction as a function of the season was highlighted for the winter and the summer 2007. Two different patterns of the local circulation can be alternately observed in the night to early morning and after the sunset to late evening. The data analysis has shown that the statistical distribution of wind direction during the night, in winter, presents great occurrence at low levels in the northeastern sector and around 100°. Moreover, it has been observed that the nocturnal components of the wind direction at low-level changes with the height, and these changes can be associated with the effects induced by the large-scale flow on the local circulation at higher levels.

The characteristics of the temporal and height variations of the temperature structure parameter $$C_\mathrm{T}^{2}$$ in strongly convective situations derived from the sodar echo-signal intensity measurements were analyzed for the first 100 m. It was corroborated that the probability density function (pdf) of the logarithm of $$C_\mathrm{T}^{2}$$ in the lower convective boundary layer is markedly non-Gaussian, whereas turbulence theory predicts it to be normal. It was also corroborated that the sum of two weighted Gaussians, which characterize the statistics of $$C_\mathrm{T}^{2}$$ within convective plumes and in their environment and the probability of plume occurrence, well approximates the observed pdfs. It was shown that the height behaviour of the arithmetic mean of $$ C_\mathrm{T}^{2}$$ (both total and within plumes) follows well a power law $$C_\mathrm{T}^{2} (z) \sim z^{-q}$$ with the exponent $$q$$ close to the theoretically predicted value of 4/3. But for the geometrical means of $$C_\mathrm{T}^{2}$$ (both total and within the plumes), $$q$$ is close to 1. The difference between arithmetically and geometrically averaged $$C_\mathrm{T}^{2}$$ profiles was analyzed. The vertical profiles of the standard deviation, skewness and kurtosis of $$\hbox {ln}C_\mathrm{T}^{2}$$ pdfs were analyzed to show their steady behaviour with height. The standard deviations of the logarithm of $$C_\mathrm{T}^{2}$$ within the plumes and between them are similar and are 1.5 times less than the total standard deviation. The estimate of the variability index $$F_\mathrm{T}$$ and its height behaviour were obtained, which can be useful to validate some theoretical and modelling predictions. The vertical profiles of the skewness and kurtosis show the negative asymmetry of pdfs and their flatness, respectively. The spectra of variations in $$\hbox {ln}C_\mathrm{T}^{2}$$ are shown to be satisfactorily fitted by the power law $$f^{-\gamma } $$ in the frequency range 0.02 and 0.2 Hz, with the average exponent $$\approx $$ 1.27 $$\pm $$ 0.22.

Alkylidene acetoacetamides are useful building blocks for the preparation of a number of biologically active derivatives, including dehydro-β-amino-acid-containing peptidomimetics. A one-pot two-step protocol for the preparation of amino-acid-derived unsaturated acetoacetamides has been optimized. The use of microwave activation avoids, or at least decreases, the need for catalysts in both steps. A leucine derivative was selected from the small collection of molecules obtained to be transformed into the corresponding dehydro-β-amino-acid-containing peptidomimetic. It is known that such fragments are able to induce β-turns into peptide sequences, and, due to the presence of the unsaturation, they may represent sites for selective modification and conjugation.

Among the different classes of antibiotics, oxazolidinone derivatives represent important drugs, since their unique mechanism of action overcomes commonly diffused multidrug-resistant bacteria. Anyway, the structural similarity of these molecules to monoamino oxidase (MAO) inhibitors, like toloxatone and blefoxatone, induces in many cases loss of selectivity as a major concern. A small library of compounds based on isoxazolidinone and dehydro-β-proline scaffold was designed with the aim to obtain antibacterial agents, evaluating at the same time the potential effects of structural features on MAO inhibitory behaviour. The structural modification introduced in the backbone, starting from Linezolid model, lead to a significant loss in antibiotic activity, while a promising inhibitory effect could be observed on monoamino oxidases. These interesting results are also in agreement with docking experiments suggesting a good binding pose of the synthesized compounds into the pocket of the oxidase enzymes, in particular of MAO-B.

Due to the presence of the indole ring in a number of bioactive compounds, novel methods for the preparation of polyfunctionalized indole derivatives are of great interest. The combined use of Lewis acid catalysis and microwave irradiation furnished satisfactory results in the Yonemitsu-type trimolecular condensation of indoles with aldehydes and 1,3-dicarbonyl compounds, such as malonates and acetoacetates. The main advantage of this procedure is the use of a catalytic amount of the Lewis acid and reduction in reaction time. The one pot procedure avoids the isolation and purification of intermediates, thus making the process more environmentally sustainable. The protocol has also been successfully applied to the preparation of novel indole-coumarin derivatives of potential biological interest.

Global warming affects the Arctic two/four times faster than any other region of the planet. The components of the climate system strongly react to changes with an immediate impact on the environment and on the whole living system. As a consequence of the increasing concern, in the last two decades the research in the Arctic has rapidly grown, with the aim to better understand processes and amplification mechanisms as well as to assess consequences at mid-latitudes and on the rest of the planet. Italian scientists have provided a relevant contribution to the Arctic science with a wide range of research activities conducted so far, not only at Ny-Alesund (Svalbard Islands), where the Italian National Research Council (CNR) manages the “Dirigibile Italia Arctic Station”, but also at Thule (Greenland) and on the surrounding seas, and in the Arctic Ocean. The strategic objectives of the wide range of activities developed since 2008 aim to reinforce the flagship sites (super-sites) as key components of an integrated pan-Arctic observing network, where it is possible to study the complex dimensions of the Arctic regional climate system and to fully develop multidisciplinary research activities in a framework of international cooperation. This special issue presents a collection of reports on recent scientific achievements and provides the state-of-the-art and future perspectives of Italian research in the Arctic.

During the 2013 Arctic campaign, direct measurements and size-segregated samplings of atmospheric aerosol were carried out from March to September at the Gruvebadet observatory in Ny-lesund (78A degrees 56'N, 11A degrees 56'E; Svalbard Islands). Continuous size distribution measurements (104 size classes) were performed both in the nano- (TSI-SMPS system) and micro-metric (TSI-APS device) range with a resolution of 10 min. Aerosol sampling was carried out on daily basis (PM10 fraction, 00:01-23:59 UTC) and with a 4-day resolution (four-stage cascade impactor). A back-trajectory analysis was performed for specific events to understand transport processes and possible source areas of aerosol reaching Ny-lesund. Aerosol samples were analyzed for ion composition (inorganic cations and anions, selected organic anions) by a three-chromatograph system after extraction in ultra-sonic bath. Special attention was spent in identifying and interpreting the seasonal pattern of natural and anthropic chemical markers. Sea spray aerosol was evenly distributed along all the sampling period with maxima related to wind speed. Its size distribution peaks in 1.0-2.5 or 2.5-10 A mu m, depending on the transport conditions and distance from source areas. Anthropic sulfate dominates the spring aerosol load (Arctic Haze), both in acidic form (H2SO4) and in partially or totally neutralized ammonium salts. Biogenic contributions, marked by methanesulfonic acid, are relatively relevant in late spring-early summer and are distributed in the finest aerosol fraction (< 1.0 A mu m).

Daily PM10 aerosol samples were collected at the Gruvebadet observatory, Ny-Ålesund (Svalbard Islands), during the spring-summer 2014 Italian Arctic Campaign. A total of 136 samples were analysed for ion (inorganic anions and cations, selected organic anions) composition aiming to evaluate the seasonal pattern of sulfate, as a key component of the Arctic haze. Ionic balances indicated a strong sulfate seasonality with mean spring concentration about 1.5 times higher than that measured in summer. The spring and summer aerosol was almost neutral, indicating that ammonia was the major neutralizing agent for atmospheric acidic species. The linear regression between sulfate from potential acidic sources (non-sea salt sulfate and non-crustal sulfate) and ammonium indicated that the mean sulfate/ammonium ratio was intermediate between semi-(NH4HSO4) and complete ((NH4)2SO4) neutralization. Using sea-salt sodium as sea-spray marker, non-sea-salt calcium as crustal marker and methanesulfonic acid as biogenic marker, a detailed source apportionment for sulfate was carried out. The anthropogenic input (calculated as the differences between total sulfate and the sum of sea-salt, crustal and biogenic contributes) was found to be the most relevant contribution to the sulfate budget in the Ny-Ålesund aerosol in summer and, especially, in spring. In this last season, crustal, sea-salt, biogenic and anthropogenic sources accounted for 3.3, 12.0, 11.5 and 74.8 %, respectively.

The object of this study was to investigate the different modal behavior of ultrafine aerosol particles collected at the Gruvebadet observatory located in Ny-lesund (Svalbard Islands, 78A degrees 55'N, 11A degrees 56'E). Aerosol particle size distribution was measured in the size range from 10 to 470 nm typically from the beginning of spring to the beginning of fall during four (non-consecutive) years (2010, 2011, 2013 and 2014). The median concentration for the whole period taken into account was 214 particles cm(-3), oscillating between the median maximum in July with a concentration of 257 particles cm(-3) and a median minimum in April with 197 particles cm(-3). The median total number concentration did not present a well-defined seasonal behavior, as shown by contrast looking at the sub/modal number concentration, where distinct trends appeared in the predominant accumulation concentration recorded during April/May and the preponderant concentration of Aitken particles during the summer months. Lastly, the short side-by-side spring 2013 campaign performed at the Zeppelin observatory with a differential mobility particle sizer was characterized by an aerosol concentration mean steady difference between the two instruments of around 14 %, thereby supporting the reliability of the device located at Gruvebadet.

A novel airborne gondola was developed to profile the Arctic boundary layer exploiting a tethered balloon system. A number of aerosol instrumentations were customized and deployed in the gondola for two test campaigns conducted in Ny-Ålesund in September 2014 and April–May 2015. The performances of the instrumental setup have been characterized and will be described in the present paper. An illustration of the main results and a discussion of the main phenomenology will be also presented. Briefly, the tethered balloon systems demonstrates the capability of successfully lifting up to 15 kg of scientific payload, featuring a power autonomy of about 3 h of continuous measurements with one battery. We demonstrate for the first time on a tethered balloon the capability of measuring at the same time aerosol light scattering, absorption coefficients and size distribution, which is very promising for deducing the aerosol optical properties as a function of height along the probed atmospheric column.

The Amundsen-Nobile Climate Change Tower (CCT) is one of the important scientific platforms operating in Ny-Alesund, Svalbard. The CCT is equipped with a consistent set of meteorological sensors installed at different heights to provide continuous measurements of the atmospheric parameters that affect the climate and its variability. In this paper, some features of the main meteorological parameters observed during the 6 years of measurements since November 2009 are presented in order to describe the thermodynamic characteristic of the lower layers of the atmosphere and the peculiarities of CCT. Monthly and seasonal behavior of temperature, humidity and wind as well as radiation budget and albedo variability are also shown. Such preliminary statistical description aims to provide an overview of the phenomenology occurring in the Kongsfjord area, useful to proceed with further analysis of the arctic climatic system. Even if the time series are not long enough to consider the parameters variability on a climatological time scale, useful assumptions can be made for detailed analysis concerning turbulence studies, data intercomparison at different time and space scales, validation of theory and numerical model results. CCT dataset is stored in a dedicated built-in digital infrastructure that allows other users, in the frame of international cooperations, to visualize, access and download the data and contribute to strengthen the collaboration within the scientific community operating in Svalbard.

The unique data set collected at the climate change tower (CCT) installed in the Arctic site of Ny-Alesund, Svalbard, allows to investigate the peculiar features of the high-latitude planetary boundary layer under different stability conditions. The analysis uses four conventional Young anemometers and Vaisala thermo-hygrometers, alternated by three lined up sonic anemometers, installed on the CCT between 2 and 33.4 m a.g.l. The data are averaged over 10 min. The results presented here highlight the problematic behavior of the vertical mixing in quasi-neutral, low-wind conditions and the properties of the similarity scaling in unstable conditions, coupled with the evaluation of the scaled second-order moments of velocity and temperature. As far as stable cases are considered, the vertical profiles of the mean velocity and of the momentum and heat fluxes are shown, for high- and low-wind conditions and for traditional and upside–down cases, respectively.

The present report shortly summarises the conclusions about the ozone column and solar UV irradiance variability that were achieved through the analysis of the data obtained from the narrow-band filter radiometer UV-RAD, operating at Ny-Alesund from 2008 to 2014. The polar summer gives the opportunity to register the solar irradiance 24 h per day during several months that provides comparatively long continuous time series as regards for the short- (diurnal) and medium-term (monthly) variations. To exclude the hypothesis about the artificial nature of the large amplitudes registered in the short-term ozone column variations, which can be due to the measurement or methodological errors, they were related to the corresponding variations in the solar UV radiation. In addition, these oscillations were studied using the methods developed for the analysis of non-linear dynamical systems that revealed a complex chaotic interaction between the ozone column and five other atmospheric factors. This approach leads to the conclusion that the short-term variations can be predicted for 10–20 h if a long history is available. The effect of a sporadic phenomenon, such as the ozone depletion event, occurred over Arctic in the spring of 2011, which can be considered an impulse perturbation of the medium-term ozone variations, on the mid-latitude ozone column and surface solar UV irradiance has been studied by analysing the data collected from six surface stations.

Multitudes of measurements are needed to understand the environment and its evolution. The Arctic region is a fundamental observation area for climate change evaluation: climate change comes first and comes faster in the arctic. The higher accuracy required to quickly capture trends; the extreme range and conditions of sensors exposure; a robust comparability asked by the different measurement networks; the need of dedicated calibration procedures, together with the logistical problems associated with such remote location, motivate the proposal for a joint effort to address metrology experience and activities for Arctic research applications. The Ny-Alesund international research base and community offers a unique infrastructure to directly link metrological traceability to on site polar measurements. The contribution reports a study on the implementation of specific calibration procedures, metrological validation of measurements and instrument tests, uncertainties evaluations including quantities of influence, and the feasibility of a metrology laboratory in Ny-Alesund.

As stated by GCOS "Long-term, high-quality and uninterrupted observations of the atmosphere, land and ocean are vital for all countries, as their economies and societies become increasingly affected by climate variability and change". High-quality observation is possible only if based on a sustained traceability to SI and with documented uncertainties associated to the measured values. Following the signature of the MRA by the WMO , in April 2010, the CCT of the CIPM , in its XXV meeting of May 2010 submitted a recommendation to CIPM. The document highlighted the need to encourage National Metrology Institutes (NMIs) [...] to face new perspectives, needs, projects and activities related to the traceability, quality assurance, calibration procedures and definitions for those quantities involved in climate studies and meteorological observations and to support a strong cooperation between NMIs and Meteorological Institutions at local, national and international levels. In response to this call, several Joint Research Projects (JRPs) in metrology have been established. Their objective is to improve calibration procedures and measurement techniques for some Essential Climate Variables (ECVs), focussing especially on temperature, pressure and water vapour. Additional objectives have included investigations of sensor characteristics and the improvement of measurement devices and their use in the field. The impact effort is demonstrated also by the involvement of key international scientific Institutions such as GRUAN ,ISTI , IAPWS , and prominent Manufacturers and Universities. The overall aim is to make a further step towards establishing full data comparability, consistency and long-term continuity, through a comprehensive evaluation of the measurement uncertainties for the quantities involved in the global climate observations. The improvement of quality of ECVs records, through the inclusion of measurement uncertainty budgets, will also highlight possible strategies for the reduction of the uncertainty. This contribution will report on JRPs advances, events and task group activities, with the vision to establish a permanent bridge between metrologists and climatologists, through which to strengthen and develop collaborations, joint activities/projects and results dissemination to the whole society.

The reactivity of alkylidene malonamides as Michael receptors in the conjugate addition of N,O - bis(trimethylsilyl)hydroxylamine has been explored . Due to the presence of several different functionalities that may be selectively transformed, the products of the conjugate addition represent versatile intermediates for the synthesis of isoxazolidinones, aziridines, oxazolines or highly functionalized β-amino-amide derivatives. These novel molecules possessing unusual backbones may be exploited as scaffolds in the preparation of bioactive molecules.

Isoxazoline-containing peptidomimetics, designed to be effective α(v)β(3) and α(5)β(1) integrin ligands, were synthesized through an original procedure involving N,O-bis(trimethylsilyl)hydroxyamine conjugate addition to alkylidene acetoacetates, followed by intramolecular hemiketalization. To mimic the RGD recognition sequence, basic and acidic terminal appendages were introduced, and the final products were tested in cell adhesion inhibition assays. All the synthesized compounds proved to be excellent ligands for both integrin receptors, and a strong influence on intracellular signaling and phosphorylation pathways was demonstrated by evaluation of fibronectin-induced phosphorylation of ERK. The molecular basis of the observed inhibitory activity was suggested on the results of docking experiments.

In order to characterise the local low-level circulation in the Tyrrhenian Sea coastal area near Rome, the wind field observed by conventional anemometers, Doppler sodar, and rawinsonde has been analysed. The prevailing diurnal behaviour of wind speed and direction as a function of season was highlighted, and the existence of two different patterns of the local c, mainly due to land and sea breezes and to the drainage flow from the mouth of the Tiber valley, revealed. The comparison between the low-level circulation and synoptic flow allowed us to determine the influence of the large-scale flow on nocturnal currents that are observed at the Pratica di Mare site and the way that wind direction evolves during the day. Numerical simulations are consistent with experimental data and depict the main features of the low-level wind field in the area. © 2011 Springer Science+Business Media B.V.

In this work we describe a new modular Multi-Tone Sodar system (PC-MTSodar) able to drive up to four antennas radiating acoustic bursts simultaneously, each at a different frequency, and based on and entirely controlled by a Personal Computer (PC). The system uses two synchronised commercial I/O cards and a specifically developed software to handle all system functi ons. It has capabilities of on-line processing of data, has a minimum of dedicated electronics and is sufficien tly versatile to be used as a sodar or a minisodar. A decreasing of maintenance and of spurious electronic problems is expected with the reduction of electronics, especially when the system is used in adverse environment. As a test of the system, working at high frequency in a minisodar configuration, a comparison of measured average vertical wind velocity and of its standard deviation σw with the results obtained with another minisodar (Remtech PA1) and with two ultrasonic anemometers has been performed. The and σw are parameters useful in pollution dispersion studies and in the analysis of boundary-layer properties. For example, σw can be used for an indirect estimation of turbulent heat and momentum fluxes and mixing- layer depth if the shear production of turbulent kinetic energy may be considered negligible. Our results indicate that the performances of the two sodar systems in measuring vertical wind are different and the results of the PC-MTSodar are in a better agreement with the ones of the ultrasonic anemometers. In particular there is only a fair agreement between measurements of with the PC-MTSodar system and the ultrasonic anemometers. Both instruments however put in evidence the same long-time average pattern with a predominance of negative during diurnal periods. Measurements of σw show an overestimation in nocturnal low turbulence conditions, due to system errors when vertical velocity fluctuations are too low, and a small u nderestimation of σw during diurnal convective conditions due to the incomplete coverage of the energy spectrum of turbulence. Our results indicate that there is a high correlation between σw measurements with the PC-MTSodar and the ultrasonic anemometers (Pearson coefficient 0.97) with a good agreement between the measurements of the two instruments for σw greater than 0.2 m/s. Zusammenfassung Ein neues modulares Multiton-Sodarsystem (PC-MTSodar), das in der Lage ist, bis zu vier Antennen gleichzeitig zu betreiben, wobei jede bei einer anderen Frequenz arbeiten kann, und welches vollstandig durch einen Personal Computer (PC) gesteuert wird, wird hier beschrieben. Das System nutzt zwei synchronisierte kommerziell verfugbare I/O-Karten und eine speziell entwickelte Software um alle Systemfunktionen zu kontrollieren. Es bietet die Moglichkeit der online-Datenverarbeitung, hat ein Minimum an zugehoriger Elektronik und kann sowohl als Sodar als auch als Minisodar betrieben werden. Es wird erwartet, dass auf Grund der reduzierten Elektronik der Wartungsaufwand und storende Elektronikprobleme gerade in ungunstigen Messumgebungen abnehmen. Zum Test wurde das System als Minisodar mit hoher Schallfrequenz betrieben und ein Vergleich der gemessenen mittleren Vertikalgeschwindigkeit und ihrer Standardabweichung σw mit den Werten von einem anderen Minisodar (Remtech PA1) und zwei Ultraschallanemometern durchgefuhrt. Diese beiden Parameter sind wichtig fur die Schadstoffausbreitung und die Analyse der Eigenschaften der atmospharischen Grenzschicht. Beispielsweise kann σw bei der indirekten Abschatzung der turbulenten Warme- und Impulsflusse und der Mischungsschichthohe benut zt werden, solange die Erzeugung von turbulenter kinetischer Energie durch Scherung vernachlassigt werden kann. Unsere Ergebnisse zeigen, dass das Verhalten der beiden Sodarsysteme bei der Messung des Vertikalwindes unterschiedlich ist, und dass die mit PC-MTSodar erhaltenen Ergebnisse besser mit denen von den Ultraschallanemometern ubereinstimmen. Insbesondere findet sich eine ausreichende Uberei nstimmung bei der Bestimmung der mittleren Vertikalgeschwindigkeit nur zwischen dem PC-MTSodar-System und den Ultraschallanemometern. Beide Instrumente zeigen jedoch im langeren Mittel das gleiche Muster mit einem Uberwiegen negativer wahrend des Tagesganges. Die Messungen von σw zeigen eine Uberschatzung der nachtlichen niedrigen Turbulenz und eine kleine Unterschatzung von σw tagsuber bei konvektiven Bedingungen. Das ist einerseits auf Systemfehler bei kleinen Geschwindigkeitsfluktuationen, andererseits auf eine unzureichende Erfassung des gesamten Turbulenzspektrums zuruckzufuhren. Die Ergebnisse weisen eine hohe Korrelation zwischen den W-Messungen vom PC-MTSodar und den Ultraschallanemometern auf (Pearson-Koeffizient 0,97) mit einer guten Ubereinstimmung zwischen den Messungen beider Instrumente fur σw -Werte groser als 0,2 m/s.

A significant improvement in the treatment of trypanosomiases has been achieved with the recent development of nifurtimox-eflornithine combination therapy (NECT). As an alternative to drug combinations and as a means to overcome most of the antitrypanosomatid drug discovery challenges, a multitarget drug design strategy has been envisaged. To begin testing this hypothesis, we designed and developed a series of quinone-coumarin hybrids against glyceraldehyde-3-phosphate dehydrogenase/trypanothione reductase (GAPDH/TR). These enzymes belong to metabolic pathways that are vital to Trypanosoma brucei and Trypanosoma cruzi, and have thus been considered promising drug targets. The synthesized molecules were characterized for their dual-target antitrypanosomal profile, both in enzyme assays and in in vitro parasite cultures. The merged derivative 2-{[3-(3-dimethylaminopropoxy)-2-oxo-2H-chromen-7-yl]oxy}anthracene-1,4-dione (10) showed an IC50 value of 5.4 μM against TbGAPDH and a concomitant Ki value of 2.32 μM against TcTR. Notably, 2-{4-[6-(2-dimethylaminoethoxy)-2-oxo-2H-chromen-3-yl]phenoxy}anthracene-1,4-dione (compound 6) displayed a remarkable EC50 value for T.brucei parasites (0.026 μM) combined with a very low cytotoxicity toward mammalian L6 cells (7.95 μM). This promising low toxicity of compound 6 might be at least partially due to the fact that it does not interfere with human glutathione reductase.

The synthesis of products (IV), (VI) and (VIII), which are obtained as a 60:40 mixture of diastereomers, is accompanied by the formation of significant amounts of bis-indolated product and non-reacted starting material.

A novel class of dehydro-β-proline-containing peptidomimetics, designed to be effective as α4β1 integrin ligands, has been developed on the basis of the fundamental requirements for the interactions of these transmembrane receptors with bioactive ligands. Dehydro-β-proline ring has been synthesized through an original pathway, involving ring closing metathesis of a diallylamino derivative. The synthesized products showed to be effective and selective as α4β1 integrin antagonists and displayed IC50 values in the nanomolar range in cell adhesion inhibition assays and in VCAM-1-induced phosphorylation of extracellular-signal-regulated kinases. Significant activity was observed also toward the homologous integrin α4β7, while they did not display any activity toward selected members of β1, β2, and β3 families. A strong dependence on the stereochemistry of the heterocyclic central core could be observed. The great importance of α4β1 integrin in chronic inflammatory and autoimmune diseases suggests a possible exploitation of these ligands as lead compounds for therapeutic tools development.

Size-segregated particle samples were collected in the Arctic (Ny-Ålesund, Svalbard) in April 2011 both at ground level and in the free atmosphere exploiting a tethered balloon equipped also with an optical particle counter (OPC) and meteorological sensors. Individual particle properties were investigated by scanning electron microscopy coupled with energy dispersive microanalysis (SEM-EDS). Results of the SEM-EDS were integrated with particle size and optical measurements of the aerosols properties at ground level and along the vertical profiles. Detailed analysis of two case studies reveals significant differences in composition despite the similar structure (layering) and the comparable texture (grain size distribution) of particles in the air column. Differences in the mineral chemistry of samples point at both local (plutonic/metamorphic complexes in Svalbard) and remote (basic/ultrabasic magmatic complexes in Greenland and/or Iceland) geological source regions for dust. Differences in the particle size and shape are put into relationship with the mechanism of particle formation, that is, primary (well sorted, small) or secondary (idiomorphic, fine to coarse grained) origin for chloride and sulfate crystals and transport/settling for soil (silicate, carbonate and metal oxide) particles. The influence of size, shape, and mixing state of particles on ice nucleation and radiative properties is also discussed.

Measurements of the mean and turbulent structure of the planetary boundary layer using a sodar and a sonic anemometer, and radiative measurements using a radiometer, were carried out in the summer of 1999–2000 at the Antarctic plateau station of Dome C during a two-month period. At Dome C strong ground-based inversions dominate for most of the year. However, in spite of the low surface temperatures (between −50 and −20 °C), and the surface always covered by snow and ice, a regular daytime boundary-layer evolution, similar to that observed at mid-latitudes, was observed during summertime. The mixed-layer height generally reaches 200–300 m at 1300–1400 LST in high summer (late December, early January); late in the summer (end of January to February), as the solar elevation decreases, it reduces to 100–200 m. A comparison between the mixed-layer height estimated from sodar measurements and that calculated using a mixed-layer growth model shows a rather satisfactory agreement if we assign a value of 0.01–0.02 m s−1 to the subsidence velocity at the top of the mixed layer, and a value of 0.003–0.004 K m−1 to the potential temperature gradient above the mixed layer.

Accurate measurements of vertical wind velocity w by sodar are useful for investigating dynamic phenomena in the PBL such as convection, subsidence, divergence, and vertical movements associated with local circulation. Moreover, its statistics may be used to derive some micrometeorological parameters. When very low vertical movements need to be measured the estimation accuracy of this parameter becomes crucial. A method is proposed to estimate the accuracy of the mean vertical velocity as measured by sodar. This method is used to evaluate the improvement that can be achieved if the loudspeaker transfer function is used to correct the spectra. The transfer function is obtained by averaging the spectra obtained when the sodar is passively recording the background environmental acoustic noise. Results show that the sodar system can be used to measure mean vertical velocities averaged over periods of 3 h or more with an uncertainty better than 0.05 m s−1, providing that a two-step procedure is used t...

Using a triaxial Doppler sodar the planetary boundary-layer structure and the wind flow dynamics at the Arctic site Ny-Alesund have been studied. The relationship between winds measured at Ny-Alesund and at the nearby atmospheric research station on Zeppelin mountain was investigated for the first time. While Ny-Alesund receives predominantly katabatic flow (from 120°) from the Kongsvegen glacier, the field is rotated within the lowest 500 m and arrives at Zeppelin from southerly directions.