Assessment of Trends and Uncertainties in the Atmospheric Boundary Layer Height Estimated Using Radiosounding Observations over Europe

Trends in atmospheric boundary layer height may represent an indication of climate changes. The related modified interaction between the surface and free atmosphere affects both thermodynamics variables and dilution of chemical constituents. Boundary layer is also a major player in various feedback mechanisms of interest for climate models. This paper investigates trends in the nocturnal and convective boundary layer height at mid-latitudes in Europe using radiosounding profiles from the Integrated Global Radiosounding Archive (IGRA). Atmospheric data from the European Centre for Medium-Range Weather Forecasts (ECMWF) ReAnalysis v5 (ERA5) and from the GCOS Reference Upper-Air Network (GRUAN) Lindenberg station are used as intercomparison datasets for the study of structural and parametric uncertainties in the trend analysis. Trends are calculated after the removal of the lag-1 autocorrelation term for each time series. The study confirms the large differences reported in literature between the boundary layer height estimates obtained with the two different algorithms used for IGRA and ERA5 data: ERA5 shows a density distribution with median values of 350 m and 1150 m for the night and the daytime data, respectively, while the corresponding IGRA median values are of 1150 m and 1750 m. An overall good agreement between the estimated trends is found for nighttime data, while daytime ERA5 boundary layer height estimates over Europe are characterized by a lower spatial homogeneity than IGRA. Parametric uncertainties due to missing data in both the time and space domain are also investigated: the former is not exceeding 1.5 m, while the latter are within 10 m during night and 17 m during the day. Recommendations on dataset filtering based on time series completeness are provided. Finally, the comparison between the Lindenberg data as processed at high-resolution by GRUAN and as provided to IGRA at a lower resolution, shows the significant impact of using high-resolution data in the determination of the boundary layer height, with differences from about 200 m to 450 m for both night and day, as well as a large deviation in the estimated trend

UV Raman lidar measurements of relative humidity for the characterization of cirrus cloud microphysical properties

Abstract. Raman lidar measurements performed in Potenza by the Raman lidar system BASIL in the presence of cirrus clouds are discussed. Measurements were performed on 6 September 2004 in the frame of the Italian phase of the EAQUATE Experiment. The major feature of BASIL is represented by its capability to perform high-resolution and accurate measurements of atmospheric temperature and water vapour, and consequently relative humidity, both in daytime and night-time, based on the application of the rotational and vibrational Raman lidar techniques in the UV. BASIL is also capable to provide measurements of the particle backscatter and extinction coefficient, and consequently lidar ratio (at the time of these measurements, only at one wavelength), which are fundamental to infer geometrical and microphysical properties of clouds. A case study is discussed in order to assess the capability of Raman lidars to measure humidity in presence of cirrus clouds, both below and inside the cloud. While air inside the cloud layers is observed to be always under-saturated with respect to water, both ice super-saturation and under-saturation conditions are found inside these clouds. Upper tropospheric moistening is observed below the lower cloud layer. The synergic use of the data derived from the ground based Raman Lidar and of spectral radiances measured by the NAST-I Airborne Spectrometer allows the determination of the temporal evolution of the atmospheric cooling/heating rates due to the presence of the cirrus cloud. Lidar measurements beneath the cirrus cloud layer have been interpreted using a 1-D cirrus cloud model with explicit microphysics. The 1-D simulations indicate that sedimentation-moistening has contributed significantly to the moist anomaly, but other mechanisms are also contributing. This result supports the hypothesis that the observed mid-tropospheric humidification is a real feature which is strongly influenced by the sublimation of precipitating ice crystals. Results illustrated in this study demonstrate that Raman lidars, like the one used in this study, can resolve the spatial and temporal scales required for the study of cirrus cloud microphysical processes and appear sensitive enough to reveal and quantify upper tropospheric humidification associated with cirrus cloud sublimation

How to better exploit the use of LCA analysis for Ultra High Performance Concrete (UHPC) through a constitutive law which integrates chloride and sulfate attack

Structural applications of advanced cementitious materials such as Ultra High Performance Concrete (UHPC) have been already assessed in harsh exposure conditions with presence of chlorides or sulfates. Nevertheless, the limited availability of design standards has not favoured so far a widespread use of these materials. Moreover, previous studies employed a constitutive model only partially representative of the real behavior of such materials when exposed to aggressive conditions. Therefore, this work, employing a “scenario dependent” constitutive law, estimates the serviceability limit state in correspondence of which it is needed to carry out the maintenance activities and investigates, through the Life Cycle Assessment (LCA) methodology, the ecological and economic profile of a UHPC water basin structure subjected to chloride and sulfate attack. The CML impact assessment method has been employed for the specific purpose to compare such structure to one made with ordinary reinforced concrete (ORC) using as system boundary the A1-B7 stages indicated in EN 15804

LCA assessment related to the evolution of the earthquake performance of a strategic structure

Several buildings and infrastructures, located in urban areas, are identified as strategic in the case of an earthquake event. This is the case of a water treatment plant which is currently built in Genoa, Italy, and which has been assessed for the scope of this research. Since the structure has been designed following the seismic design prescriptions, this work aims to provide a preliminary assessment of how the degradation mechanisms do affect its earthquake response. To this purpose, both chloride attack and carbonation are taken into account as main degradation mechanisms. Moreover, due to the importance of the water treatment plant, to develop a realistic Life Cycle Assessment (LCA) analysis, the earthquake resistance of the structure and its evolution over time as a function of the aforesaid degradation mechanisms, have been accounted as Serviceability Limit State to estimate the frequency of the maintenance activities needed in a timeframe of 100 years

The unresolved case of sacral chordoma: from misdiagnosis to challenging surgery and medical therapy resistance.

PURPOSE: A sacral chordoma is a rare, slow-growing, primary bone tumor, arising from embryonic notochordal remnants. Radical surgery is the only hope for cure. The aim of our present study is to analyse our experience with the challenging treatment of this rare tumor, to review current treatment modalities and to assess the outcome based on R status. METHODS: Eight patients were treated in our institution between 2001 and 2011. All patients were discussed by a multidisciplinary tumor board, and an en bloc surgical resection by posterior perineal access only or by combined anterior/posterior accesses was planned based on tumor extension. RESULTS: Seven patients underwent radical surgery, and one was treated by using local cryotherapy alone due to low performance status. Three misdiagnosed patients had primary surgery at another hospital with R1 margins. Reresection margins in our institution were R1 in two and R0 in one, and all three recurred. Four patients were primarily operated on at our institution and had en bloc surgery with R0 resection margins. One had local recurrence after 18 months. The overall morbidity rate was 86% (6/7 patients) and was mostly related to the perineal wound. Overall, 3 out of 7 resected patients were disease-free at a median follow-up of 2.9 years (range, 1.6-8.0 years). CONCLUSION: Our experience confirms the importance of early correct diagnosis and of an R0 resection for a sacral chordoma invading pelvic structures. It is a rare disease that requires a challenging multidisciplinary treatment, which should ideally be performed in a tertiary referral center

Spectrally resolved observations of atmospheric emitted radiance in the H2O rotation band

This paper presents the project Earth Cooling by Water Vapor Radiation, an observational programme, which aims at developing a database of spectrally resolved far infrared observations, in atmospheric dry conditions, in order to validate radiative transfer models and test the quality of water vapor continuum and line parameters. The project provides the very first set of far-infrared spectral downwelling radiance measurements, in dry atmospheric conditions, which are complemented with Raman Lidar-derived temperature and water vapor profiles

Broad-spectrum coronavirus 3C-like protease peptidomimetic inhibitors effectively block SARS-CoV-2 replication in cells: Design, synthesis, biological evaluation, and X-ray structure determination

Despite the approval of vaccines, monoclonal antibodies and restrictions during the pandemic, the demand for new efficacious and safe antivirals is compelling to boost the therapeutic arsenal against the COVID-19. The viral 3-chymotrypsin-like protease (3CLpro) is an essential enzyme for replication with high homology in the active site across CoVs and variants showing an almost unique specificity for Leu-Gln as P2-P1 residues, allowing the development of broad-spectrum inhibitors.The design, synthesis, biological activity, and cocrystal structural information of newly conceived peptidomimetic covalent reversible inhibitors are herein described. The inhibitors display an aldehyde warhead, a Gln mimetic at P1 and modified P2-P3 residues. Particularly, functionalized proline residues were inserted at P2 to stabilize the beta-turn like bioactive conformation, modulating the affinity. The most potent compounds displayed low/sub-nM potency against the 3CLpro of SARS-CoV-2 and MERS-CoV and inhibited viral replication of three human CoVs, i.e. SARS-CoV-2, MERS-CoV, and HCoV 229 in different cell lines. Particularly, derivative 12 exhibited nM-low mu M antiviral activity depending on the virus, and the highest selectivity index. Some compounds were co-crystallized with SARS-CoV-2 3CLpro validating our design. Altogether, these results foster future work toward broad-spectrum 3CLpro inhibitors to challenge CoVs related pandemics

Improved Selective Class i HDAC and Novel Selective HDAC3 Inhibitors: Beyond Hydroxamic Acids and Benzamides

The application of class I HDAC inhibitors as cancer therapies is well established, but more recently their development for nononcological indications has increased. We report here on the generation of improved class I selective human HDAC inhibitors based on an ethylketone zinc binding group (ZBG) in place of the hydroxamic acid that features the majority of HDAC inhibitors. We also describe a novel set of HDAC3 isoform selective inhibitors that show stronger potency and selectivity than the most commonly used HDAC3 selective tool compound RGFP966. These compounds are again based on an alternative ZBG with respect to the ortho-anilide that is featured in HDAC3 selective compounds reported to date

Biodegradative mechanism of the brown rot basidiomycete Gloeophyllum trabeum: evidence for an extracellular hydroquinone-driven fenton reaction

AbstractWe have identified key components of the extracellular oxidative system that the brown rot fungus Gloeophyllum trabeum uses to degrade a recalcitrant polymer, polyethylene glycol, via hydrogen abstraction reactions. G. trabeum produced an extracellular metabolite, 2,5-dimethoxy-1,4-benzoquinone, and reduced it to 2,5-dimethoxyhydroquinone. In the presence of 2,5-dimethoxy-1,4-benzoquinone, the fungus also reduced extracellular Fe3+ to Fe2+ and produced extracellular H2O2. Fe3+ reduction and H2O2 formation both resulted from a direct, non-enzymatic reaction between 2,5-dimethoxyhydroquinone and Fe3+. polyethylene glycol depolymerization by G. trabeum required both 2,5-dimethoxy-1,4-benzoquinone and Fe3+ and was completely inhibited by catalase. These results provide evidence that G. trabeum uses a hydroquinone-driven Fenton reaction to cleave polyethylene glycol. We propose that similar reactions account for the ability of G. trabeum to attack lignocellulose

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented. Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy. Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027). Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation