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

Posterior Auricular Perichondrial Cutaneous Graft Combined With Cartilage Strip in Nostril Reconstruction

Objective: Reconstruction of alar structures of the nose remains difficult. The result has to be not only functional but also aesthetic. Different solutions to reconstruct alar defects are feasible. A good result that meets the specific demands on stability, aesthetics, and stable architecture without shrinkage of the area is not easily achieved. Method: A perichondrial cutaneous graft (PCCG), a graft consisting of a perichondral layer, fatty tissue, and skin that is harvested retroauriculary, is combined with an attached cartilage strip. Case Result: A 72-year-old patient suffering from basal cell carcinoma of the ala of the nose underwent the reconstructive procedure with a good result in 1 year in terms of stability, color match, and graft take. Conclusion: First, a strip of cartilage had been included in a PCCG where tumor resection required sacrifice of more than 50% of the alar rim. The case shows that one can consider a cartilage strip–enhanced PCCG graft to reconstruct alar defects

Muscle-only versus chimeric musculocutaneous gastrocnemius pedicled flap in complex orthoplastic reconstructions of the knee region: A retrospective study

Background: The knee region represents a challenging area of soft tissue reconstruction. Specifically, in the context of total knee arthroplasty (TKA) or following high-energy trauma with fractures and hardware fixation, soft tissue defects can expose critical structures such as joint, bone or tendon, besides the implant/plates themselves, with dramatic consequences in terms of postoperative infection and hardware contamination. Methods: A retrospective study was conducted on a prospectively maintained database from January 2016 to February 2021. Inclusion criteria involved all patients who underwent an implant-associated infection of the knee and upper third of the leg coupled with a soft tissue reconstruction (STR) using the traditional gastrocnemius muscle (GM) pedicled flap or the chimeric GM-MSAP (medial sural artery perforator) flap. Results: Thirty-eight patients were included (group A, GM flap, 22 patients; group B, chimeric GM-MSAP flap, 16 patients). No statistically significant differences were detected in terms of age, comorbidities, defect size, follow-up, and flap complications. A statistically significant difference was seen among the groups in terms of successful flap re-raise (required because of a persistent infection of the implant or in a two-stage procedure setting, including the use of a cemented spacer) in favour of the GM-MSAP group. Conclusion: The chimeric GM-MSAP, being safer to reraise if required, can be a significantly more powerful tool in those cases in which a two-stage procedure is planned or when there is a high probability for secondary intervention need, reducing the need to convert to either free flap coverage or amputation

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

Identification of Isoform 2 Acid-Sensing Ion Channel Inhibitors as Tool Compounds for Target Validation Studies in CNS

Acid-sensing ion channels (ASICs) are a family of ion channels permeable to cations and largely responsible for the onset of acid-evoked ion currents both in neurons and in different types of cancer cells, thus representing a potential target for drug discovery. Owing to the limited attention ASIC2 has received so far, an exploratory program was initiated to identify ASIC2 inhibitors using diminazene, a known pan-ASIC inhibitor, as a chemical starting point for structural elaboration. The performed exploration enabled the identification of a novel series of ASIC2 inhibitors. In particular, compound 2u is a brain penetrant ASIC2 inhibitor endowed with an optimal pharmacokinetic profile. This compound may represent a useful tool to validate in animal models in vivo the role of ASIC2 in different neurodegenerative central nervous system pathologies

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

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

Editor's Choice - Infective Native Aortic Aneurysms: A Delphi Consensus Document on Terminology, Definition, Classification, Diagnosis, and Reporting Standards.

There is no consensus regarding the terminology, definition, classification, diagnostic criteria, and algorithm, or reporting standards for the disease of infective native aortic aneurysm (INAA), previously known as mycotic aneurysm. The aim of this study was to establish this by performing a consensus study. The Delphi methodology was used. Thirty-seven international experts were invited via mail to participate. Four two week Delphi rounds were performed, using an online questionnaire, initially with 22 statements and nine reporting items. The panellists rated the statements on a five point Likert scale. Comments on statements were analysed, statements revised, and results presented in iterative rounds. Consensus was defined as ≥ 75% of the panel selecting "strongly agree" or "agree" on the Likert scale, and consensus on the final assessment was defined as Cronbach's alpha coefficient > .80. All 38 panellists completed all four rounds, resulting in 100% participation and agreement that this study was necessary, and the term INAA was agreed to be optimal. Three more statements were added based on the results and comments of the panel, resulting in a final 25 statements and nine reporting items. All 25 statements reached an agreement of ≥ 87%, and all nine reporting items reached an agreement of 100%. The Cronbach's alpha increased for each consecutive round (round 1 = .84, round 2 = .87, round 3 = .90, and round 4 = .92). Thus, consensus was reached for all statements and reporting items. This Delphi study established the first consensus document on INAA regarding terminology, definition, classification, diagnostic criteria, and algorithm, as well as reporting standards. The results of this study create essential conditions for scientific research on this disease. The presented consensus will need future amendments in accordance with newly acquired knowledge

Centrality and transverse momentum dependence of elliptic flow of multi-strange hadrons and ϕ\phi meson in Au+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

We present high precision measurements of elliptic flow near midrapidity ($|y|<1.0$) for multi-strange hadrons and $\phi$ meson as a function of centrality and transverse momentum in Au+Au collisions at center of mass energy $\sqrt{s_{NN}}=$ 200 GeV. We observe that the transverse momentum dependence of $\phi$ and $\Omega$ $v_{2}$ is similar to that of $\pi$ and $p$, respectively, which may indicate that the heavier strange quark flows as strongly as the lighter up and down quarks. This observation constitutes a clear piece of evidence for the development of partonic collectivity in heavy-ion collisions at the top RHIC energy. Number of constituent quark scaling is found to hold within statistical uncertainty for both 0-30$\%$ and 30-80$\%$ collision centrality. There is an indication of the breakdown of previously observed mass ordering between $\phi$ and proton $v_{2}$ at low transverse momentum in the 0-30$\%$ centrality range, possibly indicating late hadronic interactions affecting the proton $v_{2}$.Comment: 7 pages and 4 figures, Accepted for publication in Physical Review Letter