Endothelial Glycocalyx as a Regulator of Fibrotic Processes

The endothelial glycocalyx, the gel layer covering the endothelium, is composed of glycosaminoglycans, proteoglycans, and adsorbed plasma proteins. This structure modulates vessels’ mechanotransduction, vascular permeability, and leukocyte adhesion. Thus, it regulates several physiological and pathological events. In the present review, we described the mechanisms that disturb glycocalyx stability such as reactive oxygen species, matrix metalloproteinases, and heparanase. We then focused our attention on the role of glycocalyx degradation in the induction of profibrotic events and on the possible pharmacological strategies to preserve this delicate structure.     

AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations

Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials.     

Efficient geometrical parametrization for finite-volume-based reduced order methods

In this work, we present an approach for the efficient treatment of parametrized geometries in the context of proper orthogonal decomposition (POD)-Galerkin reduced order methods based on finite-volume full order approximations. On the contrary to what is normally done in the framework of finite-element reduced order methods, different geometries are not mapped to a common reference domain: the method relies on basis functions defined on an average deformed configuration and makes use of the discrete empirical interpolation method to handle together nonaffinity of the parametrization and nonlinearities. In the first numerical example, different mesh motion strategies, based on a Laplacian smoothing technique and on a radial basis function approach, are analyzed and compared on a heat transfer problem. Particular attention is devoted to the role of the nonorthogonal correction. In the second numerical example, the methodology is tested on a geometrically parametrized incompressible Navier-Stokes problem. In this case, the reduced order model is constructed following the same segregated approach used at the full order level.     

Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation

HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents.     

Hybrid Organic/Inorganic Nanostructures for Highly Sensitive Photoelectrochemical Detection of Dissolved Oxygen in Aqueous Media

Precise, reliable, and remote measurement of dissolved oxygen in aqueous media is of great importance for many industrial, environmental, and biological applications. In particular, photoelectrochemical sensors working in differential mode have recently demonstrated promising properties, in terms of stability, sensitivity, and application potential. Here, a new approach is presented, combining visible light sensitivity, efficient photocurrent generation, and solution‐processed fabrication methods of conjugated polymers, with charge carriers selectivity, energetic alignment favorable to efficient interfacial charge transfer and high surface area achievable by using metal oxide nanostructures. Extensive characterization and optimization of the hybrid organic/inorganic system are carried out, leading to the realization of an oxygen sensor device, based on nanostructured palladium oxide/poly[(9,9‐dioctylfluorenyl‐2,7‐diyl)‐alt‐5,5‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole]/[6,6]phenyl‐C61‐butyric acid methyl ester (PdO/APFO‐3:PCBM) as materials of choice. State‐of‐the‐art sensitivity, amounting at ?5.87 μA cm^?2 ppm^?1, low background signal, in the order of ?4.85 μA cm^?2, good electrochemical stability for more than 2 h of continuous functioning and high reproducibility of the signal over the pH 1 to 10 range, are reported, making the hybrid device suitable for several practical uses. The results fully validate the mixed organic/inorganic approach for photoelectrochemical applications, and pave the way for its further exploitation in fields like waste water treatment, environmental monitoring, and water splitting.     

Mode I fracture toughness of the thermally pretreated red Verona marble by means of the two‐parameter model

The paper aims to analyse the effects of pretreatment thermal cycles on both mechanical and fracture parameters of the red Verona marble, which is a natural stone of sedimentary formation. The effects of the thermal pretreatment, consisting of freeze/thaw cycles and simulating the atmospheric ageing on the material, are evaluated in terms of changes of the aforementioned parameters. Note that a wide variety of both specimen types and methods to determine mode I plain strain fracture toughness of rocks are available in the literature. The two‐parameter model originally proposed for plain concrete is herein adopted. Such a method, based on the experimental data obtained from three‐point bending tests on single edge‐notched specimens, is able to take into account the slow nonlinear crack growth occurring before the peak load, typical of quasibrittle materials, and presents the advantages of easy specimens preparation and simple test configuration.     

Simulating Future Groundwater Recharge in Coastal and Inland Catchments

Groundwater is a primary source of drinking water in the Mediterranean, however, climate variability in conjunction with mismanagement renders it vulnerable to depletion. Spatiotemporal studies of groundwater recharge are the basis to develop strategies against this phenomenon. In this study, groundwater recharge was spatiotemporally quantified using the Soil and Water Assessment Tool (SWAT) in one coastal and one inland hydrological basin in Greece. A double calibration/validation (CV) procedure using streamflow data and MODIS ET was conducted for the inland basin of Mouriki, whereas only ET values were used in the coastal basin of Anthemountas. Calibration and simulation recharge were accurate in both sites according to statistical indicators and previous studies. In Mouriki basin, mean recharge and runoff were estimated as 16% and 9%, respectively. In Anthemountas basin recharge to the shallow aquifer and surface runoff were estimated as 12% and 16%, respectively. According to the predicted RCP 4.5 and 8.5 scenarios, significant variations in groundwater recharge are predicted in the coastal zone for the period 2020–2040 with average annual recharges decreasing by 30% (RCP 4.5) and 25% (RCP 8.5). Variations in groundwater recharge in the inland catchment of Mouriki were insignificant for the simulated period. Anthemountas basin was characterized by higher runoff rates. Groundwater management in coastal aquifers should include detailed monitoring of hydrological parameters, reinforced groundwater recharge during winter and reduced groundwater abstraction during summer depending on the spatiotemporal distribution of groundwater recharge.

     

Optical and electrical characterization of carbon nanoparticles produced in laminar premixed flames

Optical and electrical properties of carbonaceous particles produced in laboratory scale, premixed ethylene/air flames are obtained. Light absorption and Raman spectroscopy show that the change in particle nanostructure follows a graphitization trajectory as the flame richness increases. The optical band gap decreases and the size of the aromatic network in the particle increases, while the interlayer spacing between parallel layers decreases. The electrical conductivity of the materials increases by increasing flame richness in agreement to the graphitization trajectory. A non-ohmic behavior has been found and explained in terms of electron tunneling in a percolative network. Our results show that the electrical properties of flame formed carbon nanoparticles are strongly dependent on their nanostructure, and hence they have to be used carefully for the determination of particle concentration with conductometric sensors. Moreover, the dependence of the electrical properties of combustion formed particles might be useful for the development of cheap sensors for the selective detection of different classes of combustion aerosols.