Anticancer activities of anthocyanin extract from genotyped Solanum tuberosum L. "Vitelotte"

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RINTC-E: Towards seismic risk assessment of existing residential reinforced concrete buildings in Italy

The RINTC research project (RINTC Workgroup, 2018), financed by the Italian Department of Civil Protection, is aimed at evaluating the seismic risk of buildings conforming to the Italian building code. Within the framework of this project, the attention has been recently focused on existing buildings, too. In this study, case-study structures, representative of the existing residential reinforced concrete (RC) building stock in Italy, are analyzed. These structures are three-storey buildings with compact rectangular plan, and they have been defined through a simulated design process, in order to represent two types of buildings, namely designed for gravity loads only during 1970s (gravity load designed, GLD) or for moderate seismic loads during 1990s (seismic load designed, SLD). GLD buildings are assumed to be located in three different sites, namely Milan, Naples and Catania, in increasing order of seismic hazard. SLD buildings are assumed to be located in L'Aquila. The assumed design typologies are consistent with the seismic classification of the sites at the assumed ages of construction. The presence of typical nonstructural masonry infill walls (uniformly distributed in plan as external enclosure walls) is taken into account, assuming three configurations along height, namely “bare” (without infills), uniformly infilled and “pilotis” (without infills at the bottom storey) buildings. Two (not code-based) Limit States are investigated, namely Usability-Preventing Damage, corresponding to an interruption of the building use, and Collapse. RC elements are modelled with a lumped plasticity approach, through an empirical-based macromodel. The possible occurrence of shear failures in columns is taken into account through a preliminary classification of the expected failure mode (flexure- or shear-controlled, in the latter case prior to or following flexural yielding) and, if needed, a modification of the backbone of the nonlinear moment-chord rotation response, through empirical models providing the expected deformation capacity at shear and axial failure, the latter meant as the (initiation of) loss of axial-load-carrying-capacity. The nonlinear response of beam-column joints is modelled, too, with a “scissors model” based on concentrated springs representing the nonlinear response of the joint panel, at the intersection of beams' and columns' centerlines, through a preliminary evaluation of the expected failure mode (i.e. prior to or following yielding of adjacent beam/column elements). Materials properties are provided by literature studies, consistent with the age of construction of the buildings. The in-plane response of infills is modelled, taking into account the presence of openings, too. Modeling should be considered as simplified and, from some points of view, still preliminary, since advances are foreseen within the project in order to capture further failure modes that can occur in structural and nonstructural elements of older, nonductile RC buildings. Nonlinear static analyses, allowing to identify the (top) displacement capacity at the investigated Limit States, are carried out. Multiple stripe nonlinear time history bi-directional analyses of the three-dimensional structural models are carried out in order to evaluate the demand, for ten stripes - each corresponding to a return period ranging from 10 to 105 years - and for twenty couples of records for each stripe. Records were selected, within the activities of the research project, based on a Probabilistic Seismic Hazard Analysis at the sites of interest for the selected return periods. Results are illustrated, highlighting the role of a - although obsolete - seismic design in the response of the buildings and in their capacity, more specifically in terms of displacement capacity at Collapse, but also in terms of demand estimated from multiple stripe analyses. Finally, demand-to-capacity ratios at the investigated Limit States are analyzed, which allow, within the scope of the project, the assessment of the seismic risk of the case study structures

Nernst-Planck Based Description of Transport, Coulombic Interactions and Geochemical Reactions in Porous Media: Modeling Approach and Benchmark Experiments

Transport of multicomponent electrolyte solutions in saturated porous media is affected by the electrostatic interactions between charged species. Such Coulombic interactions couple the displacement of the different ions in the pore water and remarkably impact mass transfer not only under diffusion, but also under advection-dominated flow regimes. To accurately describe charge effects in flow-through systems, we propose a multidimensional modeling approach based on the Nernst-Planck formulation of diffusive/dispersive fluxes. The approach is implemented with a COMSOL-PhreeqcRM coupling allowing us to solve multicomponent ionic conservative and reactive transport problems, in domains with different dimensionality (1-D, 2-D, and 3-D), and in homogeneous and heterogeneous media. The Nernst-Planck-based coupling has been benchmarked with analytical solutions, numerical simulations with another code, and high-resolution experimental data sets. The latter include flow-through experiments that have been carried out in this study to explore the effects of electrostatic interactions in fully three-dimensional setups. The results of the simulations show excellent agreement for all the benchmarks problems, which were selected to illustrate the capabilities and the distinct features of the Nernst-Planck-based reactive transport code. The outcomes of this study illustrate the importance of Coulombic interactions during conservative and reactive transport of charged species in porous media and allow the quantification and visualization of the specific contributions to the diffusive/dispersive Nernst-Planck fluxes, including the Fickian component, the term arising from the activity coefficient gradients, and the contribution due to electromigration

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

Introduction: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated. Methods: We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy. Results: Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) > 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) >400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4–14.8) and 5.1 (3.3–6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3–4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS > 0, and AFP >400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes. Conclusions: In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials

Complete Genome Sequence of the N2-Fixing Broad Host Range Endophyte Klebsiella pneumoniae 342 and Virulence Predictions Verified in Mice

We report here the sequencing and analysis of the genome of the nitrogen-fixing endophyte, Klebsiella pneumoniae 342. Although K. pneumoniae 342 is a member of the enteric bacteria, it serves as a model for studies of endophytic, plant-bacterial associations due to its efficient colonization of plant tissues (including maize and wheat, two of the most important crops in the world), while maintaining a mutualistic relationship that encompasses supplying organic nitrogen to the host plant. Genomic analysis examined K. pneumoniae 342 for the presence of previously identified genes from other bacteria involved in colonization of, or growth in, plants. From this set, approximately one-third were identified in K. pneumoniae 342, suggesting additional factors most likely contribute to its endophytic lifestyle. Comparative genome analyses were used to provide new insights into this question. Results included the identification of metabolic pathways and other features devoted to processing plant-derived cellulosic and aromatic compounds, and a robust complement of transport genes (15.4%), one of the highest percentages in bacterial genomes sequenced. Although virulence and antibiotic resistance genes were predicted, experiments conducted using mouse models showed pathogenicity to be attenuated in this strain. Comparative genomic analyses with the presumed human pathogen K. pneumoniae MGH78578 revealed that MGH78578 apparently cannot fix nitrogen, and the distribution of genes essential to surface attachment, secretion, transport, and regulation and signaling varied between each genome, which may indicate critical divergences between the strains that influence their preferred host ranges and lifestyles (endophytic plant associations for K. pneumoniae 342 and presumably human pathogenesis for MGH78578). Little genome information is available concerning endophytic bacteria. The K. pneumoniae 342 genome will drive new research into this less-understood, but important category of bacterial-plant host relationships, which could ultimately enhance growth and nutrition of important agricultural crops and development of plant-derived products and biofuels

Structure and Ligands Interactions of <i>Citrus</i> Tryptophan Decarboxylase by Molecular Modeling and Docking Simulations

In a previous work, we in silico annotated protein sequences of Citrus genus plants as putative tryptophan decarboxylase (pTDC). Here, we investigated the structural properties of Citrus pTDCs by using the TDC sequence of Catharanthus roseus as an experimentally annotated reference to carry out comparative modeling and substrate docking analyses. The functional annotation as TDC was verified by combining 3D molecular modeling and docking simulations, evidencing the peculiarities and the structural similarities with C. roseus TDC. Docking with l-tryptophan as a ligand showed specificity of pTDC for this substrate. These combined results confirm our previous in silico annotation of the examined protein sequences of Citrus as TDC and provide support for TDC activity in this plant genus