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Probenecid Suppresses Migration, invasion and angiogenesis in hepatocellular carcinoma by modulating purinergic signaling and p38 MAPK pathway
Probenecid (PBN) is a well-established therapeutic agent traditionally used to treat gout and to regulate renal excretion by inhibiting ATP-related membrane transporters. While these properties are well documented, their potential relevance in cancer biology remains largely unexplored. Given the critical role of extracellular ATP and purinergic signaling in tumor progression, we hypothesized that PBN might exert antitumor effects by interfering
with this pathway. In this study, we investigated the anticancer activity of PBN in HepG2 human hepatocellular carcinoma cells and in an orthotopic mouse model. PBN enhanced cell adhesion and reduced migration and invasion, effects associated with altered integrin expression, selective inhibition of matrix metalloproteinase (MMP) activity, modulation of epithelial–mesenchymal transition (EMT) markers and reduced activation of the
p38 MAPK pathway. In vivo, PBN suppressed tumor growth and reduced circulating vascular endothelial growth factor (VEGF) levels, indicating impaired angiogenesis.
Altogether, these findings indicate that PBN may represent a promising candidate for drug repurposing in hepatocellular carcinoma. By modulating purinergic signaling and selectively inhibiting p38 MAPK, PBN appears to limit tumor invasiveness and angiogenesis, supporting its potential relevance for further preclinical and
clinical investigation
Numerical analysis of the effect of stationary laser beam properties on Al-Si coating mixing in 22MnB5 steel
This study presents a numerical investigation of molten pool dynamics and coating material mixing under stationary laser irradiation, using a computational fluid dynamics (CFD) model to analyse contamination effects and the resulting melt pool geometry with a fixed laser beam relative to the workpiece. The model considers a 1.6 mm-thick 22MnB5 steel coated on both sides with a 30 μm-thick Al-Si coating. A grid independency analysis, performed with mesh sizes from 15 μm to 120 μm, showed that mesh sizes at least matching the Al-Si coating thickness are required for accurate representation of fluid dynamics and contamination effects in terms of average Al content and volume percentage of the fused zone contaminated by the coating material. A numerical investigation was carried out to evaluate how variations in laser beam waist radius (0.225, 0.3, and 0.375 mm) and defocusing distance (-0.8 mm, 0, and +0.8 mm) influence the melt pool geometry and the Al-Si coating contamination in 22MnB5 steel. Results indicated that, under positive defocusing conditions, a larger beam waist radius, that is the radius of the laser beam at the focal point, favoured the formation of a Y-shaped keyhole geometry and contributed to lower Al-Si contamination levels in the melt pool. Higher contamination levels were observed in the simulations with a beam waist radius of 0.225 mm, compared to the cases with 0.3 mm and 0.375 mm, indicating an inverse relationship between beam waist radius and coating contamination
Strategie di Valorizzazione del Patrimonio Proto-Industriale della Calce in Basilicata. Valorization Strategies for Basilicata’s Lime Proto-industrial Heritage.
Calchere, the traditional vertical lime kilns characteristic of Basilicata and other Italian regions, constitute a significant example of proto-industrial heritage that illustrates the historical interplay between human settlement, environmental context, and natural resource management. Despite their cultural and technological relevance, most of these structures are currently abandoned, lacking both legal protection and systematic documentation. This research develops an integrated methodological framework for their sustainable valorization, combining heritage conservation, environmental
education, and territorial development. The proposed approach draws on the case study of La Cal de Morón (Andalusia, Spain), a UNESCO-recognized model of living lime heritage, to outline strategies for the controlled reactivation of traditional kilns as functional laboratories for vocational training, material experimentation, and the production of low-impact lime-based materials. Within the broader context of circular economy principles and sustainable innovation, the study emphasizes the potential of such initiatives to generate socio-economic value, foster community participation, and reinforce local identity through the preservation and contemporary reinterpretation of material culture
Retrieval of surface and atmospheric parameters from high resolution infrared sensors
To retrieve surface and atmospheric temperature profiles, together with trace species concentrations is a fundamental challenge in numerical weather prediction and Earth monitoring. Over the last 20 years, the development of high-resolution infrared sensors on board Earth observation satellites has opened new remote sensing opportunities, providing an unprecedented source of information. However, infrared sensors cannot probe into thick cloud layers, rendering their observations insensitive to surface under cloudy conditions. This results in spatial fields flagged with missing data, disrupting the continuity of inferred information and hindering accurate modeling of energy fluxes between the surface and the atmosphere. Consequently, advanced interpolation techniques and spatial statistics are essential to process the available (very large) data sets and produce satellite products on a regular grid mesh. This paper reviews and presents the physical modeling of radiative transfer in the atmosphere and the related mathematics of inversion, tailored for high spectral-resolution infrared sensors
Nuclear analyses in support of the water-cooled lithium lead breeding blanket design development: a prospective strategy to achieve the tritium self-sufficiency
The development of a closed tritium fuel cycle is essential for the sustainable operation of future fusion power plants. Within the EUROfusion roadmap, the Water-Cooled Lithium Lead (WCLL) breeding blanket is a key candidate for the Demonstration Fusion Power Reactor (DEMO). It uses pressurized water as coolant and a liquid lithium-lead (LiPb) eutectic alloy as both breeder and neutron multiplier. The current WCLL design features modular inboard and outboard Breeding Units (BUs) composed of helical Double Wall Tubes (DWTs) immersed in LiPb. This configuration improves heat removal and reduces the water inventory in the Breeding Zone, thereby potentially increasing tritium generation. This work presents an assessment of the WCLL DEMO nuclear performances in terms of shielding effectiveness and tritium self-sufficiency, based on 3D radiation transport simulations performed using the Monte Carlo MCNP code and JEFF nuclear data libraries. A detailed MCNP model has been developed, including a fully heterogeneous representation of the Breeding Zone and first wall (FW) water channels. Radial profiles of fast and total neutron fluxes, along with nuclear heating, are evaluated at the equatorial level, providing 3D maps of these quantities as well. The total Tritium Breeding Ratio (TBR) has been evaluated, accounting for contributions from both the BZ and LiPb manifolds. To further enhance tritium generation and support the long-term viability of the WCLL concept, design modifications to the latest layout have been explored through a prospective approach. The effectiveness of these modifications has been assessed by means of parametric studies and discussed in light of their potential impact on overall reactor performance
Organic fertilizers deriving from the sustainable valorisation of agricultural and zootechnical waste biomass: evaluation of promising products, including a newly-developed hydrochar
The ongoing global ecological crisis, characterized by widespread biodiversity loss and progressive soil degradation, poses urgent challenges to find and apply practices for sustainable agriculture. In this context, the management of agro-industrial residues, including horticultural and livestock wastes, is inefficient and conducted inappropriately, thus contributing to environmental pressures and threatening the sustainability of food production systems, while it could represent a fundamental initiative for sustainable strategies. Therefore, this work proposes a circular economy-based approach, aiming to convert agro-industrial residues into environmentally sustainable fertilizers, in line with European regulations and strategies, including Directive 2008/98/EC, Regulation (EC) 2092/91, and the Green Deal’s Farm to Fork objectives, which aim to reduce reliance on mineral fertilizers while promoting resource recovery.
The research focused on the production, characterization, and agronomic evaluation of organic fertilizers derived from agricultural and livestock by-products, highlighting their potential as effective alternatives to conventional mineral amendments. All experimental activities were carried out at the University of Salerno, Department of Pharmacy, within the AgrichemLab - Laboratory of Agricultural Chemistry, where all analytical and agronomic investigations were performed. The Biogas plant C&F Energy (Capaccio, Italy) produced solid anaerobic digestate (AD) from buffalo manure and its vermicomposted form (VC), which were extensively characterized by using elemental and nutrients analysis and advanced techniques to evaluate the composition, including CPMAS-NMR, FT-IR and Pyr-GC-MS. AD contained a higher proportion of labile carbon, whereas VC exhibited a more recalcitrant and humified structure. In-vitro and greenhouse pot trials identified optimal doses at 40% (v/v) for most crops (20% for VC on lettuce) and demonstrated that both materials enhanced growth and biomass production. NMR-based metabolomics revealed marked stimulation of carbohydrate metabolism and amino acid biosynthesis, with AD and VC outperforming mineral fertilizers in modulating primary metabolism.
Green compost (COM) from red chicory, escarole, spinach, and olive pruning residues, and its pelletized form (PEL), produced by OP TerrAmore (Eboli, Italy), were investigated as additional amendments. Compost was further characterized by 13C CPMAS-NMR, FT-IR, and Pyr-GC-MS. Pot experiments showed that both COM and PEL improved plant growth, nutrient availability, and physiological performance, with pellets offering operational advantages. Combined COM+PEL applications further enhanced soil quality and crop yield, benefitting from the synergistic action of labile and stable organic fractions.
The most innovative aspect of this thesis lies in the development of hydrochars (HC) as novel bio-based fertilizers. This process is particularly advantageous, as it converts organic biomass into new materials potentially beneficial for soil and plants through hydrothermal carbonization, which involves the reaction of fresh biomass with water under subcritical conditions. The reaction was conducted with a 1-liter reactor, using the same biomass processed to obtain the COM, excepted the olive pruning residues, with two process conditions (180 °C and 10 Bar; 215 °C and 20 Bar). Both the resulting HC liquid and solid phases were isolated, characterized and tested as beneficial agents for soil and plants. In particular, structural analysis and greenhouse trials on lettuce demonstrated that HC180 significantly promoted root and shoot growth, achieving performance comparable to that of mineral fertilization. Metabolomic profiling showed increases in sugars and amino acids involved in energy production and stress response, indicating a rapid biostimulant effect driven by nutrient availability and soil–microbiome interactions. The corresponding liquid hydrochars (LHCs) were analyzed during an internship at the University of Navarra. LHC180 was rich in soluble nutrients and hormone-like molecules (auxins, cytokinins, jasmonates, salicylic acid) and markedly improved seed germination, root architecture, biomass accumulation, and nutrient-use efficiency in Lepidium sativum and Arabidopsis thaliana, while LHC215 showed limited activity. LHC180 also activated nutrient transporters, iron-homeostasis regulators, and plasma-membrane H+-ATPases, resembling the mode of action of humic substances and supporting its suitability for sustainable fertigation strategies.
Finally, alginate-based systems (hydrogels, beads and film for a seed coating) were designed to provide slow release of water, nutrients, and humic substances extracted form AD, VC and COM. These systems were characterized for structure, water retention, ion release, and degradability. Humic-loaded coatings improved germination and early growth of watercress seeds, as confirmed by SEM and in-vitro bioassays. Iron-based beads provided effective Fe release under alkaline conditions, offering a promising approach to improve nutrient availability in challenging soils. Overall, this work demonstrates that organic fertilizers derived from agro-industrial residues, particularly hydrochar-based amendments and alginate delivery systems, represent effective, innovative, and sustainable alternatives to mineral fertilizers and synthetic biostimulants. By combining nutrient supply, biostimulant activity, and soil quality enhancement, these materials offer concrete solutions to advance sustainable agriculture and support the transition toward a circular bioeconomy
A Preliminary Study on the Role of Orexin A in Leydig Cell Steroidogenesis and Its Implications for Fertility in Alpacas (Vicugna pacos).
In Italy, the breeding of alpacas (Vicugna pacos) is on the rise, driven by the value of their
precious wool and their docile temperament. This growth is, however, severely limited by
the species’ reproductive inefficiency. This study aimed to investigate the specific role of
the neuropeptide orexin A (OxA) and its receptor OX1R in modulating testicular steroidogenesis
in the alpaca, testing the hypothesis that the OxA/OX1R pathway stimulates
testosterone production. Using testicular tissue from two groups of adult male alpacas
(five- and seven-year-olds, n = 6 per group), we combined immunohistochemistry with ex
vivo functional assays. Immunohistochemical analysis confirmed the expression of both
OxA and OX1R in Leydig cells. Functional studies on testicular fragments demonstrated
that OxA enhanced testosterone synthesis via OX1R activation. Furthermore, OxA reduced
estradiol levels by suppressing aromatase activity and counteracted the inhibitory effect
of Müllerian inhibiting substance (MIS) on testosterone secretion. These results provide
the first evidence that the peripheral OX1R pathway is functionally involved in promoting
a testosterone-dominant steroidogenic milieu in alpaca testes. This preliminary study
identifies the orexin system as a potential target for developing strategies to improve
reproductive management in this species
critic|all _ VI International Conference on Architecture Design & Criticism _ grapho-logics
“Architecture can no longer be as we had thought-imagined-constructed it”: this is what Alessandro Poli wrote – in a never-sent letter – to Adolfo Natalini, a year after humanity took its first steps on the Moon. In the stark, silent emptiness of space, the grand ideals of earthbound architecture crumble. There are no monuments, no imposing structures – just the fragile, tin-foil-wrapped spacecraft floating in the cosmic void. Poli’s words encapsulate a fundamental shift in a new world, where the boundaries of imagination and reality blur in a single, electrifying moment: architecture is not an act of imposing permanence on the world, but a continual engagement with the unknown.
This letter, that captures a decisive transition in architectural thinking, echoes in the 1978 Venice Biennale catalogue Utopia e crisi dell'antinatura. Momenti delle intenzioni architettoniche in Italia. Topologia e morfogenesi edited by Lara Vinca Masini. The two categories emerge as a search for alternative perspectives: mental, utopian territories in which the architectural image – graphical, metaphorical or performative – become a critical tool to question form, temporality and disciplinary boundaries. Among the most striking expressions of this conceptual shift, the work of the Radical groups explore architecture not as a fixed construct, but as a process that embraces unstable conditions, contradictions and latent forces – a sensibility clearly embodied in Superstudio’s La moglie di Lot, where the act of dissolution becomes a metaphor for the impossibility of permanence in the face of transformation. Revisiting radical visions today offers tools to address a present defined not by possibility, but by limits – ecological and physical – and by the need to act critically within them, reframing the role of architecture as a practice of awareness and adaptation. This change requires what Poli described as the need of “the motion of the movie camera”, a shift in gaze that navigates uncertainty
Formazione insegnanti e tecnologie digitali per la matematica: un’esperienza con GeoGebra
Holomorphic Signals of Several Complex Variables
Following the line of thought by P. Bouboulis & S. Theodoridis, [6], we take up a program of recovering kernel methods (as employed in signal analysis and machine learning theory) from real RKHS and kernels, to the complex domain. We solve the maximum problem sup{∑j=1p|f(zj)|2:‖f‖2≤E} in the complex RKHS of holomorphic L2 functions f:Ω→C, for any bounded domain Ω⊂Cn and any finite set of points z1,⋯,zp∈Ω, and apply the result to the space L2H(Bn) of holomorphic L2 functions on the unit ball Bn⊂Cn. We produce sampling expansions of functions f∈L2H(Ω) associated to infinite sequences {ζk}k≥0⊂Ω, by starting from complete orthonormal systems {φν}ν≥0⊂L2H(Ω) and approximating each φν uniformly on Ω by a linear combination of reproducing kernels. The means to said approximation are provided by the Faber-Kaczmarz-Mycielski algorithm A(h) learning (cf. [23]) from the data {(ζk,φν(ζk))}k≥0 and producing an approximating sequence {Jkφν}k≥0⊂L2H(Ω)