Il boom del Distretto del Prosecco: immagine dell'utilit\ue0 dell'inutile tra austerit\ue0 e ripresa

The industrial districts have given rise to a variety of biocultural paths, but in the post-industrial era these are continuously threatened by the trend towards product standardisation. Despite this, local districts are able to survive, albeit in a weakened state, with two possible effects: A) the risk of fading; B) the desirability of resilience. The Biocultural fingerprint of the Prosecco District (placed 3rd in the Intesa San Paolo ranking of Italian districts for 2008-2011) reveals that its clusters of municipalities are characterised by agricultural and eno-gastronomic excellence in both rural and urban contexts. Meanwhile, its tourist attractiveness index, owing to its lack of apparently "useless components" such as nature parks and protected areas, and cultural heritage, is relatively low. It follows that the marketing-image strategies devised for immediate profit appear to be insufficient at coping with the competition and ensuring a sustained level of development in the long term

Platelet Activation in Ovarian Cancer Ascites: Assessment of GPIIb/IIIa and PF4 in Small Extracellular Vesicles by Nano-Flow Cytometry Analysis

In ovarian cancer, ascites represent the microenvironment in which the platelets extravasate to play their role in the disease progression. We aimed to develop an assay to measure ascites’ platelet activation. We enriched small extracellular vesicles (EVs) (40–200 nm) from ascites of high-grade epithelial ovarian cancer patients (n = 12) using precipitation with polyethylene glycol, and we conducted single-particle phenotyping analysis by nano-flow cytometry after labelling and ultra-centrifugation. Atomic force microscopy single-particle nanomechanical analysis showed heterogeneous distributions in the size of the precipitated particles and their mechanical stiffness. Samples were fluorescently labelled with antibodies specific to the platelet markers GPIIb/IIIa and PF4, showing 2.6 to 18.16% of all particles stained positive for the biomarkers and, simultaneously, the EV membrane labelling. Single-particle phenotyping analysis allowed us to quantify the total number of non-EV particles, the number of small-EVs and the number of platelet-derived small-EVs, providing a platelet activation assessment independent of the ascites volume. The percentage of platelet-derived small-EVs was positively correlated with platelet distribution width to platelet count in sera (PDW/PLT). Overall, we presented a high-throughput method that can be helpful in future studies to determine the correlation between the extent of platelet activation in ascites and disease status

Plasma-Based Longitudinal Evaluation of ESR1 Epigenetic Status in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer

Background: Endocrine therapy (ET) is the mainstay of treatment for hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer; however, adaptive mechanisms emerge in about 25\u201330% of cases through alterations in the estrogen receptor ligand-binding domain, with a consequent ligand-independent estrogen receptor activity. Epigenetic-mediated events are less known and potentially involved in alternative mechanisms of resistance. The aim of this study was to test the feasibility of estrogen receptor 1 (ESR1) epigenetic characterization through liquid biopsy and to show its potential longitudinal application for an early ET sensitivity assessment. Methods: A cohort of 49 women with hormone receptor-positive HER2-negative MBC was prospectively enrolled and characterized through circulating tumor DNA using methylation-specific droplet digital PCR (MS-ddPCR) before treatment start (BL) and after 3 months concomitantly with computed tomography (CT) scan restaging (EV1). ESR1 epigenetic status was defined by assessing the methylation of its main promoters (promA and promB). The most established cell-free tumor DNA (ctDNA) factors associated with ET resistance [ESR1 and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations] were assessed through next-generation sequencing. Associations were tested through Mann\u2013Whitney U test, matched pairs variations through Wilcoxon signed rank test, and survival was analyzed by log-rank test. Results: The ET backbone was mainly based on aromatase inhibitors (AIs) (70.83%) in association with CDK4/6 inhibitors (93.75%). Significantly lower promA levels at baseline were observed in patients with liver metastases (P = 0.0212) and in patients with ESR1 mutations (P = 0.0091). No significant impact on PFS was observed for promA (P = 0.3777) and promB (P = 0.7455) dichotomized at the median while a 652-fold increase in promB or in either promA or promB at EV1 resulted in a significantly worse prognosis (respectively P = 0.0189, P = 0.0294). A significant increase at EV1 was observed for promB among patients with PIK3CA mutation (P = 0.0173). A trend was observed for promB in ESR1 wild-type patients and for promA in the ESR1 mutant subgroup. Conclusion: The study proofed the concept of an epigenetic characterization strategy based on ctDNA and is capable of being integrated in the current clinical workflow to give useful insights on treatment sensitivity

Integrated quantitative PIXE analysis and EDX spectroscopy using a laser-driven particle source

Among the existing elemental characterization techniques, Particle Induced X-ray Emission (PIXE) and Energy Dispersive X-ray (EDX) spectroscopy are two of the most widely used in different scientific and technological fields. Here we present the first quantitative laser-driven PIXE and laser-driven EDX experimental investigation performed at the Centro de L\'aseres Pulsados in Salamanca. Thanks to their potential for compactness and portability, laser-driven particle sources are very appealing for materials science applications, especially for materials analysis techniques. We demonstrate the possibility to exploit the X-ray signal produced by the co-irradiation with both electrons and protons to identify the elements in the sample. We show that, using the proton beam only, we can successfully obtain quantitative information about the sample structure through laser-driven PIXE analysis. These results pave the way towards the development of a compact and multi-functional apparatus for the elemental analysis of materials based on a laser-driven particle source.Comment: This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ENSURE grant agreement No. 647554). Submitted to Science Advances on 20th May 2

Monocyte-to-lymphocye ratio (MLR) and LDH level in metastatic colorectal cancer (mCRC) patients (pts)

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Geometries of Light and Shadows, from Piero della Francesca to James Turrell

This chapter addresses the problem of representing light and shadow in the artistic culture, from its uncertain beginnings, related to the studies on conical linear perspective in the Fifteenth Century, to the applications of light projection in the installations of contemporary art. Here are examined in particular two works by two artists, representing two different conceptual approaches to the perception and symbolism of light and shadow. The first is the so-called Brera Madonna by Piero della Francesca, where the image projected from a luminous radiation is employed with a narrative purpose, supporting the apparently hidden script of the painting and according to the artist\u2019s own speculations about perspective as a means to clarify the phenomenal world. The second is one of James Turrell\u2019s Dark Spaces installations, where quantum electrodynamics interpretation of light is taken into account: for Turrell, light is physical and thus can shape spaces where the visitors, or viewers, can \u201csee themselves seeing.\u201d In his body of work, perceptual deceptions are carefullyproduced by the interaction of the senses with his phenomenal staging of light and darkness, but a strong symbolic component is always present, often related to his own speculative interests. In both cases, light and shadow, through their geometries, emphasize both phenomenal and spiritual contents of the work of art, intended as a device to expand the perception and the knowledge of the viewer

Mutations in the Mitochondrial Methionyl-tRNA Synthetase Cause a Neurodegenerative Phenotype in Flies and a Recessive Ataxia (ARSAL) in Humans

The study of Drosophila neurodegenerative mutants combined with genetic and biochemical analyses lead to the identification of multiple complex mutations in 60 patients with a novel form of ataxia/leukoencephalopathy