232 research outputs found

    Calabi-Yau cones from contact reduction

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    We consider a generalization of Einstein-Sasaki manifolds, which we characterize in terms both of spinors and differential forms, that in the real analytic case corresponds to contact manifolds whose symplectic cone is Calabi-Yau. We construct solvable examples in seven dimensions. Then, we consider circle actions that preserve the structure, and determine conditions for the contact reduction to carry an induced structure of the same type. We apply this construction to obtain a new hypo-contact structure on S^2\times T^3.Comment: 30 pages; v2: typos corrected, presentation improved, one reference added. To appear in Ann. Glob. Analysis and Geometr

    Productivity Enhancement in Directed Energy Deposition: The Oscillating Scanning Strategy Approach

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    Directed Energy Deposition (DED) is an additive manufacturing process that enables the production of large metal components by melting the feedstock material while being deposited. An improvement of the production speed of this process would further increase its applicability in many industrial fields. The DED building rate is strictly related to the building parameters adopted, in particular to the laser spot diameter, which also affects the build accuracy and the surface quality of the components. The possibility of using a variable laser spot would result in a significant increase in the production rate in bulky zones, while also providing a good surface quality where needed. In the present work, an oscillating scanning strategy was used to create a large apparent laser spot (+ 170% of the nominal value) to produce 316L stainless steel samples via DED. The optimisation of the DED parameters with the oscillating strategy was performed using the single scan tracks (SSTs) approach. The morphologies of the SSTs obtained with different process parameters were assessed and the geometrical features related to the melt pools were analysed in order to select the most suitable X and Z displacements for the production of the cubic samples. The analyses of the cubes revealed that, if the correct overlap among nearby scans is selected, it is possible to obtain dense samples with all the oscillating diameters tested. Finally, comparing the building rate and powder efficiency values confirmed that this method can accelerate the building process and improve its overall performance

    Multiparametric magnetic resonance imaging for the differential diagnosis between granulomatous prostatitis and prostate cancer: a literature review to an intriguing diagnostic challenge

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    Multiparametric magnetic resonance imaging (mpMRI) is currently the most effective diagnostic tool for detecting prostate cancer (PCa) and evaluating adenocarcinoma-mimicking lesions of the prostate gland, among which granulomatous prostatitis (GP) represents the most interesting diagnostic challenge. GP consists of a heterogeneous group of chronic inflammatory lesions that can be differentiated into four types: idiopathic, infective, iatrogenic, and associated with systemic granulomatous disease. The incidence of GP is growing due to the increase in endourological surgical interventions and the adoption of intravesical instillation of Bacillus Calmette-Guerin in patients with non-muscle invasive bladder cancer; therefore, the difficulty lies in identifying specific features of GP on mpMRI to avoid the use of transrectal prostate biopsy as much as possible

    Liposomes Loaded With Phosphatidylinositol 5-Phosphate Improve the Antimicrobial Response to Pseudomonas aeruginosa in Impaired Macrophages From Cystic Fibrosis Patients and Limit Airway Inflammatory Response

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    Despite intensive antimicrobial and anti-inflammatory therapies, cystic fibrosis (CF) patients are subjected to chronic infections due to opportunistic pathogens, including multidrug resistant (MDR) Pseudomonas aeruginosa. Macrophages from CF patients show many evidences of reduced phagocytosis in terms of internalization capability, phagosome maturation, and intracellular bacterial killing. In this study, we investigated if apoptotic body-like liposomes (ABLs) loaded with phosphatidylinositol 5-phosphate (PI5P), known to regulate actin dynamics and vesicular trafficking, could restore phagocytic machinery while limiting inflammatory response in in vitro and in vivo models of MDR P. aeruginosa infection. Our results show that the in vitro treatment with ABL carrying PI5P (ABL/PI5P) enhances bacterial uptake, ROS production, phagosome acidification, and intracellular bacterial killing in human monocyte-derived macrophages (MDMs) with pharmacologically inhibited cystic fibrosis transmembrane conductance regulator channel (CFTR), and improve uptake and intracellular killing of MDR P. aeruginosa in CF macrophages with impaired bactericidal activity. Moreover, ABL/PI5P stimulation of CFTR-inhibited MDM infected with MDR P. aeruginosa significantly reduces NF-ÎșB activation and the production of TNF-α, IL-1ÎČ, and IL-6, while increasing IL-10 and TGF-ÎČ levels. The therapeutic efficacy of ABL/PI5P given by pulmonary administration was evaluated in a murine model of chronic infection with MDR P. aeruginosa. The treatment with ABL/PI5P significantly reduces pulmonary neutrophil infiltrate and the levels of KC and MCP-2 cytokines in the lungs, without affecting pulmonary bacterial load. Altogether, these results show that the ABL/PI5P treatment may represent a promising host-directed therapeutic approach to improve the impaired phagocytosis and to limit the potentially tissue-damaging inflammatory response in CF

    Combining thermal imaging with photogrammetry of an active volcano using UAV : an example from Stromboli, Italy

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    The authors would like to thank the Istituto Nazionale di Geofisica e Vulcanologia – Sezione di Catania (INGV‐CT) for granting permission to conduct the UAV surveys over the Stromboli volcano. This work was supported by the School for Early Career Researchers at the University of Aberdeen, UK. Dougal Jerram is partly funded through a Norwegian Research Council Centres of Excellence project (project number 223272, CEED). The team would like to thank Angelo Cristaudo for logistical help during the fieldwork efforts on Stromboli.Peer reviewedPostprin

    Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis

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    Mitochondria physically associate with the endoplasmic reticulum to coordinate interorganelle calcium transfer and regulate fundamental cellular processes, including inflammation. Deregulated endoplasmic reticulum–mitochondria cross-talk can occur in cystic fibrosis, contributing to hyperinflammation and disease progression. We demonstrate that Pseudomonasaeruginosainfection increases endoplasmic reticulum–mitochondria associations in cystic fibrosis bronchial cells by stabilizing VAPB-PTPIP51 (vesicle-associated membrane protein–associated protein B–protein tyrosine phosphatase interacting protein 51) tethers, affecting autophagy. Impaired autophagy induced mitochondrial unfolding protein response and NLRP3 inflammasome activation, contributing to hyperinflammation. The mechanism by which VAPB-PTPIP51 tethers regulate autophagy in cystic fibrosis involves calcium transfer via mitochondrial calcium uniporter. Mitochondrial calcium uniporter inhibition rectified autophagy and alleviated the inflammatory response in vitro and in vivo, resulting in a valid therapeutic strategy for cystic fibrosis pulmonary disease

    Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.

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    Background: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. Results: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. Conclusions: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studie

    A compact Time-Of-Flight detector for space applications: The LIDAL system

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    Abstract LIDAL (Light Ion Detector for ALTEA system) is a compact detector designed to upgrade ALTEA (Anomalous Long Term Effects on Astronauts) silicon detector apparatus, in order to study in detail the low-Z part of ions spectrum inside the International Space Station (ISS) and to enhance the Particle Identification (PID) capability of the system. The new detector is designed to trigger ALTEA and to perform Time-Of-Flight measurements. It is based on plastic scintillators for fast timing applications read by Photo-Multiplier-Tubes (PMTs). A custom Front End Electronics (FEE) has been designed to reach time resolutions less than 100 ps ( σ ) for protons. A LIDAL prototype has been developed at the University of Rome Tor Vergata to test the timing performance of the scintillators, the PMTs and of the custom FEE using the proton beam line at the TIFPA (Trento Institute for Fundamentals Physics Applications) center in Trento, Italy. The results of these tests are reported and discussed. They have also been used for a preliminary evaluation of the Particle Identification (PID) capability of the final LIDAL-ALTEA detector system in response to the ions spectra expected on-board the ISS

    BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression

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    Introduction Brain-Derived Neurotrophic Factor (BDNF) and its most common polymorphism Val66Met are known to have a role in Multiple Sclerosis (MS) pathogenesis. Evidence is accumulating that there is an involvement of DNA methylation in the regulation of BDNF expression. The aim of this study was to assess in blood samples of MS patients the correlation between the methylation status of the CpG site near BDNF-Val66Met polymorphism and the severity of the disease. Methods We recruited 209 MS patients that were genotyped for the BDNF Val66Met polymorphism. For each patient we quantitatively measured the methylation level of cytosine included in the exonic CpG site that can be created or abolished by the Val66Met BDNF polymorphism. Furthermore, we analyzed the clinical history of each patient and determined the time elapsed since the onset of the disease and an EDSS score of 6.0. Results The genetic analysis identified 122 (58.4%) subjects carrying the Val/Val genotype, 81 (38.8%) with Val/Met genotype, and 6 (2.8%) carrying the Met/Met genotype. When the endpoint of an EDSS score of 6 was taken into account by means of a survival analysis, 52 failures (i.e., reaching an EDSS score of 6) were reported. When the sample was stratified according to the percentage of the BDNF methylation, subjects falling below the median (median methylation = 81%) were at higher risk of failure (IRD = 0.016; 95%CI = 0.0050- 0.0279; p = 0.004). Conclusions In patients with a high disease progression the hypomethylation of the BDNF gene could increase the secretion of the protective neurotrophin, so epigenetic modifications could be the organism response to limit a brain functional reserve loss. Our study suggests that the percentage of methylation of the BDNF gene could be used as a prognostic factor for disease progression toward a high disability in MS patient
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