569 research outputs found

    Characterization of fine metal particles using hyperspectral imaging in automatic WEEE recycling systems

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    Waste from electric and electronic equipment (WEEE) represents the fastest growing waste stream in EU. The large amount and the high variability of electric and electronic products introduced every year in the market make the WEEE recycling process a complex task, especially considering that mechanical processes currently used by recycling companies are not flexible enough. In this context, hyperspectral imaging systems (HSI) can represent an enabling technology able to improve the recycling rates and the quality of the output products. This study shows the preliminary results achieved using a HSI technology in a WEEE recycling pilot plant, for the characterization of fine metal particles derived from WEEE shredding

    Sensitive and quantitative method to evaluate DNA methylation of the positive regulatory domains (PRDI, PRDII) and cAMP response element (CRE) in human endothelial nitric oxide synthase promote

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    Nitric oxide plays a prominent role in the cardiovascular system and much attention has been devoted in the last years on deciphering the regulation of human endothelial nitric oxide synthase (eNOS) expression. Epigenetic-based mechanisms have a key role in the eNOS expression and their pathologic perturbations may have profound effects on the steady state RNA levels in the endothelium. The human eNOS promoter lacks a canonical TATA box and it does not contain a proximal CpG island. A differentially DNA methylated region (DMR) in the native eNOS proximal promoter is involved in gene expression regulation. Here we describe a quantitative, sensitive and cost-effective method that, relying on a novel normalization strategy, allows the quantification of DNA methylation status of the positive regulatory domains (PRDI, PRDII) and cAMP response element (CRE) in human eNOS promoter. This technique will enable to explore the functional relevance of DNA methylation perturbations of eNOS promoter both under pathological and physiological conditions

    Cyclophilin A : a key player for human disease

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    Cyclophilin A (CyPA) is a ubiquitously distributed protein belonging to the immunophilin family. CyPA has peptidyl prolyl cis-trans isomerase (PPIase) activity, which regulates protein folding and trafficking. Although CyPA was initially believed to function primarily as an intracellular protein, recent studies have revealed that it can be secreted by cells in response to inflammatory stimuli. Current research in animal models and humans has provided compelling evidences supporting the critical function of CyPA in several human diseases. This review discusses recently available data about CyPA in cardiovascular diseases, viral infections, neurodegeneration, cancer, rheumatoid arthritis, sepsis, asthma, periodontitis and aging. It is believed that further elucidations of the role of CyPA will provide a better understanding of the molecular mechanisms underlying these diseases and will help develop novel pharmacological therapies

    Precise Therapy for Thoracic Aortic Aneurysm in Marfan Syndrome: A Puzzle Nearing Its Solution.

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    Abstract Marfan Syndrome (MFS) is a rare connective tissue disorder, resulting from mutations in the fibrillin-1 gene, characterized by pathologic phenotypes in multiple organs, the most detrimental of which affects the thoracic aorta. Indeed, thoracic aortic aneurysms (TAA), leading to acute dissection and rupture, are today the major cause of morbidity and mortality in adult MFS patients. Therefore, there is a compelling need for novel therapeutic strategies to delay TAA progression and counteract aortic dissection occurrence. Unfortunately, the wide phenotypic variability of MFS patients, together with the lack of a complete genotype-phenotype correlation, have represented until now a barrier hampering the conduction of translational studies aimed to predict disease prognosis and drug discovery. In this review, we will illustrate available therapeutic strategies to improve the health of MFS patients. Starting from gold standard surgical overtures and the description of the main pharmacological approaches, we will comprehensively review the state-of-the-art of in vivo MFS models and discuss recent clinical pharmacogenetic results. Finally, we will focus on induced pluripotent stem cells (iPSC) as a technology that, if integrated with preclinical research and pharmacogenetics, could contribute in determining the best therapeutic approach for each MFS patient on the base of individual differences. Finally, we will suggest the integration of preclinical studies, pharmacogenetics and iPSC technology as the most likely strategy to help solve the composite puzzle of precise medicine in this condition

    Connecting Galaxy Evolution, Star Formation and the X-ray Background

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    As a result of deep hard X-ray observations by Chandra and XMM-Newton a significant fraction of the cosmic X-ray background (CXRB) has been resolved into individual sources. These objects are almost all active galactic nuclei (AGN) and optical followup observations find that they are mostly obscured Type 2 AGN, have Seyfert-like X-ray luminosities (i.e., L_X ~ 10^{43-44} ergs s^{-1}), and peak in redshift at z~0.7. Since this redshift is similar to the peak in the cosmic star-formation rate, this paper proposes that the obscuring material required for AGN unification is regulated by star-formation within the host galaxy. We test this idea by computing CXRB synthesis models with a ratio of Type 2/Type 1 AGN that is a function of both z and 2-10 keV X-ray luminosity, L_X. The evolutionary models are constrained by parameterizing the observed Type 1 AGN fractions from the recent work by Barger et al. The parameterization which simultaneously best accounts for Barger's data, the CXRB spectrum and the X-ray number counts has a local, low-L_X Type 2/Type 1 ratio of 4, and predicts a Type 2 AGN fraction which evolves as (1+z)^{0.3}. Models with no redshift evolution yielded much poorer fits to the Barger Type 1 AGN fractions. This particular evolution predicts a Type 2/Type 1 ratio of 1-2 for log L_X > 44, and thus the deep X-ray surveys are missing about half the obscured AGN with these luminosities. These objects are likely to be Compton thick. Overall, these calculations show that the current data strongly supports a change to the AGN unification scenario where the obscuration is connected with star formation in the host galaxy rather than a molecular torus alone. The evolution of the obscuration implies a close relationship between star formation and AGN fueling, most likely due to minor mergers or interactions.Comment: 36 pages, 8 figures, ApJ in press. Minor changes to match published versio

    High-throughput analysis of selected urinary hydroxy polycyclic aromatic hydrocarbons by an innovative automated solid-phase microextraction

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    High-throughput screening of samples is the strategy of choice to detect occupational exposure biomarkers, yet it requires a user-friendly apparatus that gives relatively prompt results while ensuring high degrees of selectivity, precision, accuracy and automation, particularly in the preparation process. Miniaturization has attracted much attention in analytical chemistry and has driven solvent and sample savings as easier automation, the latter thanks to the introduction on the market of the three axis autosampler. In light of the above, this contribution describes a novel user-friendly solid-phase microextraction (SPME) off- and on-line platform coupled with gas chromatography and triple quadrupole-mass spectrometry to determine urinary metabolites of polycyclic aromatic hydrocarbons 1- and 2-hydroxy-naphthalene, 9-hydroxy-phenanthrene, 1-hydroxy-pyrene, 3- and 9-hydroxy-benzoantracene, and 3-hydroxy-benzo[a]pyrene. In this new procedure, chromatography’s sensitivity is combined with the user-friendliness of N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide on-fiber SPME derivatization using direct immersion sampling; moreover, specific isotope-labelled internal standards provide quantitative accuracy. The detection limits for the seven OH-PAHs ranged from 0.25 to 4.52 ng/L. Intra-(from 2.5 to 3.0%) and inter-session (from 2.4 to 3.9%) repeatability was also evaluated. This method serves to identify suitable risk-control strategies for occupational hygiene conservation programs

    Late Pleistocene-Holocene volcanic activity in northern Victoria Land recorded in Ross Sea (Antarctica) marine sediments

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    Eight pyroclastic fall deposits have been identified in cores of Late Pleistocene-Holocene marine sediments from the Ross Sea (Antarctica), and their components, granulometry and clast morphologies were analysed. Sedimentological, petrographic and geochemical analysis of clasts, with 40Ar-39Ar dating of alkali feldspar grains, indicate that during this period at least five explosive eruptions of mid to high intensity (plinian to subplinian) occurred, and that three of these eruptions took place from Mount Melbourne volcanic complex, between 137.1 \ub1 3.4 and 12 ka. Geochemical comparison of the studied tephra with micro and crypto-tephra recovered from deep Antarctic ice cores and from nearby englacial tephra at Frontier Mountain indicates that eruptive activity in the Melbourne Volcanic Province of northern Victoria Land was intense during the Late Pleistocene-Holocene, but only a general area of provenance for the majority of the identified tephra can be identified

    Development of Quinazolinone Derivatives as Modulators of Virulence Factors of Pseudomonas aeruginosa Cystic Fibrosis Strains

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    Pseudomonas aeruginosa (PA), one of the ESKAPE pathogens, is an opportunistic Gram-negative bacterium responsible for nosocomial infections in humans but also for infections in patients affected by AIDS, cancer, or cystic fibrosis (CF). Treatment of PA infections in CF patients is a global healthcare problem due to the ability of PA to gain antibiotic tolerance through biofilm formation. Anti-virulence compounds represent a promising approach as adjuvant therapy, which could reduce or eliminate the pathogenicity of PA without impacting its growth. Pyocyanin is one of the virulence factors whose production is modulated by the Pseudomonas quinolone signal (PQS) through its receptor PqsR. Different PqsR modulators have been synthesized over the years, highlighting this new powerful therapeutic strategy. Based on the promising structure of quinazolin-4(3H)-one, we developed compounds 7a–d, 8a,b, 9, 10, and 11a–f able to reduce biofilm formation and the production of virulence factors (pyocyanin and pyoverdine) at 50 μM in two PA strains responsible for CF acute and chronic infections. The developed compounds did not reduce the cell viability of IB3-1 bronchial CF cells, and computational studies confirmed the potential ability of novel compounds to act as potential Pqs system modulators

    The anti-microbial peptide (Lin-SB056-1)2-K reduces pro-inflammatory cytokine release through interaction with Pseudomonas aeruginosa lipopolysaccharide

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    The ability of many anti-microbial peptides (AMPs) to modulate the host immune response has highlighted their possible therapeutic use to reduce uncontrolled inflammation during chronic infections. In the present study, we examined the anti-inflammatory potential of the semi-synthetic peptide lin-SB056-1 and its dendrimeric derivative (lin-SB056-1)2-K, which were previously found to have anti-microbial activity against Pseudomonas aeruginosa in in vivo-like models mimicking the challenging environment of chronically infected lungs (i.e., artificial sputum medium and 3-D lung mucosa model). The dendrimeric derivative exerted a stronger anti-inflammatory activity than its monomeric counterpart towards lung epithelial-and macrophage-cell lines stimulated with P. aeruginosa lipopolysaccharide (LPS), based on a marked decrease (up to 80%) in the LPS-induced production of different pro-inflammatory cytokines (i.e., IL-1β, IL-6 and IL-8). Accordingly, (lin-SB056-1)2-K exhibited a stronger LPS-binding affinity than its monomeric counterpart, thereby suggesting a role of peptide/LPS neutralizing interactions in the observed anti-inflammatory effect. Along with the anti-bacterial and anti-biofilm properties, the anti-inflammatory activity of (lin-SB056-1)2-K broadens its therapeutic potential in the context of chronic (biofilm-associated) infections
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