A dynamic model of ballasted rail track with bituminous sub-ballast layer

The bituminous sub-ballast layer within the ballasted rail track allows some mechanical and environmental advantages. An analytical model of a ballasted rail track with sub-ballast layer has been proposed by considering the rail as viscous-elastic continuous beam discretely supported, at four levels of elasticity. The model was used to compare the mechanical performance of both ballasted track with and without bituminous sub-ballast layer. The results confirmed that the bituminous sub-ballast layer reduces the dynamic forces on the ground and achieves the technical objectives as reduction of ground borne vibrations and increase of the design life of the rail track

Experimental Survey on Dry Asphalt Rubber Concrete for Sub-ballast Layers

This paper presents the results of an experimental survey on the potential application of DARC (dry asphalt rubber concrete) in rail superstructure, within sub-ballast layers by measuring its damping and mechanical properties. Based on the environmental friendly point of view the DARC has the significant advantage as the backfill material of sub-ballast layer because the rubber comes from the waste tires of truck and its usage can results a significant recycling of non-biodegradable wastes. After a preliminary mix-design of several DARCs, with different rubber content that confirmed by using the Marshall test, the stiffness modulus and damping ratio both of a standard bituminous mixture and of dry asphalt rubber concrete with a rubber content equal to 1.5% were determined using the four points bending device. The experimental results were compared and a numerical analysis by means of a 2D lumped mass model was developed in order to evaluate the different performance within the rail superstructure in terms both of the deflection and of the pressure on sub-grade. Both the results on the mechanical and dissipative properties of the DARC and the mechanical behavior of the correlate rail superstructure encourage the authors to continue the research on the application of such material for sub-ballast layers

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Roles of P2 receptors in glial cells: focus on astrocytes

Central nervous system glial cells release and respond to nucleotides under both physiological and pathological conditions, suggesting that these molecules play key roles in both normal brain function and in repair after damage. In particular, ATP released from astrocytes activates P2 receptors on astrocytes and other brain cells, allowing a form of homotypic and heterotypic signalling, which also involves microglia, neurons and oligodendrocytes. Multiple P2X and P2Y receptors are expressed by both astrocytes and microglia; however, these receptors are differentially recruited by nucleotides, depending upon specific pathophysiological conditions, and also mediate the long-term trophic changes of these cells during inflammatory gliosis. In astrocytes, P2-receptor-induced gliosis occurs via activation of the extracellular-regulated kinases (ERK) and protein kinase B/Akt pathways and involves induction of inflammatory and anti-inflammatory genes, cyclins, adhesion and antiapoptotic molecules. While astrocytic P2Y1 and P2Y2,4 are primarily involved in short-term calcium-dependent signalling, multiple P2 receptor subtypes seem to cooperate to astrocytic long-term changes. Conversely, in microglia, exposure to inflammatory and immunological stimuli results in differential functional changes of distinct P2 receptors, suggesting highly specific roles in acquisition of the activated phenotype. We believe that nucleotide-induced activation of astrocytes and microglia may originally start as a defence mechanism to protect neurons from cytotoxic and ischaemic insults; dysregulation of this process in chronic inflammatory diseases eventually results in neuronal cell damage and loss. On this basis, full elucidation of the specific roles of P2 receptors in these cells may help exploit the beneficial neuroprotective features of activated glia while attenuating their harmful properties and thus provide the basis for novel neuroprotective strategies that specifically target the purinergic system

A FEM model of rail track-ground system to calculate the ground borne vibrations: A case of rail track with wooden sleepers and k-fastenings at Castelvetrano

The prediction of ground borne vibrations is an important issue that needs a multidisciplinary research approach. The principal topics concern both the interaction between train and rail and the interaction between rail track and ground

Modulation of the TGF-β1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells

Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling. The stimulation of A2A receptor reduced the overexpression of the EMT-related markers, mainly through the cAMP-dependent PKA pathway, as confirmed by cell pre-treatment with Myr-PKI. Both A1 and P2Y1 receptor stimulation exacerbated the TGF-β1-driven effects, which were reduced by cell pre-treatment with the MAPK inhibitor PD98059, according to the increased ERK1/2 phosphorylation upon receptor activation. The effects induced by P2Y11 receptor activation were oppositely modulated by PKA or MAPK inhibition, in line with the dual nature of the Gs- and Gq-coupled receptor. Differently, P2X7 receptor induced, per se, similar and not additive effects compared to TGF-β1, after prolonged cell exposure to BzATP. These results suggest a putative role of purine receptors as target for anti-fibrotic agents

Novel biomarker combination improves the diagnosis of serious bacterial infections in Malawian children

<p>Abstract</p> <p>Background</p> <p>High throughput technologies offer insight into disease processes and heightens opportunities for improved diagnostics. Using transcriptomic analyses, we aimed to discover and to evaluate the clinical validity of a combination of reliable and functionally important biomarkers of serious bacterial infection (SBI).</p> <p>Methods</p> <p>We identified three previously reported biomarkers of infection (neutrophil gelatinase-associated lipocalin (NGAL), granulysin and resistin) and measured gene expression using quantitative real-time PCR. Protein products related to the three transcripts were measured by immunoassays.</p> <p>Results</p> <p>Relative gene expression values of NGAL and resistin were significantly increased, and expression of granulysin significantly decreased in cases compared to controls. Plasma concentrations of NGAL and resistin were significantly increased in children with confirmed SBI compared to children with no detectable bacterial infection (NBI), and to controls (287 versus 128 versus 62 ng/ml and 195 versus 90 versus 18 ng/ml, respectively, p < 0.05). Plasma protein concentrations of NGAL and resistin were significantly increased in non-survivors compared to survivors (306 versus 211 and 214 versus 150 ng/ml, p = 0.02). The respective areas under the curve (AUC) for NGAL, resistin and procalcitonin in predicting SBI were 0.79, 0.80 and 0.86, whilst a combination of NGAL, resistin and procalcitonin achieved an AUC of 0.90.</p> <p>Conclusions</p> <p>We have demonstrated a unique combination of diagnostic biomarkers of SBI using transcriptomics, and demonstrated translational concordance with the corresponding protein. The addition of NGAL and resistin protein measurement to procalcitonin significantly improved the diagnosis of SBI.</p

Pharmacological Activation of Group-II Metabotropic Glutamate Receptors Corrects a Schizophrenia-Like Phenotype Induced by Prenatal Stress in Mice

Prenatal exposure to restraint stress causes long-lasting changes in neuroplasticity that likely reflect pathological modifications triggered by early-life stress. We found that the offspring of dams exposed to repeated episodes of restraint stress during pregnancy (here named 'prenatal restraint stress mice' or 'PRS mice') developed a schizophrenia-like phenotype, characterized by a decreased expression of brain-derived neurotrophic factor and glutamic acid decarboxylase 67, an increased expression of type-1 DNA methyl transferase (DNMT1) in the frontal cortex, and a deficit in social interaction, locomotor activity, and prepulse inhibition. PRS mice also showed a marked decrease in metabotropic glutamate 2 (mGlu2) and mGlu3 receptor mRNA and protein levels in the frontal cortex, which was manifested at birth and persisted in adult life. This decrease was associated with an increased binding of DNMT1 to CpG-rich regions of mGlu2 and mGlu3 receptor promoters and an increased binding of MeCP2 to the mGlu2 receptor promoter. Systemic treatment with the selective mGlu2/3 receptor agonist LY379268 (0.5 mg/kg, i.p., twice daily for 5 days), corrected all the biochemical and behavioral abnormalities shown in PRS mice. Our data show for the first time that PRS induces a schizophrenia-like phenotype in mice, and suggest that epigenetic changes in mGlu2 and mGlu3 receptors lie at the core of the pathological programming induced by early-life stress