Improved design of an overhead rail current conductor for application in underground lines

Overhead rail current collector systems for railway traction offer certain features, such as low installation height and reduced maintenance, which make them predominantly suitable for use in underground train infrastructures. Due to the increased demands of modern catenary systems and higher running speeds of new vehicles, a more capable design of the conductor rail is needed. A new overhead conductor rail has been developed and its design has been patented [13]. Modern simulation and modelling techniques were used in the development approach. The new conductor rail profile has a dynamic behaviour superior to that of the system currently in use. Its innovative design permits either an increase of catenary support spacing or a higher vehicle running speed. Both options ensure savings in installation or operating costs. The simulation model used to optimise the existing conductor rail profile included both a finite element model of the catenary and a three-dimensional multi-body system model of the pantograph. The contact force that appears between pantograph and catenary was obtained in simulation. A sensitivity analysis of the key parameters that influence in catenary dynamics was carried out, finally leading to the improved design.

Fenómenos de resonancia asociados al transporte de mercancías líquidas por ferrocarril

Los vagones de mercancías se unen entre sí mediante acoplamientos UIC estándar. Aunque cada plataforma está equipada con un tensor de enganche en ambos extremos, sólo uno de ellos se utiliza, mientras que el otro descansa apoyado en un gancho. Debido a los efectos de oleaje del líquido contenido en las cisternas, este tensor en reposo puede entrar en resonancia con la frecuencia natural de algunos fluidos, llegando a oscilar de forma apreciable. En ocasiones llega a saltar fuera de su alojamiento, provocando ciertas molestias durante la circulación, aunque sin entrañar ningún riesgo para la seguridad de la marcha. Con el propósito de simular la influencia de diversos factores sobre el comportamiento dinámico asociado a estos fenómenos de oleaje, se ha desarrollado un modelo de la interacción fluido-vehículo, empleado técnicas de modelado de sistemas multicuerpo y de elementos finitos.

Influencia de las condiciones de procesado mediante FDM sobre las propiedades físicas y mecánicas del plástico ABS

El propósito del presente proyecto fue seleccionar la configuración de fabricación de probetas obtenidas mediante el proceso de Modelado por Deposición Fundida (FDM) con el termoplástico acrilonitrilo butadieno estireno (ABS), que optimice las propiedades mecánicas de las probetas y el ahorro de material de apoyo. Se aplicaron técnicas de caracterización física y mecánica y de microscopia electrónica de barrido (SEM). Los resultados indicaron que las probetas verticales presentaron aproximadamente el 6 % de pérdida de material frente cerca de un 40% de las probetas horizontales. La rotura de los cordones se produjo longitudinalmente en el borde de las probetas horizontales mientras que en el borde de las probetas verticales fueron por despegue de los cordones de ABS. La rotura de los cordones en el interior de ambas probetas fue en la dirección de los cordones. ABSTRACT The purpose of this project was to select the manufacture design in test specimens obtained using Fused Deposition Modeling (FDM) with Acrylonitrile Butadiene Styrene (ABS), thus optimizing the mechanical properties of the test specimens and saving the support material. The study was carried out by mean of mechanical and physical characterization techniques as well as Scanning Electron Microscopy (SEM). The results indicated that the horizontal test specimen showed approximately 40% of material loss compared to the vertical test specimen showed a loss 8%. The ABS filament breakage occurred longitudinally on the edge of the horizontal test specimen while the ABS filament breakage was transversely by the separation of the ABS filament on the edge of the vertical tests. The breakage of the filament inside both test specimens was in the direction of the filaments.

A novel alternate secretory pathway for the export of Plasmodium proteins into the host erythrocyte

The malarial parasite dramatically alters its host cell by exporting and targeting proteins to specific locations within the erythrocyte. Little is known about the mechanisms by which the parasite is able to carry out this extraparasite transport. The fungal metabolite brefeldin A (BFA) has been used to study the secretory pathway in eukaryotes. BFA treatment of infected erythrocytes inhibits protein export and results in the accumulation of exported Plasmodium proteins into a compartment that is at the parasite periphery. Parasite proteins that are normally localized to the erythrocyte membrane, to nonmembrane bound inclusions in the erythrocyte cytoplasm, or to the parasitophorous vacuolar membrane accumulate in this BFA-induced compartment. A single BFA-induced compartment is detected per parasite and the various exported proteins colocalize to this compartment regardless of their final destinations. Parasite membrane proteins do not accumulate in this novel compartment, but accumulate in the endoplasmic reticulum (ER), suggesting that the parasite has two secretory pathways. This alternate secretory pathway is established immediately after merozoite invasion and at least some dense granule proteins also use the alternate pathway. The BFA-induced compartment exhibits properties that are similar to the ER, but it is clearly distinct from the ER. We propose to call this new organelle the secondary ER of apicomplexa. This ER-like organelle is an early, if not the first, step in the export of Plasmodium proteins into the host erythrocyte.

A Cannabinoid CB1 Receptor Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with no Psychoactive Effects

Peer reviewed

A trait-based approach for predicting species responses to environmental change from sparse data : how well might terrestrial mammals track climate change?

Funded by COST (European Cooperation in Science and Technology) CEH projects. Grant Numbers: NEC05264, NEC05100 Natural Environment Research Council UK. Grant Number: NE/J008001/1 © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

GRADE Evidence to Decision (EtD) frameworks : A systematic and transparent approach to making well-informed healthcare choices. 1. Introduction

Funding: Work on this article has been partially funded by the European Commission FP7 Program (grant agreement 258583) as part of the DECIDE project. Sole responsibility lies with the authors; the European Commission is not responsible for any use that may be made of the information contained therein.

GRADE Evidence to Decision (EtD) frameworks : a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines

Funding: Work on this article has been partially funded by the European Commission FP7 Program (grant agreement 258583) as part of the DECIDE project. Sole responsibility lies with the authors; the European Commission is not responsible for any use that may be made of the information contained therein.

Macrophage inflammatory protein-2: Chromosomal regulation in rat small intestinal epithelial cells

Nonpathogenic, resident bacteria participate in the pathogenesis of inflammation in the small intestine, but the molecular messages produced by such bacteria are unknown. Inflammatory responses involve the recruitment of specific leukocyte subsets. We, therefore, hypothesized that butyrate, a normal bacterial metabolite, may modulate chemokine secretion by epithelial cells, by amplifying their response to proinflammatory signals. We studied the expression of the chemokine, macrophage inflammatory protein-2 (MIP-2) by the rat small intestinal epithelial cell line, IEC-6. Cells were stimulated with lipopolysaccharide or with interleukin 1β (IL-1β) and incubated with sodium butyrate. Acetylation of histones was examined in Triton X acetic acid–urea gels by PAGE. Unstimulated IEC-6 cells did not secrete MIP-2. However, lipopolysaccharide and IL-1β induced MIP-2 expression. Butyrate enhanced MIP-2 secretion both in lipopolysaccharide-stimulated and IL-1β-stimulated enterocytes; but butyrate alone did not induce MIP-2 expression. Butyrate increased the acetylation of histones extracted from the nuclei of IEC-6 cells. Furthermore, acetylation of histones (induced by trichostatin A, a specific inhibitor of histone deacetylase) enhanced MIP-2 expression by cells stimulated with IL-1β. In conclusion, trichostatin A reproduced the effects of butyrate on MIP-2 secretion. Butyrate, therefore, increases MIP-2 secretion in stimulated cells by increasing histone acetylation. We speculate that butyrate carries information from bacteria to epithelial cells. Epithelial cells transduce this signal through histone deacetylase, modulating the secretion of chemokines.

An essential role of phosphatidylinositol 3-kinase in myogenic differentiation

The oncogene p3k, coding for a constitutively active form of phosphatidylinositol 3-kinase (PI 3-kinase; EC 2.7.1.137), strongly enhances myogenic differentiation in cultures of chicken-embryo myoblasts. It increases the size of the myotubes and induces elevated levels of the muscle-specific proteins MyoD, myosin heavy chain, creatine kinase, and desmin. Inhibition of PI 3-kinase activity with LY294002 or with dominant-negative mutants of PI 3-kinase interferes with myogenic differentiation and with the induction of muscle-specific genes. PI 3-kinase is therefore an upstream mediator for the expression of the muscle-specific genes and is both necessary and rate-limiting for the process of myogenesis.

5-Lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases

5-lipoxygenase (5-LO) catalyzes the initial steps in the formation of leukotrienes, a group of inflammatory mediators derived from arachidonic acid (AA). Here we describe that activation of p38 mitogen-activated protein kinase in human polymorphonuclear leukocytes and in Mono Mac 6 cells leads to activation of downstream kinases, which can subsequently phosphorylate 5-LO in vitro. Different agents activated the 5-LO kinase activities, including stimuli for cellular leukotriene biosynthesis (A23187, thapsigargin, N-formyl-leucyl-phenylalanine), compounds that up-regulate the capacity for leukotriene biosynthesis (phorbol 12-myristate 13-acetate, tumor necrosis factor α, granulocyte/macrophage colony-stimulating factor), and well known p38 stimuli as sodium arsenite and sorbitol. For all stimuli, 5-LO kinase activation was counteracted by SB203580 (3 μM or less), an inhibitor of p38 kinase. At least two p38-dependent 5-LO kinase activities were found. Based on migration properties in in-gel kinase assays and immunoreactivity, one of these was identified as mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP kinase 2). The other appeared to be MAPKAP kinase 3; however, it could not be excluded that also other p38-dependent kinases contributed. When polymorphonuclear leukocytes were incubated with sodium arsenite (strong activator of 5-LO kinases), platelet-activating factor and exogenous AA, there was a 4-fold increase in 5-LO activity as compared with incubations with only platelet-activating factor and AA. This indicates that 5-LO phosphorylation can be one factor determining cellular 5-LO activity.

Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells

Phosphatidylinositol 3-kinase (PI 3-kinase) is a signaling molecule that controls numerous cellular properties and activities. The oncogene v-p3k is a homolog of the gene coding for the catalytic subunit of PI 3-kinase, p110α. P3k induces transformation of cells in culture, formation of hemangiosarcomas in young chickens, and myogenic differentiation in myoblasts. Here, we describe a role of PI 3-kinase in angiogenesis. Overexpression of the v-P3k protein or of cellular PI 3-kinase equipped with a myristylation signal, Myr-P3k, can induce angiogenesis in the chorioallantoic membrane (CAM) of the chicken embryo. This process is characterized by extensive sprouting of new blood vessels and enlargement of preexisting vessels. Overexpression of the myristylated form of the PI 3-kinase target Akt, Myr-Akt, also induces angiogenesis. Overexpression of the tumor suppressor PTEN or of dominant-negative constructs of PI 3-kinase inhibits angiogenesis in the yolk sac of chicken embryos, suggesting that PI 3-kinase and Akt signaling is required for normal embryonal angiogenesis. The levels of mRNA for vascular endothelial growth factor (VEGF) are elevated in cells expressing activated PI 3-kinase or Myr-Akt. VEGF mRNA levels are also increased by insulin treatment through the PI 3-kinase-dependent pathway. VEGF mRNA levels are decreased in cells treated with the PI 3-kinase inhibitor LY294002 and restored by overexpression of v-P3k or Myr-Akt. Overexpression of VEGF by the RCAS vector induces angiogenesis in chicken embryos. These results suggest that PI 3-kinase plays an important role in angiogenesis and regulates VEGF expression.

Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B

The oncogene p3k, coding for a constitutively active form of phosphatidylinositol 3-kinase (PI 3-kinase), strongly activates myogenic differentiation. Inhibition of endogenous PI 3-kinase activity with the specific inhibitor LY294002, or with dominant-negative mutants of PI 3-kinase, interferes with myotube formation and with the expression of muscle-specific proteins. Here we demonstrate that a downstream target of PI 3-kinase, serine-threonine kinase Akt, plays an important role in myogenic differentiation. Expression of constitutively active forms of Akt dramatically enhances myotube formation and expression of the muscle-specific proteins MyoD, creatine kinase, myosin heavy chain, and desmin. Transdominant negative forms of Akt inhibit myotube formation and the expression of muscle-specific proteins. The inhibition of myotube formation and the reduced expression of muscle-specific proteins caused by the PI 3-kinase inhibitor LY294002 are completely reversed by constitutively active forms of Akt. Wild-type cellular Akt effects a partial reversal of LY294002-induced inhibition of myogenic differentiation. This result suggests that Akt can substitute for PI 3-kinase in the stimulation of myogenesis; Akt may be an essential downstream component of PI 3-kinase-induced muscle differentiation.