Limits and opportunities of risk analysis application in railway systems

Risk Analysis is a collection of methods widely used in many industrial sectors. In the transport sector it has been particularly used for air transport applications. The reasons for this wide use are well-known: risk analysis allows to approach the safety theme in a stochastic - rather than deterministic - way, it forces to break down the system in sub-components, last but not least it allows a comparison between solutions with different costs, introducing de facto an element of economic feasibility of the project alternatives in the safety field. Apart from the United Kingdom, in Europe the application of this tool in the railway sector is relatively recent. In particular Directive 2004/49/EC (the "railway safety directive") provides for compulsory risk assessment in relation to the activities of railway Infrastructure Managers (IMs) and of Railway Undertakings (RUs). Nevertheless the peculiarity of the railway system - in which human, procedural, environmental and technological components have a continuous interchange and in which human responsibilities and technological functions often overlap - induced the EC to allow wide margins of subjectivity in the interpretation of risk assessment. When enacting Commission Regulation (EC) No 352/2009 which further regulates this subject, a risk assessment is considered positive also if the IM or RU declare to take safety measures widely used in normal practice. The paper shows the results of a structured comparative analysis of the rail sector and other industrial sectors, which illustrate the difficulties, but also the opportunities, of a transfer towards the railway system of the risk analysis methods currently in use for the other systems

Statistical ensemble of gene regulatory networks of macrophage differentiation

Background: Macrophages cover a major role in the immune system, being the most plastic cell yielding several key immune functions. Methods: Here we derived a minimalistic gene regulatory network model for the differentiation of macrophages into the two phenotypes M1 (pro-) and M2 (anti-inflammatory). Results: To test the model, we simulated a large number of such networks as in a statistical ensemble. In other words, to enable the inter-cellular crosstalk required to obtain an immune activation in which the macrophage plays its role, the simulated networks are not taken in isolation but combined with other cellular agents, thus setting up a discrete minimalistic model of the immune system at the microscopic/intracellular (i.e., genetic regulation) and mesoscopic/intercellular scale. Conclusions: We show that within the mesoscopic level description of cellular interaction and cooperation, the gene regulatory logic is coherent and contributes to the overall dynamics of the ensembles that shows, statistically, the expected behaviour

Technical-economical analysis of cold-ironing. Case study of Venice cruise terminal

Cold-ironing is the practice that enables to power commercial ships by a link to fixed electricity network, in order to reduce pollutant emissions in the port areas caused by marine fuels in auxiliaries engines feeding on board installations during ships stops at quays. The present paper aims to provide an overview of the most important technical and functional features of the concerned ships power systems and to analyze the technical, economic and financial feasibility of this system. In the first part the main technical-constructive elements for the application of Cold-ironing to different types of ship (such as voltage, frequency, power supply and power demand on the quay) are analyzed. The variety of functional situations does not allow to establish general constructive solutions since the cold-ironing system is depending both on the operational mode and the layout of each terminal. In the second part of the paper it has been analyzed the case study of the cruise terminal in Venice (VTP Spa Venice Passenger Terminal) with the aim of verifying the feasibility of a cold-ironing system for power supply of cruise ships on quays. The analysis was based on ships timetable for the year 2012, which includes the arrivals and the departures of 86 different ships with a global volume of 570 movements. Starting from data on dwell times, following the guidelines of the MEET methodology for estimating emission factors [3] it has been estimated pollutant emissions (nitrogen oxide NOx, sulfur oxides SOx, volatile organic compounds VOC, particulates PM, carbon monoxide CO) as a basis to calculate externalities to be considered for the Cost-Benefit Analysis (CBA). Based on a probabilistic analysis of the terminal occupation by ships (disposal of ship stalls on each quays) five operational scenarios were defined. Each scenario has been defined on the basis of an economic evaluation by means of a cost-benefit parametric analysis with the aim of providing the maximum financial results for assigned budgets. From a comparison of the results of the cost-benefit analysis and an estimate of possible investment costs obtained from USA case studies, it is noticed that the scenario providing coverage of both financial and economic investment includes the minimum number of electrified stalls and a ships journeys reorganization. It was also proposed a sensitivity analysis of CBA for the evaluation of indicators variations according to reference conditions variation

Gene regulatory network modeling of macrophage differentiation corroborates the continuum hypothesis of polarization states

Macrophages derived from monocyte precursors undergo specific polarization processes which are influenced by the local tissue environment: classically activated (M1) macrophages, with a pro-inflammatory activity and a role of effector cells in Th1 cellular immune responses, and alternatively activated (M2) macrophages, with anti-inflammatory functions and involved in immunosuppression and tissue repair. At least three different subsets of M2 macrophages, namely, M2a, M2b, and M2c, are characterized in the literature based on their eliciting signals. The activation and polarization of macrophages is achieved through many, often intertwined, signaling pathways. To describe the logical relationships among the genes involved in macrophage polarization, we used a computational modeling methodology, namely, logical (Boolean) modeling of gene regulation. We integrated experimental data and knowledge available in the literature to construct a logical network model for the gene regulation driving macrophage polarization to the M1, M2a, M2b, and M2c phenotypes. Using the software GINsim and BoolNet, we analyzed the network dynamics under different conditions and perturbations to understand how they affect cell polarization. Dynamic simulations of the network model, enacting the most relevant biological conditions, showed coherence with the observed behavior of in vivo macrophages. The model could correctly reproduce the polarization toward the four main phenotypes as well as to several hybrid phenotypes, which are known to be experimentally associated to physiological and pathological conditions. We surmise that shifts among different phenotypes in the model mimic the hypothetical continuum of macrophage polarization, with M1 and M2 being the extremes of an uninterrupted sequence of states. Furthermore, model simulations suggest that anti-inflammatory macrophages are resilient to shift back to the pro-inflammatory phenotype

X-chromosome-linked miR548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis.

Sex dimorphism in cell response to stress has previously been investigated by different research groups. This dimorphism could be at least in part accounted for by sex-biased expression of regulatory elements such as microRNAs (miRs). In order to spot previously unknown miR expression differences we took advantage of prior knowledge on specialized databases to identify X chromosome-encoded miRs potentially escaping X chromosome inactivation (XCI). MiR-548am-5p emerged as potentially XCI escaper and was experimentally verified to be significantly up-regulated in human XX primary dermal fibroblasts (DFs) compared to XY ones. Accordingly, miR-548am-5p target mRNAs, e.g. the transcript for Bax, was differently modulated in XX and XY DFs. Functional analyses indicated that XY DFs were more prone to mitochondria-mediated apoptosis than XX ones. Experimentally induced overexpression of miR548am-5p in XY cells by lentivirus vector transduction decreased apoptosis susceptibility, whereas its down-regulation in XX cells enhanced apoptosis susceptibility. These data indicate that this approach could be used to identify previously unreported sex-biased differences in miR expression and that a miR identified with this approach, miR548am-5p, can account for sex-dependent differences observed in the susceptibility to mitochondrial apoptosis of human DFs

Virtual Art Therapy. Application of Michelangelo Effect to Neurorehabilitation of Patients with Stroke

In neurorehabilitation, some studies reported the effective use of art therapy for reducing psychological disorders and for enhancing physical functions and cognitive abilities. Neuroaesthetical studies showed that seeing an art masterpiece can spontaneously elicit a widespread brain arousal, also involving motor networks. To combine contemplative and performative benefits of art therapy protocols, we have developed an immersive virtual reality system, giving subjects the illusion that they are able to paint a copy of famous artistic paintings. We previously observed that during this virtual task, subjects perceived less fatigue and performed more accurate movements than when they were asked to color the virtual canvas. We named this upshot the Michelangelo effect. The aim of this study was to test the rehabilitative efficacy of our system. Ten patients with stroke in the subacute phase were enrolled and trained for one month with virtual art therapy (VAT) and physiotherapy. Their data were compared with those of ten patients matched for pathology, age and clinical parameters, trained only with conventional therapy for the same amount of time. The VAT group showed a significantly higher improvements in the Barthel Index score, a measure of independency in activities of daily living (66 ± 33% vs. 31 ± 28%, p = 0.021), and in pinching strength (66 ± 39% vs. 18 ± 33%, p = 0.008), with respect to the group treated with conventional rehabilitation

Spectral Properties of Brain Activity Under Two Anesthetics and Their Potential for Inducing Natural Sleep in Birds

Both mammals and birds exhibit two sleep states, slow wave sleep (SWS) and rapid eye movement (REM) sleep. Studying certain aspects of sleep-related electrophysiology in freely behaving animals can present numerous methodological constraints, particularly when even fine body movements interfere with electrophysiological signals. Interestingly, under light general anesthesia, mammals and birds also exhibit slow waves similar to those observed during natural SWS. For these reasons, slow waves occurring under general anesthesia are commonly used in the investigation of sleep-related neurophysiology. However, how spectral properties of slow waves induced by anesthesia correspond to those occurring during natural SWS in birds has yet to be investigated systematically. In this study, we systematically analyzed spectral properties of electroencephalographic (EEG) patterns of pigeons (Columba livia) occurring under two commonly used anesthetics, isoflurane and urethane. These data were compared with EEG patterns during natural sleep. Slow waves occurring during spontaneous SWS, and those induced with isoflurane and urethane all showed greatest absolute power in the slowest frequencies (<3 Hz). Isoflurane and urethane-induced slow waves had near-identical power spectra, and both had higher mean power than that observed during SWS for all frequencies examined (0–25 Hz). Interestingly, burst suppression EEG activity observed under deeper planes of isoflurane anesthesia could occur bihemispherically or unihemispherically. Electrophysiological patterns while under isoflurane and urethane share phenomenological and spectral similarities to those occurring during SWS, notably the generation of high amplitude, slow waves, and peak low-frequency power. These results build upon other studies which suggest that some anesthetics exert their effects by acting on natural sleep pathways. As such, anesthesia-induced slow waves appear to provide an acceptable model for researchers interested in investigating sleep-related slow waves utilizing electrophysiological methods not suitable for use in freely behaving birds

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte