Towards designing robust coupled networks

Natural and technological interdependent systems have been shown to be highly vulnerable due to cascading failures and an abrupt collapse of global connectivity under initial failure. Mitigating the risk by partial disconnection endangers their functionality. Here we propose a systematic strategy of selecting a minimum number of autonomous nodes that guarantee a smooth transition in robustness. Our method which is based on betweenness is tested on various examples including the famous 2003 electrical blackout of Italy. We show that, with this strategy, the necessary number of autonomous nodes can be reduced by a factor of five compared to a random choice. We also find that the transition to abrupt collapse follows tricritical scaling characterized by a set of exponents which is independent on the protection strategy

Facilitating return to work through early specialist health-based interventions (FRESH): protocol for a feasibility randomised controlled trial

Background Over one million people sustain traumatic brain injury each year in the UK and more than 10 % of these are moderate or severe injuries, resulting in cognitive and psychological problems that affect the ability to work. Returning to work is a primary rehabilitation goal but fewer than half of traumatic brain injury survivors achieve this. Work is a recognised health service outcome, yet UK service provision varies widely and there is little robust evidence to inform rehabilitation practice. A single-centre cohort comparison suggested better work outcomes may be achieved through early occupational therapy targeted at job retention. This study aims to determine whether this intervention can be delivered in three new trauma centres and to conduct a feasibility, randomised controlled trial to determine whether its effects and cost effectiveness can be measured to inform a definitive trial. Methods/design Mixed methods study, including feasibility randomised controlled trial, embedded qualitative studies and feasibility economic evaluation will recruit 102 people with traumatic brain injury and their nominated carers from three English UK National Health Service (NHS) trauma centres. Participants will be randomised to receive either usual NHS rehabilitation or usual rehabilitation plus early specialist traumatic brain injury vocational rehabilitation delivered by an occupational therapist. The primary objective is to assess the feasibility of conducting a definitive trial; secondary objectives include measurement of protocol integrity (inclusion/exclusion criteria, intervention adherence, reasons for non-adherence) recruitment rate, the proportion of eligible patients recruited, reasons for non-recruitment, spectrum of TBI severity, proportion of and reasons for loss to follow-up, completeness of data collection, gains in face-to-face Vs postal data collection and the most appropriate methods of measuring primary outcomes (return to work, retention) to determine the sample size for a larger trial. Discussion To our knowledge, this is the first feasibility randomised controlled trial of a vocational rehabilitation health intervention specific to traumatic brain injury. The results will inform the design of a definitive trial

Textile industry manufacturing by-products induce human melanoma cell proliferation via ERK1/2 activation

OBJECTIVES: Textiles used to make clothing can represent a source, often ignored, of chemicals potentially noxious to both skin and the whole organism. Among the most frequently produced potentially noxious chemical manufacturing by-products are formaldehyde (FA), nickel (Ni) and hexavalent chromium (Cr); they are of potential clinical interest as all are known to be carcinogenic to humans and to be potent skin sensitizers. The aim of this study was to investigate, in vitro, effects of these potentially dangerous compounds on two different melanoma cell lines. In particular, attention was focused on A375P, a poorly metastatic and low invasive cell line and SK-MEL-28, a highly metastatic cell line. MATERIALS AND METHODS: Effects of these compounds was evaluated on A375P and SK-MEL-28 cells. FA (1-5 7 10(-5) m), NiSO4 (10(-6) -10(-3) m), K2 Cr2 O7 (10(-7) -10(-6) m) effects on cell proliferation were evaluated by cell counting, while ERK pathway involvement was evaluated by Western blot analysis. RESULTS: Low concentrations of the chemicals, covering a range that corresponds to commonly accepted limits in textile production, induced a significant increase in cell proliferation concomitant with transient activation of phosphorylated ERK expression. CONCLUSIONS: Data obtained suggest that increasing attention must be focused on these by-products' potentially harmful effects in chemical manufacturing of clothes and accessories, that remain for long periods of time, in contact with human skin

Collective Excitations of Holographic Quantum Liquids in a Magnetic Field

We use holography to study N=4 supersymmetric SU(Nc) Yang-Mills theory in the large-Nc and large-coupling limits coupled to a number Nf << Nc of (n+1)-dimensional massless supersymmetric hypermultiplets in the Nc representation of SU(Nc), with n=2,3. We introduce a temperature T, a baryon number chemical potential mu, and a baryon number magnetic field B, and work in a regime with mu >> T,\sqrt{B}. We study the collective excitations of these holographic quantum liquids by computing the poles in the retarded Green's function of the baryon number charge density operator and the associated peaks in the spectral function. We focus on the evolution of the collective excitations as we increase the frequency relative to T, i.e. the hydrodynamic/collisionless crossover. We find that for all B, at low frequencies the tallest peak in the spectral function is associated with hydrodynamic charge diffusion. At high frequencies the tallest peak is associated with a sound mode similar to the zero sound mode in the collisionless regime of a Landau Fermi liquid. The sound mode has a gap proportional to B, and as a result for intermediate frequencies and for B sufficiently large compared to T the spectral function is strongly suppressed. We find that the hydrodynamic/collisionless crossover occurs at a frequency that is approximately B-independent.Comment: 45 pages, 8 png and 47 pdf images in 22 figure

Biphasic effect of extracellular ATP on human and rat airways is due to multiple P2 purinoceptor activation

BACKGROUND: Extracellular ATP may modulate airway responsiveness. Studies on ATP-induced contraction and [Ca(2+)](i )signalling in airway smooth muscle are rather controversial and discrepancies exist regarding both ATP effects and signalling pathways. We compared the effect of extracellular ATP on rat trachea and extrapulmonary bronchi (EPB) and both human and rat intrapulmonary bronchi (IPB), and investigated the implicated signalling pathways. METHODS: Isometric contraction was measured on rat trachea, EPB and IPB isolated rings and human IPB isolated rings. [Ca(2+)](i )was monitored fluorimetrically using indo 1 in freshly isolated and cultured tracheal myocytes. Statistical comparisons were done with ANOVA or Student's t tests for quantitative variables and χ(2 )tests for qualitative variables. Results were considered significant at P < 0.05. RESULTS: In rat airways, extracellular ATP (10(-6)–10(-3 )M) induced an epithelium-independent and concentration-dependent contraction, which amplitude increased from trachea to IPB. The response was transient and returned to baseline within minutes. Similar responses were obtained with the non-hydrolysable ATP analogous ATP-γ-S. Successive stimulations at 15 min-intervals decreased the contractile response. In human IPB, the contraction was similar to that of rat IPB but the time needed for the return to baseline was longer. In isolated myocytes, ATP induced a concentration-dependent [Ca(2+)](i )response. The contractile response was not reduced by thapsigargin and RB2, a P2Y receptor inhibitor, except in rat and human IPB. By contrast, removal of external Ca(2+), external Na(+ )and treatment with D600 decreased the ATP-induced response. The contraction induced by α-β-methylene ATP, a P2X agonist, was similar to that induced by ATP, except in IPB where it was lower. Indomethacin and H-89, a PKA inhibitor, delayed the return to baseline in extrapulmonary airways. CONCLUSION: Extracellular ATP induces a transient contractile response in human and rat airways, mainly due to P2X receptors and extracellular Ca(2+ )influx in addition with, in IPB, P2Y receptors stimulation and Ca(2+ )release from intracellular Ca(2+ )stores. Extracellular Ca(2+ )influx occurs through L-type voltage-dependent channels activated by external Na(+ )entrance through P2X receptors. The transience of the response cannot be attributed to ATP degradation but to purinoceptor desensitization and, in extrapulmonary airways, prostaglandin-dependent PKA activation

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C