Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

The Political Economy of Non-Traditional Security: Explaining the Governance of Avian Influenza in Indonesia

Given the common association of non-traditional security (NTS) problems with globalisation, surprisingly little attention has been paid to how the political economy context of given NTS issues shape how they are securitised and managed in practice. We argue that security and its governance are always highly contested because different modes of security governance invariably privilege particular interests and normative agendas in state and society, which relate directly to the political economy. Drawing on critical political geography, we argue that, because NTS issues are perceived as at least potentially transnational, their securitisation often involves strategic attempts by actors and coalitions to ‘rescale’ their governance beyond the national political and institutional arenas, into new, expert-dominated modes of governance. Such efforts are often resisted by other coalitions, for which this rescaling is deleterious. As evidenced by a case study of avian influenza in Indonesia, particular governance outcomes depend upon the nature of the coalitions assembled for and against rescaling in specific situations, while these coalitions’ make-up and relative strength is shaped by the political economy of the industries that rescaling would affect, viewed against the broader backdrop of state-society relations

A state-of-the-art review of curve squeal noise: Phenomena, mechanisms, modelling and mitigation

[EN] Curve squeal is an intense tonal noise occurring when a rail vehicle negotiates a sharp curve. The phenomenon can be considered to be chaotic, with a widely differing likelihood of occurrence on different days or even times of day. The term curve squeal may include several different phenomena with a wide range of dominant frequencies and potentially different excitation mechanisms. This review addresses the different squeal phenomena and the approaches used to model squeal noise; both time-domain and frequency-domain approaches are discussed and compared. Supporting measurements using test rigs and field tests are also summarised. A particular aspect that is addressed is the excitation mechanism. Two mechanisms have mainly been considered in previous publications. In many early papers the squeal was supposed to be generated by the so-called falling friction characteristic in which the friction coefficient reduces with increasing sliding velocity. More recently the mode coupling mechanism has been raised as an alternative. These two mechanisms are explained and compared and the evidence for each is discussed. Finally, a short review is given of mitigation measures and some suggestions are offered for why these are not always successful.Squicciarini, G.; Thompson, D.; Ding, B.; Baeza González, LM. (2018). A state-of-the-art review of curve squeal noise: Phenomena, mechanisms, modelling and mitigation. Notes on Numerical Fluid Mechanics and Multidisciplinary Design. 139:3-41. https://doi.org/10.1007/978-3-319-73411-8_1S341139Anderson, D., Wheatley, N., Fogarty, B., Jiang, J., Howie, A., Potter, W.: Mitigation of curve squeal noise in Queensland, New South Wales and South Australia. In: Conference on Railway Engineering. pp. 625–636, Perth, Australia (2008)Hanson, D., Jiang, J., Dowdell, B., Dwight, R.: Curve squeal: causes, treatments and results. 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Springer, Heidelberg (2015)Zenzerovic, I., Kropp, W., Pieringer, A.: An engineering time-domain model for curve squeal: tangential point-contact model and Green’s functions approach. J. Sound Vib. 376, 149–165 (2016)Pieringer, A., Torstensson, P.T., Giner, J., Baeza, L.: Investigation of railway curve squeal using a combination of frequency- and time-domain models. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp 81–93. Springer, Heidelberg (2018)Chen, G.X., Xiao, J.B., Liu, Q.Y., Zhou. Z.R.: Complex eigenvalue analysis of railway curve squeal. In: Schulte-Werning, B., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 99, pp. 433–439. Springer, Heidelberg (2008)Fourie, D.J., Gräbe, P.J., Heyns, P.S., Fröhling, R.D.: Analysis of wheel squeal due to unsteady longitudinal creepage using the complex eigenvalue method. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp 55–67. Springer, Heidelberg (2018)Wang, C., Dwight, R., Li, W., Jiang, J.: Prediction on curve squeal in the case of constant wheel rail friction coefficient. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp XXX–XXX. Springer, Heidelberg (2018)Ding, B., Squicciarini, G., Thompson, D.J.: Effects of rail dynamics and friction characteristics on curve squeal. In: XIII International Conference on Motion and Vibration Control and XII International Conference on Recent Advances in Structural Dynamics (MoViC/RASD), Southampton (2016)Bleedorn, T.G., Johnstone. B.: Steerable steel wheel systems and wheel noise suppression. In: Conference Rec IAS 12th Annual Meeting, Los Angeles, California (1977)Koch, J.R., Vincent, N., Chollet, H., Chiello, O.: Curve squeal of urban rolling stock—part 2: parametric study on a 1/4 scale test rig. J. 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Wear 265(9), 1309–1316 (2008)Fletcher, D.I., Lewis, S.: Creep curve measurement to support wear and adhesion modelling, using a continuously variable creep twin disc machine. Wear 298–299, 57–65 (2013)Fletcher, D.I.: A new two-dimensional model of rolling–sliding contact creep curves for a range of lubrication types. Proc. Inst. Mech. Eng. Part J: J. Eng. Tribol. 227(6), 529–537 (2013)Matsumoto, A., Sato, Y., Ono, H., Wang, Y., Yamamoto, M., Tanimoto, M., Oka, Y.: Creep force characteristics between rail and wheel on scaled model. Wear 253(1), 199–203 (2002)Janssens, M.H.A., van Vliet, W.J., Kooijman, P.P., De Beer, F.G.: Curve squeal of railbound vehicles (part 3): measurement method and results. In: Proceedings of Internoise, vol. 3, pp. 1568–1571, Nice, France (2000)Monk-Steel, A.D., Thompson, D.J., De Beer, F.G., Janssens, M.H.A.: An investigation into the influence of longitudinal creepage on railway squeal noise due to lateral creepage. J. 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Dyn. 33(4), 233–259 (2000)Bruni, S., Goodall, R., Mei, T.X., Tsunashima, H.: Control and monitoring for railway vehicle dynamics. Veh. Syst. Dyn. 45(7–8), 743–779 (2007)Hiensch, M., Larsson, P.O., Nilsson, O., Levy, D., Kapoor, A., Franklin, F., Nielsen, J., Ringsberg, J., Josefson, L.: Two-material rail development: field test results regarding rolling contact fatigue and squeal noise behaviour. Wear 258(7), 964–972 (2005)Kopp, E.: Fünf Jahre Erfahrungen mit asymmetrisch geschliffenen Schienenprofilen. Eisenbahn Techn. Rundsch. 40, 665 (1991

Mixed-strain housing for female C57BL/6, DBA/2, and BALB/c mice: validating a split-plot design that promotes refinement and reduction

Abstract Background Inefficient experimental designs are common in animal-based biomedical research, wasting resources and potentially leading to unreplicable results. Here we illustrate the intrinsic statistical power of split-plot designs, wherein three or more sub-units (e.g. individual subjects) differing in a variable of interest (e.g. genotype) share an experimental unit (e.g. a cage or litter) to which a treatment is applied (e.g. a drug, diet, or cage manipulation). We also empirically validate one example of such a design, mixing different mouse strains -- C57BL/6, DBA/2, and BALB/c -- within cages varying in degree of enrichment. As well as boosting statistical power, no other manipulations are needed for individual identification if co-housed strains are differentially pigmented, so also sparing mice from stressful marking procedures. Methods The validation involved housing 240 females from weaning to 5 months of age in single- or mixed- strain trios, in cages allocated to enriched or standard treatments. Mice were screened for a range of 26 commonly-measured behavioural, physiological and haematological variables. Results Living in mixed-strain trios did not compromise mouse welfare (assessed via corticosterone metabolite output, stereotypic behaviour, signs of aggression, and other variables). It also did not alter the direction or magnitude of any strain- or enrichment-typical difference across the 26 measured variables, or increase variance in the data: indeed variance was significantly decreased by mixed- strain housing. Furthermore, using Monte Carlo simulations to quantify the statistical power benefits of this approach over a conventional design demonstrated that for our effect sizes, the split- plot design would require significantly fewer mice (under half in most cases) to achieve a power of 80 %. Conclusions Mixed-strain housing allows several strains to be tested at once, and potentially refines traditional marking practices for research mice. Furthermore, it dramatically illustrates the enhanced statistical power of split-plot designs, allowing many fewer animals to be used. More powerful designs can also increase the chances of replicable findings, and increase the ability of small-scale studies to yield significant results. Using mixed-strain housing for female C57BL/6, DBA/2 and BALB/c mice is therefore an effective, efficient way to promote both refinement and the reduction of animal-use in research

β-Catenin Signaling Increases during Melanoma Progression and Promotes Tumor Cell Survival and Chemoresistance

Beta-catenin plays an important role in embryogenesis and carcinogenesis by controlling either cadherin-mediated cell adhesion or transcriptional activation of target gene expression. In many types of cancers nuclear translocation of beta-catenin has been observed. Our data indicate that during melanoma progression an increased dependency on the transcriptional function of beta-catenin takes place. Blockade of beta-catenin in metastatic melanoma cell lines efficiently induces apoptosis, inhibits proliferation, migration and invasion in monolayer and 3-dimensional skin reconstructs and decreases chemoresistance. In addition, subcutaneous melanoma growth in SCID mice was almost completely inhibited by an inducible beta-catenin knockdown. In contrast, the survival of benign melanocytes and primary melanoma cell lines was less affected by beta-catenin depletion. However, enhanced expression of beta-catenin in primary melanoma cell lines increased invasive capacity in vitro and tumor growth in the SCID mouse model. These data suggest that beta-catenin is an essential survival factor for metastatic melanoma cells, whereas it is dispensable for the survival of benign melanocytes and primary, non-invasive melanoma cells. Furthermore, beta-catenin increases tumorigenicity of primary melanoma cell lines. The differential requirements for beta-catenin signaling in aggressive melanoma versus benign melanocytic cells make beta-catenin a possible new target in melanoma therapy

Connectivity within and among a Network of Temperate Marine Reserves

Networks of marine reserves are increasingly being promoted as a means of conserving marine biodiversity. One consideration in designing systems of marine reserves is the maintenance of connectivity to ensure the long-term persistence and resilience of populations. Knowledge of connectivity, however, is frequently lacking during marine reserve design and establishment. We characterise patterns of genetic connectivity of 3 key species of habitat-forming macroalgae across an established network of temperate marine reserves on the east coast of Australia and the implications for adaptive management and marine reserve design. Connectivity varied greatly among species. Connectivity was high for the subtidal macroalgae Ecklonia radiata and Phyllospora comosa and neither species showed any clear patterns of genetic structuring with geographic distance within or among marine parks. In contrast, connectivity was low for the intertidal, Hormosira banksii, and there was a strong pattern of isolation by distance. Coastal topography and latitude influenced small scale patterns of genetic structure. These results suggest that some species are well served by the current system of marine reserves in place along this temperate coast but it may be warranted to revisit protection of intertidal habitats to ensure the long-term persistence of important habitat-forming macroalgae. Adaptively managing marine reserve design to maintain connectivity may ensure the long-term persistence and resilience of marine habitats and the biodiversity they support

Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats

International audienceBACKGROUND: Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. METHODS AND FINDINGS: Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. CONCLUSIONS: Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression