236 research outputs found

    From bore-soliton-splash to a new wave-to-wire wave-energy model

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    We explore extreme nonlinear water-wave amplification in a contraction or, analogously, wave amplification in crossing seas. The latter case can lead to extreme or rogue-wave formation at sea. First, amplification of a solitary-water-wave compound running into a contraction is disseminated experimentally in a wave tank. Maximum amplification in our bore–soliton–splash observed is circa tenfold. Subsequently, we summarise some nonlinear and numerical modelling approaches, validated for amplifying, contracting waves. These amplification phenomena observed have led us to develop a novel wave-energy device with wave amplification in a contraction used to enhance wave-activated buoy motion and magnetically induced energy generation. An experimental proof-of-principle shows that our wave-energy device works. Most importantly, we develop a novel wave-to-wire mathematical model of the combined wave hydrodynamics, wave-activated buoy motion and electric power generation by magnetic induction, from first principles, satisfying one grand variational principle in its conservative limit. Wave and buoy dynamics are coupled via a Lagrange multiplier, which boundary value at the waterline is in a subtle way solved explicitly by imposing incompressibility in a weak sense. Dissipative features, such as electrical wire resistance and nonlinear LED loads, are added a posteriori. New is also the intricate and compatible finite-element space–time discretisation of the linearised dynamics, guaranteeing numerical stability and the correct energy transfer between the three subsystems. Preliminary simulations of our simplified and linearised wave-energy model are encouraging and involve a first study of the resonant behaviour and parameter dependence of the device

    Mucosal sensitization to German cockroach involves protease-activated receptor-2

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    <p>Abstract</p> <p>Background</p> <p>Allergic asthma is on the rise in developed countries. A common characteristic of allergens is that they contain intrinsic protease activity, and many have been shown to activate protease-activated receptor (PAR)-2 <it>in vitro</it>. The role for PAR-2 in mediating allergic airway inflammation has not been assessed using a real world allergen.</p> <p>Methods</p> <p>Mice (wild type or PAR-2-deficient) were sensitized to German cockroach (GC) feces (frass) or protease-depleted GC frass by either mucosal exposure or intraperitoneal injection and measurements of airway inflammation (IL-5, IL-13, IL-17A, and IFNγ levels in the lung, serum IgE levels, cellular infiltration, mucin production) and airway hyperresponsiveness were performed.</p> <p>Results</p> <p>Following systemic sensitization, GC frass increased airway hyperresponsiveness, Th2 cytokine release, serum IgE levels, cellular infiltration and mucin production in wild type mice. Interestingly, PAR-2-deficient mice had similar responses as wild type mice. Since these data were in direct contrast to our finding that mucosal sensitization with GC frass proteases regulated airway hyperresponsiveness and mucin production in BALB/c mice (Page et. al. 2007 Resp Res 8:91), we backcrossed the PAR-2-deficient mice into the BALB/c strain. Sensitization to GC frass could now occur via the more physiologically relevant method of intratracheal inhalation. PAR-2-deficient mice had significantly reduced airway hyperresponsiveness, Th2 and Th17 cytokine release, serum IgE levels, and cellular infiltration compared to wild type mice when sensitization to GC frass occurred through the mucosa. To confirm the importance of mucosal exposure, mice were systemically sensitized to GC frass or protease-depleted GC frass via intraperitoneal injection. We found that removal of proteases from GC frass had no effect on airway inflammation when administered systemically.</p> <p>Conclusions</p> <p>We showed for the first time that allergen-derived proteases in GC frass elicit allergic airway inflammation via PAR-2, but only when allergen was administered through the mucosa. Importantly, our data suggest the importance of resident airway cells in the initiation of allergic airway disease, and could make allergen-derived proteases attractive therapeutic targets.</p

    Earnings management and audit quality:stakeholders’ perceptions

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    This paper examines the perceptions of Libyan Commercial Banks’ (LCBs) stakeholders regarding the role of the external auditor in relation to earnings management (EM). A total of 28 semi-structured interviews were carried out with a range of LCB stakeholders comprising preparers of financial statements, users, regulators and academics. A questionnaire survey of stakeholders which yielded 102 Responses (response rate 53%) was also carried out. A variety of views were held which varied to some extent according to stakeholder group. A widely held perception amongst interviewees was that the auditor has the ability to detect EM practices but may not be able to prevent it. However questionnaire respondents were, in aggregate, more confident of the auditor’s ability to deter EM due to the influence of the audit report. The paper provides insights into stakeholders’ perceptions of the quality of bank audits. The findings are of particular relevance to regulators, and specifically, the Central Bank of Libya. Perceptions of audit quality raise questions about its guidance and regulations especially in connection with audit firm rotation. Perceptions of audit quality, and therefore, of the credibility of financial statements should be of interest to all stakeholders. The importance of the banking sector for society has been amply demonstrated in recent years. A well-functioning audit function is a key component of its regulation. To the best of our knowledge, this paper is the first to examine issues related to banks’ audit quality and audit firm rotation in Libya

    Determination of Therapeutic Equivalence of Generic Products of Gentamicin in the Neutropenic Mouse Thigh Infection Model

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    Background: Drug regulatory agencies (DRA) support prescription of generic products of intravenous antibiotics assuming therapeutic equivalence from pharmaceutical equivalence. Recent reports of deaths associated with generic heparin and metoprolol have raised concerns about the efficacy and safety of DRA-approved drugs. Methodology/Principal Findings: To challenge the assumption that pharmaceutical equivalence predicts therapeutic equivalence, we determined in vitro and in vivo the efficacy of the innovator product and 20 pharmaceutically equivalent generics of gentamicin. The data showed that, while only 1 generic product failed in vitro (MIC = 45.3 vs. 0.7 mg/L, P,0.05), 10 products (including gentamicin reference powder) failed in vivo against E. coli due to significantly inferior efficacy (E max = 4.81 to 5.32 vs. 5.99 log 10 CFU/g, P#0.043). Although the design lacked power to detect differences in survival after thigh infection with P. aeruginosa, dissemination to vital organs was significantly higher in animals treated with generic gentamicin despite 4 days of maximally effective treatment. Conclusion: Pharmaceutical equivalence does not predict therapeutic equivalence of generic gentamicin. Stricter criteri

    New Foundations: Pseudo-pacification and special liberty as potential cornerstones of a multi-level theory of homicide and serial murder

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    Over the past 30 years the industrialized West has witnessed a move towards space, heterogeneity and subjectivity in the criminological study of violence and homicide. Although large-scale quantitative studies of the temporal and spatial distribution of homicide continue to provide a broad empirical context, aetiological explanations tend to be based on analyses of the heterogeneous psychological interactions and experiences of individual subjects at the micro-level. However, mid-range studies of the temporal and spatial distribution of perpetrators and victims of homicide between unrelated adults have provided a useful link between the micro- and macro-levels. Focusing primarily on British homicide and serial murder, this article attempts to strengthen this link by combining contemporary micro-analyses of the subjective motives of perpetrators with mid-range analyses of space, which can therefore be seen as part of the structural tradition of theorizing about homicide and serial murder. Placing these analyses in a broad underlying context constituted by major historical shifts in political economy and the cultural forms of ‘pseudo-pacification’ and ‘special liberty’ will lay the initial cornerstones for an integrated multi-level theory. © The Author(s) 2014

    The Leukemia-Specific Fusion Gene ETV6/RUNX1 Perturbs Distinct Key Biological Functions Primarily by Gene Repression

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    -positive leukemic cell lines.-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories “stem cell properties”, “B-cell differentiation”, “immune response”, “cell adhesion” and “DNA damage” with RT-qPCR. fusion gene interferes with key regulatory functions that shape the biology of this leukemia subtype. E/R may thus indeed constitute the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets

    Childhood Predictors of Desistance and Level of Persistence in Offending in Early Onset Offenders

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    Childhood predictors of adolescent offending careers were studied in 310 boys from the longitudinal Pittsburgh Youth Study who started offending prior to age 12. Three main groups were distinguished: serious persisters (n = 95), moderately serious persisters (n = 117), desisters (n = 63), and an intermittent group (n = 35). Group membership was predicted using risk and promotive factors measured in childhood. Serious and moderately serious persisters could be distinguished well from desisters (29.2% and 32.3% explained variance). Distinction between the two persister groups proved somewhat more difficult (20.9% explained variance). More serious persisters than desisters showed disruptive behavior, while moderately serious persisters fell in between. Further, more moderately serious persisters were marked by social disadvantage. Family involvement, small family and positive peer relationships were promotive of desistance. Concluding, early onset offenders show considerable heterogeneity in their adolescent offending careers which seem to some extent to be predicted by different sets of risk and promotive factors
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