455 research outputs found

    A motif-based approach to network epidemics

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    Networks have become an indispensable tool in modelling infectious diseases, with the structure of epidemiologically relevant contacts known to affect both the dynamics of the infection process and the efficacy of intervention strategies. One of the key reasons for this is the presence of clustering in contact networks, which is typically analysed in terms of prevalence of triangles in the network. We present a more general approach, based on the prevalence of different four-motifs, in the context of ODE approximations to network dynamics. This is shown to outperform existing models for a range of small world networks

    The influence of pre-fermentative maceration and ageing factors on ester profile and marker determination of Pedro Ximenez sparkling wines

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    The influence of pre-fermentative maceration and ageing factors on the ester profiles of Pedro Ximenez sparkling wines was evaluated. The pre-fermentative maceration consisted of the skin-maceration of musts at 10 degrees C for 6 h. The sparkling wines were produced following the Champenoise method. Samples were monitored at 3, 6 and 9 months of ageing on lees. Sparkling wines with pre fermentative maceration displayed higher contents of ethyl esters of branched acids and cinnamates. Meanwhile, those without maceration showed higher levels of ethyl esters of fatty acids and higher alcohol acetates. The study of statistical interactions elucidated different hydrolytic kinetics and developments in higher alcohol acetates and ethyl esters of branched acids during ageing. The application of a dual criterion based on univariate (ANOVA) and multivariate analyses (OPLS-DA) allowed us to identify new potential volatile markers related to pre-fermentative maceration and ageing time, reported for the first time in sparkling wines

    CTLA-4 Signaling Regulates the Intensity of Hypersensitivity Responses to Food Antigens, but is Not Decisive in the Induction of Sensitization

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    Although food allergy has emerged as a major health problem, the mechanisms that are decisive in the development of sensitization to dietary Ag remain largely unknown. CTLA-4 signaling negatively regulates immune activation, and may play a crucial role in preventing induction and/or progression of sensitization to food Ag. To elucidate the role of CTLA-4 signaling in responses to food allergens, a murine model of peanut allergy was used. During oral exposure to peanut protein extract (PPE) together with the mucosal adjuvant cholera toxin (CT), which induces peanut allergy, CTLA-4 ligation was prevented using a CTLA-4 mAb. Additionally, the effect of inhibition of the CTLA-4 pathway on oral exposure to PPE in the absence of CT, which leads to unresponsiveness to peanut Ag, was explored. During sensitization, anti-CTLA-4 treatment considerably enhanced IgE responses to PPE and the peanut allergens, Ara h 1, Ara h 3, and Ara h 6, resulting in elevated mast cell degranulation upon an oral challenge. Remarkably, antagonizing CTLA-4 during exposure to PPE in the absence of CT resulted in significant induction of Th2 cytokines and an elevation in total serum IgE levels, but failed to induce allergen-specific IgE responses and mast cell degranulation upon a PPE challenge. These results indicate that CTLA-4 signaling is not the crucial factor in preventing sensitization to food allergens, but plays a pivotal role in regulating the intensity of a food allergic sensitization response. Furthermore, these data indicate that a profoundly Th2-biased cytokine environment is insufficient to induce allergic responses against dietary Ag

    Combined over-expression of two cytochrome P450 genes exacerbates the fitness cost of pyrethroid resistance in the major African malaria vector Anopheles funestus

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    Metabolic resistance driven by multiple P450 genes is worsening insecticide resistance in malaria vectors. However, it remains unclear whether such multiple over-expression imposes an additive fitness cost in the vectors. Here, we showed that two highly over-expressed P450 genes (CYP6P9a and CYP6P9b) combine to impose additive fitness costs in pyrethroid-resistant Anopheles funestus. Genotyping of the CYP6P9b resistance allele in hybrid mosquitoes from a pyrethroid-resistant FUMOZ-R and the susceptible FANG strains revealed that this gene imposes a fitness cost in resistant mosquitoes similar to CYP6P9a. Homozygote susceptible CYP6P9b_S (SS) significantly lay more eggs than the resistant (OR = 2.2, P = 0.04) and with greater hatching rate (p < 0.04). Homozygote resistant larvae CYP6P9b_R (RR) developed significantly slower than homozygote susceptible from L1-L4 (χ2 = 7.2; P = 0.007) with a late pupation observed for RR compared to both heterozygotes and homozygotes susceptible (χ 2 = 11.17; P = 0.0008). No difference was observed between genotypes for adult longevity with no change in allele frequency and gene expression across the lifespan. Furthermore, we established that CYP6P9b combines with CYP6P9a to additively exacerbate the fitness cost of pyrethroid resistance with a greater reduction in fecundity/fertility and increased developmental time of double homozygote resistant mosquitoes. Moreover, an increased proportion of double homozygote susceptible individuals was noted over 10 generations in the insecticide-free environment (χ2 = 6.3; P = 0.01) suggesting a reversal to susceptibility in the absence of selection. Such greater fitness cost imposed by multiple P450 genes shows that resistance management strategy based on rotation could help slow the spread of resistance

    Weak measurement of arrival time

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    The arrival time probability distribution is defined by analogy with the classical mechanics. The difficulty of requirement to have the values of non-commuting operators is circumvented using the concept of weak measurements. The proposed procedure is suitable to the free particles and to the particles subjected to an external potential, as well. It is shown that such an approach imposes an inherent limitation to the accuracy of the arrival time determination.Comment: 3 figure

    The rationale for heart team decision-making for patients with stable, complex coronary artery disease

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    Stable complex coronary artery disease can be treated with coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Multidisciplinary decision-making has gained more emphasis over the recent years to select the most optimal treatment strategy for individual patients with stable complex coronary artery disease. However, the so-called 'Heart Team' concept has not been widely implemented. Yet, decision-making has shown to remain suboptimal; there is large variability in PCI-to-CABG ratios, which may predominantly be the consequence of physician-related factors that have raised concerns regarding overuse, underuse, and inappropriate selection of revascularization. In this review, we summarize these and additional data to support the statement that a multidisciplinary Heart Team consisting of at least a clinical/non-invasive cardiologist, interventional cardiologist, and cardiac surgeon, can together better analyse and interpret the available diagnostic evidence, put into context the clinical condition of the patient as well as consider individual preference and local expertise, and through shared decision-making with the patient can arrive at a most optimal joint treatment strategy recommendation for patients with stable co

    Lattice dynamics effects on small polaron properties

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    This study details the conditions under which strong-coupling perturbation theory can be applied to the molecular crystal model, a fundamental theoretical tool for analysis of the polaron properties. I show that lattice dimensionality and intermolecular forces play a key role in imposing constraints on the applicability of the perturbative approach. The polaron effective mass has been computed in different regimes ranging from the fully antiadiabatic to the fully adiabatic. The polaron masses become essentially dimension independent for sufficiently strong intermolecular coupling strengths and converge to much lower values than those tradition-ally obtained in small-polaron theory. I find evidence for a self-trapping transition in a moderately adiabatic regime at an electron-phonon coupling value of .3. Our results point to a substantial independence of the self-trapping event on dimensionality.Comment: 8 pages, 5 figure
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