534 research outputs found

    Paying for Status? - The effect of frequent flier program member status on air fare choice

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    Frequent flier programs (FFPs) are said to affect airline customer behaviour such that revenue of sponsoring airlines increases. To this end prior research relies on assumptions of competition, lock-in effects and variations in scale and scope of FFPs. Whether a FFP by itself induces a price premium remains unanswered. In an effort to shine some light on this question, we apply discrete choice analysis to a new proprietary data set of actual frequent flier member flight behaviour (fares paid, FFP points received) over a 12-months period. We take advantage of the variations in the structure of FFPs (Gold, Silver and Bronze tier levels), to assess both the existence of a FFP price premium and the price premiums average monetary value in US$ per FFP member. Our findings suggest that FFP members are willing to pay a price premium of up to six percent, which is directly attributable to the FFP.discrete choice analysis, loyalty programs, relationship marketing, price premium, frequent flier program, CRM

    The Effect of Convection on a Propagating Front with a Liquid Product: Comparison of Theory and Experiments

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    This work is devoted to the investigation of propagating polymerization fronts converting a liquid monomer into a liquid polymer. We consider a simplified mathematical model which consists of the heat equation and equation for the depth of conversion for one-step chemical reaction and of the Navier-Stokes equations under the Boussinesq approximation. We fulfill the linear stability analysis of the stationary propagating front and find conditions of convective and thermal instabilities. We show that convection can occur not only for ascending fronts but also for descending fronts. Though in the latter case the exothermic chemical reaction heats the cold monomer from above, the instability appears and can be explained by the interaction of chemical reaction with hydrodynamics. Hydrodynamics changes also conditions of the thermal instability. The front propagating upwards becomes less stable than without convection, the front propagating downwards more stable. The theoretical results are compared with experiments. The experimentally measured stability boundary for polymerization of benzyl acrylate in dimethyl formamide is well approximated by the theoretical stability boundary. (C) 1998 American Institute of Physics

    P2X7 Receptor Primes IL-1β and the NLRP3 Inflammasome in Astrocytes Subjected to Mechanical Strain

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    Inflammatory responses play a key role in many neural pathologies, with localized signaling from non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune signaling and can link neural insult to chronic inflammation. Stimulation of the NLRP3 inflammasome is a two-stage process. The priming stage involves upregulation of the biosynthesis of the structural components while activation results in their assembly into the actual inflammasome complex and subsequent activation. The priming step can be rate limiting and can connect insult to chronic inflammation but our knowledge of the signals that regulate NLRP3 inflammasome priming in sterile inflammatory conditions is limited. This study examined the link between mechanical strain and inflammasome priming in neural systems. Transient non-ischemic elevation of intraocular pressure (IOP) increased mRNA for inflammasome components IL-1β, NLRP3, ASC, CASP1 and IL-6 in rat and mouse retinas. The P2X7 receptor was implicated in the in vivo mechanosensitive priming of IL-1β and IL-6 transcription and translation. In vitro experiments with optic nerve head astrocytes demonstrated enhanced expression of the IL-1β and IL-6 genes following stretching or swelling. The increase in IL-1β expression was inhibited by degradation of extracellular ATP with apyrase, blocking pannexin hemichannels with carbenoxolone, probenecid or 10Panx1 peptide, P2X7 receptor antagonists (BBG, A839977 or A740003) as well inhibition of the NFκB transcription factor with Bay 11-7082. The swelling-dependent fall in expression of the NFκB inhibitor IκB-α was reduced by treatment of cells with A839977 and in P2X7 knockout mice. In summary, our data suggest that mechanical trauma to the retina results in priming of the NLRP3 inflammasome components and upregulated IL-6 expression and release. This was dependent upon ATP release through pannexin hemichannels and autostimulation of the P2X7 receptor. Since the P2X7 receptor can also trigger inflammasome activation it appears to have a central role in linking mechanical strain to neuroinflammation

    Structural and biophysical analysis of nuclease protein antibiotics

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    © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. Protein antibiotics (bacteriocins) are a large and diverse family of multidomain toxins that kill specific Gram-negative bacteria during intraspecies competition for resources. Our understanding of the mechanism of import of such potent toxins has increased significantly in recent years, especially with the reporting of several structures of bacteriocin domains. Less well understood is the structural biochemistry of intact bacteriocins and how these compare across bacterial species. Here, we focus on endonuclease (DNase) bacteriocins that target the genomes of Escherichia coli and Pseudomonas aeruginosa, known as E-Type colicins and S-Type pyocins, respectively, bound to their specific immunity (Im) proteins. First, we report the 3.2 Å structure of the DNase colicin ColE9 in complex with its ultra-high affinity Im protein, Im9. In contrast with Im3, which when bound to the ribonuclease domain of the homologous colicin ColE3 makes contact with the translocation (T) domain of the toxin, we find that Im9 makes no such contact and only interactions with the ColE9 cytotoxic domain are observed. Second, we report small-Angle X-ray scattering data for two S-Type DNase pyocins, S2 and AP41, into which are fitted recently determined X-ray structures for isolated domains. We find that DNase pyocins and colicins are both highly elongated molecules, even though the order of their constituent domains differs. We discuss the implications of these architectural similarities and differences in the context of the translocation mechanism of protein antibiotics through the cell envelope of Gram-negative bacteria

    Understanding the lived experiences of healthcare professionals during the COVID-19 pandemic : an interpretative phenomenological analysis

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    Background: Little research has examined the impact of working within the context of COVID-19 on UK healthcare professionals (HCPs) mental health and well-being, despite previous pandemic findings indicating that HCPs are particularly vulnerable to suffering PTSD and other mental health difficulties due to the nature of healthcare work. Specifically, it appears that no research has employed qualitative methodologies to explore the effects of working amidst COVID-19 on mental health for HCPs in the UK. Objective: To qualitatively examining the lived experiences of HCPs in Northern Ireland, working during the early stages of the pandemic and lockdown period (14.04.20 and 29.04.20). Method: Interpretative phenomenological analysis (IPA) was used to explore the experiences of healthcare professionals, who were working during the COVID-19 outbreak. Ten HCPs were recruited via a social media campaign and snowball sampling. All interviews were conducted via telephone and transcribed verbatim. Results: Three superordinate themes with subordinate themes were elicited through the analysis. Theme one centred on specific challenges of HCPs working during the pandemic, such as redeployment, isolation from loved ones, infection concerns, lack of PPE and impact on patient interpersonal care. Theme two offered insights into the mental health and wellbeing of HCPs, while many experienced feelings of fear, sadness and hypervigilance, all also demonstrated a marked resilience. Finally, many felt undervalued and misunderstood, and wished to press upon the general public seriousness of the disease. Conclusion: To the authors’ knowledge this is the first study to explore in depth, the unique experiences of frontline HCPs in Northern Ireland, offering a detailed account of the challenges confronted in these unprecedented circumstances and highlighting support needs within this cohort

    Structures of the Ultra-High-Affinity Protein-Protein Complexes of Pyocins S2 and AP41 and Their Cognate Immunity Proteins from Pseudomonas aeruginosa

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    © 2015 The Authors. Published by Elsevier Ltd. How ultra-high-affinity protein-protein interactions retain high specificity is still poorly understood. The interaction between colicin DNase domains and their inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is essential for the neutralisation of endogenous DNase catalytic activity and for protection against exogenous DNase bacteriocins. The colicin DNase-Im interaction is a model system for the study of high-affinity protein-protein interactions. However, despite the fact that closely related colicin-like bacteriocins are widely produced by Gram-negative bacteria, this interaction has only been studied using colicins from Escherichia coli. In this work, we present the first crystal structures of two pyocin DNase-Im complexes from Pseudomonas aeruginosa, pyocin S2 DNase-ImS2 and pyocin AP41 DNase-ImAP41. These structures represent divergent DNase-Im subfamilies and are important in extending our understanding of protein-protein interactions for this important class of high-affinity protein complex. A key finding of this work is that mutations within the immunity protein binding energy hotspot, helix III, are tolerated by complementary substitutions at the DNase-Immunity protein binding interface. Im helix III is strictly conserved in colicins where an Asp forms polar interactions with the DNase backbone. ImAP41 contains an Asp-to-Gly substitution in helix III and our structures show the role of a co-evolved substitution where Pro in DNase loop 4 occupies the volume vacated and removes the unfulfilled hydrogen bond. We observe the co-evolved mutations in other DNase-Immunity pairs that appear to underpin the split of this family into two distinct groups

    T1R3: A human calcium taste receptor

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    Many animals can detect the taste of calcium but it is unclear how or whether humans have this ability. We show here that calcium activates hTAS1R3-transfected HEK293 cells and that this response is attenuated by lactisole, an inhibitor of hT1R3. Moreover, trained volunteers report that lactisole reduces the calcium intensity of calcium lactate. Thus, humans can detect calcium by taste, T1R3 is a receptor responsible for this, and lactisole can reduce the taste perception of calcium by acting on T1R3

    The echinoderm innate humoral immune response

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    Abstract: Multicellular organisms have an immune system, which is essential for the survival of living beings. Interest in the immune system has been expanded since common characteristics of innate immunity between Drosophila melanogaster (Meigen, 1830) and mammals were discovered in the 1980. Since then, immunology has mainly focused on the adaptive immune system that seems to be restricted to vertebrates. Unlike the innate immunity, the adaptive one is acquired after exposure to a specific antigen (Ag) and includes: antigen-presenting cells such as macrophages, proliferation of B and T lymphocytes, Ag-specific antibody/cytokine production and immunological memory. Innate immunity is instead a process of cellular defense at low specificity, which is designed to prevent and combat infectious agents that penetrate at the tissue level, and may be the only form of immunity present in invertebrates such as sea urchins. The immune system of invertebrates acts through (i) cellular components (cell-mediated immunity) in which the effectors of defense reactions are represented by immune cells; (ii) soluble factors (humoral immunity), secreted by the immune cells, such as lectins, agglutinins, lysins, antimicrobial peptides and the prophenoloxidase (proPO) activating system, which act in parallel with the immune cells to fight pathogens and other foreign substances. Here we aim to deepen the study on humoral immunity of invertebrates, especially referring to the phylum Echinodermata because of its features shared with protostomes and other deuterostomes, and suggesting a key step during evolution

    Knowing your place and commanding space:de/constructions of gendered embodiment in mixed-sex karate

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    Feminists have long acknowledged that gendered divisions in access to spaces of leisure, and how women and men physically take up that space, reproduces gender inequality. This article will explore how karate practitioners participate in the space of mixed-sex karate practice and how such uses of space de/construct gendered embodiments and a gender hierarchy. Data presented is drawn from nine months of ethnographic emersion within three karate clubs and fifteen photo-elicitation interviews with karate participants from the three clubs. The findings of this paper suggest that whilst women often occupied spaces of expertise within the karate hall, gendered distinctions in uses of space emerged in the more subtle ways in which women and men used their voice, responded to the tacit and smelt dilemmas of sweat, and moved their bodies across physical space. This research highlights both the potential of physical leisure practice to ‘undo’ conventional gendered embodiments that particularly restrict women’s intentionality in the world (Young, 1980), and the power of spatially-attuned research to illuminate the minute ways in which unequal gender relations are naturalised, legitimised and done
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