Aprotinin inhibits proinflammatory activation of endothelial cells by thrombin through the protease-activated receptor 1

ObjectiveThrombin is generated in significant quantities during cardiopulmonary bypass and mediates adverse events, such as platelet aggregation and proinflammatory responses, through activation of the high-affinity thrombin receptor protease-activated receptor 1, which is expressed on platelets and endothelium. Thus antagonism of protease-activated receptor 1 might have broad therapeutic significance. Aprotinin, used clinically to reduce transfusion requirements and the inflammatory response to bypass, has been shown to inhibit protease-activated receptor 1 on platelets in vitro and in vivo. Here we have examined whether aprotinin inhibits endothelial protease-activated receptor 1 activation and resulting proinflammatory responses induced by thrombin.MethodsProtease-activated receptor 1 expression and function were examined in cultured human umbilical vein endothelial cells after treatment with α-thrombin at 0.02 to 0.15 U/mL in the presence or absence of aprotinin (200-1600 kallikrein inhibitory units/mL). Protease-activated receptor 1 activation was assessed by using an antibody, SPAN-12, which detects only the unactivated receptor, and thrombin-mediated calcium fluxes. Other thrombin-dependent inflammatory pathways investigated were phosphorylation of the p42/44 mitogen-activated protein kinase, upregulation of the early growth response 1 transcription factor, and production of the proinflammatory cytokine interleukin 6.ResultsPretreatment of cultured endothelial cells with aprotinin significantly spared protease-activated receptor 1 receptor cleavage (P < .0001) and abrogated calcium fluxes caused by thrombin. Aprotinin inhibited intracellular signaling through p42/44 mitogen-activated protein kinase (P < .05) and early growth response 1 transcription factor (P < .05), as well as interleukin 6 secretion caused by thrombin (P < .005).ConclusionsThis study demonstrates that endothelial cell activation by thrombin and downstream inflammatory responses can be inhibited by aprotinin in vitro through blockade of protease-activated receptor 1. Our results provide a new molecular basis to help explain the anti-inflammatory properties of aprotinin reported clinically

Benchmark low-mass objects in Moving Groups

This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.In order to compile a sample of ultracool dwarfs that will serve as benchmarks for testing theoretical formation and evolutionary models, we selected low-mass cool (>M7) objects that are potentially members of five known young Moving Groups in the solar neighbourhood. We have studied the kinematics of the sample, finding that 49 targets belong to the young disk area, from which 36 are kinematic member of one of the five moving groups under study. Some of the identified low-mass members have been spectroscopically characterised (T-eff, log g) and confirmed as young members through a detailed study of age indicators

Lifetime distributions in the methods of non-equilibrium statistical operator and superstatistics

A family of non-equilibrium statistical operators is introduced which differ by the system age distribution over which the quasi-equilibrium (relevant) distribution is averaged. To describe the nonequilibrium states of a system we introduce a new thermodynamic parameter - the lifetime of a system. Superstatistics, introduced in works of Beck and Cohen [Physica A \textbf{322}, (2003), 267] as fluctuating quantities of intensive thermodynamical parameters, are obtained from the statistical distribution of lifetime (random time to the system degeneracy) considered as a thermodynamical parameter. It is suggested to set the mixing distribution of the fluctuating parameter in the superstatistics theory in the form of the piecewise continuous functions. The distribution of lifetime in such systems has different form on the different stages of evolution of the system. The account of the past stages of the evolution of a system can have a substantial impact on the non-equilibrium behaviour of the system in a present time moment.Comment: 18 page

'Support our networking and help us belong!': listening to beginning secondary school science teachers

This study, drawing on the voice of beginning teachers, seeks to illuminate their experiences of building professional relationships as they become part of the teaching profession. A networking perspective was taken to expose and explore the use of others during the first three years of a teacher’s workplace experience. Three case studies, set within a wider sample of 11 secondary school science teachers leaving one UK university’s PostGraduate Certificate in Education, were studied. The project set out to determine the nature of the networks used by teachers in terms of both how they were being used for their own professional development and perceptions of how they were being used by others in school. Affordances and barriers to networking were explored using notions of identity formation through social participation. The focus of the paper is on how the teachers used others to help shape their sense of belonging to this, their new workplace. The paper develops ideas from network theories to argue that membership of the communities are a subset of the professional inter‐relationships teachers utilise for their professional development. During their first year of teaching, eight teachers were interviewed, completing 13 semi‐structured interviews. This was supplemented in Year 2 by a questionnaire survey of their experiences. In the third year of the programme, 11 teachers (including the original sample of eight) were surveyed using a network mapping tool in which they represented their communications with people, groups and resources. Finally, three of the teachers (common to both samples) were then interviewed specifically about their networking practices and experiences using the generation of their network map as a stimulated recall focus. The implications of the analysis of these accounts are that these beginning teachers did not perceive of themselves wholly as novices and that their personal aspirations to increase participation in practical science, develop a career or work for pupils holistically did not always sit comfortably with the school communities into which they were being accommodated. While highlighting the importance of trust and respect in establishing relationships, these teachers’ accounts highlight the importance of finding ‘peers’ from whom they can find support and with whom they can reflect and potentially collaborate towards developing practice. They also raise questions about who these ‘peers’ might be and where they might be found

Protecting the environment through insect farming as a means to produce protein for use as livestock, poultry, and aquaculture feed

Securing protein for the approximate 10 billion humans expected to inhabit our planet by 2050 is a major priority for the global community. Evidence has accrued over the past 30 years that strongly supports and justifies the sustainable use of insects as a means to produce protein products as feed for pets, livestock, poultry, and aquacultured species. Researchers and entrepreneurs affiliated with universities and industries, respectively, from 18 nations distributed across North and South America, Europe, Asia, Africa and Australia contributed to the development of this article, which is an indication of the global interest on this topic. A brief overview of insects as feed for the aquaculture industry along with a review of the black soldier fly, Hermetia illucens (Diptera: Stratiomyidae), as a model for such systems is provided

Damage in single lap joints of woven fabric reinforced polymeric composites subjected to transverse impact loading

Single lap joints of woven glass fabric reinforced phenolic composites, having four different overlap widths, were impacted transversely using a hemispherical impactor with different velocities in the low velocity impact range. The resulting damage was observed at various length scales (from micro to macro) using transmission photography, ultrasonic c-scan and x-ray micro tomography (XMT), in support of each other. These experimental observations were used for classification of damage in terms of damage scale, location (i.e. ply, interfaces between plies or bond failure between the two adherends) and mechanisms, with changing overlap width and impact velocity. In addition, finite element analysis was used to simulate delamination and disbond failure. These simulations were used to further explain the observed dependence of damage on overlap width and impact velocity. The results from these experiments and simulations lead to the proposal of a concept of lower and upper characteristic overlap width. These bounds relate the dominant damage pattern (i.e. scale, location and mechanism) with overlap width of the joint for a given impact velocity range.National University of Sciences and Technology, NUST, Pakistan: The University of Manchester, EPS fellowshi