Cell Invasion by Neisseria meningitidis Requires a Functional Interplay between the Focal Adhesion Kinase, Src and Cortactin

Entry of Neisseria meningitidis (the meningococcus) into human brain microvascular endothelial cells (HBMEC) is mediated by fibronectin or vitronectin bound to the surface protein Opc forming a bridge to the respective integrins. This interaction leads to cytoskeletal rearrangement and uptake of meningococci. In this study, we determined that the focal adhesion kinase (FAK), which directly associates with integrins, is involved in integrin-mediated internalization of N. meningitidis in HBMEC. Inhibition of FAK activity by the specific FAK inhibitor PF 573882 reduced Opc-mediated invasion of HBMEC more than 90%. Moreover, overexpression of FAK mutants that were either impaired in the kinase activity or were not capable of autophosphorylation or overexpression of the dominant-negative version of FAK (FRNK) blocked integrin-mediated internalization of N. meningitidis. Importantly, FAK-deficient fibroblasts were significantly less invaded by N. meningitidis. Furthermore, N. meningitidis induced tyrosine phosphorylation of several host proteins including the FAK/Src complex substrate cortactin. Inhibition of cortactin expression by siRNA silencing and mutation of critical amino acid residues within cortactin, that encompass Arp2/3 association and dynamin binding, significantly reduced meningococcal invasion into eukaryotic cells suggesting that both domains are critical for efficient uptake of N. meningitidis into eukaryotic cells. Together, these results indicate that N. meningitidis exploits the integrin signal pathway for its entry and that FAK mediates the transfer of signals from activated integrins to the cytoskeleton. A cooperative interplay between FAK, Src and cortactin then enables endocytosis of N. meningitidis into host cells

The performance of youth voice on the airwaves

This paper uses the case study of a youth-led community radio station, KCC Live, to argue that community radio is not a cure-all solution for disenfranchised and silenced young people. Drawing on 18 months of participant observation at KCC Live and data from in-depth interviews with volunteers, I argue that, owing to institutional constraints by station management; college management; and the regulatory body Ofcom, young people consider the airwaves to be a supervised, as opposed to emancipatory, arena. However, in attempting to combat the restricting nature of the airwaves, young people find new, performative ways to communicate. This paper provides empirical evidence which goes beyond previous simplistic conceptualisations of voice in youth media production and argues that romanticised notions of youth voice preclude performance and creativity. This paper offers an important contribution to children’s geographies in finding that pretend play, characterised by performance, can be considered a ‘life-span activity’

An exploration of the basis for patient complaints about the oldness of magazines in practice waiting rooms: cohort study

Objective To explore the basis for patient complaints about the oldness of most magazines in practice waiting rooms. Design Cohort study. Setting Waiting room of a general practice in Auckland, New Zealand. Participants 87 magazines stacked into three mixed piles and placed in the waiting room: this included non-gossipy magazines (Time magazine, the Economist, Australian Women’s Weekly, National Geographic, BBC History) and gossipy ones (not identified for fear of litigation). Gossipy was defined as having five or more photographs of celebrities on the front cover and most gossipy as having up to 10 such images. Interventions The magazines were marked with a unique number on the back cover, placed in three piles in the waiting room, and monitored twice weekly. Main outcome measures Disappearance of magazines less than 2 months old versus magazines 3-12 months old, the overall rate of loss of magazines, and the rate of loss of gossipy versus non-gossipy magazines. Results 47 of the 82 magazines with a visible date on the front cover were aged less than 2 months. 28 of these 47 (60%) magazines and 10 of the 35 (29%) older magazines disappeared (P=0.002). After 31 days, 41 of the 87 (47%, 95% confidence interval 37% to 58%) magazines had disappeared. None of the 19 non-gossipy magazines (the Economist and Time magazine) had disappeared compared with 26 of the 27 (96%) gossipy magazines (P<0.001). All 15 of the most gossipy magazines and all 19 of the non-gossipy magazines had disappeared by 31 days. The study was terminated at this point. Conclusions General practice waiting rooms contain mainly old magazines. This phenomenon relates to the disappearance of the magazines rather than to the supply of old ones. Gossipy magazines were more likely to disappear than non-gossipy ones. On the grounds of cost we advise practices to supply old copies of non-gossipy magazines. A waiting room science curriculum is urgently needed

Parametric Design, Comparison and Evaluation of Air Intake Types for Bleedless Aircraft

The development of aircraft in civil aviation has led to higher cruise flight altitude and Mach number. At the same time, economical and ecological requirements as well as comfort demands are increasing. This requires a new concept for the aircraft design, which may be the more electrical aircraft. In the proposed more electrical aircraft, all auxiliary systems are electric powered. This substitutes the pneumatic and hydraulic systems used in current aircrafts. The propulsion turbines of the next generation of aircraft will be designed for higher efficiency and durability. The bleed air outlets in a turbine decrease the efficiency and, by inducing vibrations on the blades, also significantly the durability of the engine. Moreover, the distribution of hydraulic fluid from the engine requires tubing throughout the aircraft, requiring fixed space and adding additional weight. Therefore, the increase in both efficiency and durability will be achieved by the electrification of the aircraft, which eliminates both bleed air and centralized hydraulic fluid distribution. In current aircraft, the bleed air is used partly to get compressed and warm air for the cabin air conditioning. In the next generation aircraft, the cabin air has to be provided by an air intake in combination with a compressor and an air conditioning system. The conventional centralized hydraulic system has to be replaced by electrical actuators or local hydraulic units. These components require also cooling air from the outside atmosphere, which has to be inducted by additional air intakes. Current civil transport aircraft commonly use NACA-type air intakes. The proposed new system design of the more electrical aircraft is characterized by the distribution of the consumers throughout the aircraft, which have to be cooled. This may require a wider variety of air intakes. Therefore a new design process including different types of air intakes has to be established. This work addresses the methods for the intake design process. One method to distinguish aerodynamic design methods is to categorize by the dimensions of the approach. One-dimensional approaches are most commonly used and combine streamline theory with empirical factors. They are used in preliminary design, as a relatively accurate estimation. In many cases, correction factors are used to extend the applicability of the method to describe the flow situation more realistically. Since empirical factors are used, the accuracy of these approaches is limited by the accuracy and portability of these factors usually obtained through experimental investigations. The objective of this work is to develop a method for preliminary air intake design. The focal point of the considerations is the intake design for supplying a compressor used in a civil transport aircraft at cruise flight condition at Mach0.82 and an altitude of 39000ft. Different intake types are investigated in order to identify an optimal configuration in terms of high pressure recovery as well as for low additional drag force on the aircraft. The main objective of the design process of the air intake is to maximize the total pressure recovery from the free-stream air in order to minimize the required compressor power.The method for preliminary intake design is supposed to be one-dimensional and applicable to various intake types. The effects of varying boundary layer thickness, mass flow rate, and flight altitude are taken into account. Furthermore, parameters that specify the geometry of the air intake are evaluated with regard to optimal performance. The chosen method is implemented into a software tool, which allows the calculation of different air intakes and the comparison of those with regard to the requirements. This new calculation tool allows for prediction of intake performance in an early design stage. Dependencies between total pressure recovery, drag, and mass flow of the different intake types are investigated

Implementing transnational telemedicine solutions: a connected health project in rural and remote areas of six northern periphery countries

This is the first article in a Series on collaborative projects between European countries, relevant for general practice/family medicine and primary healthcare. Telemedicine, in particular the use of the Internet, videoconferencing and handheld devices such as smartphones, holds the potential for further strides in the application of technology for the delivery of healthcare, particularly to communities in rural and remote areas within and without the European Union where this study is taking place. The Northern Periphery Programme has funded the \u27Implementing Transnational Telemedicine Solutions\u27 (ITTS) project from September 2011 to December 2013, led by the Centre for Rural Health in Inverness, Scotland. Ten sustainable projects based on videoconsultation (speech therapy, renal services, emergency psychiatry, diabetes), mobile patient self-management (physical activity, diabetes, inflammatory bowel disease) and home-based health services (medical and social care emergencies, rehabilitation, multi-morbidity) are being implemented by the six partner countries: Scotland, Finland, Ireland, Northern Ireland, Norway and Sweden. In addition, an International Telemedicine Advisory Service, created for the project, provides business expertise and advice. Community panels contribute feedback on the design and implementation of services and ensure \u27user friendliness\u27. The project goals are to improve accessibility of healthcare in rural and remote communities, reducing unnecessary hospital visits and travel in a sustainable way. Opportunities will be provided for comparative research studies. This article provides an introduction to the ITTS project and how it aims to fulfil these needs. The ITTS team encourage all healthcare providers to at least explore possible technological solutions within their own context