9,085 research outputs found

    Crystal structure of the human p58 killer cell inhibitory receptor (KIR2DL3) specific for HLA-Cw3-related MHC class I

    Get PDF
    AbstractBackground: T cells and natural killer (NK) cells perform complementary roles in the cellular immune system. T cells identify infected cells directly through recognition of antigenic peptides that are displayed at the target cell surface by the classical major histocompatibility complex (MHC) class I molecules. NK cells monitor the target cell surface for malfunction of this display system, lysing potentially infected cells that might otherwise evade recognition by the T cells. Human killer cell inhibitory receptors (KIRs) control this process by either inhibiting or activating the cytotoxic activity of NK cells via specific binding to MHC class I molecules on the target cell.Results: We report the crystal structure of the extracellular region of the human p58 KIR (KIR2DL3), which is specific for the human MHC class I molecule HLA-Cw3 and related alleles. The structure shows the predicted topology of two tandem immunoglobulin-like domains, but comparison with the previously reported structure of the related receptor KIR2DL1 reveals an unexpected change of 23° in the relative orientation of these domains.Conclusions: The altered orientation of the immunoglobulin-like domains maintains an unusually acute interdomain elbow angle, which therefore appears to be a distinctive feature of the KIRs. The putative MHC class I binding site is located on the outer surface of the elbow, spanning both domains. The unexpected observation that this binding site can be modulated by differences in the relative domain orientations has implications for the general mechanism of KIR–MHC class I complex formation

    Tribology: The Story of Lubrication and Wear

    Get PDF
    Topics addressed include: lubrication and design of high speed rolling element bearings, high speed gears, and traction drives

    Establishing viable fault management strategies for distributed electrical propulsion aircraft

    Get PDF
    Electrical propulsion has the potential to increase aircraft performance. However, this will require the design and development of an appropriate aircraft electrical system to power the propulsor motors. In order to protect this system against electrical faults, which have the potential to threaten the safety of the aircraft, a robust fault management strategy (FMS) is required. The FMS will comprise aspects of system design such as redundancy, reliability and reconfiguration and will rely on a range of protection devices deployed on the electrical system to intercept and manage faults. The electrical architecture will be shaped by the FMS as this will determine the optimal configuration to enable security of supply. The protection system is integral to the system design. Hence it must to be considered from the outset, as part of the wider aircraft concept development. This paper presents a robust framework to develop the optimal FMS for an electrical propulsion aircraft, which is subject to all the relevant aircraft constraints and incorporates the available protection devices for a chosen aircraft for a given developmental timeframe. A case study is then presented in which this protection design methodology is applied to the NASA STARC-ABL aircraft concept in order to demonstrate that the available protection for an electrical propulsion aircraft defines the possible electrical architectures

    Automation of large scale transient protein expression in mammalian cells

    Get PDF
    Traditional mammalian expression systems rely on the time-consuming generation of stable cell lines; this is difficult to accommodate within a modern structural biology pipeline. Transient transfections are a fast, cost-effective solution, but require skilled cell culture scientists, making man-power a limiting factor in a setting where numerous samples are processed in parallel. Here we report a strategy employing a customised CompacT SelecT cell culture robot allowing the large-scale expression of multiple protein constructs in a transient format. Successful protocols have been designed for automated transient transfection of human embryonic kidney (HEK) 293T and 293S GnTI⁻ cells in various flask formats. Protein yields obtained by this method were similar to those produced manually, with the added benefit of reproducibility, regardless of user. Automation of cell maintenance and transient transfection allows the expression of high quality recombinant protein in a completely sterile environment with limited support from a cell culture scientist. The reduction in human input has the added benefit of enabling continuous cell maintenance and protein production, features of particular importance to structural biology laboratories, which typically use large quantities of pure recombinant proteins, and often require rapid characterisation of a series of modified constructs. This automated method for large scale transient transfection is now offered as a Europe-wide service via the P-cube initiative

    Denitrification by sulfur-oxidizing bacteria in a eutrophic lake

    Get PDF
    Understanding the mechanistic controls of microbial denitrification is of central importance to both environmental microbiology and ecosystem ecology. Loss of nitrate (NO3 −) is often attributed to carbon-driven (heterotrophic) denitrification. However, denitrification can also be coupled to sulfur (S) oxidation by chemolithoautotrophic bacteria. In the present study, we used an in situ stable isotope (15NO3 −) tracer addition in combination with molecular approaches to understand the contribution of sulfur-oxidizing bacteria to the reduction of NO3 − in a eutrophic lake. Samples were incubated across a total dissolved sulfide (H2S) gradient (2 to 95 μM) between the lower epilimnion and the upper hypolimnion. Denitrification rates were low at the top of the chemocline (4.5 m) but increased in the deeper waters (5.0 and 5.5 m), where H2S was abundant. Concomitant with increased denitrification at depths with high sulfide was the production of sulfate (SO4 2−), suggesting that the added NO3 − was used to oxidize H2S to SO4 2−. Alternative nitrate removal pathways, including dissimilatory nitrate reduction to ammonium (DNRA) and anaerobic ammonium oxidation (anammox), did not systematically change with depth and accounted for 1 to 15% of the overall nitrate loss. Quantitative PCR revealed that bacteria of the Sulfurimonas genus that are known denitrifiers increased in abundance in response to NO3 − addition in the treatments with higher H2S. Stoichiometric estimates suggest that H2S oxidation accounted for more than half of the denitrification at the depth with the highest sulfide concentration. The present study provides evidence that microbial coupling of S and nitrogen (N) cycling is likely to be important in eutrophic freshwater ecosystems

    Impact of key design constraints on fault management strategies for distributed electrical propulsion aircraft

    Get PDF
    Electrically driven distributed propulsion has been presented as a possible solution to reduce aircraft noise and emissions, despite increasing global levels of air travel. In order to realise electrical propulsion, novel aircraft electrical systems are required. Since the electrical system must maintain security of power supply to the motors during flight, the protection devices employed on an electrical propulsion aircraft will form a crucial part of system design. However, electrical protection for complex aircraft electrical systems poses a number of challenges, particularly with regard to the weight, volume and efficiency constraints specific to aerospace applications. Furthermore, electrical systems will need to operate at higher power levels and incorporate new technologies, many of which are unproven at altitude and in the harsh aircraft environment. Therefore, today’s commercially available aerospace protection technologies are likely to require significant development before they can be considered as part of a fault management strategy for a next generation aircraft. By mapping the protection device trade space based on published literature to date, the discrepancy between the current status of protection devices and the target specifications can be identified for a given time frame. This paper will describe a process of electrical network design that is driven by the protection system requirements, incorporates key technology constraints and analyses the protection device trade space to derive feasible fault management strategies

    Comparison of candidate architectures for future distributed propulsion aircraft

    Get PDF
    Turbine engine driven distributed electrical aircraft power systems (also referred to as Turboelectric Distributed Propulsion (TeDP)) are proposed for providing thrust for future aircraft with superconducting components operating at 77K in order for performance and emissions targets to be met. The proposal of such systems presents a radical change from current state-of-the-art aero-electrical power systems. Central to the development of such power systems are architecture design trades which must consider system functionality and performance, system robustness and fault ride-through capability, in addition to the balance between mass and efficiency. This paper presents a quantitative comparison of the three potential candidate architectures for TeDP electrical networks. This analysis provides the foundations for establishing the feasibility of these different architectures subject to design and operational constraints. The findings of this paper conclude that a purely AC synchronous network performs best in terms of mass and efficiency, but similar levels of functionality and controllability to an architecture with electrical decoupling via DC cannot readily be achieved. If power electronic converters with cryocoolers are found to be necessary for functionality and controllability purposes, then studies show that a significant increase in the efficiency of solid state switching components is necessary to achieve specified aircraft performance targets

    Development of voltage standards for turbo-electric distributed propulsion aircraft power systems

    Get PDF
    Distributed propulsion is being considered as a possible solution to increase aircraft efficiency, reduce fuel costs and reduce emissions. The size, weight and efficiency of components within a Turbo-electric Distributed Propulsion (TeDP) system are dependent on the voltage level of the electrical power network. Current aircraft voltage standards do not address the architecture of distributed propulsion and so a review of voltage standards from different industries is conducted with areas of commonality addressed. An example of TeDP architecture is presented and analyzed to highlight how current aircraft standards may not apply to TeDP. A summary of challenges in developing standards for a TeDP is compiled with a stakeholder analysis to demonstrate the wide range of industries and personnel with vested interests in the development of voltage standards and recommended practices for TeDP

    The effects of a video intervention on posthospitalization pulmonary rehabilitation uptake

    Get PDF
    Rationale: Pulmonary rehabilitation (PR) after hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life and reduces readmissions. However, posthospitalization PR uptake is low. To date, no trials of interventions to increase uptake have been conducted.Objectives: To study the effect of a codesigned education video as an adjunct to usual care on posthospitalization PR uptake.Methods: The present study was an assessor- and statistician-blinded randomized controlled trial with nested, qualitative interviews of participants in the intervention group. Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including PR information leaflet) or usual care plus the codesigned education video delivered via a handheld tablet device at discharge. Randomization used minimization to balance age, sex, FEV1 % predicted, frailty, transport availability, and previous PR experience.Measurements and Main Results: The primary outcome was PR uptake within 28 days of hospital discharge. A total of 200 patients were recruited, and 196 were randomized (51% female, median FEV1% predicted, 36 [interquartile range, 27-48]). PR uptake was 41% and 34% in the usual care and intervention groups, respectively (P = 0.37), with no differences in secondary (PR referral and completion) or safety (readmissions and death) endpoints. A total of 6 of the 15 participants interviewed could not recall receiving the video.Conclusions: A codesigned education video delivered at hospital discharge did not improve posthospitalization PR uptake, referral, or completion

    Managing conflict between bats and humans: The response of soprano pipistrelles (pipistrellus pygmaeus) to exclusion from roosts in houses

    Get PDF
    Copyright: © 2015 Stone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Conflict can arise when bats roost in human dwellings and householders are affected adversely by their presence. In the United Kingdom, the exclusion of bats from roosts can be licensed under exceptional circumstances to alleviate conflict, but the fate of excluded bats and the impact on their survival and reproduction is not well understood. Using radiotracking, we investigated the effects of exclusion on the soprano pipistrelle Pipistrellus pygmaeus, a species that commonly roosts in buildings in Europe. Exclusions were performed under licence at five roosts in England in spring, when females were in the early stages of pregnancy. Following exclusion, all bats found alternative roosts and colonies congregated in nearby known roosts that had been used by radio-tagged bats prior to exclusion. We found no difference in roosting behaviour before and after exclusion. Both the frequency of roost switching and the type of roosts used by bats remained unchanged. We also found no change in foraging behaviour. Bats foraged in the same areas, travelled similar distances to reach foraging areas and showed similar patterns of habitat selection before and after exclusion. Population modelling suggested that any reduction in survival following exclusion could have a negative impact on population growth, whereas a reduction in productivity would have less effect. While the number of soprano pipistrelle exclusions currently licensed each year is likely to have little effect on local populations, the cumulative impacts of licensing the destruction of large numbers of roosts may be of concern
    corecore