10,161 research outputs found

    Different calcium sources control somatic versus dendritic SK channel activation during action potentials

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    Small-conductance calcium-activated potassium (SK) channels play an important role in regulating neuronal excitability. While SK channels at the soma have long been known to contribute to the medium afterhyperpolarization (mAHP), recent evidence indicate

    Improved hydrogen gas production in microbial electrolysis cells using inexpensive recycled carbon fibre fabrics

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    Growing energy demands of wastewater treatment have made it vital for water companies to develop less energy intensive processes for treating wastewater if net zero emissions are to be achieved by 2050. Microbial electrolysis cells (MECs) have the potential to do this by treating water and producing renewable hydrogen gas as a product, but capital and operational costs have slowed their deployment. By using recycled carbon fibre mats, commercially viable MECs can brought closer to reality, where recycled carbon fibre anode MECs treating real wastewater (normalised ~3100 L d−1) were producing 66.77 L H2 d−1 while graphite felt anode MECs produced 3.65 L H2 d−1 per 1 m3 reactor, anodes costing £5.53 m−2 and £88.36 m−2 respectively, resulting in a total anode cost saving of 93%. This could incentivise the development of larger pilot systems, opening the door for generating greater value and a more sustainable wastewater treatment industry

    Experimental Intradermal Granuloma Formation**From the Department of Pathology, Beth Israel Hospital, Harvard Medical School, and the Division of Tumor Immunology, Children's Cancer Research Foundation, Boston, Massachusetts. (Reprint requeats to Dr. E. J. Kasdon, Department of Pathology, Beth Israel Hospital, 330 Brookline Avenue, Boston, Mass. 02215.)

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    Experimental induction of an intradermal granulomatous hypersensitivity reaction in the primarily immunized guinea pig was studied by means of tight microscopy during the course of the immune response. Animals were sensitized to dinitrophenylated human serum albumin (DNP10-HSA), and challenged with this antigen covalently linked to Sepharose 2B beads by the cyanogen bromide reaction. At appropriate intervals, the dermal changes produced by this complex antigen were compared with those produced by DNP10-HSA or soluble antigen. Sepharose 2B beads atone, and DNP10-HSA plus Sepharose 2B in the same animal. The complex antigen produced lesions characteristic of granulomatous hypersensitivity 5 and 11 days beyond the time of the skin test. The others showed the characteristic responses of hypersensitivity, foreign-body reaction, and a mixture of delayed-hypersensitivity and foreign-body reaction, but the intensity of the reactions had diminished by 5 days and had disappeared after 11 days. These results indicate that a dermal granulomatous hypersensitivity reaction may be differentiated from a foreign-body reaction. They also suggest that locally retained antigen interacts with sensitized lymphocytes to contribute to granuloma formation

    Tectonostratigraphic controls on pore fluid pressure distribution across the Taranaki Basin, New Zealand

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    Significant variations in pore pressure across the Taranaki Basin, New Zealand, are attributed to changes in lithofacies and structure, usefully illustrated in terms of ten areas that we term geopressure provinces, each displaying individual pore pressure trends. Cretaceous to Early Miocene formations in different parts of the basin can be either normally pressured (near or at hydrostatic) or significantly overpressured (up to 28 MPa) at the same depth. Variations in Eocene–Oligocene facies types and thicknesses both within and between geopressure provinces provide first-order control on the magnitude, distribution and maintenance of overpressure across the basin. Examples of hydraulic compartmentalisation due to sealing faults and stratigraphic architecture are identified within the basin. Deep pore pressure transitions are sealed by diagenetic, structural or stratigraphic mechanisms in different places and are associated with an increase in mudrock volume (reduced permeability) or gas generation. Thus, pore pressure distribution in the Taranaki Basin is controlled by a combination of sediment loading, lithofacies variations, fault zone permeability and structural architecture. This work represents an appraisal of the pore pressure distribution across the whole of a multiphase structurally complex basin, and the approach taken provides a framework for better understanding the distribution of pore fluid pressures and pore fluid migration in other sedimentary basins

    Establishing viable fault management strategies for distributed electrical propulsion aircraft

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    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

    IUPHAR-DB: An Expert-Curated, Peer-Reviewed Database of Receptors and Ion Channels

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    The International Union of Basic and Clinical Pharmacology database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of about a third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. Individual gene pages provide a comprehensive description of the genes and their functions, with information on protein structure, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). The phenotypes resulting from altered gene expression (e.g. in genetically altered animals) and genetic mutations are described. Links are provided to bioinformatics resources such as NCBI RefSeq, OMIM, PubChem, human, rat and mouse genome databases. Recent developments include the addition of ligand-centered pages summarising information about unique ligand molecules in IUPHAR-DB. IUPHAR-DB represents a novel approach to biocuration because most data are provided through manual curation of published literature by a network of over 60 expert subcommittees coordinated by NC-IUPHAR. Data are referenced to the primary literature and linked to PubMed. The data are checked to ensure accuracy and consistency by the curators, added to the production server using custom-built submission tools and peer-reviewed by NC-IUPHAR, before being transferred to the public database. Data are reviewed and updated regularly (at least biennially). Other website features include comprehensive database search tools, online and downloadable gene lists and links to recent publications of interest to the field, such as reports on receptor-ligand pairings. The database is freely available at "http://www.iuphar-db.org":http://www.iuphar-db.org. Curators can be reached at curators [at] iuphar-db.org. We thank British Pharmacological Society, UNESCO (through the ICSU Grants Programme), Incyte, GlaxoSmithKline, Novartis, Servier and Wyeth for their support

    The Role of Information Provision in Economic Evaluations of Newborn Bloodspot Screening: A Systematic Review

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    BACKGROUND: The extent to which economic evaluations have included the healthcare resource and outcome-related implications of information provision in national newborn bloodspot screening programmes (NBSPs) is not currently known. OBJECTIVES: To identify if, and how, information provision has been incorporated into published economic evaluations of NBSPs. METHODS: A systematic review of economic evaluations of NBSPs (up to November 2014) was conducted. Three electronic databases were searched (Ovid: Medline, Embase, CINAHL) using an electronic search strategy combining a published economic search filter with terms related to national NBSPs and screening-related technologies. These electronic searches were supplemented by searching the NHS Economic Evaluations Database (NHS EED) and hand-searching identified study reference lists. The results were tabulated and summarised as part of a narrative synthesis. RESULTS: A total of 27 economic evaluations [screening-related technologies (n = 11) and NBSPs (n = 16)] were identified. The majority of economic evaluations did not quantify the impact of information provision in terms of healthcare costs or outcomes. Five studies did include an estimate of the time cost associated with information provision. Four studies included a value to reflect the disutility associated with parental anxiety caused by false-positive results, which was used as a proxy for the impact of imperfect information. CONCLUSION: A limited evidence base currently quantifies the impact of information provision on the healthcare costs and impact on the users of NBSPs; the parents of newborns. We suggest that economic evaluations of expanded NBSPs need to take account of information provision otherwise the impact on healthcare costs and the outcomes for newborns and their parents may be underestimated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40258-015-0177-2) contains supplementary material, which is available to authorized users

    Comparison of candidate architectures for future distributed propulsion aircraft

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    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
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