765 research outputs found

    Development of a floating tidal energy system suitable for use in shallow water

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    A proposal is made for the use of a traditional streamwaterwheel suspended between two floating catamaranNPL series demi-hulls as means of generating electricalpower. Two prototype devices, of lengths 1.6m and 4.5m,have been developed, constructed and tested. It was foundthat the concept is sound although greater investment isrequired with regards to the materials and bothhydrodynamic and aerodynamic design of the waterwheelto ensure an economically viable system. The workpresented concentrates on practical aspects associated withdesign, construction and trial testing in Southampton waterof the 4.5m prototype. The relatively low cost, ease ofdeployment, and the fact that conventional boat mooringsystems are effective, combine to make this an attractivealternative energy solution for remote communities

    Functional asymmetry in the lysyl-tRNA synthetase explored by molecular dynamics, free energy calculations and experiment

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    BACKGROUND: Charging of transfer-RNA with cognate amino acid is accomplished by the aminoacyl-tRNA synthetases, and proceeds through an aminoacyl adenylate intermediate. The lysyl-tRNA synthetase has evolved an active site that specifically binds lysine and ATP. Previous molecular dynamics simulations of the heat-inducible Escherichia coli lysyl-tRNA synthetase, LysU, have revealed differences in the binding of ATP and aspects of asymmetry between the nominally equivalent active sites of this dimeric enzyme. The possibility that this asymmetry results in different binding affinities for the ligands is addressed here by a parallel computational and biochemical study. RESULTS: Biochemical experiments employing isothermal calorimetry, steady-state fluorescence and circular dichroism are used to determine the order and stoichiometries of the lysine and nucleotide binding events, and the associated thermodynamic parameters. An ordered mechanism of substrate addition is found, with lysine having to bind prior to the nucleotide in a magnesium dependent process. Two lysines are found to bind per dimer, and trigger a large conformational change. Subsequent nucleotide binding causes little structural rearrangement and crucially only occurs at a single catalytic site, in accord with the simulations. Molecular dynamics based free energy calculations of the ATP binding process are used to determine the binding affinities of each site. Significant differences in ATP binding affinities are observed, with only one active site capable of realizing the experimental binding free energy. Half-of-the-sites models in which the nucleotide is only present at one active site achieve their full binding potential irrespective of the subunit choice. This strongly suggests the involvement of an anti-cooperative mechanism. Pathways for relaying information between the two active sites are proposed. CONCLUSIONS: The asymmetry uncovered here appears to be a common feature of oligomeric aminoacyl-tRNA synthetases, and may play an important functional role. We suggest a manner in which catalytic efficiency could be improved by LysU operating in an alternating sites mechanism

    A Formalization of the Theorem of Existence of First-Order Most General Unifiers

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    This work presents a formalization of the theorem of existence of most general unifiers in first-order signatures in the higher-order proof assistant PVS. The distinguishing feature of this formalization is that it remains close to the textbook proofs that are based on proving the correctness of the well-known Robinson's first-order unification algorithm. The formalization was applied inside a PVS development for term rewriting systems that provides a complete formalization of the Knuth-Bendix Critical Pair theorem, among other relevant theorems of the theory of rewriting. In addition, the formalization methodology has been proved of practical use in order to verify the correctness of unification algorithms in the style of the original Robinson's unification algorithm.Comment: In Proceedings LSFA 2011, arXiv:1203.542

    Biomimetic Behaviours in Hydrogel Artificial Cells through Embedded Organelles

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    Artificial cells are biomimetic structures formed from molecular building blocks that replicate biological processes, behaviors, and architectures. Of these building blocks, hydrogels have emerged as ideal, yet underutilized candidates to provide a gel-like chassis in which to incorporate both biological and nonbiological componentry which enables the replication of cellular functionality. Here, we demonstrate a microfluidic strategy to assemble biocompatible cell-sized hydrogel-based artificial cells with a variety of different embedded functional subcompartments, which act as engineered synthetic organelles. The organelles enable the recreation of increasingly biomimetic behaviors, including stimulus-induced motility, content release through activation of membrane-associated proteins, and enzymatic communication with surrounding bioinspired compartments. In this way, we showcase a foundational strategy for the bottom–up construction of hydrogel-based artificial cell microsystems which replicate fundamental cellular behaviors, paving the way for the construction of next-generation biotechnological devices

    Characteristics of young people accessing recently implemented Community Forensic Child and Adolescent Mental Health Services (F:CAMHS) in England: insights from national service activity data

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    Children and young people in contact with forensic child and adolescent mental health services present with more complex needs than young people in the general population. Recent policy in child and adolescent mental health has led to the implementation of new workstreams and programmes to improve service provision. This research examines the characteristics of children and young people referred to recently commissioned Community Forensic Child and Adolescent Services (F:CAMHS) and service activity during the frst 24 months of service. The study is a national cohort study to describe the population and investigate service provision and access across England. Secondary data on 1311 advice cases and 1406 referrals are included in analysis. Findings show that 71.9% of the sample had accessed mainstream CAMHS before their referral, 50.9% had experienced/witnessed multiple traumatic events and 58.4% of young people presented with multiple difculties. The results of the study highlight the complexity of the cohort and a need for interagency trauma-informed working. This is the frst study to describe the characteristics of children and young people referred to Community F:CAMHS and provides valuable information on pathways and needs to inform service policy and provision

    Several types of types in programming languages

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    Types are an important part of any modern programming language, but we often forget that the concept of type we understand nowadays is not the same it was perceived in the sixties. Moreover, we conflate the concept of "type" in programming languages with the concept of the same name in mathematical logic, an identification that is only the result of the convergence of two different paths, which started apart with different aims. The paper will present several remarks (some historical, some of more conceptual character) on the subject, as a basis for a further investigation. The thesis we will argue is that there are three different characters at play in programming languages, all of them now called types: the technical concept used in language design to guide implementation; the general abstraction mechanism used as a modelling tool; the classifying tool inherited from mathematical logic. We will suggest three possible dates ad quem for their presence in the programming language literature, suggesting that the emergence of the concept of type in computer science is relatively independent from the logical tradition, until the Curry-Howard isomorphism will make an explicit bridge between them.Comment: History and Philosophy of Computing, HAPOC 2015. To appear in LNC

    Traveling ionospheric disturbances induced by the secondary gravity waves from the Tonga eruption on 15 January 2022:Modeling with MESORAC-HIAMCM-SAMI3 and comparison with GPS/TEC and ionosonde data

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    We simulate the gravity waves (GWs) and traveling ionospheric disturbances (TIDs) created by the Hunga Tonga-Hunga Ha'apai (hereafter “Tonga”) volcanic eruption on 15 January 2022 at ∌04:15 UT. We calculate the primary GWs and forces/heatings generated where they dissipate with MESORAC, the secondary GWs with HIAMCM, and the TIDs with SAMI3. We find that medium and large-scale TIDs (MSTIDs and LSTIDs) are induced by the secondary GWs, with horizontal phase speeds cH ≃ 100–750 m/s, horizontal wavelengths λH ≃ 600–6,000 km, and ground-based periods τr ≃ 30 min to 3 hr. The LSTID amplitudes over New Zealand are ≃2–3 TECU, but decrease sharply ≃ 5,000 km from Tonga. The LSTID amplitudes are extremely small over Australia and South Africa because body forces create highly asymmetric GW fields and the GWs propagate perpendicular to the magnetic field there. We analyze the TIDs from SAMI3 and find that a 30 min detrend window eliminates the fastest far-field LSTIDs. We analyze the GPS/TEC via detrending with 2–3 hr windows, and find that the fastest LSTIDs reach the US and South America at ∌8:30–9:00 UT with cH ≃ 680 m/s, λH ≃ 3,400 km, and τr ≃ 83 min, in good agreement with model results. We find good agreement between modeled and observed TIDs over New Zealand, Australia, Hawaii, Japan and Norway. The observed F-peak height, hmF2, drops by ≃ 110–140 km over the western US with a 2.8 hr periodicity from 8:00 to 13:00 UT. We show that the Lamb waves (LWs) observed by AIRS with λH = 380 km have amplitudes that are ≃ 2.3% that of the primary GWs at z ≃ 110 km. We conclude that the observed TIDs can be fully explained by secondary GWs rather than by “leaked” LWs

    RPO, Second-order Contexts, and Lambda-calculus

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    First, we extend Leifer-Milner RPO theory, by giving general conditions to obtain IPO labelled transition systems (and bisimilarities) with a reduced set of transitions, and possibly finitely branching. Moreover, we study the weak variant of Leifer-Milner theory, by giving general conditions under which the weak bisimilarity is a congruence. Then, we apply such extended RPO technique to the lambda-calculus, endowed with lazy and call by value reduction strategies. We show that, contrary to process calculi, one can deal directly with the lambda-calculus syntax and apply Leifer-Milner technique to a category of contexts, provided that we work in the framework of weak bisimilarities. However, even in the case of the transition system with minimal contexts, the resulting bisimilarity is infinitely branching, due to the fact that, in standard context categories, parametric rules such as the beta-rule can be represented only by infinitely many ground rules. To overcome this problem, we introduce the general notion of second-order context category. We show that, by carrying out the RPO construction in this setting, the lazy observational equivalence can be captured as a weak bisimilarity equivalence on a finitely branching transition system. This result is achieved by considering an encoding of lambda-calculus in Combinatory Logic.Comment: 35 pages, published in Logical Methods in Computer Scienc

    Defining Lineage Potential and Fate Behavior of Precursors during Pancreas Development

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    Pancreas development involves a coordinated process in which an early phase of cell segregation is followed by a longer phase of lineage restriction, expansion, and tissue remodeling. By combining clonal tracing and whole-mount reconstruction with proliferation kinetics and single-cell transcriptional profiling, we define the functional basis of pancreas morphogenesis. We show that the large-scale organization of mouse pancreas can be traced to the activity of self-renewing precursors positioned at the termini of growing ducts, which act collectively to drive serial rounds of stochastic ductal bifurcation balanced by termination. During this phase of branching morphogenesis, multipotent precursors become progressively fate-restricted, giving rise to self-renewing acinar-committed precursors that are conveyed with growing ducts, as well as ductal progenitors that expand the trailing ducts and give rise to delaminating endocrine cells. These findings define quantitatively how the functional behavior and lineage progression of precursor pools determine the large-scale patterning of pancreatic sub-compartments
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