1,282 research outputs found

    Three results on the Energy conservation for the 3D Euler equations

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    We consider the 3D Euler equations for incompressible homogeneous fluids and we study the problem of energy conservation for weak solutions in the space-periodic case. First, we prove the energy conservation for a full scale of Besov spaces, by extending some classical results to a wider range of exponents. Next, we consider the energy conservation in the case of conditions on the gradient, recovering some results which were known, up to now, only for the Navier-Stokes equations and for weak solutions of the Leray-Hopf type. Finally, we make some remarks on the Onsager singularity problem, identifying conditions which allow to pass to the limit from solutions of the Navier-Stokes equations to solution of the Euler ones, producing weak solutions which are energy conserving

    Effect of disbonds on the fatigue endurance of composite scarf joints

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    The certification of scarf repairs requires that the repair is capable of handling flight loads in the presence of disbonds. This paper presents a study of the fatigue disbond growth behaviour of scarf joints. By determining the strain energy release rates of a disbond in a scarf joint subjected to a unit load, a predictive model based on linear elastic fracture mechanics is presented, which is shown to correlate well with experimental results. This method offers a promising technique for predicting the fatigue life of composite scarf joints with disbonds

    Development of Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

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    Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating genetic cutaneous blistering condition caused by loss-of-function mutations in COL7A1, encoding type VII collagen (C7), central in anchoring fibril (AF) formation at the dermal-epidermal junction (DEJ). Presently no curative treatments exist for RDEB. Reconstitution of COL7A1 expression in autologous primary keratinocytes (KC) and fibroblasts (FB) by ex vivo gene therapy was hypothesised to restore C7 expression and AF construction at the DEJ and ameliorate the RDEB skin phenotype. Feasibility of this approach was demonstrated using a therapeutic grade, self-inactivating- lentiviral vector, encoding codon-optimised COL7A1 (LV-COL7) to transduce primary RDEB KCs and FBs. Expression and secretion of full-length de novo C7 was confirmed, with transduced cells exhibiting supranormal levels of protein expression and functional recovery in in vitro migration assays. A human:murine chimeric preclinical RDEB skin graft model was developed to assess functional correction mediated by the transduced cells in vivo. RDEB grafts lacking C7 expression exhibited severe blistering recapitulating the disease phenotype. Gene- modified grafts, showed C7 deposition at the DEJ, with re-establishment of basement membrane zone integrity. Functional correction was confirmed by an abundance of de novo synthesised AF structures throughout the DEJ securing dermal-epidermal attachment. Gene- corrected FBs were shown to mediate a superior therapeutic benefit. In addition, an alternative strategy was developed using zinc finger nucleases (ZFN) for the targeted editing of COL7A1 and site-specific restoration of endogenous C7 expression. Incorporation of ZFNs into non-integrating lentiviral vectors (NILV) resulted in a marked improvement of their cleavage activity. ZFN-mediated disruption of COL7A1 in KCs confirmed at both genomic and protein level initially enabled the in vitro modelling of RDEB, with observed regression of migration speeds. A dsDNA donor repair template was designed and codon optimised for co-delivery with the ZFNs. Sequencing across the ZFN binding site confirmed site-specific template insertion by targeted homologous recombination. In conclusion, gene correction of primary RDEB cells by LV-COL7 can mediate restoration of protein and structural defects in an RDEB model forming the proposal for therapeutic application in man. Furthermore, development of an alternative site-specific targeting strategy for correction of COL7A1 provides a promising insight into the realm of patient-tailored therapy

    The social, relational and mental health characteristics of justice-involved men in the south-west England

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    peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=rjfp2

    Scheduling and lot-sizing in the dairy industry: the yoghurt production case

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    In this work, a continuous-time Mixed-Integer Linear Programming model (MILP) is developed for the short-term scheduling and lot-sizing problem in a multi-product yoghurt production line of a real-life dairy plant. The problem under question is mainly focused on the packaging stage considering though accurate timing and capacity constraints with respect to the fermentation stage. Packaging units are operating in parallel and share common resources. Sequence-dependent times and costs are explicitly taken into account and optimized by the proposed framework. Daily production line shut-down and setup times are also introduced, as a production policy to guarantee high quality of final products. To the best of our knowledge, the proposed approach is the first systematic attempt to explicitly address all the aforementioned issues in tandem. Several cases of a large-scale Greek dairy plant have been considered using the proposed model. Solutions obtained are presented, criticized and assessed in a real industrial environment. A number of benefits due to the use of optimization-based techniques are revealed. Finally, concluding remarks are drawn.Peer ReviewedPostprint (published version

    A host–guest approach for determining drug–DNA interactions: an example using netropsin

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    Netropsin is a well-characterized DNA minor groove binding compound that serves as a model for the study of drug–DNA interactions. Our laboratory has developed a novel host–guest approach to study drug–DNA interactions in which the host, the N-terminal fragment of Moloney murine leukemia virus reverse transcriptase (MMLV RT) is co-crystallized with a DNA oligonucleotide guest in the presence and absence of drug. We have co-crystallized netropsin with the RT fragment bound to the symmetric 16mer d(CTTAATTCGAATTAAG)(2) and determined the structure of the complex at 1.85 Å. In contrast to previously reported netropsin–DNA structures, our oligonucleotide contains two AATT sites that bind netropsin with flanking 5′ and 3′ sequences that are not symmetric. The asymmetric unit of the RT fragment–DNA–netropsin crystals contains one protein molecule and one-half of the 16mer with one netropsin molecule bound. The guanidinium moiety of netropsin binds in a narrow part of the minor groove, while the amidinium is bound in the widest region within the site. We compare this structure to other Class I netropsin–DNA structures and find that the asymmetry of minor groove widths in the AATT site contributes to the orientation of netropsin within the groove while hydrogen bonding patterns vary in the different structures

    Do quiescent arachnoid cysts alter CNS functional organization? An fMRI and morphometric study

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    OBJECTIVE: To investigate whether congenital and clinically quiescent arachnoid cysts (AC) in the left temporal fossa alter the functional organization of adjacent cortices. METHODS: fMRI mapping was applied in five right-handed asymptomatic patients to determine the functional organization of language. Moreover, morphometry was performed in each patient to gain the size of cortical surface areas and cortical thickness values in the neighboring brain adjacent to the AC and explicitly in the left opercular region. RESULTS: Four patients showed a clear left hemisphere language dominance regardless of the cyst size; a mixed laterality of language organization was found in the remaining patient. An interesting dissociation of morphometric data was assessed when comparing strongly language-related cortices in the inferior frontal gyrus with the entire neighboring cortices. Morphometry in the neighboring brain regions of the AC showed 1) overall reduced cortical surface areas and 2) a decrease in cortical thickness compared to the homologous right side. However, the surface area of the fronto-opercular region in the left inferior frontal gyrus-i.e., the pars triangularis and the pars opercularis-was larger on the left as compared to the right side. Both structures have earlier been identified to represent the morphologic substrate of language dominance in the left hemisphere. CONCLUSION: Arachnoid cysts do not disturb the normal asymmetry of hemisphere language organization despite delicate locations adjacent to the left inferior frontal gyrus

    Grid resolution and turbulent inflow boundary condition recommendations for NPARC calculations

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    The effects of grid resolution and specification of turbulent inflow boundary conditions were examined using the NPARC code with the Baldwin-Lomax and Chien k-e turbulence models. Three benchmark turbulent test cases were calculated: two were wall bounded flows and the third was a compressible mixing layer. The wall bounded flows were essentially insensitive to axial grid density; however, the location of the first point off the wall had a substantial effect on flow solutions. It was determined that the first point off the wall must be in the laminar sublayer (y+ less than or equal to 5) for the entire boundary layer. For the compressible mixing layer cases, the axial grid density affected the capturing of oblique shock waves in the mixing region, but the overall mixing rate was not strongly dependent on grid resolution. In specifying the inflow turbulent boundary conditions, it was very important to match the boundary layer and momentum thicknesses of the two flows entering the mixing region; calculations obtained with smaller or no boundary layers resulted in substantially reduced mixing. The solutions were relatively insensitive to freestream turbulence level
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