636 research outputs found

    Modelling and Optimising of a Light-Weight Rockfall Catch Fence System

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    Rockfall catch fence is a mechanical barrier system that is used at the foot of cliffs to stop and retain falling rocks from reaching nearby infrastructures. A typical system comprises of a high tensile strength wire mesh that is anchored to the ground by rigid posts and strengthened to the lateral and upslope sides by anchoring tension cables. Additional components, such as shock absorbers, might be added to improve the system capacity to dissipate energy. This multi-component system characterises by geometrical complexity and high nonlinear response to impact loads. A light-weight catch fence system is a simple system that can be easily installed in a time efficient manner using manpower rather than heavy machinery, which makes it ideal for railways located in mountainous and difficult terrain regions where there is difficulty in accessing sites with limited workspaces and restricted installation times. However, this should be combined with a proper design to ensure that the system provides the required protection to impede falling rocks from reaching the train lines. In this paper, a parametric study based on finite element analysis is developed to optimise the design of a light-weight catch fence system that has an energy absorption capacity of up to 100 kJ

    REVIEW - A reference data set for retinal vessel profiles

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    This paper describes REVIEW, a new retinal vessel reference dataset. This dataset includes 16 images with 193 vessel segments, demonstrating a variety of pathologies and vessel types. The vessel edges are marked by three observers using a special drawing tool. The paper also describes the algorithm used to process these segments to produce vessel profiles, against which vessel width measurement algorithms can be assessed. Recommendations are given for use of the dataset in performance assessment. REVIEW can be downloaded from http://ReviewDB.lincoln.ac.uk

    Cross Domain Mathematical Concept Formation

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    Procs of AISB'00 Symposium on Creative and Cultural Aspects of AI and Cognitive ScienceMany interesting concepts in mathematics are essentially "cross-domain" in nature, relating objects from more than one area of mathematics, e.g. prime order groups. These concepts are often vital to the formation of a mathematical theory. Often, the introduction of cross-domain concepts to an investigation seems to exercise a mathematician's creative ability. The HR program, (Colton, 1999), proposes new concepts in mathematics. Its original implementation was limited to working in one mathematical domain at a time, so it was unable to create cross-domain concepts. Here, we describe an extension of HR to multiple domains. Cross-domain concept formation is facilitated by generalisation of the data structures and heuristic measures employed by the program, and the implementation of a new production rule. Results achieved include generation of the concepts of prime order groups, graph nodes of maximal degree and an interesting class of graph

    Describing many-body bosonic waveguide scattering with the truncated Wigner method

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    We consider quasi-stationary scattering of interacting bosonic matter waves in one-dimensional waveguides, as they arise in guided atom lasers. We show how the truncated Wigner (tW) method, which corresponds to the semiclassical description of the bosonic many-body system on the level of the diagonal approximation, can be utilized in order to describe such many-body bosonic scattering processes. Special emphasis is put on the discretization of space at the exact quantum level, in order to properly implement the semiclassical approximation and the tW method, as well as on the discussion of the results to be obtained in the continuous limit.Comment: 9 pages, 3 figure

    ARL3 mutations cause Joubert syndrome by disrupting ciliary protein composition

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    Joubert syndrome (JBTS) is a genetically heterogeneous autosomal recessive neurodevelopmental ciliopathy. We investigated further the underlying genetic etiology of Joubert syndrome by studying two unrelated families in whom JBTS was not associated with pathogenic variants in known JBTSrelated genes. Combined autozygosity mapping of both families highlighted a candidate locus on chromosome 10 (chr10: 101569997-109106128 (hg 19)), and exome sequencing revealed two missense variants in ARL3 within the candidate locus. The encoded protein, ADP Ribosylation Factor-Like GTPase 3, ARL3, is a small GTP-binding protein that is involved in directing lipid-modified proteins into the cilium in a GTP-dependent manner. Both missense variants replace the highly conserved Arg149 residue, which we show to be necessary for the interaction with its guanine nucleotide exchange factor ARL13B, such that the mutant protein is associated with reduced INPP5E and NPHP3 localisation in cilia. We propose that ARL3 provides a potential hub in the network of encoded ciliopathy genes, whereby perturbation of ARL3 results in the mislocalisation of multiple ciliary proteins due to abnormal displacement of lipidated protein cargo

    The IBER study: a feasibility randomised controlled trial of imagery based emotion regulation for the treatment of anxiety in bipolar disorder

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    BACKGROUND: Intrusive mental imagery is associated with anxiety and mood instability within bipolar disorder and therefore represents a novel treatment target. Imagery Based Emotion Regulation (IBER) is a brief structured psychological intervention developed to enable people to use the skills required to regulate the emotional impact of these images. METHODS: Participants aged 18 and over with a diagnosis of bipolar disorder and at least a mild level of anxiety were randomly assigned (1:1) to receive IBER plus treatment as usual (IBER + TAU) or treatment as usual alone (TAU). IBER was delivered in up to 12 sessions overs 16 weeks. Clinical and health economic data were collected at baseline, end of treatment and 16-weeks follow-up. Objectives were to inform the recruitment process, timeline and sample size estimate for a definitive trial and to refine trial procedures. We also explored the impact on participant outcomes of anxiety, depression, mania, and mood stability at 16-weeks and 32-weeks follow-up. RESULTS: Fifty-seven (28: IBER + TAU, 27: TAU) participants from two sites were randomised, with 50 being recruited within the first 12 months. Forty-seven (82%) participants provided outcome data at 16 and 32-weeks follow-up. Thirty-five participants engaged in daily mood monitoring at the 32-week follow-up stage. Retention in IBER treatment was high with 27 (96%) attending ≥ 7 sessions. No study participants experienced a serious adverse event. DISCUSSION: The feasibility criteria of recruitment, outcome completion, and intervention retention were broadly achieved, indicating that imagery-focused interventions for bipolar disorder are worthy of further investigation

    Systemic gene therapy rescues retinal dysfunction and hearing loss in a model of Norrie disease

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    Deafness affects 5% of the world's population, yet there is a lack of treatments to prevent hearing loss due to genetic causes. Norrie disease is a recessive X-linked disorder, caused by NDP gene mutation. It manifests as blindness at birth and progressive sensorineural hearing loss, leading to debilitating dual sensory deprivation. To develop a gene therapy, we used a Norrie disease mouse model (Ndptm1Wbrg ), which recapitulates abnormal retinal vascularisation and progressive hearing loss. We delivered human NDP cDNA by intravenous injection of adeno-associated viral vector (AAV)9 at neonatal, juvenile and young adult pathological stages and investigated its therapeutic effects on the retina and cochlea. Neonatal treatment prevented the death of the sensory cochlear hair cells and rescued cochlear disease biomarkers as demonstrated by RNAseq and physiological measurements of auditory function. Retinal vascularisation and electroretinograms were restored to normal by neonatal treatment. Delivery of NDP gene therapy after the onset of the degenerative inner ear disease also ameliorated the cochlear pathology, supporting the feasibility of a clinical treatment for progressive hearing loss in people with Norrie disease

    Systemic gene therapy rescues retinal dysfunction and hearing loss in a model of Norrie disease

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    Deafness affects 5% of the world's population, yet there is a lack of treatments to prevent hearing loss due to genetic causes. Norrie disease is a recessive X‐linked disorder, caused by NDP gene mutation. It manifests as blindness at birth and progressive sensorineural hearing loss, leading to debilitating dual sensory deprivation. To develop a gene therapy, we used a Norrie disease mouse model (Ndptm1Wbrg^{tm1Wbrg}), which recapitulates abnormal retinal vascularisation and progressive hearing loss. We delivered human NDP cDNA by intravenous injection of adeno‐associated viral vector (AAV)9 at neonatal, juvenile and young adult pathological stages and investigated its therapeutic effects on the retina and cochlea. Neonatal treatment prevented the death of the sensory cochlear hair cells and rescued cochlear disease biomarkers as demonstrated by RNAseq and physiological measurements of auditory function. Retinal vascularisation and electroretinograms were restored to normal by neonatal treatment. Delivery of NDP gene therapy after the onset of the degenerative inner ear disease also ameliorated the cochlear pathology, supporting the feasibility of a clinical treatment for progressive hearing loss in people with Norrie disease

    Universal typological dependencies should be detectable in the history of language families

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    1. Introduction We claim that making sense of the typological diversity of languages demands a historical/evolutionary approach.We are pleased that the target paper (Dunn et al. 2011a) has served to bring discussion of this claim into prominence, and are grateful that leading typologists have taken the time to respond (commentaries denoted by boldface). It is unfortunate though that a number of the commentaries in this issue of LT show significant misunderstandings of our paper. Donohue thinks we were out to show the stability of typological features, but that was not our target at all (although related methods can be used to do that: see, e.g., Greenhill et al. 2010a, Dediu 2011a). Plank seems to think we were arguing against universals of any type, but our target was in fact just the implicational universals of word order that have been the bread and butter of typology. He also seems to think we ignore diachrony, whereas in fact the method introduces diachrony centrally into typological reasoning, thereby potentially revolutionising typology (see Cysouw’s commentary). Levy & Daumé think we were testing for lineage-specificity, whereas that was in fact an outcome (the main finding) of our testing for correlated evolution. Dryer thinks we must account for the distribution of language types around the world, but that was not our aim: our aim was to test the causal connection between linguistic variables by taking the perspective of language evolution (diversification and change). Longobardi & Roberts seem to think we set out to extract family trees from syntactic features, but our goal was in fact to use trees based on lexical cognates and hang reconstructed syntactic states on each node of these trees, thereby reconstructing the processes of language change
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