783 research outputs found
Distribution of presenilins and amyloid precursor protein in detergent-insoluble membrane domains.
No full textLipid rafts: Linking Alzheimer's amyloid-β production, aggregation, and toxicity at neuronal membranes
Full text linkLipid rafts are membrane microdomains, enriched in cholesterol and sphingolipids, into which specific subsets of proteins and lipids partition, creating cell-signalling platforms that are vital for neuronal functions. Lipid rafts play at least three crucial roles in Alzheimer's Disease (AD), namely, in promoting the generation of the amyloid-β (Aβ) peptide, facilitating its aggregation upon neuronal membranes to form toxic oligomers and hosting specific neuronal receptors through which the AD-related neurotoxicity and memory impairments of the Aβ oligomers are transduced. Recent evidence suggests that Aβ oligomers may exert their deleterious effects through binding to, and causing the aberrant clustering of, lipid raft proteins including the cellular prion protein and glutamate receptors. The formation of these pathogenic lipid raft-based platforms may be critical for the toxic signalling mechanisms that underlie synaptic dysfunction and neuropathology in AD. Copyright 2011 Jo V. Rushworth and Nigel M. Hooper
Also By The Same Author: AKTiveAuthor, a Citation Graph Approach to Name Disambiguation
No full textThe desire for definitive data and the semantic web drive for inference over heterogeneous data sources requires co-reference resolution to be performed on those data. In particular, name disambiguation is required to allow accurate publication lists, citation counts and impact measures to be determined. This paper describes a graph-based approach to author disambiguation on large-scale citation networks. Using self-citation, co-authorship and document source analyses, AKTiveAuthor clusters papers, achieving precision of 0.997 and recall of 0.818 over a test group of eight surname clusters
Biochemistry / David Hames and Nigel Hooper.
No full textPreviously published in 2000 as: Instant notes.Includes bibliographical references (p. 419-424) and index.vi, 438 pages. :A major update of the highly popular second edition, with changes in the content and organisation that reflect advances in the subject. As with the first two editions, the third edition of Instant Notes in Biochemistry provides the essential facts of biochemistry with detailed explanations and clear illustrations. It also includes new and expanded topics such as cytoskeleton, molecular motors, bioimaging, biomembranes, cell signaling, protein structure and enzymes regulation
Maine Interview piece with Nigel Calder of Alna, author of the Boatowners\u27s M
No full textMaine Interview piece with Nigel Calder of Alna, author of the Boatowners\u27s Mechanical and Electrical Manual, which has sold over 90,000 copies, and a number of other books, including The Cruising Guide to the Northwest Caribbean and Cuba: A Cruising Guide
Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months
No full textBackgroundPlantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA.Methods A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson’s correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures.ResultsAt baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially.Conclusions We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures
Semiometrics: Applying Ontologies across Large-Scale Digital Libraries
No full textAs large-scale digital libraries become more available and complete, not to mention more numerous, it is clear there is a need for services that can draw together and perform inference calculations on the metadata produced. However, the traditional Relational Database Management System (RDBMS) model, while efficiently constructed and optimised for many business structures, does not necessarily cope well with issues of concurrent data updates and retrieval at the scale of hundreds of thousands of papers. At the same time the growth of RDF and the increasing interest in Semantic Web technologies perhaps begins to present a viable alternative at a scalable, practical level. This paper considers a specific application of large-scale metadata analysis and conducts scalability tests using real-world data. It concludes that RDF technologies are both a scalable and performance-realistic alternative to traditional RDBMS approaches. It also shows that for relationship-based queries on large-scale metadata stores, RDF technologies can significantly out-perform traditional RDBMS approaches by allowing both retrieval and updating of data in a timely manner
The epidemiology and clinical importance of forefoot bursae in patients with rheumatoid arthritis
No full textThe epidemiology of foot complications in patients with rheumatoid arthritis (RA) is poorly understood. A number of patients report ongoing foot-related pain, impairment, footwear restriction and activity limitation, despite developments in pharmacological disease management. Forefoot bursae (fluid filled sacks, FFB) have been previously shown to be highly prevalent and related to foot complications in patients with RA. However, the longitudinal epidemiology and clinical importance of FFB in this patient population remains unclear. It is anticipated that an improved understanding of the mechanisms by which FFB are responsive to, or contribute to, fluctuations in RA disease activity will inform future evaluation of foot health and novel therapeutic targets. Through a series of four experimental studies this work has shown that ultrasound (US) detectable FFB are highly prevalent in patients with RA compared to healthy volunteers (HV) and are clinically relevant. The natural history of FFB remains consistent longitudinally in a cohort of patients with established RA disease at baseline. US-detectable FFB were determined to be significant prognostic indicators of foot-related disability after three years. Furthermore, the distribution of US-detected FFB across forefoot sites was identified as significantly different between HV and patients with predominantly inflammatory or degenerative arthritis; uniquely patients with RA have a number of FFB within the central forefoot region, in addition to those located laterally, which were frequently present in all comparative groups. Thus, in patients with RA ~50% of US-detected FFB may be of greatest clinical relevance, due to their positioning within the central forefoot region. Detection of FFB using MRI defined a series of FFB characteristics of clinical relevance in patients with RA. The presence of plantar forefoot fluid lesions or intermetatarsal soft tissue lesions was significantly related to RA disease activity. The presence of plantar soft tissue lesions was significantly related to increased biomechanical impairment. However, a high proportion of plantar predominantly soft tissue FFB was also noted to be actively inflamed whilst other MRI-based markers of disease activity within the forefoot were minimal
Distributed human computation framework for linked data co-reference resolution
Full text linkDistributed Human Computation (DHC) is a technique used to solve computational problems by incorporating the collaborative effort of a large number of humans. It is also a solution to AI-complete problems such as natural language processing. The Semantic Web with its root in AI is envisioned to be a decentralised world-wide information space for sharing machine-readable data with minimal integration costs. There are many research problems in the Semantic Web that are considered as AI-complete problems. An example is co-reference resolution, which involves determining whether different URIs refer to the same entity. This is considered to be a significant hurdle to overcome in the realisation of large-scale Semantic Web applications. In this paper, we propose a framework for building a DHC system on top of the Linked Data Cloud to solve various computational problems. To demonstrate the concept, we are focusing on handling the co-reference resolution in the Semantic Web when integrating distributed datasets. The traditional way to solve this problem is to design machine-learning algorithms. However, they are often computationally expensive, error-prone and do not scale. We designed a DHC system named iamResearcher, which solves the scientific publication author identity co-reference problem when integrating distributed bibliographic datasets. In our system, we aggregated 6 million bibliographic data from various publication repositories. Users can sign up to the system to audit and align their own publications, thus solving the co-reference problem in a distributed manner. The aggregated results are published to the Linked Data Cloud
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