Institution
Newcastle University
Education•Newcastle upon Tyne, United Kingdom•
About: Newcastle University is a education organization based out in Newcastle upon Tyne, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 31772 authors who have published 71187 publications receiving 2539147 citations. The organization is also known as: University of Newcastle upon Tyne.
Papers published on a yearly basis
Papers
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TL;DR: It is proposed that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair and exploited in order to kill BRCA2-deficient tumours by PARP inhibition alone.
Abstract: Poly(ADP-ribose) polymerase (PARP1) facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Nevertheless, PARP1-/- mice are viable, fertile and do not develop early onset tumours. Here, we show that PARP inhibitors trigger gamma-H2AX and RAD51 foci formation. We propose that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair. Furthermore, we show that BRCA2-deficient cells, as a result of their deficiency in homologous recombination, are acutely sensitive to PARP inhibitors, presumably because resultant collapsed replication forks are no longer repaired. Thus, PARP1 activity is essential in homologous recombination-deficient BRCA2 mutant cells. We exploit this requirement in order to kill BRCA2-deficient tumours by PARP inhibition alone. Treatment with PARP inhibitors is likely to be highly tumour specific, because only the tumours (which are BRCA2-/-) in BRCA2+/- patients are defective in homologous recombination. The use of an inhibitor of a DNA repair enzyme alone to selectively kill a tumour, in the absence of an exogenous DNA-damaging agent, represents a new concept in cancer treatment.
4,262 citations
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Newcastle upon Tyne Hospitals NHS Foundation Trust1, Newcastle University2, Mayo Clinic3, University of Nottingham4, Istanbul University5, University of British Columbia6, University of California, Los Angeles7, Veterans Health Administration8, Drexel University9, Stavanger University Hospital10, Tohoku University11, King's College London12, Pierre-and-Marie-Curie University13, University of California, San Diego14, McGill University15, Rush University Medical Center16, Autonomous University of Madrid17, Neuroscience Research Australia18, National Institutes of Health19, University of Tokyo20, University of North Carolina at Chapel Hill21, Tel Aviv University22, University of Pennsylvania23, University College London24, University of Louisville25, Lund University26, University of Pittsburgh27, University of Washington28, Juntendo University29, Complutense University of Madrid30, University of Göttingen31, Kanazawa University32
TL;DR: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them as mentioned in this paper.
Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.
4,258 citations
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University of Zurich1, University of California, Berkeley2, Lawrence Berkeley National Laboratory3, Max Planck Society4, University of Oldenburg5, Leibniz University of Hanover6, University of Antwerp7, Oregon State University8, Technische Universität München9, Cornell University10, Newcastle University11, University of Florence12, Weizmann Institute of Science13
TL;DR: In this article, a new generation of experiments and soil carbon models were proposed to predict the SOM response to global warming, and they showed that molecular structure alone alone does not control SOM stability.
Abstract: Globally, soil organic matter (SOM) contains more than three times as much carbon as either the atmosphere or terrestrial vegetation. Yet it remains largely unknown why some SOM persists for millennia whereas other SOM decomposes readily—and this limits our ability to predict how soils will respond to climate change. Recent analytical and experimental advances have demonstrated that molecular structure alone does not control SOM stability: in fact, environmental and biological controls predominate. Here we propose ways to include this understanding in a new generation of experiments and soil carbon models, thereby improving predictions of the SOM response to global warming.
4,219 citations
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26 Oct 2011TL;DR: A system for accurate real-time mapping of complex and arbitrary indoor scenes in variable lighting conditions, using only a moving low-cost depth camera and commodity graphics hardware, which fuse all of the depth data streamed from a Kinect sensor into a single global implicit surface model of the observed scene in real- time.
Abstract: We present a system for accurate real-time mapping of complex and arbitrary indoor scenes in variable lighting conditions, using only a moving low-cost depth camera and commodity graphics hardware. We fuse all of the depth data streamed from a Kinect sensor into a single global implicit surface model of the observed scene in real-time. The current sensor pose is simultaneously obtained by tracking the live depth frame relative to the global model using a coarse-to-fine iterative closest point (ICP) algorithm, which uses all of the observed depth data available. We demonstrate the advantages of tracking against the growing full surface model compared with frame-to-frame tracking, obtaining tracking and mapping results in constant time within room sized scenes with limited drift and high accuracy. We also show both qualitative and quantitative results relating to various aspects of our tracking and mapping system. Modelling of natural scenes, in real-time with only commodity sensor and GPU hardware, promises an exciting step forward in augmented reality (AR), in particular, it allows dense surfaces to be reconstructed in real-time, with a level of detail and robustness beyond any solution yet presented using passive computer vision.
4,184 citations
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University of Bristol1, University of Oxford2, Wellcome Trust Centre for Human Genetics3, Churchill Hospital4, National Health Service5, University of London6, Imperial College London7, University of Oulu8, National Institutes of Health9, Medical Research Council10, Wellcome Trust Sanger Institute11, Newcastle University12, Royal London Hospital13, Queen Mary University of London14, University of Dundee15, Ninewells Hospital16
TL;DR: A genome-wide search for type 2 diabetes–susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI).
Abstract: Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.
4,184 citations
Authors
Showing all 32219 results
Name | H-index | Papers | Citations |
---|---|---|---|
Martin White | 196 | 2038 | 232387 |
Barry Halliwell | 173 | 662 | 159518 |
Adrian L. Harris | 170 | 1084 | 120365 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Frank J. Gonzalez | 160 | 1144 | 96971 |
David W. Bates | 159 | 1239 | 116698 |
Nicholas J. Talley | 158 | 1571 | 90197 |
Hans Lassmann | 155 | 724 | 79933 |
Stephen J. O'Brien | 153 | 1062 | 93025 |
Edmund T. Rolls | 153 | 612 | 77928 |
David J. Brooks | 152 | 1056 | 94335 |
Andrew J. Lees | 140 | 877 | 91605 |
Daniel Thomas | 134 | 846 | 84224 |
Peter Hall | 132 | 1640 | 85019 |
Paul Brennan | 132 | 1221 | 72748 |