Perry A.S.,Trinity College Dublin |
O'Hurley G.,RCSI ERC Beaumont Hospital |
Raheem O.A.,St James's Hospital |
Brennan K.,Trinity College Dublin |
And 14 more authors.
International Journal of Cancer | Year: 2013
Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer. What's new? Aberrant Wnt signaling is a characteristic of many cancers, but its causes are poorly understood. In a comprehensive gene expression and DNA methylation study, the authors identify a set of Wnt-related genes that are dysregulated in prostate cancer. They further demonstrate frequent hypermethylation of the SFRP family of Wnt antagonist genes, especially SFRP2, in tumors and pre-invasive lesions. These results bring new insight into the causes of dysregulated Wnt signaling and point toSFRP2 methylation as a novel biomarker in prostate cancer. Copyright © 2012 UICC.
Delaney S.J.,Tullow Oil plc |
O'Brien G.S.,Tullow Oil plc |
Short R.,Irish Center for High End Computing |
Civario G.,Irish Center for High End Computing
Geophysics | Year: 2015
We have developed a 3D reverse time migration (RTM) implementation, with an extended imaging condition, in the presence of tilted transverse isotropy (TTI), using finite-difference time-domain solvers on the rotated staggered grid (RSG) and the Lebedev grid. We have evaluated dispersion analysis of both schemes for a sample TTI medium. Using synthetic and real seismic data in realistic execution configurations, we found surprising inconsistency with quantitative cost estimates in the literature. For fixed accuracy, the RSG scheme proved most efficient in our tests, and not two to three times less efficient, as had been posited. Of course, variability may arise with particular medium properties, computer architectures, or software implementations. Having analyzed wavefield modeling performance in detail, we then quantified the realistic costs associated with the imaging condition in RTM, especially extended imaging conditions. For large extensions of the imaging condition, the associated cost dominates the total execution time and adds very significantly to the total cost of the migration. Our implementation targets both shared and distributed memory parallelism, making it suitable for general CPU clusters, nonuniform memory access architectures, and Intel Xeon-Phi. We have also discussed other aspects of our implementation in detail. In particular, we have explored an alternative method to achieve concurrent communication and computation in RTM. © 2016 Society of Exploration Geophysicists.
Stops A.J.F.,National University of Ireland |
Heraty K.B.,National University of Ireland |
Browne M.,Irish Center for High End Computing |
O'Brien F.J.,Royal College of Surgeons in Ireland |
And 2 more authors.
Journal of Biomechanics | Year: 2010
Mesenchymal stem cell (MSC) differentiation can be influenced by biophysical stimuli imparted by the host scaffold. Yet, causal relationships linking scaffold strain magnitudes and inlet fluid velocities to specific cell responses are thus far underdeveloped. This investigation attempted to simulate cell responses in a collagen-glycosaminoglycan (CG) scaffold within a bioreactor. CG scaffold deformation was simulated using μ-computed tomography (CT) and an in-house finite element solver (FEEBE/. linear). Similarly, the internal fluid velocities were simulated using the afore-mentioned μCT dataset with a computational fluid dynamics solver (ANSYS/CFX). From the ensuing cell-level mechanics, albeit octahedral shear strain or fluid velocity, the proliferation and differentiation of the representative cells were predicted from deterministic functions. Cell proliferation patterns concurred with previous experiments. MSC differentiation was dependent on the level of CG scaffold strain and the inlet fluid velocity. Furthermore, MSC differentiation patterns indicated that specific combinations of scaffold strains and inlet fluid flows cause phenotype assemblies dominated by single cell types. Further to typical laboratory procedures, this predictive methodology demonstrated loading-specific differentiation lineages and proliferation patterns. It is hoped these results will enhance in-vitro tissue engineering procedures by providing a platform from which the scaffold loading applications can be tailored to suit the desired tissue. © 2009 Elsevier Ltd.
Brown A.C.,Queen's University of Belfast |
Hutchinson S.,Queen's University of Belfast |
Lysaght M.A.,Irish Center for High End Computing |
Van Der Hart H.W.,Queen's University of Belfast
Physical Review Letters | Year: 2012
We investigate the influence of the autoionizing 3s3p6n ℓ resonances on the fifth harmonic generated by 200-240 nm laser fields interacting with Ar. To determine the influence of a multielectron response we develop the capability within time-dependent R-matrix theory to determine the harmonic spectra generated. The fifth harmonic is affected by interference between the response of a 3s electron and the response of a 3p electron, as demonstrated by the asymmetric profiles in the harmonic yields as functions of wavelength. © 2012 American Physical Society.
Farber R.,Irish Center for High End Computing
Scientific Computing | Year: 2011
Many solid-state devices such as SATA and PCIe interface are evolving significantly. The low-end SSD drives cost around $1.50 per gigabyte. Gartner predicts SSD prices will drop to a dollar per gigabyte in 2012. Switching a 320 GB hard disk drive to a smaller capacity 256 GB SSD disk when purchasing an Apple MacBook Pro will add $650 to the price of a system. The cachet in caching is that enterprise customers see the performance benefits of SSD without paying for an all solid-state storage solution. Storage arrays can use solid-state storage dynamically like a large power-safe cache. Active data that creates a hot-spot of frequent accesses in the storage array can be transparently moved from mechanical disk to solid-state disk. The requirement is that the active data such as hot spot fit inside the available high-speed SSD storage. The hot-spots can be dynamically migrated on and off the expensive, fast storage to best maintain high storage performance.
Eagan B.,Irish Center for High End Computing |
Eagan B.,BlackBerry |
Civario G.,Irish Center for High End Computing |
Miceli R.,University of Rennes 1
Advances in Parallel Computing | Year: 2014
OpenACC is a high-level programming model that uses directives for offloading computation to accelerators. This paper explores the benefit of using OpenACC performance tuning directives to manually specify GPU scheduling, versus the scheduling OpenACC applies by default. We performed manual scheduling using gang and vector clauses in a directive, and applied to matrix-matrix multiply and Classical Gram-Schmidt orthonormalisation test cases. We then tested using the NVIDIA M2090 and K20 GPGPUs, in conjunction with both the PGI and CAPS implementations of OpenACC. The speedup realised by tuning the gang and vector values ranged from 1.0 to 3.1 in the test cases examined. This shows that the gang and vector values have a large impact on performance, and in some cases the compilers are able to automatically select ideal gang and vector values. © 2014 The authors and IOS Press.
O'Brien E.,Irish Center for High End Computing |
Ralph A.,Irish Center for High End Computing
Energy Procedia | Year: 2015
Performance of a wind-forecasting system for a wind-farm in Ireland is reported. Forecasts were based on ensembles constructed from HARMONIE model runs every 6 hours, along with extra high-resolution HARMONIE runs every 12 hours. Statistical post-processing with Bayes Model Averaging (BMA) removed bias very effectively. The "raw" incremental skill provided by each extra ensemble member was negligible, but the net value, after BMA post-processing, was significantly larger. Thus, a small ensemble with BMA is more skillful than a larger ensemble with simple averaging only. A larger ensemble is still more skillful than a smaller one, if both use BMA. © 2015 The Authors.
Harrison N.M.,National University of Ireland |
McDonnell P.,National University of Ireland |
Mullins L.,National University of Ireland |
Wilson N.,Irish Center for High End Computing |
And 2 more authors.
Biomechanics and Modeling in Mechanobiology | Year: 2013
Trabecular bone tissue failure can be considered as consisting of two stages: damage and fracture; however, most failure analyses of 3D high-resolution trabecular bone samples are confined to damage mechanisms only, that is, without fracture. This study aims to develop a computational model of trabecular bone consisting of an explicit representation of complete failure, incorporating damage criteria, fracture criteria, cohesive forces, asymmetry and large deformation capabilities. Following parameter studies on a test specimen, and experimental testing of bone sample to complete failure, the asymmetric critical tissue damage and fracture strains of ovine vertebral trabecular bone were calibrated and validated to be compression damage -1.16 %, tension damage 0.69 %, compression fracture -2.91 % and tension fracture 1.98 %. Ultimate strength and post-ultimate strength softening were captured by the computational model, and the failure of individual struts in bending and shear was also predicted. This modelling approach incorporated a cohesive parameter that provided a facility to calibrate ductile-brittle behaviour of bone tissue in this non-linear geometric and non-linear constitutive property analyses tool. Finally, the full accumulation of tissue damage and tissue fracture has been monitored from range of small magnitude (normal daily loading) through to specimen yielding, ultimate strength and post-ultimate strength softening. © 2012 Springer-Verlag.
Hazeleger W.,Royal Netherlands Meteorological Institute |
Severijns C.,Royal Netherlands Meteorological Institute |
Semmler T.,Met Eireann |
Stefanescu S.,European Center for Medium Range Weather Forecasts |
And 29 more authors.
Bulletin of the American Meteorological Society | Year: 2010
The EC-Earth consortium is a grouping of meteorologists and Earth-system scientists from 10 European countries, put together to face the challenges of climate and weather forecasting. The NWP system of the European Centre for Medium-Range Weather Forecasts (ECWMF) forms the basis of the EC-Earth Earth-system model. NWP models are designed to accurately capture short-term atmospheric fluctuations. They are used for forecasts at daily-to-seasonal time scales and include data assimilation capabilities. Climate models are designed to represent the global coupled ocean-atmosphere system. The atmospheric model of EC-Earth version 2, is based on ECMWF's Integrated Forecasting System (IFS), cycle 31R1, corresponding to the current seasonal forecast system of ECMWF. The EC-Earth consortium and ECMWF are collaborating on development of initialization procedures to improve long-term predictions. The EC-Earth model displays good performance from daily up to inter-annual time scales and for long-term mean climate.