Breaking supercontinents; no need to choose between passive or active

Much debate has centred on whether continental break-up is predominantly caused by active upwelling in the mantle (e.g. plumes) or by long-range extensional stresses in the lithosphere.We propose the hypothesis that global supercontinent break-up events should always involve both. The fundamental principle involved is the conservation of mass within the spherical shell of the mantle, which requires a return flow for any major upwelling beneath a supercontinent. This shallow horizontal return flow away from the locus of upwelling produces extensional stress. We demonstrate this principle with numerical models, which simultaneously exhibit both upwellings and significant lateral flow in the upper mantle. For non-global break-up the impact of the finite geometry of the mantle will be less pronounced, weakening this process. This observation should motivate future studies of continental break-up to explicitly consider the global perspective, even when observations or models are of regional extent

Understanding the thermal evolution of earth

Studying the thermal history of Earth's mantle can provide a better understanding of Earth's evolution on a planetary scale. In this work, several mechanisms affecting the thermal evolution of Earth's mantle are investigated. The Nusselt-Rayleigh power law relationship (Nu(Ra)) was calculated from the results of a series of models with three dimensional spherical geometry and free slip boundary conditions. Basally and internally heated convection was examined. For Nu(Ra) = aRaP, (5 was found to be 0.294 0.004 for basally heated systems and 0.337 0.009 for internally heated systems. Model cases were extended to Rayleigh numbers higher than any previous study (109). 0 was not observed to reduce at high Rayleigh number, therefore, as this mechanism cannot be invoked to moderate thermal flux in the past, the influence of time dependent layering on thermal evolution was considered. A parameter space exploration of Rayleigh number and 660 km phase change Clapeyron slope demonstrates that present day Earth could have a partially layered mantle and that full two layer convection is possible in the past at higher Rayleigh numbers. Evolution of mantle temperature was modelled, with the models cooling from an initially layered state. As layering breaks down at high Rayleigh numbers, the mantle passes through a wide domain of partial layering before achieving whole mantle convection. The partially layered regime is characterised by a series of avalanches from the upper into the lower mantle. When an avalanche reaches the core mantle boundary it triggers a pulse of plume-like instabilities in the opposing hemisphere, producing a pulse in global surface heat flux. As the mantle cools, the avalanche-pulse events evolve towards higher frequency and lower magnitude. If this mechanism occurs within Earth, the gradualist view of Earth's thermal evolution may need to yield to a more event-driven model. The mechanics of avalanche-pulse events could also provide an explanation for geochemical observations of periodic maxima in melt extraction from the mantle. The modelling of Earth's mantle produces large data volumes. A distributed computing solution to the data storage problem was investigated. The system, MantleStor, is based on Peer-to-Peer technology and intended to operate over hundreds of standard workstations. A trial implementation demonstrates that MantleStor is able to safely store data in a challenging network environment. Data integrity was maintained with over 30% loss of storage machines. MantleStor is an example of an e-Science project, a discussion of e-Science and its implications is presented.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Understanding the thermal evolution of earth

Studying the thermal history of Earth's mantle can provide a better understanding of Earth's evolution on a planetary scale. In this work, several mechanisms affecting the thermal evolution of Earth's mantle are investigated. The Nusselt-Rayleigh power law relationship (Nu(Ra)) was calculated from the results of a series of models with three dimensional spherical geometry and free slip boundary conditions. Basally and internally heated convection was examined. For Nu(Ra) = aRaP, (5 was found to be 0.294 0.004 for basally heated systems and 0.337 0.009 for internally heated systems. Model cases were extended to Rayleigh numbers higher than any previous study (109). 0 was not observed to reduce at high Rayleigh number, therefore, as this mechanism cannot be invoked to moderate thermal flux in the past, the influence of time dependent layering on thermal evolution was considered. A parameter space exploration of Rayleigh number and 660 km phase change Clapeyron slope demonstrates that present day Earth could have a partially layered mantle and that full two layer convection is possible in the past at higher Rayleigh numbers. Evolution of mantle temperature was modelled, with the models cooling from an initially layered state. As layering breaks down at high Rayleigh numbers, the mantle passes through a wide domain of partial layering before achieving whole mantle convection. The partially layered regime is characterised by a series of avalanches from the upper into the lower mantle. When an avalanche reaches the core mantle boundary it triggers a pulse of plume-like instabilities in the opposing hemisphere, producing a pulse in global surface heat flux. As the mantle cools, the avalanche-pulse events evolve towards higher frequency and lower magnitude. If this mechanism occurs within Earth, the gradualist view of Earth's thermal evolution may need to yield to a more event-driven model. The mechanics of avalanche-pulse events could also provide an explanation for geochemical observations of periodic maxima in melt extraction from the mantle. The modelling of Earth's mantle produces large data volumes. A distributed computing solution to the data storage problem was investigated. The system, MantleStor, is based on Peer-to-Peer technology and intended to operate over hundreds of standard workstations. A trial implementation demonstrates that MantleStor is able to safely store data in a challenging network environment. Data integrity was maintained with over 30% loss of storage machines. MantleStor is an example of an e-Science project, a discussion of e-Science and its implications is presented

The Far-Infrared Spectral Energy Distributions of X-ray-selected Active Galaxies

[Abridged] We present ISO far-infrared (IR) observations of 21 hard X-ray selected AGN from the HEAO-1 A2 sample. We compare the far-IR to X-ray spectral energy distributions (SEDs) of this sample with various radio and optically selected AGN samples. The hard-X-ray selected sample shows a wider range of optical/UV shapes extending to redder near-IR colors. The bluer objects are Seyfert 1s, while the redder AGN are mostly intermediate or type 2 Seyferts. This is consistent with a modified unification model in which the amount of obscuring material increases with viewing angle and may be clumpy. Such a scenario, already suggested by differing optical/near-IR spectroscopic and X-ray AGN classifications, allows for different amounts of obscuration of the continuum emission in different wavebands and of the broad emission line region which results in a mixture of behaviors for AGN with similar optical emission line classifications. The resulting limits on the column density of obscuring material through which we are viewing the redder AGN are 100 times lower than for the standard optically thick torus models. The resulting decrease in optical depth of the obscuring material allows the AGN to heat more dust at larger radial distances. We show that an AGN-heated, flared, dusty disk with mass 10^9 solar and size of few hundred pc is able to generate optical-far-IR SEDs which reproduce the wide range of SEDs present in our sample with no need for an additional starburst component to generate the long-wavelength, cooler part of the IR continuum.Comment: 40 pages, 14 figures, accepted for publication in Astrophysical Journal, V. 590, June 10, 200

Development of a Single Vector System that Enhances Trans-Splicing of SMN2 Transcripts

RNA modalities are developing as a powerful means to re-direct pathogenic pre-mRNA splicing events. Improving the efficiency of these molecules in vivo is critical as they move towards clinical applications. Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical copy gene called SMN2 produces low levels of functional protein due to alternative splicing. We previously reported a trans-splicing RNA (tsRNA) that re-directed SMN2 splicing. Now we show that reducing the competition between endogenous splices sites enhanced the efficiency of trans-splicing. A single vector system was developed that expressed the SMN tsRNA and a splice-site blocking antisense (ASO-tsRNA). The ASO-tsRNA vector significantly elevated SMN levels in primary SMA patient fibroblasts, within the central nervous system of SMA mice and increased SMN-dependent in vitro snRNP assembly. These results demonstrate that the ASO-tsRNA strategy provides insight into the trans-splicing mechanism and a means of significantly enhancing trans-splicing activity in vivo

Systems Biology in ELIXIR: modelling in the spotlight

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR\u27s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Developing reproducible bioinformatics analysis workflows for heterogeneous computing environments to support African genomics

Background: The Pan-African bioinformatics network, H3ABioNet, comprises 27 research institutions in 17 African countries. H3ABioNet is part of the Human Health and Heredity in Africa program (H3Africa), an African-led research consortium funded by the US National Institutes of Health and the UK Wellcome Trust, aimed at using genomics to study and improve the health of Africans. A key role of H3ABioNet is to support H3Africa projects by building bioinformatics infrastructure such as portable and reproducible bioinformatics workflows for use on heterogeneous African computing environments. Processing and analysis of genomic data is an example of a big data application requiring complex interdependent data analysis workflows. Such bioinformatics workflows take the primary and secondary input data through several computationally-intensive processing steps using different software packages, where some of the outputs form inputs for other steps. Implementing scalable, reproducible, portable and easy-to-use workflows is particularly challenging. Results: H3ABioNet has built four workflows to support (1) the calling of variants from high-throughput sequencing data; (2) the analysis of microbial populations from 16S rDNA sequence data; (3) genotyping and genome-wide association studies; and (4) single nucleotide polymorphism imputation. A week-long hackathon was organized in August 2016 with participants from six African bioinformatics groups, and US and European collaborators. Two of the workflows are built using the Common Workflow Language framework (CWL) and two using Nextflow. All the workflows are containerized for improved portability and reproducibility using Docker, and are publicly available for use by members of the H3Africa consortium and the international research community. Conclusion: The H3ABioNet workflows have been implemented in view of offering ease of use for the end user and high levels of reproducibility and portability, all while following modern state of the art bioinformatics data processing protocols. The H3ABioNet workflows will service the H3Africa consortium projects and are currently in use. All four workflows are also publicly available for research scientists worldwide to use and adapt for their respective needs. The H3ABioNet workflows will help develop bioinformatics capacity and assist genomics research within Africa and serve to increase the scientific output of H3Africa and its Pan-African Bioinformatics Network