A critical appraisal of tools available for monitoring epigenetic changes in clinical samples from patients with myeloid malignancies

Research over the past decade has confirmed that epigenetic alterations act in concert with genetic lesions to deregulate gene expression in acute myeloid leukemia and myelodysplastic syndromes. In addition, we now have the capability to pharmaceutically target epigenetic modifications, and there is an urgent need forearly validation of the efficacy of the drugs. Also, an improved understanding of the functionality of epigenetic modifications may further pave the road towards an individualized therapy. Here, we provide the pros and cons of the currently most feasible methods used for characterizing the methylome in clinical samples, and give a brief introduction to novel approaches to sequencing that may revolutionize our abilities to characterize the genomes and epigenomes in acute myeloid leukemia and myelodysplastic syndrome patients.

A comparison of nitogen fate and transport in catchments underlain by high and low permeability aquifers using chemical and isotopic tools.

Variability in nitrogen fate and transport in different catchments types is often not considered. This research considers the importance of such nitrogen processes within groundwater pathways in two agricultural catchments in Ireland; a well drained catchment, underlain by karstified Carboniferous limestone, and a poorly drained catchment, underlain by Silurian greywacke.
Depth specific low-flow groundwater sampling was used to evaluate the hydrochemical stratification in groundwater. Groundwater samples, as well as surface water samples, along river courses were analysed for nitrogen species (NO3, NH4 and NO2) and nitrate isotopes (d15N and d18O) as well as field parameters and major ions
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The dominant nitrate (NO3) groundwater pathway in the poorly drained greywacke catchment is through the shallow weathered bedrock, as indicated by transmissivity values and the ionic and isotopic signatures, and a clear reduction in NO3 concentration is observed with depth. A similar chloride trend would suggest dilution is a major factor, however d15N and d18O isotopic values producing an enrichment ratio of 1.8 indicate that denitrification is also an important process involved in the fate of the NO3 within the groundwater flow system. This consistent trend with depth is in contrast to the stratification pattern observed in the karstified catchment. NO3 was not detected in the shallow groundwater pathway; the dominant groundwater pathway is in the deeper groundwater where there is little change in the nitrate isotope values with depth (d15N values range between 4.1 and 4.6 ‰). This deeper groundwater contributes the dominant proportion of the river flow through a number of springs. As a result, the deeper groundwater, springs and river have a similar ionic signature and NO3 concentration range (23 ± 3 mg/l). Despite this pattern, the NO3 isotopes show a distinct difference in isotopic values between the deeper groundwater in the diffuse karst and the springs indicating some denitrification is occurring during groundwater discharge into the river. Furthermore the isotopes give an indication of the variability of the spatial extent of the springs and the complexities of the fissures through which they are fed. The results of this study clearly show the importance of the geology in the fate and transport of NO3 in agricultural catchments.

Assessing health service needs:tools for health planning.

As fiscal pressures mount, health-planning and decision-making at smaller geographics scales must be more effective. Involving local constituents in needs assessments, it is believed, would lead to better identification and serving of regional demands and needs for health services. This article examines needs assessment as a tool to determine a community's service needs and establish priorities for the creation of programs. Various approaches used in needs assessments are described, including survey methods, structured groups and geographic information systems.

Techniques and tools for parallelizing software

With the emergence of multicore and manycore processors, engineers must design and develop software in drastically new ways to benefit from the computational power of all cores. However, developing parallel software is much harder than sequential software because parallelism can't be abstracted away easily. Authors Hans Vandierendonck and Tom Mens provide an overview of technologies and tools to support developers in this complex and error-prone task. © 2012 IEEE.

JISC Workshop Report: E-Research Resources, Tools and Methods for Historic Place Name Analysis

A substantial amount of the 'critical mass' of digital data available to scholarship contains place-names, and it is now recognised that spatial and temporal data points, including place-names, are a vital part of the e-research infrastructure that supports the use, re-use and advanced analysis of data using ICT tools and methods. Place-names can also be linked semantically to contribute to the web of data, and to enrich content through linking existing data, and identifying new collections for digitization to strategically enhance existing digital collections. However, existing e-projects rely on modern gazetteers limiting them to the modern and the near-contemporary. This workshop explored how to further integrate the wealth of historical place-name scholarship, and the resulting digital resources generated within UK academia, so enabling integration of local knowledge over much longer periods.

Accessibility and Health: Towards Walkability Tools for Planning Practice

There is increasing research interest in how we can most effectively intervene in the built environment to change behaviours such as physical activity and improve health. Much of this work has focussed around the concept of walkability and the identification of those attributes of our cities that encourage pedestrian activity, including density, connectivity and the aesthetic of the urban realm (Saelens et al 2003, Frank et al 2010). Much of the existing research has clarified the strength of the relationships between various environmental attributes and the differential impact on different demographic groups (e.g. Panter et al 2011). This has not yet been effectively translated into tools to help integrate the concepts of walkability into decision-making by statutory authorities that can help shape the spatial development and delivery of public services which can support more active lifestyles. A key reason for this has been that standard models for transport planning and accessibility are based on networks of road infrastructure, which provides a weak basis for modelling pedestrian accessibility (Chin et al 2008).

This paper reports the findings of Knowledge Exchange project funded by UK’s Economic and Social Research Council (ES/J010588/1) and partners including Belfast and Derry City Councils and Northern Ireland’s Public Health Agency, the Department of Regional Development and Belfast Healthy Cities, that has attempted to address this problem. This project has mapped city-wide footpath networks and used these to assist partner organisations in developing the evidence base for making decisions on public services based on health impacts and pedestrian access. The paper describes the tool developed, uses a number of examples to highlight its impact on areas of decision-making and evaluates the benefits of further integrating walkability into planning and development practice.

Using Mesh-Geometry Relationships to Transfer Analysis Models between CAE Tools

Integrating analysis and design models is a complex task due to differences between the models and the architectures of the toolsets used to create them. This complexity is increased with the use of many different tools for specific tasks during an analysis process. In this work various design and analysis models are linked throughout the design lifecycle, allowing them to be moved between packages in a way not currently available. Three technologies named Cellular Modeling, Virtual Topology and Equivalencing are combined to demonstrate how different finite element meshes generated on abstract analysis geometries can be linked to their original geometry. Establishing the equivalence relationships between models enables analysts to utilize multiple packages for specialist tasks without worrying about compatibility issues or rework.

Experimental and numerical studies on rock breaking with TBM tools under high stress confinement

The understanding of rock breaking and chipping due to the TBM cutter disks mechanism in deep tunnels is considered in this paper. The interest stems from the use of TBMs for the excavation of long Trans-Alpine tunnels. Some tests that simulate the disk cutter action at the tunnel face by means of an indenter, acting on a rock specimen are proposed. The rock specimen is confined through a flat-jack and a confinement-free area on one side of the specimen simulates the formation of a groove near the indenter, like it occurs in TBM excavation conditions. Results show a limited influence of the confinement stress versus the thrust increment required for breaking the rock between the indenter and the free side of the specimen. Numerical modelling of the cutter disk action on confined material has also been carried out in order to investigate further aspects of the fracture initiation. Also in this case the importance of the relative position between disk cutter and groove is pointed out. © 2006 Springer-Verlag.