Population subdivision and molecular sequence variation: Theory and analysis of Drosophila ananassae data

Population subdivision complicates analysis of molecular variation. Even if neutrality is assumed, three evolutionary forces need to be considered: migration, mutation, and drift. Simplification can be achieved by assuming that the process of migration among and drift within subpopulations is occurring fast compared to Mutation and drift in the entire population. This allows a two-step approach in the analysis: (i) analysis of population subdivision and (ii) analysis of molecular variation in the migrant pool. We model population subdivision using an infinite island model, where we allow the migration/drift parameter Theta to vary among populations. Thus, central and peripheral populations can be differentiated. For inference of Theta, we use a coalescence approach, implemented via a Markov chain Monte Carlo (MCMC) integration method that allows estimation of allele frequencies in the migrant pool. The second step of this approach (analysis of molecular variation in the migrant pool) uses the estimated allele frequencies in the migrant pool for the study of molecular variation. We apply this method to a Drosophila ananassae sequence data set. We find little indication of isolation by distance, but large differences in the migration parameter among populations. The population as a whole seems to be expanding. A population from Bogor (Java, Indonesia) shows the highest variation and seems closest to the species center.

Exact error estimates and optimal randomized algorithms for integration

Exact error estimates for evaluating multi-dimensional integrals are considered. An estimate is called exact if the rates of convergence for the low- and upper-bound estimate coincide. The algorithm with such an exact rate is called optimal. Such an algorithm has an unimprovable rate of convergence. The problem of existing exact estimates and optimal algorithms is discussed for some functional spaces that define the regularity of the integrand. Important for practical computations data classes are considered: classes of functions with bounded derivatives and Holder type conditions. The aim of the paper is to analyze the performance of two optimal classes of algorithms: deterministic and randomized for computing multidimensional integrals. It is also shown how the smoothness of the integrand can be exploited to construct better randomized algorithms.

Collaborative grid infrastructure for molecular simulations: The eMinerals minigrid as a prototype integrated computer and data grid

This paper describes a prototype grid infrastructure, called the eMinerals minigrid, for molecular simulation scientists. which is based on an integration of shared compute and data resources. We describe the key components, namely the use of Condor pools, Linux/Unix clusters with PBS and IBM's LoadLeveller job handling tools, the use of Globus for security handling, the use of Condor-G tools for wrapping globus job submit commands, Condor's DAGman tool for handling workflow, the Storage Resource Broker for handling data, and the CCLRC dataportal and associated tools for both archiving data with metadata and making data available to other workers.

Strategic organization in projects and firms through software integration

As integrated software solutions reshape project delivery, they alter the bases for collaboration and competition across firms in complex industries. This paper synthesises and extends literatures on strategy in project-based industries and digitally-integrated work to understand how project-based firms interact with digital infrastructures for project delivery. Four identified strategies are to: 1) develop and use capabilities to shape the integrated software solutions that are used in projects; 2) co-specialize, developing complementary assets to work repeatedly with a particular integrator firm; 3) retain flexibility by developing and maintaining capabilities in multiple digital technologies and processes; and 4) manage interfaces, translating work into project formats for coordination while hiding proprietary data and capabilities in internal systems. The paper articulates the strategic importance of digital infrastructures for delivery as well as product architectures. It concludes by discussing managerial implications of the identified strategies and areas for further research.

Integration of remote sensing and GIS for modelling flash floods in Wadi Hudain catchment, Egypt

This paper presents a new approach to modelling flash floods in dryland catchments by integrating remote sensing and digital elevation model (DEM) data in a geographical information system (GIS). The spectral reflectance of channels affected by recent flash floods exhibit a marked increase, due to the deposition of fine sediments in these channels as the flood recedes. This allows the parts of a catchment that have been affected by a recent flood event to be discriminated from unaffected parts, using a time series of Landsat images. Using images of the Wadi Hudain catchment in southern Egypt, the hillslope areas contributing flow were inferred for different flood events. The SRTM3 DEM was used to derive flow direction, flow length, active channel cross-sectional areas and slope. The Manning Equation was used to estimate the channel flow velocities, and hence the time-area zones of the catchment. A channel reach that was active during a 1985 runoff event, that does not receive any tributary flow, was used to estimate a transmission loss rate of 7·5 mm h−1, given the maximum peak discharge estimate. Runoff patterns resulting from different flood events are quite variable; however the southern part of the catchment appears to have experienced more floods during the period of study (1984–2000), perhaps because the bedrock hillslopes in this area are more effective at runoff production than other parts of the catchment which are underlain by unconsolidated Quaternary sands and gravels. Due to high transmission loss, runoff generated within the upper reaches is rarely delivered to the alluvial fan and Shalateen city situated at the catchment outlet. The synthetic GIS-based time area zones, on their own, cannot be relied on to model the hydrographs reliably; physical parameters, such as rainfall intensity, distribution, and transmission loss, must also be considered.

Advances in sequential data assimilation and numerical weather forecasting: an Ensemble Transform Kalman-Bucy Filter, a study on clustering in deterministic Ensemble Square Root Filters, and a test of a new time stepping scheme in an atmospheric model

This dissertation deals with aspects of sequential data assimilation (in particular ensemble Kalman filtering) and numerical weather forecasting. In the first part, the recently formulated Ensemble Kalman-Bucy (EnKBF) filter is revisited. It is shown that the previously used numerical integration scheme fails when the magnitude of the background error covariance grows beyond that of the observational error covariance in the forecast window. Therefore, we present a suitable integration scheme that handles the stiffening of the differential equations involved and doesn’t represent further computational expense. Moreover, a transform-based alternative to the EnKBF is developed: under this scheme, the operations are performed in the ensemble space instead of in the state space. Advantages of this formulation are explained. For the first time, the EnKBF is implemented in an atmospheric model. The second part of this work deals with ensemble clustering, a phenomenon that arises when performing data assimilation using of deterministic ensemble square root filters in highly nonlinear forecast models. Namely, an M-member ensemble detaches into an outlier and a cluster of M-1 members. Previous works may suggest that this issue represents a failure of EnSRFs; this work dispels that notion. It is shown that ensemble clustering can be reverted also due to nonlinear processes, in particular the alternation between nonlinear expansion and compression of the ensemble for different regions of the attractor. Some EnSRFs that use random rotations have been developed to overcome this issue; these formulations are analyzed and their advantages and disadvantages with respect to common EnSRFs are discussed. The third and last part contains the implementation of the Robert-Asselin-Williams (RAW) filter in an atmospheric model. The RAW filter is an improvement to the widely popular Robert-Asselin filter that successfully suppresses spurious computational waves while avoiding any distortion in the mean value of the function. Using statistical significance tests both at the local and field level, it is shown that the climatology of the SPEEDY model is not modified by the changed time stepping scheme; hence, no retuning of the parameterizations is required. It is found the accuracy of the medium-term forecasts is increased by using the RAW filter.

The integration of proteomics and systems approaches to map regulatory mechanisms underpinning platelet function.

Platelets in the circulation are triggered by vascular damage to activate, aggregate and form a thrombus that prevents excessive blood loss. Platelet activation is stringently regulated by intracellular signalling cascades, which when activated inappropriately lead to myocardial infarction and stroke. Strategies to address platelet dysfunction have included proteomics approaches which have lead to the discovery of a number of novel regulatory proteins of potential therapeutic value. Global analysis of platelet proteomes may enhance the outcome of these studies by arranging this information in a contextual manner that recapitulates established signalling complexes and predicts novel regulatory processes. Platelet signalling networks have already begun to be exploited with interrogation of protein datasets using in silico methodologies that locate functionally feasible protein clusters for subsequent biochemical validation. Characterization of these biological systems through analysis of spatial and temporal organization of component proteins is developing alongside advances in the proteomics field. This focused review highlights advances in platelet proteomics data mining approaches that complement the emerging systems biology field. We have also highlighted nucleated cell types as key examples that can inform platelet research. Therapeutic translation of these modern approaches to understanding platelet regulatory mechanisms will enable the development of novel anti-thrombotic strategies.

Glycogen synthase kinase 3 (GSK3) in the heart: a point of integration in hypertrophic signalling and a therapeutic target? A critical analysis

Glycogen synthase kinase 3 (GSK3, of which there are two isoforms, GSK3alpha and GSK3beta) was originally characterized in the context of regulation of glycogen metabolism, though it is now known to regulate many other cellular processes. Phosphorylation of GSK3alpha(Ser21) and GSK3beta(Ser9) inhibits their activity. In the heart, emphasis has been placed particularly on GSK3beta, rather than GSK3alpha. Importantly, catalytically-active GSK3 generally restrains gene expression and, in the heart, catalytically-active GSK3 has been implicated in anti-hypertrophic signalling. Inhibition of GSK3 results in changes in the activities of transcription and translation factors in the heart and promotes hypertrophic responses, and it is generally assumed that signal transduction from hypertrophic stimuli to GSK3 passes primarily through protein kinase B/Akt (PKB/Akt). However, recent data suggest that the situation is far more complex. We review evidence pertaining to the role of GSK3 in the myocardium and discuss effects of genetic manipulation of GSK3 activity in vivo. We also discuss the signalling pathways potentially regulating GSK3 activity and propose that, depending on the stimulus, phosphorylation of GSK3 is independent of PKB/Akt. Potential GSK3 substrates studied in relation to myocardial hypertrophy include nuclear factors of activated T cells, beta-catenin, GATA4, myocardin, CREB, and eukaryotic initiation factor 2Bvarepsilon. These and other transcription factor substrates putatively important in the heart are considered. We discuss whether cardiac pathologies could be treated by therapeutic intervention at the GSK3 level but conclude that any intervention would be premature without greater understanding of the precise role of GSK3 in cardiac processes.

Connecting mean field models of neural activity to EEG and fMRI data

Progress in functional neuroimaging of the brain increasingly relies on the integration of data from complementary imaging modalities in order to improve spatiotemporal resolution and interpretability. However, the usefulness of merely statistical combinations is limited, since neural signal sources differ between modalities and are related non-trivially. We demonstrate here that a mean field model of brain activity can simultaneously predict EEG and fMRI BOLD with proper signal generation and expression. Simulations are shown using a realistic head model based on structural MRI, which includes both dense short-range background connectivity and long-range specific connectivity between brain regions. The distribution of modeled neural masses is comparable to the spatial resolution of fMRI BOLD, and the temporal resolution of the modeled dynamics, importantly including activity conduction, matches the fastest known EEG phenomena. The creation of a cortical mean field model with anatomically sound geometry, extensive connectivity, and proper signal expression is an important first step towards the model-based integration of multimodal neuroimages.

Integration of Space and In Situ Observations to Study Global Climate Change

The currently available model-based global data sets of atmospheric circulation are a by-product of the daily requirement of producing initial conditions for numerical weather prediction (NWP) models. These data sets have been quite useful for studying fundamental dynamical and physical processes, and for describing the nature of the general circulation of the atmosphere. However, due to limitations in the early data assimilation systems and inconsistencies caused by numerous model changes, the available model-based global data sets may not be suitable for studying global climate change. A comprehensive analysis of global observations based on a four-dimensional data assimilation system with a realistic physical model should be undertaken to integrate space and in situ observations to produce internally consistent, homogeneous, multivariate data sets for the earth's climate system. The concept is equally applicable for producing data sets for the atmosphere, the oceans, and the biosphere, and such data sets will be quite useful for studying global climate change.

Realistic mean field forward predictions for the integration of co-registered EEG/fMRI

Brain activity can be measured non-invasively with functional imaging techniques. Each pixel in such an image represents a neural mass of about 105 to 107 neurons. Mean field models (MFMs) approximate their activity by averaging out neural variability while retaining salient underlying features, like neurotransmitter kinetics. However, MFMs incorporating the regional variability, realistic geometry and connectivity of cortex have so far appeared intractable. This lack of biological realism has led to a focus on gross temporal features of the EEG. We address these impediments and showcase a "proof of principle" forward prediction of co-registered EEG/fMRI for a full-size human cortex in a realistic head model with anatomical connectivity, see figure 1. MFMs usually assume homogeneous neural masses, isotropic long-range connectivity and simplistic signal expression to allow rapid computation with partial differential equations. But these approximations are insufficient in particular for the high spatial resolution obtained with fMRI, since different cortical areas vary in their architectonic and dynamical properties, have complex connectivity, and can contribute non-trivially to the measured signal. Our code instead supports the local variation of model parameters and freely chosen connectivity for many thousand triangulation nodes spanning a cortical surface extracted from structural MRI. This allows the introduction of realistic anatomical and physiological parameters for cortical areas and their connectivity, including both intra- and inter-area connections. Proper cortical folding and conduction through a realistic head model is then added to obtain accurate signal expression for a comparison to experimental data. To showcase the synergy of these computational developments, we predict simultaneously EEG and fMRI BOLD responses by adding an established model for neurovascular coupling and convolving "Balloon-Windkessel" hemodynamics. We also incorporate regional connectivity extracted from the CoCoMac database [1]. Importantly, these extensions can be easily adapted according to future insights and data. Furthermore, while our own simulation is based on one specific MFM [2], the computational framework is general and can be applied to models favored by the user. Finally, we provide a brief outlook on improving the integration of multi-modal imaging data through iterative fits of a single underlying MFM in this realistic simulation framework.

Pragmatic oriented data interoperability for smart healthcare information systems

Smart healthcare is a complex domain for systems integration due to human and technical factors and heterogeneous data sources involved. As a part of smart city, it is such a complex area where clinical functions require smartness of multi-systems collaborations for effective communications among departments, and radiology is one of the areas highly relies on intelligent information integration and communication. Therefore, it faces many challenges regarding integration and its interoperability such as information collision, heterogeneous data sources, policy obstacles, and procedure mismanagement. The purpose of this study is to conduct an analysis of data, semantic, and pragmatic interoperability of systems integration in radiology department, and to develop a pragmatic interoperability framework for guiding the integration. We select an on-going project at a local hospital for undertaking our case study. The project is to achieve data sharing and interoperability among Radiology Information Systems (RIS), Electronic Patient Record (EPR), and Picture Archiving and Communication Systems (PACS). Qualitative data collection and analysis methods are used. The data sources consisted of documentation including publications and internal working papers, one year of non-participant observations and 37 interviews with radiologists, clinicians, directors of IT services, referring clinicians, radiographers, receptionists and secretary. We identified four primary phases of data analysis process for the case study: requirements and barriers identification, integration approach, interoperability measurements, and knowledge foundations. Each phase is discussed and supported by qualitative data. Through the analysis we also develop a pragmatic interoperability framework that summaries the empirical findings and proposes recommendations for guiding the integration in the radiology context.

AmalgamScope: merging annotations data across the human genome

The past years have shown an enormous advancement in sequencing and array-based technologies, producing supplementary or alternative views of the genome stored in various formats and databases. Their sheer volume and different data scope pose a challenge to jointly visualize and integrate diverse data types. We present AmalgamScope a new interactive software tool focusing on assisting scientists with the annotation of the human genome and particularly the integration of the annotation files from multiple data types, using gene identifiers and genomic coordinates. Supported platforms include next-generation sequencing and microarray technologies. The available features of AmalgamScope range from the annotation of diverse data types across the human genome to integration of the data based on the annotational information and visualization of the merged files within chromosomal regions or the whole genome. Additionally, users can define custom transcriptome library files for any species and use the file exchanging distant server options of the tool.

Big Data and ecosystem research programmes

The size and complexity of data sets generated within ecosystem-level programmes merits their capture, curation, storage and analysis, synthesis and visualisation using Big Data approaches. This review looks at previous attempts to organise and analyse such data through the International Biological Programme and draws on the mistakes made and the lessons learned for effective Big Data approaches to current Research Councils United Kingdom (RCUK) ecosystem-level programmes, using Biodiversity and Ecosystem Service Sustainability (BESS) and Environmental Virtual Observatory Pilot (EVOp) as exemplars. The challenges raised by such data are identified, explored and suggestions are made for the two major issues of extending analyses across different spatio-temporal scales and for the effective integration of quantitative and qualitative data.