Continuous flow displacement immunosensors: a computational study

Numerical modeling has been used to investigate the disparity in performance and sensitivity that has been reported for flow displacement immunosensors based on bead-packed columns, membranes, and capillary tubes. The simulations strongly suggest that the high surface areas in the porous media systems may actually be detrimental to sensor performance because of large numbers of free antibody binding sites. Since the free antibody sites are created during the wash step in which the baseline is established, wash protocols are critical in optimizing the sensitivity for a given displacement sensor.     

Bioinformatics: harvesting information for plant and crop science

Bioinformatics is an integral aspect of plant and crop science research. Developments in data management and analytical software are reviewed with an emphasis on applications in functional genomics. This includes information resources for Arabidopsis and crop species, and tools available for analysis and visualisation of comparative genomic data. Approaches used to explore relationships between plant genes and expressed sequences are compared, including use of ontologies. The impact of bioinformatics in forward and reverse genetics is described, together with the potential from data mining. The role of bioinformatics is explored in the wider context of plant and crop science.     

CytoITMprobe: a network information flow plugin for Cytoscape

ABSTRACT: BACKGROUND: Cytoscape is a well-developed flexible platform for visualization, integration and analysis of network data. Apart from the sophisticated graph layout and visualization routines, it hosts numerous user-developed plugins that significantly extend its core functionality. Earlier, we developed a network information flow framework and implemented it as a web application, called ITM Probe. Given a context consisting of one or more user-selected nodes, ITM Probe retrieves other network nodes most related to that context. It requires neither user restriction to subnetwork of interest nor additional and possibly noisy information. However, plugins for Cytoscape with these features do not yet exist. To provide the Cytoscape users the possibility of integrating ITM Probe into their workflows, we developed CytoITMprobe, a new Cytoscape plugin. FINDINGS: CytoITMprobe maintains all the desirable features of ITM Probe and adds additional flexibility not achievable through its web service version. It provides access to ITM Probe either through a web server or locally. The input, consisting of a Cytoscape network, together with the desired origins and/or destinations of information and a dissipation coefficient, is specified through a query form. The results are shown as a subnetwork of significant nodes and several summary tables. Users can control the composition and appearance of the subnetwork and interchange their ITM Probe results with other software tools through tab-delimited files. CONCLUSIONS: The main strength of CytoITMprobe is its flexibility. It allows the user to specify as input any Cytoscape network, rather than being restricted to the pre-compiled protein-protein interaction networks available through the ITM Probe web service. Users may supply their own edge weights and directionalities. Consequently, as opposed to ITM Probe web service, CytoITMprobe can be applied to many other domains of network-based research beyond protein-networks. It also enables seamless integration of ITM Probe results with other Cytoscape plugins having complementary functionality for data analysis.     

Effectiveness of journal ranking schemes as a tool for locating information

Background

The rise of electronic publishing [1], preprint archives, blogs, and wikis is raising concerns among publishers, editors, and scientists about the present day relevance of academic journals and traditional peer review [2]. These concerns are especially fuelled by the ability of search engines to automatically identify and sort information [1]. It appears that academic journals can only remain relevant if acceptance of research for publication within a journal allows readers to infer immediate, reliable information on the value of that research.

Methodology/Principal Findings

Here, we systematically evaluate the effectiveness of journals, through the work of editors and reviewers, at evaluating unpublished research. We find that the distribution of the number of citations to a paper published in a given journal in a specific year converges to a steady state after a journal-specific transient time, and demonstrate that in the steady state the logarithm of the number of citations has a journal-specific typical value. We then develop a model for the asymptotic number of citations accrued by papers published in a journal that closely matches the data.

Conclusions/Significance

Our model enables us to quantify both the typical impact and the range of impacts of papers published in a journal. Finally, we propose a journal-ranking scheme that maximizes the efficiency of locating high impact research.     

Arterial pulsation-driven cerebrospinal fluid flow in the perivascular space: a computational model

This study was conducted to determine whether local arterial pulsations are sufficient to cause cerebrospinal fluid (CSF) flow along perivascular spaces (PVS) within the spinal cord. A theoretical model of the perivascular space surrounding a "typical" small artery was analysed using computational fluid dynamics. Systolic pulsations were modelled as travelling waves on the arterial wall. The effects of wave geometry and variable pressure conditions on fluid flow were investigated. Arterial pulsations induce fluid movement in the PVS in the direction of arterial wave travel. Perivascular flow continues even in the presence of adverse pressure gradients of a few kilopascals. Flow rates are greater with increasing pulse wave velocities and arterial deformation, as both an absolute amplitude and as a proportion of the PVS. The model suggests that arterial pulsations are sufficient to cause fluid flow in the perivascular space even against modest adverse pressure gradients. Local increases in flow in this perivascular pumping mechanism or reduction in outflow may be important in the etiology of syringomyelia.     

A computational study of the flow through a vitreous cutter

Vitrectomy is an ophthalmic microsurgical procedure that removes part or all of the vitreous humor from the eye. The procedure uses a vitreous cutter consisting of a narrow shaft with a small orifice at the end through which the humor is aspirated by an applied suction. An internal guillotine oscillates back and forth across the orifice to alter the local shear response of the humor. In this work, a computational study of the flow in a vitreous cutter is conducted in order to gain better understanding of the vitreous behavior and provide guidelines for a new vitreous cutter design. The flow of a Newtonian surrogate of vitreous in a two-dimensional analog geometry is investigated using a finite difference-based immersed boundary method with an algebraically formulated fractional-step method. A series of numerical experiments is performed to evaluate the impact of cutting rate, aspiration pressure, and opening/closing transition on the vitreous cutter flow rate and transorifice pressure variation during vitrectomy. The mean flow rate is observed to increase approximately linearly with aspiration pressure and also increase nearly linearly with duty cycle. A study of time-varying flow rate, velocity field, and vorticity illuminates the flow behavior during each phase of the cutting cycle and shows that the opening/closing transition plays a key role in improving the vitreous cutter's efficacy and minimizing the potential damage to surrounding tissue. The numerical results show similar trend in flow rate as previous in vitro experiments using water and balanced saline solution and also demonstrate that high duty cycle and slow opening/closing phases lead to high flow rate and minor disturbance to the eye during vitrectomy, which are the design requirements of an ideal vitreous cutter.     

A simulated dye method for flow visualization with a computational model for blood flow

A numerical dye method for the visualization of unsteady three-dimensional flow calculations is introduced by coupling the unsteady convection-diffusion equation to the Navier-Stokes equation for mass and momentum. This system of equations is descretized using a finite volume projection-like algorithm with generalized coordinates and overset grids. A powerful pressure prediction method is used to accelerate the convergence of the Pressure Poisson equation. To demonstrate the visualization technique, blood flow through the aortic arch region and the three main arterial branches is computed using various Womersley numbers. In this technique, parcels of fluid are followed in time as a function of the cardiac cycle without having to track individual particles, which in turn aids us to better understand some important aspects of the three-dimensionality of the developing unsteady flow. Using this numerical dye method we analyze the strength of the cross flow during the cardiac cycle, the relationship between the penetration of blood into the aortic branches from its relative position in the ascending aortic region and the effects of the Womersley parameter. This technique can be very useful in the design and development of stents where the topology of the device would require understanding where the blood emanating from the heart ends up at the end of the cardiac cycle. Moreover, this method could be useful in investigating the influence of flow and geometry on the local introduction of medication.     

Implementation of a configurable laboratory information management system for use in cellular process development and manufacturing

Background aimsRegulatory requirements for the manufacturing of cell products for clinical investigation require a significant level of record-keeping, starting early in process development and continuing through to the execution and requisite follow-up of patients on clinical trials. Central to record-keeping is the management of documentation related to patients, raw materials, processes, assays and facilities.MethodsTo support these requirements, we evaluated several laboratory information management systems (LIMS), including their cost, flexibility, regulatory compliance, ongoing programming requirements and ability to integrate with laboratory equipment. After selecting a system, we performed a pilot study to develop a user-configurable LIMS for our laboratory in support of our pre-clinical and clinical cell-production activities. We report here on the design and utilization of this system to manage accrual with a healthy blood-donor protocol, as well as manufacturing operations for the production of a master cell bank and several patient-specific stem cell products.ResultsThe system was used successfully to manage blood donor eligibility, recruiting, appointments, billing and serology, and to provide annual accrual reports. Quality management reporting features of the system were used to capture, report and investigate process and equipment deviations that occurred during the production of a master cell bank and patient products.ConclusionsOverall the system has served to support the compliance requirements of process development and phase I/II clinical trial activities for our laboratory and can be easily modified to meet the needs of similar laboratories.     

Bioinformatics meets user-centred design: a perspective

Designers have a saying that "the joy of an early release lasts but a short time. The bitterness of an unusable system lasts for years." It is indeed disappointing to discover that your data resources are not being used to their full potential. Not only have you invested your time, effort, and research grant on the project, but you may face costly redesigns if you want to improve the system later. This scenario would be less likely if the product was designed to provide users with exactly what they need, so that it is fit for purpose before its launch. We work at EMBL-European Bioinformatics Institute (EMBL-EBI), and we consult extensively with life science researchers to find out what they need from biological data resources. We have found that although users believe that the bioinformatics community is providing accurate and valuable data, they often find the interfaces to these resources tricky to use and navigate. We believe that if you can find out what your users want even before you create the first mock-up of a system, the final product will provide a better user experience. This would encourage more people to use the resource and they would have greater access to the data, which could ultimately lead to more scientific discoveries. In this paper, we explore the need for a user-centred design (UCD) strategy when designing bioinformatics resources and illustrate this with examples from our work at EMBL-EBI. Our aim is to introduce the reader to how selected UCD techniques may be successfully applied to software design for bioinformatics.     

Enabling high-throughput data management for systems biology: the Bioinformatics Resource Manager

The Bioinformatics Resource Manager (BRM) is a software environment that provides the user with data management, retrieval and integration capabilities. Designed in collaboration with biologists, BRM simplifies mundane analysis tasks of merging microarray and proteomic data across platforms, facilitates integration of users' data with functional annotation and interaction data from public sources and provides connectivity to visual analytic tools through reformatting of the data for easy import or dynamic launching capability. BRM is developed using Java and other open-source technologies for free distribution. AVAILABILITY: BRM, sample data sets and a user manual can be downloaded from http://www.sysbio.org/dataresources/brm.stm.     

Bioinformatics methods for the analysis of expression arrays: data clustering and information extraction

Expression arrays facilitate the monitoring of changes in the expression patterns of large collections of genes. The analysis of expression array data has become a computationally-intensive task that requires the development of bioinformatics technology for a number of key stages in the process, such as image analysis, database storage, gene clustering and information extraction. Here, we review the current trends in each of these areas, with particular emphasis on the development of the related technology being carried out within our groups.     

Bridging the information gap: computational tools for intermediate resolution structure interpretation

Due to large sizes and complex nature, few large macromolecular complexes have been solved to atomic resolution. This has lead to an under-representation of these structures, which are composed of novel and/or homologous folds, in the library of known structures and folds. While it is often difficult to achieve a high-resolution model for these structures, X-ray crystallography and electron cryomicroscopy are capable of determining structures of large assemblies at low to intermediate resolutions. To aid in the interpretation and analysis of such structures, we have developed two programs: helixhunter and foldhunter. Helixhunter is capable of reliably identifying helix position, orientation and length using a five-dimensional cross-correlation search of a three-dimensional density map followed by feature extraction. Helixhunter's results can in turn be used to probe a library of secondary structure elements derived from the structures in the Protein Data Bank (PDB). From this analysis, it is then possible to identify potential homologous folds or suggest novel folds based on the arrangement of alpha helix elements, resulting in a structure-based recognition of folds containing alpha helices. Foldhunter uses a six-dimensional cross-correlation search allowing a probe structure to be fitted within a region or component of a target structure. The structural fitting therefore provides a quantitative means to further examine the architecture and organization of large, complex assemblies. These two methods have been successfully tested with simulated structures modeled from the PDB at resolutions between 6 and 12 A. With the integration of helixhunter and foldhunter into sequence and structural informatics techniques, we have the potential to deduce or confirm known or novel folds in domains or components within large complexes.     

A molecularly imprinted catalyst designed by a computational approach in catalysing a transesterification process

A computational approach was developed to optimize the monomer formulation of molecularly imprinted catalysts. A virtual library of the intermediates of a lipase-catalysed transesterification process was constructed using Chem3D software with p-nitrophenyl acetate as substrate. The energies of the intermediates were minimized using the semi-empirical MOPAC method with the most stable intermediate expected to lead to a higher turn over rate. According to the optimization results, a MIC was prepared by co-polymerising 4(5)-vinylimidazole and itaconic acid with trimethylpropanol trimethacrylate micro spheres in the presence of p-nitrophenyl acetate. The MIC achieved of the transesterification process between p-nitrophenyl acetate and hexanol with a turn over rate of 26.2 min(-1), and showed substrate specificity towards its template with a 6.5-fold preference for p-nitrophenyl acetate over p-nitrophenyl salicylate.