Towards a lightweight generic computational grid framework for biological research

Background: An increasing number of scientific research projects require access to large-scale computational resources. This is particularly true in the biological field, whether to facilitate the analysis of large high-throughput data sets, or to perform large numbers of complex simulations – a characteristic of the emerging field of systems biology. Results: In this paper we present a lightweight generic framework for combining disparate computational resources at multiple sites (ranging from local computers and clusters to established national Grid services). A detailed guide describing how to set up the framework is available from the following URL: http://igrid-ext.cryst.bbk.ac.uk/portal_guide/. Conclusion: This approach is particularly (but not exclusively) appropriate for large-scale biology projects with multiple collaborators working at different national or international sites. The framework is relatively easy to set up, hides the complexity of Grid middleware from the user, and provides access to resources through a single, uniform interface. It has been developed as part of the European ImmunoGrid project

GPCRTree: online hierarchical classification of GPCR function

Background: G protein-coupled receptors (GPCRs) play important physiological roles transducing extracellular signals into intracellular responses. Approximately 50% of all marketed drugs target a GPCR. There remains considerable interest in effectively predicting the function of a GPCR from its primary sequence. Findings: Using techniques drawn from data mining and proteochemometrics, an alignment-free approach to GPCR classification has been devised. It uses a simple representation of a protein's physical properties. GPCRTree, a publicly-available internet server, implements an algorithm that classifies GPCRs at the class, sub-family and sub-subfamily level. Conclusion: A selective top-down classifier was developed which assigns sequences within a GPCR hierarchy. Compared to other publicly available GPCR prediction servers, GPCRTree is considerably more accurate at every level of classification. The server has been available online since March 2008 at URL: http://igrid-ext.cryst.bbk.ac.uk/gpcrtree

HMG-boxes, ribosomopathies and neurodegenerative disease

The UBTF E210K neuroregression syndrome is a predominantly neurological disorder caused by recurrent de novo dominant variants in Upstream Binding Factor, that is, essential for transcription of the ribosomal RNA genes. This unusual form of ribosomopathy is characterized by a slow decline in cognition, behavior, and sensorimotor functioning during the critical period of development. UBTF (or UBF) is a multi-HMGB-box protein that acts both as an epigenetic factor to establish “open” chromatin on the ribosomal genes and as a basal transcription factor in their RNA Polymerase I transcription. Here we review the possible mechanistic connections between the UBTF variants, ribosomal RNA gene transcription and the neuroregression syndrome, and suggest that DNA topology may play an important role

Preprocedural neutrophil count predicts outcome in patients with advanced peripheral vascular disease undergoing percutaneous transluminal angioplasty

BackgroundThe neutrophil count has been associated with adverse cardiovascular events after percutaneous coronary intervention. There are limited data on risk stratification of patients with advanced peripheral vascular disease (PVD) using white blood cell (WBC) subtypes. This study assessed the association of total and differential WBC counts with adverse outcome in patients with advanced PVD undergoing percutaneous transluminal angioplasty (PTA).MethodsIn a retrospective cohort study, consecutive de novo procedures were analyzed for patients with Rutherford category 4 or 5 PVD who underwent successful nonemergency PTA. Cardiovascular risk factors, baseline total and differential WBC counts, and angiographic data were recorded. Primary outcome was a composite of events of target vessel revascularization (repeat PTA or vascular bypass operation) or lower limb amputation.ResultsA total of 101 patients were studied. Their mean age was 76 ± 10 years, 54% had diabetes mellitus, 68% were hypertensive, and 12% had had previous myocardial infarction. We observed 29 events during a median period of 14 months (interquartile range, 4-26). Cox regression analysis found diabetes mellitus (odds ratio [OR], 4.67; 95% confidence interval [CI], 1.35-16.14; P = .02), Rutherford category 5 (OR, 4.18; 95% CI, 1.06-16.51; P = .04), poor tibial runoff (OR, 4.42; 95% CI, 1.16-16.82; P = .03), and preprocedural neutrophil count in the third tertile (OR, 10.77; 95% CI, 2.19-52.91; P = .003) were independent predictors of outcome.ConclusionsThe results suggest that the preprocedural neutrophil count could be used in global risk factor assessment of patients with advanced PVD who are being considered for PTA. The neutrophil count may reflect the burden of atherosclerosis and tissue damage, and so could identify patients who need more aggressive intervention for advanced PVD

Evaluation of a prototype tool for communicating body perception disturbances in complex regional pain syndrome

Patients with Complex Regional Pain Syndrome (CRPS) experience distressing changes in body perception. However representing body perception is a challenge. A digital media tool for communicating body perception disturbances was developed. A proof of concept study evaluating the acceptability of the application for patients to communicate their body perception is reported in this methods paper. Thirteen CRPS participants admitted to a 2-week inpatient rehabilitation program used the application in a consultation with a research nurse. Audio recordings were made of the process and a structured questionnaire was administered to capture experiences of using the tool. Participants produced powerful images of disturbances in their body perception. All reported the tool acceptable for communicating their body perception. Participants described the positive impact of now seeing an image they had previously only imagined and could now convey to others. The application has provided a novel way for communicating perceptions that are otherwise difficult to convey

Modulation of cognitive performance and mood by aromas of peppermint and ylang-ylang

This study provides further evidence for the impact of the aromas of plant essential oils on aspects of cognition and mood in healthy participants. One hundred and forty-four volunteers were randomly assigned to conditions of ylang-ylang aroma, peppermint aroma, or no aroma control. Cognitive performance was assessed using the Cognitive Drug Research computerized assessment battery, with mood scales completed before and after cognitive testing. The analysis of the data revealed significant differences between conditions on a number of the factors underpinning the tests that constitute the battery. Peppermint was found to enhance memory whereas ylang-ylang impaired it, and lengthened processing speed. In terms of subjective mood peppermint increased alertness and ylang-ylang decreased it, but significantly increased calmness. These results provide support for the contention that the aromas of essential oils can produce significant and idiosyncratic effects on both subjective and objective assessments of aspects of human behavior. They are discussed with reference to possible pharmacological and psychological modes of influence

All Together Now: A Framework for Research on Mob Programming

Mob programming (MP) is a relatively new phenomenon in software development. So far, the academic literature has not published in this domain. The goal of this paper is to develop a framework for researching the MP phenomenon. We first outline current practitioner descriptions of and justifications for MP. We then examine concepts from team theory and practices from agile development to identify the team processes and taskwork involved in MP. Based on these, we present a research framework for the academic study of MP. We conclude by considering how the framework can be used by IS researchers

Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets

Background: Protein structures provide a valuable resource for rational drug design. For a protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate a complementary small-molecule drug. However, pocket prediction against single static structures may miss features of pockets that arise from proteins’ dynamic behaviour. In particular, ligand-binding conformations can be observed as transiently populated states of the apo protein, so it is possible to gain insight into ligand-bound forms by considering conformational variation in apo proteins. This variation can be explored by considering sets of related structures: computationally generated conformers, solution NMR ensembles, multiple crystal structures, homologues or homology models. It is non-trivial to compare pockets, either from different programs or across sets of structures. For a single structure, difficulties arise in defining particular pocket’s boundaries. For a set of conformationally distinct structures the challenge is how to make reasonable comparisons between them given that a perfect structural alignment is not possible. Results: We have developed a computational method, Provar, that provides a consistent representation of predicted binding pockets across sets of related protein structures. The outputs are probabilities that each atom or residue of the protein borders a predicted pocket. These probabilities can be readily visualised on a protein using existing molecular graphics software. We show how Provar simplifies comparison of the outputs of different pocket prediction algorithms, of pockets across multiple simulated conformations and between homologous structures. We demonstrate the benefits of use of multiple structures for protein-ligand and protein-protein interface analysis on a set of complexes and consider three case studies in detail: i) analysis of a kinase superfamily highlights the conserved occurrence of surface pockets at the active and regulatory sites ii) a simulated ensemble of unliganded Bcl2 structures reveals extensions of a known ligand-binding pocket not apparent in the apo crystal structure; iii) visualisations of interleukin-2 and its homologues highlight conserved pockets at the known receptor interfaces and regions whose conformation is known to change on inhibitor binding. Conclusions: Through post-processing of the output of a variety of pocket prediction software, Provar provides a flexible approach to the analysis and visualization of the persistence or variability of pockets in sets of related protein structures

Black Holes with a Generalized Gravitational Action

Microscopic black holes are sensitive to higher dimension operators in the gravitational action. We compute the influence of these operators on the Schwarzschild solution using perturbation theory. All (time reversal invariant) operators of dimension six are included (dimension four operators don't alter the Schwarzschild solution). Corrections to the relation between the Hawking temperature and the black hole mass are found. The entropy is calculated using the Gibbons-Hawking prescription for the Euclidean path integral and using naive thermodynamic reasoning. These two methods agree, however, the entropy is not equal to 1/4 the area of the horizon.Comment: plain tex(uses phyzzx.tex), 8 pages, CALT-68-185

Operationalising cognitive fatigability in multiple sclerosis: a Gordian knot that can be cut?

Background: Researchers have attempted to operationalise objective measures of cognitive fatigability in multiple sclerosis (MS) to overcome the perceived subjectivity of patient-reported outcomes of fatigue (PROs). Measures of cognitive fatigability examine decrements in performance during sustained neurocognitive tasks. Objective: This personal viewpoint briefly summarises available evidence for measures of cognitive fatigability in MS and considers their overall utility. Results: Studies suggest there may be a construct that is distinct from self-reported fatigue, reflecting a new potential intervention target. However, assessments vary and findings across and within measures are inconsistent. Few measures have been guided by a coherent theory, and those identified are likely to be influenced by other confounds, such as cognitive impairment caused more directly by disease processes, depression and assessment biases. Conclusion: Future research may benefit from (a) developing a guiding theory of cognitive fatigability, (b) examining ecological and construct validity of existing assessments and (c) exploring whether the more promising cognitive fatigability measures are correlated with impaired functioning after accounting for possible confounds. Given the issues raised, we caution that our purposes as researchers may be better served by continuing our search for a more objective cognitive fatigability construct that runs in parallel with improving, rather than devaluing, current PROs