Local pre-processing for node classification in networks : application in protein-protein interaction

Network modelling provides an increasingly popular conceptualisation in a wide range of domains, including the analysis of protein structure. Typical approaches to analysis model parameter values at nodes within the network. The spherical locality around a node provides a microenvironment that can be used to characterise an area of a network rather than a particular point within it. Microenvironments that centre on the nodes in a protein chain can be used to quantify parameters that are related to protein functionality. They also permit particular patterns of such parameters in node-centred microenvironments to be used to locate sites of particular interest. This paper evaluates an approach to index generation that seeks to rapidly construct microenvironment data. The results show that index generation performs best when the radius of microenvironments matches the granularity of the index. Results are presented to show that such microenvironments improve the utility of protein chain parameters in classifying the structural characteristics of nodes using both support vector machines and neural networks

Towards a unified model of stellar rotation II: Model-dependent characteristics of stellar populations

Rotation has a number of important effects on the evolution of stars. Apart from structural changes because of the centrifugal force, turbulent mixing and meridional circulation caused by rotation can dramatically affect a star's chemical evolution. This leads to changes in the surface temperature and luminosity as well as modifying its lifetime. Observationally rotation decreases the surface gravity, causes enhanced mass loss and leads to surface abundance anomalies of various chemical isotopes. The replication of these physical effects with simple stellar evolution models is very difficult and has resulted in the use of numerous different formulations to describe the physics. Using stellar evolution calculations based on several physical models we discuss the features of the resulting simulated stellar populations which can help to distinguish between the models.Comment: 14 pages, 13 figures. Accepted for publication in MNRA

Abundances and Physical Conditions in the Warm Neutral Medium Towards mu Columbae

We present ultraviolet interstellar absorption line measurements for the sightline towards the O9.5 V star mu Columbae obtained with the Goddard High Resolution Spectrograph (GHRS) on board the Hubble Space Telescope. These archival data represent the most complete GHRS interstellar absorption line measurements for any line of sight towards an early-type star. The 3.5 km/s resolution of the instrument allow us to accurately derive the gas-phase column densities of many important ionic species in the diffuse warm neutral medium using a combination of apparent column density and component fitting techniques, and we study in detail the contamination from ionized gas along this sightline. The low-velocity material shows gas-phase abundance patterns similar to the warm cloud (cloud A) towards the disk star zeta Oph, while the component at v = +20.1 km/s shows gas-phase abundances similar to those found in warm halo clouds. We find the velocity-integrated gas-phase abundances of Zn, P, and S relative to H along this sightline are indistinguishable from solar system abundances. We discuss the implications of our gas-phase abundance measurements for the composition of interstellar dust. The relative ionic column density ratios of the intermediate velocity components show the imprint both of elemental incorporation into grains and (photo)ionization. The components at v = -30 and -48 km/s along this sightline likely trace shocked gas with very low hydrogen column densities. Appendices include a new derivation of the GHRS instrumental line spread function, and a new very accurate determination of the total H I column along this sightline. (Abridged)Comment: Accepted for publication in the Astrophysical Journal. 80 pages including 19 embedded figures and 12 embedded tables. Version with higher resolution figures can be downloaded from http://fuse.pha.jhu.edu/~howk/Papers/papers.htm

Stellar evolution of massive stars with a radiative alpha-omega dynamo

Models of rotationally-driven dynamos in stellar radiative zones have suggested that magnetohydrodynamic transport of angular momentum and chemical composition can dominate over the otherwise purely hydrodynamic processes. A proper consideration of the interaction between rotation and magnetic fields is therefore essential. Previous studies have focused on a magnetic model where the magnetic field strength is derived as a function of the stellar structure and angular momentum distribution. We have adapted our one-dimensional stellar rotation code, RoSE, to model the poloidal and toroidal magnetic field strengths with a pair of time-dependent advection-diffusion equations coupled to the equations for the evolution of the angular momentum distribution and stellar structure. This produces a much more complete, though still reasonably simple, model for the magnetic field evolution. Our model reproduces well observed surface nitrogen enrichment of massive stars in the Large Magellanic Cloud. In particular it reproduces a population of slowly-rotating nitrogen-enriched stars that cannot be explained by rotational mixing alone alongside the traditional rotationlly-enriched stars. The model further predicts a strong mass-dependency for the dynamo-driven field. Above a threshold mass, the strength of the magnetic dynamo decreases abruptly and so we predict that more massive stars are much less likely to support a dynamo-driven field than less massive stars.Comment: Accepted for publication in MNRAS. 15 pages, 13 figure

Dose-limiting, adverse event-associated bradycardia with β-blocker treatment of atrial fibrillation in the GENETIC-AF trial

Background: Heart failure (HF) patients with atrial fibrillation (AF) often have conduction system disorders, which may be worsened by β-blocker therapy.Objective: In a post hoc analysis we examined the prevalence of bradycardia and its association with adverse events (AEs) and failure to achieve target dose in the GENETIC-AF trial.Methods: Patients randomized to metoprolol (n = 125) or bucindolol (n = 131) entering 24-week efficacy follow-up and receiving study medication were evaluated. Bradycardia was defined as an electrocardiogram (ECG) heart rate (HR) &lt;60 beats per minute (bpm) and severe bradycardia &lt;50 bpm.Results: Mean HR in sinus rhythm (SR) was 62.6 ± 12.5 bpm for metoprolol and 68.3 ± 11.1 bpm for bucindolol (P &lt; .0001), but in AF HRs were not different (87.5 bpm vs 89.7 bpm, respectively). Episodes per patient for bucindolol vs metoprolol were 0.82 vs 2.08 (P &lt; .001) for bradycardia and 0.24 vs 0.57 for severe bradycardia (P &lt; .001), with 98.9% of the episodes occurring in SR. Patients experiencing bradycardia had a 4.15-fold higher prevalence of study medication dose reduction (P &lt;.0001) compared to patients without bradycardia. Fewer patients receiving metoprolol were at target dose (61.7% vs 74.9% for bucindolol, P &lt; .0001) at ECG recordings, and bradycardia AEs were more prevalent in the metoprolol group (13 vs 1 for bucindolol, P = .001). On multivariate analysis of 21 candidate bradycardia predictors including presence of a device with pacing capability, bucindolol treatment was associated with the greatest degree of prevention (Zodds ratio -4.24, P &lt; .0001).Conclusion: In AF-prone HF patients bradycardia may limit the effectiveness of β blockers, and this property is agent-dependent.</p

Broad Balmer Wings in BA Hyper/Supergiants Distorted by Diffuse Interstellar Bands: Five Examples in the 30 Doradus Region from the VLT-FLAMES Tarantula Survey

Extremely broad emission wings at Hβ and Hα have been found in VLT-FLAMES Tarantula Survey data for five very luminous BA supergiants in or near 30 Doradus in the Large Magellanic Cloud. The profiles of both lines are extremely asymmetrical, which we have found to be caused by very broad diffuse interstellar bands (DIBs) in the longward wing of Hβ and the shortward wing of Hα. These DIBs are well known to interstellar but not to many stellar specialists, so that the asymmetries may be mistaken for intrinsic features. The broad emission wings are generally ascribed to electron scattering, although we note difficulties for that interpretation in some objects. Such profiles are known in some Galactic hyper/supergiants and are also seen in both active and quiescent Luminous Blue Variables (LBVs). No prior or current LBV activity is known in these 30 Dor stars, although a generic relationship to LBVs is not excluded; subject to further observational and theoretical investigation, it is possible that these very luminous supergiants are approaching the LBV stage for the first time. Their locations in the HRD and presumed evolutionary tracks are consistent with that possibility. The available evidence for spectroscopic variations of these objects is reviewed, while recent photometric monitoring does not reveal variability. A search for circumstellar nebulae has been conducted, with an indeterminate result for one of them

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Using microenvironments to identify allosteric binding sites

Protein amino acid residues can be classified by their chemical properties and data mining can be used to make predictions about their structure and function. However, the properties of the surrounding residues contribute to the overall chemical context. This paper defines microenvironments as the spherical volume around a point in space and uses these volumes to determine average properties of the encompassed residues. The approach to index generation rapidly constructs microenvironment data. The averaged chemical properties are then employed in allosteric site prediction using support vector machines and neural networks. The results show that index generation performs best when microenvironment radius matches the granularity of the index and that microenvironments improve the classification accuracy