On the smoothness of the multi-BMPV black hole spacetime

We demonstrate that, in a multi-BMPV black hole spacetime, the event horizon is not smooth. We explicitly show that for a simpler configuration comprising a line of static extremal black holes and a single BMPV black hole, the metric at the horizon of the BMPV black hole is once, but not twice, continuously differentiable. We argue that this result is also valid when all the black holes are rotating. The Maxwell field strength is shown to be continuous, but not differentiable at the horizon. We also briefly demonstrate that previous work done to show lack of smoothness of static multi-centre solutions in five dimensions is not significantly modified by the inclusion of a higher derivative term in the action for five dimensional supergravity.Comment: 17 pages; reference adde

What is an ROC curve?

The paper by Body et al is concerned with the evaluation of decision aids, which can be used to identify potential acute coronary syndromes (ACS) in the ED. The authors previously developed the Manchester Acute Coronary Syndromes model (MACS) decision aid, which uses several clinical variables and two biomarkers to ‘rule in’ and ‘rule out’ ACS. However, one of the two biomarkers (heart-type fatty acid bindingprotein, H-FABP) is not widely used so a revised decision aid has been developed (Troponin-only Manchester Acute Coronary Syndromes, T-MACS), which include a single biomarker hs-cTnT. In this issue, the authors show how they derive a revised decision aid and describe its performance in a number of independent diagnostic cohort studies. Decision aids (as well as other types of ‘diagnostic tests’) are often evaluated in terms of diagnostic testing parameters such as the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. In this article, we explain how the ROC analysis is conducted and why it is an essential step towards developing a test with the desirable levels of sensitivity and specificity

Life and death of a hero - Lessons learned from modeling the dwarf spheroidal Hercules: an incorrect orbit?

Hercules is a dwarf spheroidal satellite of the Milky Way, found at a distance of about 138 kpc, and showing evidence of tidal disruption. It is very elongated and exhibits a velocity gradient of 16 +/- 3 km/s/kpc. Using this data a possible orbit of Hercules has previously been deduced in the literature. In this study we make use of a novel approach to find a best fit model that follows the published orbit. Instead of using trial and error, we use a systematic approach in order to find a model that fits multiple observables simultaneously. As such, we investigate a much wider parameter range of initial conditions and ensure we have found the best match possible. Using a dark matter free progenitor that undergoes tidal disruption, our best-fit model can simultaneously match the observed luminosity, central surface brightness, effective radius, velocity dispersion, and velocity gradient of Hercules. However, we find it is impossible to reproduce the observed elongation and the position angle of Hercules at the same time in our models. This failure persists even when we vary the duration of the simulation significantly, and consider a more cuspy density distribution for the progenitor. We discuss how this suggests that the published orbit of Hercules is very likely to be incorrect.Comment: accepted by MNRAS; 19 pages, 19 figures, 2 table

Ursa Major II - Reproducing the observed properties through tidal disruption

Recent deep photometry of the dwarf spheroidal Ursa Major II's morphology, and spectroscopy of individual stars, have provided a number of new constraints on its properties. With a velocity dispersion $\sim$6 km s$^{-1}$, and under the assumption that the galaxy is virialised, the mass-to-light ratio is found to be approaching $\sim$2000 - apparently heavily dark matter dominated. Using N-Body simulations, we demonstrate that the observed luminosity, ellipticity, irregular morphology, velocity gradient, and the velocity dispersion can be well reproduced through processes associated with tidal mass loss, and in the absence of dark matter. These results highlight the considerable uncertainty that exists in measurements of the dark matter content of Ursa Major II. The dynamics of the inner tidal tails, and tidal stream, causes the observed velocity dispersion of stars to be boosted to values of $>$5 km s$^{-1}$ ($>$20 km s$^{-1}$ at times). This effect is responsible for raising the velocity dispersion of our model to the observed values in UMaII. We test an iterative rejection technique for removing unbound stars from samples of UMaII stars whose positions on the sky, and line-of-sight velocities, are provided. We find this technique is very effective at providing an accurate bound mass from this information, and only fails when the galaxy has a bound mass less than 10$$ of its initial mass. However when $<2$ mass remains bound, mass overestimation by $>$3 orders of magnitude are seen. Additionally we find that mass measurements are sensitive to measurement uncertainty in line-of-sight velocities. Measurement uncertainties of 1-4 km s$^{-1}$ result in mass overestimates by a factor of $\sim$1.3-5.7.Comment: 17 pages, 12 figures, accepted to MNRAS: 23rd, May, 201

Vaccination against Clostridium difficile using toxin fragments: Observations and analysis in animal models

Clostridium difficile is a major cause of antibiotic associated diarrhea. Recently, we have shown that effective protection can be mediated in hamsters through the inclusion of specific recombinant fragments from toxin A and B in a systemically delivered vaccine. Interestingly while neutralizing antibodies to the binding domains of both toxin A and B are moderately protective, enhanced survival is observed when fragments from the glucosyltransferase region of toxin B replace those from the binding domain of this toxin. In this addendum, we discuss additional information that has been derived from such vaccination studies. This includes observations on efficacy and cross-protection against different ribotypes mediated by these vaccines and the challenges that remain for a vaccine which prevents clinical symptoms but not colonization. The use and value of vaccination both in the prevention of infection and for treatment of disease relapse will be discussed

The sensitivity of harassment to orbit: Mass loss from early-type dwarfs in galaxy clusters

We conduct a comprehensive numerical study of the orbital dependence of harassment on early-type dwarfs consisting of 168 different orbits within a realistic, Virgo-like cluster, varying in eccentricity and pericentre distance. We find harassment is only effective at stripping stars or truncating their stellar discs for orbits that enter deep into the cluster core. Comparing to the orbital distribution in cosmological simulations, we find that the majority of the orbits (more than three quarters) result in no stellar mass loss. We also study the effects on the radial profiles of the globular cluster systems of early-type dwarfs. We find these are significantly altered only if harassment is very strong. This suggests that perhaps most early-type dwarfs in clusters such as Virgo have not suffered any tidal stripping of stars or globular clusters due to harassment, as these components are safely embedded deep within their dark matter halo. We demonstrate that this result is actually consistent with an earlier study of harassment of dwarf galaxies, despite the apparent contradiction. Those few dwarf models that do suffer stellar stripping are found out to the virial radius of the cluster at redshift = 0, which mixes them in with less strongly harassed galaxies. However when placed on phase-space diagrams, strongly harassed galaxies are found offset to lower velocities compared to weakly harassed galaxies. This remains true in a cosmological simulation, even when haloes have a wide range of masses and concentrations. Thus phase-space diagrams may be a useful tool for determining the relative likelihood that galaxies have been strongly or weakly harassed

Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA

Many pathogenic Gram-negative bacteria possess tripartite transporters that catalyze drug extrusion across the inner and outer membranes, thereby conferring resistance. These transporters consist of inner (IMP) and outer (OMP) membrane proteins, which are coupled by a periplasmic membrane fusion (MFP) protein. However, it is not know whether the MFP translocates the drug between the membranes, by acting as a channel, or whether it brings the IMP and OMP together, facilitating drug transfer. The MFP EmrA has an elongated periplasmic domain, which binds transported drugs, and is anchored to the inner membrane by a single -helix, which contains a leucine zipper dimerization domain. Consistent with CD and hydrodynamic analyses, the periplasmic domain is predicted to be composed of a -sheet subdomain and an -helical coiled-coil. We propose that EmrA forms a trimer in which the coiled-coils radiate across the periplasm, where they could sequester the OMP TolC. The "free" leucine zipper in the EmrA trimer might stabilize the interaction with the IMP EmrB, which also possesses leucine zipper motifs in the putative N- and C-terminal helices. The -sheet subdomain of EmrA would sit at the membrane surface adjacent to the EmrB, from which it receives the transported drug, inducing a conformational change that triggers the interaction with the OMP

The Sensitivity of Harassment to Orbit: Mass Loss from Early-Type Dwarfs in Galaxy Clusters

We conduct a comprehensive numerical study of the orbital dependence of harassment on early-type dwarfs consisting of 168 different orbits within a realistic, Virgo-like cluster, varying in eccentricity and pericentre distance. We find harassment is only effective at stripping stars or truncating their stellar disks for orbits that enter deep into the cluster core. Comparing to the orbital distribution in cosmological simulations, we find that the majority of the orbits (more than three quarters) result in no stellar mass loss. We also study the effects on the radial profiles of the globular cluster systems of early-type dwarfs. We find these are significantly altered only if harassment is very strong. This suggests that perhaps most early-type dwarfs in clusters such as Virgo have not suffered any tidal stripping of stars or globular clusters due to harassment, as these components are safely embedded deep within their dark matter halo. We demonstrate that this result is actually consistent with an earlier study of harassment of dwarf galaxies, despite the apparent contradiction. Those few dwarf models that do suffer stellar stripping are found out to the virial radius of the cluster at redshift=0, which mixes them in with less strongly harassed galaxies. However when placed on phase-space diagrams, strongly harassed galaxies are found offset to lower velocities compared to weakly harassed galaxies. This remains true in a cosmological simulation, even when halos have a wide range of masses and concentrations. Thus phase-space diagrams may be a useful tool for determining the relative likelihood that galaxies have been strongly or weakly harassed.Comment: 17 pages, 13 figures, Accepted to MNRAS 8th September 201

Infection of hamsters with the UK Clostridium difficile ribotype 027 outbreak strain R20291

Clostridium difficile is the main cause of antibiotic-associated disease, a disease of high socio-economical importance that has recently been compounded by the global spread of the 027 (BI/NAP1/027) ribotype. C. difficile cases attributed to ribotype 027 strains have high recurrence rates (up to 36 %) and increased disease severity. The hamster model of infection is widely accepted as an appropriate model for studying aspects of C. difficile host–pathogen interactions. Using this model we characterized the infection kinetics of the UK 2006 outbreak strain, R20291. Hamsters were orally given a dose of clindamycin, followed 5 days later with 10 000 C. difficile spores. All 100 % of the hamsters succumbed to infection with a mean time to the clinical end point of 46.7 h. Colonization of the caecum and colon were observed 12 h post-infection reaching a maximum of approximately 3×104 c.f.u. per organ, but spores were not detected until 24 h post-infection. At 36 h post-infection C. difficile numbers increased significantly to approximately 6×107 c.f.u. per organ where numbers remained high until the clinical end point. Increasing levels of in vivo toxin production coincided with increases in C. difficile numbers in organs reaching a maximum at 36 h post-infection in the caecum. Epithelial destruction and polymorphonuclear leukocyte (PMN) recruitment occurred early on during infection (24 h) accumulating as gross microvilli damage, luminal PMN influx, and blood associated with mucosal muscle and microvilli. These data describe the fatal infection kinetics of the clinical UK epidemic C. difficile strain R20291 in the hamster infection model