The hot gas content of fossil galaxy clusters

We investigate the properties of the hot gas in four fossil galaxy systems detected at high significance in the Planck Sunyaev-Zeldovich (SZ) survey. XMM-Newton observations reveal overall temperatures of kT ~ 5-6 keV and yield hydrostatic masses M500,HE > 3.5 x 10e14 Msun, confirming their nature as bona fide massive clusters. We measure the thermodynamic properties of the hot gas in X-rays (out to beyond R500 in three cases) and derive their individual pressure profiles out to R ~ 2.5 R500 with the SZ data. We combine the X-ray and SZ data to measure hydrostatic mass profiles and to examine the hot gas content and its radial distribution. The average Navarro-Frenk-White (NFW) concentration parameter, c500 = 3.2 +/- 0.4, is the same as that of relaxed `normal' clusters. The gas mass fraction profiles exhibit striking variation in the inner regions, but converge to approximately the cosmic baryon fraction (corrected for depletion) at R500. Beyond R500 the gas mass fraction profiles again diverge, which we interpret as being due to a difference in gas clumping and/or a breakdown of hydrostatic equilibrium in the external regions. Overall our observations point to considerable radial variation in the hot gas content and in the gas clumping and/or hydrostatic equilibrium properties in these fossil clusters, at odds with the interpretation of their being old, evolved and undisturbed. At least some fossil objects appear to be dynamically young.Comment: 4 pages, 2 figures. Accepted for publication in A&

Numerical investigation aerodynamics nacelle-strake effect

The focus of this investigation is on the numerical prediction of the nacelle-strake effect on the lift coefficient for transport aircraft in high-lift configurations, i.e. the configurations used in the EUROLIFT II project. Within this project high-Reynolds-number wind-tunnel tests were conducted in the European Transonic Windtunnel (ETW) from 2004 to 2007. The geometry considered, also considered in the present investigation, was a commercial wide-body twin-jet high-lift configuration with flaps and slats in landing configuration. The wind-tunnel model considered is a wing/fuselage configuration with a high bypass ratio through-flow-nacelle with a core body. The complexity of the wind-tunnel model was increased in three successive stages. The final stage III geometry features a nacelle strake on the nacelle inboard surface to optimize the performance of the high-lift configuration. The applied CFD methods include the usage of hexahedral elements in regions of vortical flow, a RSM-g turbulence model and a version of the dissipation model in terms of Scalar and Matrix dissipation with various coefficients. Analysis of the results of the performed computations show that for the present configuration, the nacelle strake effect on maximum lift coefficient can be captured with high accuracy by using steady-flow computations and the CFD practices outlined in this paper

The stellar mass function of galaxies in Planck-selected clusters at 0.5 < z < 0.7: new constraints on the timescale and location of satellite quenching

We study the abundance of star-forming and quiescent galaxies in a sample of 21 massive clusters at 0.5<z<0.7, detected with the Planck satellite. We measure the cluster galaxy stellar mass function (SMF), which is a fundamental observable to study and constrain the formation and evolution of galaxies. Our measurements are based on homogeneous and deep multi-band photometry spanning u- to the Ks-band for each cluster and are supported by spectroscopic data from different programs. The galaxy population is separated between quiescent and star-forming galaxies based on their rest-frame U-V and V-J colours. The SMF is compared to that of field galaxies at the same redshifts, using data from the COSMOS/UltraVISTA survey. We find that the shape of the SMF of star-forming galaxies does not depend on environment, while the SMF of quiescent galaxies has a significantly steeper low-mass slope in the clusters compared to the field. We estimate the environmental quenching efficiency (f_EQ), i.e. the probability for a galaxy that would normally be star forming in the field, to be quenched due to its environment. The f_EQ shows no stellar-mass dependence in any environment, but it increases from 40% in the cluster outskirts to ~90% in the cluster centres. The radial signature of f_EQ provides constraints on where the dominant quenching mechanism operates in these clusters and on what timescale. Exploring these using a simple model based on galaxy orbits obtained from an N-body simulation, we find a clear degeneracy between both parameters. For example, the quenching process may either be triggered on a long (~3 Gyr) time scale at large radii (r~8R_500), or happen well within 1 Gyr at r<R_500. The radius where quenching is triggered is at least r_quench> 0.67R_500 (95%CL). The ICM density at this location suggests that ram-pressure stripping of the cold gas is a likely cause of quenching. [Abridged]Comment: 16 pages, 12 figures, accepted for publication in A&

PID Comes Full Circle: Applications of V(D)J Recombination Excision Circles in Research, Diagnostics and Newborn Screening of Primary Immunodeficiency Disorders

The vast majority of patients suffering from a primary immunodeficiency (PID) have defects in their T- and/or B-cell compartments. Despite advances in molecular diagnostics, in many patients no underlying genetic defect has been identified. B- and T-lymphocytes are unique in their ability to create a receptor by genomic rearrangement of their antigen receptor genes via V(D)J recombination. During this process, stable circular excision products are formed that do not replicate when the cell proliferates. Excision circles can be reliably quantified using real-time quantitative (RQ-)PCR techniques. Frequently occurring δREC–ψJα T-cell receptor excision circles (TRECs) have been used to assess thymic output and intronRSS–Kde recombination excision circles (KREC) to quantify B-cell replication history. In this perspective, we describe how TRECs and KRECs are formed during precursor – T- and B-cell differentiation, respectively. Furthermore, we discuss new insights obtained with TRECs and KRECs and specifically how these excision circles can be applied to support therapy monitoring, patient classification and newborn screening of PID

Asymptotic Conformal Yano--Killing Tensors for Schwarzschild Metric

The asymptotic conformal Yano--Killing tensor proposed in J. Jezierski, On the relation between metric and spin-2 formulation of linearized Einstein theory [GRG, in print (1994)] is analyzed for Schwarzschild metric and tensor equations defining this object are given. The result shows that the Schwarzschild metric (and other metrics which are asymptotically ``Schwarzschildean'' up to O(1/r^2) at spatial infinity) is among the metrics fullfilling stronger asymptotic conditions and supertranslations ambiguities disappear. It is also clear from the result that 14 asymptotic gravitational charges are well defined on the ``Schwarzschildean'' background.Comment: 8 pages, latex, no figure

Immunological and Clinical Effects of Vaccines Targeting p53-Overexpressing Malignancies

Approximately 50% of human malignancies carry p53 mutations, which makes it a potential antigenic target for cancer immunotherapy. Adoptive transfer with p53-specific cytotoxic T-lymphocytes (CTL) and CD4+ T-helper cells eradicates p53-overexpressing tumors in mice. Furthermore, p53 antibodies and p53-specific CTLs can be detected in cancer patients, indicating that p53 is immunogenic. Based on these results, clinical trials were initiated. In this paper, we review immunological and clinical responses observed in cancer patients vaccinated with p53 targeting vaccines. In most trials, p53-specific vaccine-induced immunological responses were observed. Unfortunately, no clinical responses with significant reduction of tumor-burden have occurred. We will elaborate on possible explanations for this lack of clinical effectiveness. In the second part of this paper, we summarize several immunopotentiating combination strategies suitable for clinical use. In our opinion, future p53-vaccine studies should focus on addition of these immunopotentiating regimens to achieve clinically effective therapeutic vaccination strategies for cancer patients

The effect of cavity-filling mutations on the thermostability of Bacillus stearothermophilus neutral protease

Cavities in the hydrophobic core of the neutral protease of Bacillus stearothermophilus were analyzed using a three-dimensional model that was inferred from the crystal structure of thermolysin, the highly homologous neutral protease of B.thermoproteolyticus (85% sequence identity). Site-directed mutagenesis was used to fill some of these cavities, thereby improving hydrophobic packing in the protein interior. The mutations had small effects on the thermostability, even after drastic changes, such as Leu284 --> Trp and Met168 --> Trp. The effects on T50, the temperature at which 50% of the enzyme is irreversibly inactivated in 30 min, ranged from 0.0 to +0.4-degrees-C. These results can be explained by assuming that the mutations have positive and negative structural effects of approximately the same magnitude. Alternatively, it could be envisaged that the local unfolding steps, which render the enzyme susceptible towards autolysis and which are rate limiting in the process of thermal inactivation, are only slightly affected by alterations in the hydrophobic core

Recurrence of ventricular arrhythmias in ischaemic secondary prevention implantable cardioverter defibrillator recipients: long-term follow-up of the Leiden out-of-hospital cardiac arrest study (LOHCAT)

Aims to assess the long-term rate of mortality and the recurrence of potentially life-threatening ventricular arrhythmias in secondary prevention implantable cardioverter defibrillator (ICD) patients and to construct a model for baseline risk stratification.Methods and resultsSince 1996, all patients with ischaemic heart disease, receiving ICD therapy for secondary prevention of sudden death, were included in the current study. Patients were evaluated at implantation and during long-term follow-up. A total of 456 patients were included in the analysis and followed for 54 ± 35 months. During follow-up, 100 (22) patients died and ICD therapy was noted in 216 (47) patients, of which 138 (30) for fast, potentially life-threatening ventricular arrhythmia. Multivariate analysis revealed a history of atrial fibrillation or flutter (AF), ventricular tachycardia as presenting arrhythmia, and wide QRS and poor left ventricular ejection fraction as independent predictors of life-threatening ventricular arrhythmias. The strongest predictor was AF with a hazard ratio of 2.1 (95 confidence interval 1.3-3.2). On the basis of the available clinical data, it was not possible to identify a group which exhibited no risk on recurrence of potentially life-threatening ventricular arrhythmias.ConclusionIschaemic secondary prevention ICD recipients exhibit a high recurrence rate of potentially life-threatening ventricular arrhythmias. Factors that increase risk can be identified but, even with these factors, it was not possible to distinguish a recurrence-free group

Efficient Visual Search from Synchronized Auditory Signals Requires Transient Audiovisual Events

BACKGROUND: A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is critical to observe audiovisual integration. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that temporal coincidence (i.e., synchrony) of auditory and visual components can trigger audiovisual interaction in cluttered displays and consequently produce very fast and efficient target identification. In visual search experiments, subjects found a modulating visual target vastly more efficiently when it was paired with a synchronous auditory signal. By manipulating the kind of temporal modulation (sine wave vs. square wave vs. difference wave; harmonic sine-wave synthesis; gradient of onset/offset ramps) we show that abrupt visual events are required for this search efficiency to occur, and that sinusoidal audiovisual modulations do not support efficient search. CONCLUSIONS/SIGNIFICANCE: Thus, audiovisual temporal alignment will only lead to benefits in visual search if the changes in the component signals are both synchronized and transient. We propose that transient signals are necessary in synchrony-driven binding to avoid spurious interactions with unrelated signals when these occur close together in time

Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening

Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The objective of the study was to assess the morbidity, mortality, and diagnostic and therapeutic delay in children with SCID in the Netherlands in the last 15 years. These data may help to judge whether SCID should be considered to be included in our national neonatal screening program. In the period 1998–2013, 43 SCID patients were diagnosed in the Netherlands, 11 of whom were atypical SCID (presentation beyond the first year). The median interval between the first symptom and diagnosis was 2 months (range 0–1173 months). The total mortality was 42 %. In total, 32 patients were treated with HSCT of whom 8 were deceased. Nine patients died due to severe infectious complications before curative treatment could be initiated. Conclusion: Because of a high mortality of patients with SCID before HSCT could be initiated, only a national newborn screening program and pre-emptive HSCT or GT will be able to improve survival of these patients