Modeling Correlation in Vehicle Routing Problems with Makespan Objectives and Stochastic Travel Times

The majority of stochastic vehicle routing models consider travel times to be independent. However, in reality, travel times are often stochastic and correlated, such as in urban areas. We examine a vehicle routing problem with a makespan objective incorporating both stochastic and correlated travel times. We develop an approach based on extreme-value theory to estimate the expected makespan (and standard deviation) and embed this within a routing heuristic. We present results that demonstrate the impact of different correlation patterns and levels of correlation on route planning

Galaxy cluster outskirts: a universal entropy profile for relaxed clusters?

We fit a functional form for a universal ICM entropy profile to the scaled entropy profiles of a catalogue of X-ray galaxy cluster outskirts results, which are all relaxed cool core clusters at redshift below 0.25. We also investigate the functional form suggested by Lapi et al. and Cavaliere et al. for the behaviour of the entropy profile in the outskirts and find it to fit the data well outside 0.3r200 . We highlight the discrepancy in the entropy profile behaviour in the outskirts between observations and the numerical simulations of Burns et al., and show that the entropy profile flattening due to gas clumping calculated by Nagai & Lau is insufficient to match observations, suggesting that gas clumping alone cannot be responsible for all of the entropy profile flattening in the cluster outskirts. The entropy profiles found with Suzaku are found to be consistent with ROSAT, XMM-Newton and Planck results.Comment: 5 pages, 5 figures. Accepted for publication in MNRA

Thermodynamics of the Coma Cluster Outskirts

We present results from a large mosaic of Suzaku observations of the Coma Cluster, the nearest and X-ray brightest hot, dynamically active, non-cool core system, focusing on the thermodynamic properties of the ICM on large scales. For azimuths not aligned with an infalling subcluster towards the southwest, our measured temperature and X-ray brightness profiles exhibit broadly consistent radial trends, with the temperature decreasing from about 8.5 keV at the cluster center to about 2 keV at a radius of 2 Mpc, which is the edge of our detection limit. The SW merger significantly boosts the surface brightness, allowing us to detect X-ray emission out to ~2.2 Mpc along this direction. Apart from the southwestern infalling subcluster, the surface brightness profiles show multiple edges around radii of 30-40 arcmin. The azimuthally averaged temperature profile, as well as the deprojected density and pressure profiles, all show a sharp drop consistent with an outward propagating shock front located at 40 arcmin, corresponding to the outermost edge of the giant radio halo observed at 352 MHz with the WSRT. The shock front may be powering this radio emission. A clear entropy excess inside of r_500 reflects the violent merging events linked with these morphological features. Beyond r_500, the entropy profiles of the Coma Cluster along the relatively relaxed directions are consistent with the power-law behavior expected from simple models of gravitational large-scale structure formation. The pressure is also in agreement at these radii with the expected values measured from SZ data from the Planck satellite. However, due to the large uncertainties associated with the Coma Cluster measurements, we cannot yet exclude an entropy flattening in this system consistent with that seen in more relaxed cool core clusters.Comment: submitted to ApJ; revised after first referee repor

Large-scale Motions in the Perseus Galaxy Cluster

By combining large-scale mosaics of ROSAT PSPC, XMM-Newton, and Suzaku X-ray observations, we present evidence for large-scale motions in the intracluster medium of the nearby, X-ray bright Perseus Cluster. These motions are suggested by several alternating and interleaved X-ray bright, low-temperature, low-entropy arcs located along the east-west axis, at radii ranging from ~10 kpc to over a Mpc. Thermodynamic features qualitatively similar to these have previously been observed in the centers of cool core clusters, and were successfully modeled as a consequence of the gas sloshing/swirling motions induced by minor mergers. Our observations indicate that such sloshing/swirling can extend out to larger radii than previously thought, on scales approaching the virial radius.Comment: 6 pages, 6 figures, accepted for publication in Ap

The gas distribution in the outer regions of galaxy clusters

We present the analysis of a local (z = 0.04 - 0.2) sample of 31 galaxy clusters with the aim of measuring the density of the X-ray emitting gas in cluster outskirts. We compare our results with numerical simulations to set constraints on the azimuthal symmetry and gas clumping in the outer regions of galaxy clusters. We exploit the large field-of-view and low instrumental background of ROSAT/PSPC to trace the density of the intracluster gas out to the virial radius. We perform a stacking of the density profiles to detect a signal beyond r200 and measure the typical density and scatter in cluster outskirts. We also compute the azimuthal scatter of the profiles with respect to the mean value to look for deviations from spherical symmetry. Finally, we compare our average density and scatter profiles with the results of numerical simulations. As opposed to some recent Suzaku results, and confirming previous evidence from ROSAT and Chandra, we observe a steepening of the density profiles beyond \sim r500. Comparing our density profiles with simulations, we find that non-radiative runs predict too steep density profiles, whereas runs including additional physics and/or treating gas clumping are in better agreement with the observed gas distribution. We report for the first time the high-confidence detection of a systematic difference between cool-core and non-cool core clusters beyond \sim 0.3r200, which we explain by a different distribution of the gas in the two classes. Beyond \sim r500, galaxy clusters deviate significantly from spherical symmetry, with only little differences between relaxed and disturbed systems. We find good agreement between the observed and predicted scatter profiles, but only when the 1% densest clumps are filtered out in the simulations. [Abridged]Comment: The data for the average profiles and individual clusters can be downloaded at: http://www.isdc.unige.ch/~deckert/newsite/The_Planck_ROSAT_project.htm

CP2K: An electronic structure and molecular dynamics software package - Quickstep: Efficient and accurate electronic structure calculations

CP2K is an open source electronic structure and molecular dynamics software package to perform atomistic simulations of solid-state, liquid, molecular, and biological systems. It is especially aimed at massively parallel and linear-scaling electronic structure methods and state-of-the-art ab initio molecular dynamics simulations. Excellent performance for electronic structure calculations is achieved using novel algorithms implemented for modern high-performance computing systems. This review revisits the main capabilities of CP2K to perform efficient and accurate electronic structure simulations. The emphasis is put on density functional theory and multiple post–Hartree–Fock methods using the Gaussian and plane wave approach and its augmented all-electron extension

The Novel Immunosuppressive Protein Kinase C Inhibitor Sotrastaurin Has No Pro-Viral Effects on the Replication Cycle of Hepatitis B or C Virus

The pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients

Development of practice and consensus-based strategies including a treat-to-target approach for the management of moderate and severe juvenile dermatomyositis in Germany and Austria

Background: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- and practice-based strategies in order to harmonize diagnosis, treatment and monitoring of JDM. Methods: The JDM working group was established in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and dermatologists with expertise in the management of JDM. Current practice patterns of management in JDM had previously been identified via an online survey among pediatric rheumatologists and neurologists. Using a consensus process consisting of online surveys and a face-to-face consensus conference statements were defined regarding the diagnosis, treatment and monitoring of JDM. During the conference consensus was achieved via nominal group technique. Voting took place using an electronic audience response system, and at least 80% consensus was required for individual statements. Results: Overall 10 individual statements were developed, finally reaching a consensus of 92 to 100% regarding (1) establishing a diagnosis, (2) case definitions for the application of the strategies (moderate and severe JDM), (3) initial diagnostic testing, (4) monitoring and documentation, (5) treatment targets within the context of a treat-totarget strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target strategy, (8) various glucocorticoid regimens, including intermittent intravenous methylprednisolone pulse and high-dose oral glucocorticoid therapies with tapering, (9) initial glucocorticoid-sparing therapy and (10) management of refractory disease. Conclusion: Using a consensus process among JDM experts, statements regarding the management of JDM were defined. These statements and the strategies aid in the management of patients with moderate and severe JDM

A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations