Tail asymptotics for processor sharing queues

The basic queueing system considered in this paper is the M/G/1 processor-sharing queue with or without impatience and with finite or infinite capacity. Under some mild assumptions, a criterion for the validity of the reduced-service-rate approximation is established when service times are heavy tailed. This result is applied to various models based on M/G/1 processor-sharing queues

Stellar Mass Black Hole Binaries as ULXs

Ultraluminous X-ray sources (ULXs) with Lx > 10^{39} ergs/s have been discovered in great numbers in external galaxies with ROSAT, Chandra, and XMM. The central question regarding this important class of sources is whether they represent an extension in the luminosity function of binary X-ray sources containing neutron stars and stellar-mass black holes (BHs), or a new class of objects, e.g., systems containing intermediate-mass black holes (100-1000 Msun). We have carried out a theoretical study to test whether a large fraction of the ULXs, especially those in galaxies with recent star formation activity, can be explained with binary systems containing stellar-mass black holes. To this end, we have applied a unique set of binary evolution models for black-hole X-ray binaries, coupled to a binary population synthesis code, to model the ULXs observed in external galaxies. We find that for donor stars with initial masses >10 Msun the mass transfer driven by the normal nuclear evolution of the donor star is sufficient to potentially power most ULXs. This is the case during core hydrogen burning and, to an even more pronounced degree, while the donor star ascends the giant branch, though the latter phases lasts only ~5% of the main sequence phase. We show that with only a modest violation of the Eddington limit, e.g., a factor of ~10, both the numbers and properties of the majority of the ULXs can be reproduced. One of our conclusions is that if stellar-mass black-hole binaries account for a significant fraction of ULXs in star-forming galaxies, then the rate of formation of such systems is ~3 x 10^{-7} per year normalized to a core-collapse supernova rate of 0.01 per year.Comment: 15 pages, 12 figure

Gravitational waves from intermediate-mass black holes in young clusters

Massive young clusters (YCs) are expected to host intermediate-mass black holes (IMBHs) born via runaway collapse. These IMBHs are likely in binaries and can undergo mergers with other compact objects, such as stellar mass black holes (BHs) and neutron stars (NSs). We derive the frequency of such mergers starting from information available in the Local Universe. Mergers of IMBH-NS and IMBH-BH binaries are sources of gravitational waves (GWs), which might allow us to reveal the presence of IMBHs. We thus examine their detectability by current and future GW observatories, both ground- and space-based. In particular, as representative of different classes of instruments we consider Initial and Advanced LIGO, the Einstein gravitational-wave Telescope (ET) and the Laser Interferometer Space Antenna (LISA). We find that IMBH mergers are unlikely to be detected with instruments operating at the current sensitivity (Initial LIGO). LISA detections are disfavored by the mass range of IMBH-NS and IMBH-BH binaries: less than one event per year is expected to be observed by such instrument. Advanced LIGO is expected to observe a few merger events involving IMBH binaries in a 1-year long observation. Advanced LIGO is particularly suited for mergers of relatively light IMBHs (~100 Msun) with stellar mass BHs. The number of mergers detectable with ET is much larger: tens (hundreds) of IMBH-NS (IMBH-BH) mergers might be observed per year, according to the runaway collapse scenario for the formation of IMBHs. We note that our results are affected by large uncertainties, produced by poor observational constraints on many of the physical processes involved in this study, such as the evolution of the YC density with redshift.[abridged]Comment: 29 pages, 4 figures, accepted for publication in Ap

3D architecture of DNA Pol α reveals the functional core of multi-subunit replicative polymerases

Eukaryotic DNA replication requires the coordinated activity of the multi-subunit DNA polymerases: Pol α, Pol δ and Pol ɛ. The conserved catalytic and regulatory B subunits associate in a constitutive heterodimer that represents the functional core of all three replicative polymerases. Here, we combine X-ray crystallography and electron microscopy (EM) to describe subunit interaction and 3D architecture of heterodimeric yeast Pol α. The crystal structure of the C-terminal domain (CTD) of the catalytic subunit bound to the B subunit illustrates a conserved mechanism of accessory factor recruitment by replicative polymerases. The EM reconstructions of Pol α reveal a bilobal shape with separate catalytic and regulatory modules. Docking of the B–CTD complex in the EM reconstruction shows that the B subunit is tethered to the polymerase domain through a structured but flexible linker. Our combined findings provide a structural template for the common functional architecture of the three major replicative DNA polymerases

On the formation and evolution of black-hole binaries

We present the results of a systematic study of the formation and evolution of binaries containing black holes and normal-star companions with a wide range of masses. We first reexamine the standard formation scenario for close black-hole binaries, where the spiral-in of the companion in the envelope of a massive star causes the ejection of the envelope. We estimate the formation rates for different companion masses and different assumptions about the common-envelope structure and other model parameters. We find that black-hole binaries with intermediate- and high-mass secondaries can form for a wide range of assumptions, while black-hole binaries with low-mass secondaries can only form with apparently unrealistic assumptions (in agreement with previous studies). We then present detailed binary evolution sequences for black-hole binaries with secondaries of 2 to 17 Msun and demonstrate that in these systems the black hole can accrete appreciably even if accretion is Eddington limited (up to 7 Msun for an initial black-hole mass of 10 Msun) and that the black holes can be spun up significantly in the process. We discuss the implications of these calculations for well-studied black-hole binaries (in particular GRS 1915+105), ultra-luminous X-ray sources and Cygnus X-1. Finally, we discuss how some of the assumptions in the standard model could be relaxed to allow the formation of low-mass, short-period black-hole binaries which appear to be very abundant in Nature. (Abstract abridged)Comment: 21 pages, 9 figures, accepted by MNRAS, Figs. 2a/2b and 5 in very reduced forma

Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT)

<p>Abstract</p> <p>Background</p> <p>The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. The aim of the present study was to examine the relationship between the Val158Met COMT gene polymorphism and anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) in the general adult population.</p> <p>Methods</p> <p>In the Nord-Trøndelag Health Study (HUNT) the association between the Val158Met polymorphism and anxiety and depression was evaluated in a random sample of 5531 individuals. Two different cut off scores (≥ 8 and ≥ 11) were used to identify cases with anxiety (HADS-A) and depression (HADS-D), whereas controls had HADS-A <8 and HADS-D <8.</p> <p>Results</p> <p>The COMT genotype distribution was similar between controls and individuals in the groups with anxiety and depression using cut-off scores of ≥ 8. When utilizing the alternative cut-off score HADS-D ≥ 11, Met/Met genotype and Met allele were less common among men with depression compared to the controls (genotype: p = 0.017, allele: p = 0.006). In the multivariate analysis, adjusting for age and heart disease, depression (HADS-D ≥ 11) was less likely among men with the Met/Met genotype than among men with the Val/Val genotype (OR = 0.37, 95% CI = 0.18–0.76).</p> <p>Conclusion</p> <p>In this population-based study, no clear association between the Val158Met polymorphism and depression and anxiety was revealed. The Met/Met genotype was less likely among men with depression defined as HADS-D ≥ 11, but this may be an incidental finding.</p

Crystal Structure of Escherichia coli CusC, the Outer Membrane Component of a Heavy Metal Efflux Pump

Background: While copper has essential functions as an enzymatic co-factor, excess copper ions are toxic for cells, necessitating mechanisms for regulating its levels. The cusCBFA operon of E. coli encodes a four-component efflux pump dedicated to the extrusion of Cu(I) and Ag(I) ions. Methodology/Principal Findings: We have solved the X-ray crystal structure of CusC, the outer membrane component of the Cus heavy metal efflux pump, to 2.3 A ˚ resolution. The structure has the largest extracellular opening of any outer membrane factor (OMF) protein and suggests, for the first time, the presence of a tri-acylated N-terminal lipid anchor. Conclusions/Significance: The CusC protein does not have any obvious features that would make it specific for metal ions, suggesting that the narrow substrate specificity of the pump is provided by other components of the pump, most likely by the inner membrane component CusA

Star Formation and Dynamics in the Galactic Centre

The centre of our Galaxy is one of the most studied and yet enigmatic places in the Universe. At a distance of about 8 kpc from our Sun, the Galactic centre (GC) is the ideal environment to study the extreme processes that take place in the vicinity of a supermassive black hole (SMBH). Despite the hostile environment, several tens of early-type stars populate the central parsec of our Galaxy. A fraction of them lie in a thin ring with mild eccentricity and inner radius ~0.04 pc, while the S-stars, i.e. the ~30 stars closest to the SMBH (<0.04 pc), have randomly oriented and highly eccentric orbits. The formation of such early-type stars has been a puzzle for a long time: molecular clouds should be tidally disrupted by the SMBH before they can fragment into stars. We review the main scenarios proposed to explain the formation and the dynamical evolution of the early-type stars in the GC. In particular, we discuss the most popular in situ scenarios (accretion disc fragmentation and molecular cloud disruption) and migration scenarios (star cluster inspiral and Hills mechanism). We focus on the most pressing challenges that must be faced to shed light on the process of star formation in the vicinity of a SMBH.Comment: 68 pages, 35 figures; invited review chapter, to be published in expanded form in Haardt, F., Gorini, V., Moschella, U. and Treves, A., 'Astrophysical Black Holes'. Lecture Notes in Physics. Springer 201

Recognition of vitamin B metabolites by mucosal-associated invariant T cells

The mucosal-associated invariant T-cell antigen receptor (MAIT TCR) recognizes MR1 presenting vitamin B metabolites. Here we describe the structures of a human MAIT TCR in complex with human MR1 presenting a non-stimulatory ligand derived from folic acid and an agonist ligand derived from a riboflavin metabolite. For both vitamin B antigens, the MAIT TCR docks in a conserved manner above MR1, thus acting as an innate-like pattern recognition receptor. The invariant MAIT TCR a-chain usage is attributable to MR1-mediated interactions that prise open the MR1 cleft to allow contact with the vitamin B metabolite. Although the non-stimulatory antigen does not contact the MAIT TCR, the stimulatory antigen does. This results in a higher affinity of the MAIT TCR for a stimulatory antigen in comparison with a non-stimulatory antigen. We formally demonstrate a structural basis for MAIT TCR recognition of vitamin B metabolites, while illuminating how TCRs recognize microbial metabolic signatures