X-ray luminosity function of high-mass X-ray binaries: Studying the signatures of different physical processes using detailed binary evolution calculations

The ever-expanding observational sample of X-ray binaries (XRBs) makes them excellent laboratories for constraining binary evolution theory. Such constraints can be obtained by studying the effects of various physical assumptions on synthetic X-ray luminosity functions (XLFs) and comparing to observed XLFs. In this work, we focus on high-mass XRBs (HMXBs) and study the effects on the XLF of various, poorly-constrained assumptions regarding physical processes such as the common-envelope phase, the core-collapse, and wind-fed accretion. We use the new binary population synthesis code POSYDON, which employs extensive pre-computed grids of detailed stellar structure and binary evolution models, to simulate the evolution of binaries. We generate 96 synthetic XRB populations corresponding to different combinations of model assumptions. The generated HMXB XLFs are feature-rich, deviating from the commonly assumed single-power law. We find a break in our synthetic XLF at luminosity $\sim 10^{38}$ erg s$^{-1}$, similar to observed XLFs. However, we find also a general overabundance of XRBs (up to a factor of $\sim$10 for certain model parameter combinations) driven primarily by XRBs with black hole accretors. Assumptions about the transient behavior of Be-XRBs, asymmetric supernova kicks, and common-envelope physics can significantly affect the shape and normalization of our synthetic XLFs. We find that less well-studied assumptions regarding the circularization of the orbit at the onset of Roche-lobe overflow and criteria for the formation of an X-ray emitting accretion disk around wind-accreting black holes can also impact our synthetic XLFs. Our study reveals the importance of large-scale parameter studies, highlighting the power of XRBs in constraining binary evolution theory.Comment: 31 pages, 32 figures, Accepted by A&A. Fixed typos and updated references. Referee's comments were addresse

Investigating the Lower Mass Gap with Low Mass X-ray Binary Population Synthesis

Mass measurements from low-mass black hole X-ray binaries (LMXBs) and radio pulsars have been used to identify a gap between the most massive neutron stars (NSs) and the least massive black holes (BHs). BH mass measurements in LMXBs are typically only possible for transient systems: outburst periods enable detection via all-sky X-ray monitors, while quiescent periods enable radial-velocity measurements of the low-mass donor. We quantitatively study selection biases due to the requirement of transient behavior for BH mass measurements. Using rapid population synthesis simulations (COSMIC), detailed binary stellar-evolution models (MESA), and the disk instability model of transient behavior, we demonstrate that transient-LMXB selection effects introduce observational biases, and can suppress mass-gap BHs in the observed sample. However, we find a population of transient LMXBs with mass-gap BHs form through accretion-induced collapse of a NS during the LMXB phase, which is inconsistent with observations. These results are robust against variations of binary evolution prescriptions. The significance of this accretion-induced collapse population depends upon the maximum NS birth mass $M_\mathrm{ NS, birth-max}$. To reflect the observed dearth of low-mass BHs, COSMIC and MESA models favor $M_\mathrm{ NS, birth-max} \lesssim2M_{\odot}$. In the absence of further observational biases against LMXBs with mass-gap BHs, our results indicate the need for additional physics connected to the modeling of LMXB formation and evolution.Comment: 21 pages, accepted to Ap

POSYDON: A General-Purpose Population Synthesis Code with Detailed Binary-Evolution Simulations

Most massive stars are members of a binary or a higher-order stellar systems, where the presence of a binary companion can decisively alter their evolution via binary interactions. Interacting binaries are also important astrophysical laboratories for the study of compact objects. Binary population synthesis studies have been used extensively over the last two decades to interpret observations of compact-object binaries and to decipher the physical processes that lead to their formation. Here, we present POSYDON, a novel, binary population synthesis code that incorporates full stellar-structure and binary-evolution modeling, using the MESA code, throughout the whole evolution of the binaries. The use of POSYDON enables the self-consistent treatment of physical processes in stellar and binary evolution, including: realistic mass-transfer calculations and assessment of stability, internal angular-momentum transport and tides, stellar core sizes, mass-transfer rates and orbital periods. This paper describes the detailed methodology and implementation of POSYDON, including the assumed physics of stellar- and binary-evolution, the extensive grids of detailed single- and binary-star models, the post-processing, classification and interpolation methods we developed for use with the grids, and the treatment of evolutionary phases that are not based on pre-calculated grids. The first version of POSYDON targets binaries with massive primary stars (potential progenitors of neutron stars or black holes) at solar metallicity.Comment: 60 pages, 33 figures, 8 tables, referee's comments addressed. The code and the accompanying documentations and data products are available at https:\\posydon.or

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

The Role of the Parkinson's Disease Gene PARK9 in Essential Cellular Pathways and the Manganese Homeostasis Network in Yeast

YPK9 (Yeast PARK9; also known as YOR291W) is a non-essential yeast gene predicted by sequence to encode a transmembrane P-type transport ATPase. However, its substrate specificity is unknown. Mutations in the human homolog of YPK9, ATP13A2/PARK9, have been linked to genetic forms of early onset parkinsonism. We previously described a strong genetic interaction between Ypk9 and another Parkinson's disease (PD) protein α-synuclein in multiple model systems, and a role for Ypk9 in manganese detoxification in yeast. In humans, environmental exposure to toxic levels of manganese causes a syndrome similar to PD and is thus an environmental risk factor for the disease. How manganese contributes to neurodegeneration is poorly understood. Here we describe multiple genome-wide screens in yeast aimed at defining the cellular function of Ypk9 and the mechanisms by which it protects cells from manganese toxicity. In physiological conditions, we found that Ypk9 genetically interacts with essential genes involved in cellular trafficking and the cell cycle. Deletion of Ypk9 sensitizes yeast cells to exposure to excess manganese. Using a library of non-essential gene deletions, we screened for additional genes involved in tolerance to excess manganese exposure, discovering several novel pathways involved in manganese homeostasis. We defined the dependence of the deletion strain phenotypes in the presence of manganese on Ypk9, and found that Ypk9 deletion modifies the manganese tolerance of only a subset of strains. These results confirm a role for Ypk9 in manganese homeostasis and illuminates cellular pathways and biological processes in which Ypk9 likely functions

Rational Design and Characterization of D-Phe-Pro-D-Arg-Derived Direct Thrombin Inhibitors

The tremendous social and economic impact of thrombotic disorders, together with the considerable risks associated to the currently available therapies, prompt for the development of more efficient and safer anticoagulants. Novel peptide-based thrombin inhibitors were identified using in silico structure-based design and further validated in vitro. The best candidate compounds contained both l- and d-amino acids, with the general sequence d-Phe(P3)-Pro(P2)-d-Arg(P1)-P1′-CONH2. The P1′ position was scanned with l- and d-isomers of natural or unnatural amino acids, covering the major chemical classes. The most potent non-covalent and proteolysis-resistant inhibitors contain small hydrophobic or polar amino acids (Gly, Ala, Ser, Cys, Thr) at the P1′ position. The lead tetrapeptide, d-Phe-Pro-d-Arg-d-Thr-CONH2, competitively inhibits α-thrombin's cleavage of the S2238 chromogenic substrate with a Ki of 0.92 µM. In order to understand the molecular details of their inhibitory action, the three-dimensional structure of three peptides (with P1′ l-isoleucine (fPrI), l-cysteine (fPrC) or d-threonine (fPrt)) in complex with human α-thrombin were determined by X-ray crystallography. All the inhibitors bind in a substrate-like orientation to the active site of the enzyme. The contacts established between the d-Arg residue in position P1 and thrombin are similar to those observed for the l-isomer in other substrates and inhibitors. However, fPrC and fPrt disrupt the active site His57-Ser195 hydrogen bond, while the combination of a P1 d-Arg and a bulkier P1′ residue in fPrI induce an unfavorable geometry for the nucleophilic attack of the scissile bond by the catalytic serine. The experimental models explain the observed relative potency of the inhibitors, as well as their stability to proteolysis. Moreover, the newly identified direct thrombin inhibitors provide a novel pharmacophore platform for developing antithrombotic agents by exploring the conformational constrains imposed by the d-stereochemistry of the residues at positions P1 and P1′

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human osteosarcoma. Finally, the current position of canine osteosarcoma genetic research is discussed and areas for additional work within the canine population are identified