Ultra-compact binaries: relevance and role of Utrecht

We present a short overview of the formation and evolution of ultra-compact binaries. They are relevant to a surprisingly large number of astrophysical phenomena (binary interactions, mass transfer stability, explosive phenomena such as type Ia supernovae and gravitational waves).Comment: To appear in proceedings of "370 years of astronomy in Utrecht", Noordwijkerhout, The Netherlands, April 2-5, 2012 (ASP Conference Series

Population synthesis of classical low-mass X-ray binaries in the Galactic Bulge

Aims. We model the present-day population of 'classical' low-mass X-ray binaries (LMXBs) with neutron star accretors, which have hydrogen-rich donor stars. Their population is compared with that of hydrogen-deficient LMXBs, known as ultracompact X-ray binaries (UCXBs). We model the observable LMXB population and compare it to observations. Methods. We combine the binary population synthesis code SeBa with detailed LMXB evolutionary tracks to model the size and properties of the present-day LMXB population in the Galactic Bulge. Whether sources are persistent or transient, and what their instantaneous X-ray luminosities are, is predicted using the thermal-viscous disk instability model. Results. We find a population of ~2.1 x 10^3 LMXBs with neutron star accretors. Of these about 15 - 40 are expected to be persistent (depending on model assumptions), with luminosities higher than 10^35 erg s^-1. About 7 - 20 transient sources are expected to be in outburst at any given time. Within a factor of two these numbers are consistent with the observed population of bright LMXBs in the Bulge. This gives credence to our prediction of the existence of a population of ~1.6 x 10^3 LMXBs with low donor masses that have gone through the period minimum, and have present-day mass transfer rates below 10^-11 Msun yr^-1. Conclusions. Even though the observed population of hydrogen-rich LMXBs in the Bulge is larger than the observed population of (hydrogen-deficient) UCXBs, the latter have a higher formation rate. While UCXBs may dominate the total LMXB population at the present, the majority would be very faint, or may have become detached and produced millisecond radio pulsars. In that case UCXBs would contribute significantly more to the formation of millisecond radio pulsars than hydrogen-rich LMXBs. [abridged]Comment: 8 pages, 10 figures. Accepted for publication in Astronomy and Astrophysics. v2: minor language correction

Formation of the planet around the millisecond pulsar J1719-1438

Context. Recently the discovery of PSR J1719-1438, a 5.8 ms pulsar with a companion in a 2.2 hr orbit, was reported. The combination of this orbital period and the very low mass function is unique. The discoverers, Bailes et al., proposed an ultracompact X-ray binary (UCXB) as the progenitor system. However, the standard UCXB scenario would not produce this system as the time required to reach this orbital period exceeds the current estimate of the age of the Universe. The detached state of the system aggravates the problem. Aims. We want to understand the evolutionary history of PSR J1719-1438, and determine under which circumstances it could have evolved from an UCXB. Methods. We model UCXB evolution varying the donor size and investigate the effect of a wind mass loss from the donor, and compare the results with the observed characteristics of PSR J1719-1438. Results. An UCXB can reach a 2.2 hr orbit within the age of the Universe, provided that 1) the millisecond pulsar can significantly heat and expand the donor by pulsar irradiation, or 2) the system loses extra orbital angular momentum, e.g. via a fast wind from the donor. Conclusions. The most likely scenario for the formation of PSR J1719-1438 is UCXB evolution driven by angular momentum loss via the usual gravitational wave emission, which is enhanced by angular momentum loss via a donor wind of ~3x10^-13 Msun/yr. Depending on the size of the donor during the evolution, the companion presently probably has a mass of ~1-3 Jupiter masses, making it a very low mass white dwarf as proposed by Bailes et al. Its composition can be either helium or carbon-oxygen. A helium white dwarf companion makes the long (for an UCXB) orbital period easier to explain, but the required inclination makes it a priori less likely than a carbon-oxygen white dwarf.Comment: 5 pages, 4 figures. Accepted for publication in Astronomy and Astrophysics. v2: Updated a referenc

Time-resolved X-Shooter spectra and RXTE light curves of the ultra-compact X-ray binary candidate 4U 0614+091

In this paper we present X-Shooter time resolved spectroscopy and RXTE PCA light curves of the ultra-compact X-ray binary candidate 4U 0614+091. The X-Shooter data are compared to the GMOS data analyzed previously by Nelemans et al. (2004). We confirm the presence of C III and O II emission features at ~ 4650 {\AA} and ~ 5000 {\AA}. The emission lines do not show evident Doppler shifts that could be attributed to the motion of the donor star/hot spot around the center of mass of the binary. We note a weak periodic signal in the red-wing/blue-wing flux ratio of the emission feature at ~ 4650 {\AA}. The signal occurs at P = 30.23 +/- 0.03 min in the X-Shooter and at P = 30.468 +/- 0.006 min in the GMOS spectra when the source was in the low/hard state. Due to aliasing effects the period in the GMOS and X-Shooter data could well be the same. We deem it likely that the orbital period is thus close to 30 min, however, as several photometric periods have been reported for this source in the literature already, further confirmation of the 30 min period is warranted. We compare the surface area of the donor star and the disc of 4U 0614+091 with the surface area of the donor star and the disc in typical hydrogen-rich low-mass X-ray binaries and the class of AM Canum Venaticorum stars and argue that the optical emission in 4U 0614+091 is likely dominated by the disc emission. Additionally, we search for periodic signals in all the publicly available RXTE PCA light curves of 4U 0614+091 which could be associated with the orbital period of this source. A modulation at the orbital period with an amplitude of ~ 10% such as those that have been found in other ultra-compact X-ray binaries (4U 0513-40, 4U 1820-30) is not present in 4U 0614+091.Comment: Accepted for publication in MNRAS, 11 pages, 7 figure

Constitutive behavior of as-cast A356

The constitutive behavior of aluminum alloy A356 in the as-cast condition has been characterized using compression tests performed over a wide range of deformation temperatures (30-500{\deg}C) and strain rates (\approx0.1-10 /s). This work is intended to support the development of process models for a wide range of conditions including those relevant to casting, forging and machining. The flow stress behavior as a function of temperature and strain rate has been fit to a modified Johnson-Cook and extended Ludwik-Hollomon expression. The data has also been assessed with both the strain-independent Kocks-Mecking and Zener-Hollomon frameworks. The predicted plastic flow stress for each expression are compared. The results indicate that the extended Ludwik-Hollomon is best suited to describe small strain conditions (stage III hardening), while the Kocks-Mecking is best employed for large strain (stage IV). At elevated temperatures, it was found that the Zener-Hollomon model provides the best prediction of flow stress.Comment: 34 pages, 12 figure

Partner independent fusion gene detection by multiplexed CRISPR-Cas9 enrichment and long read nanopore sequencing

Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment. Fusion gene partner choice and breakpoint-position promiscuity restricts diagnostic detection, even for known and recurrent configurations. Here, we develop FUDGE (FUsion Detection from Gene Enrichment) to accurately and impartially identify fusions. FUDGE couples target-selected and strand-specific CRISPR-Cas9 activity for fusion gene driver enrichment - without prior knowledge of fusion partner or breakpoint-location - to long read nanopore sequencing with the bioinformatics pipeline NanoFG. FUDGE has flexible target-loci choices and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in one sequencing run. We observe on-average 665 fold breakpoint-site enrichment and identify nucleotide resolution fusion breakpoints within 2 days. The assay identifies cancer cell line and tumor sample fusions irrespective of partner gene or breakpoint-position. FUDGE is a rapid and versatile fusion detection assay for diagnostic pan-cancer fusion detection

The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNF alpha Treatment in Crohn's Disease

Background: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor- (TNF) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage. Aim: The aim of this study was to investigated whether early changes in the VICM (citrullinated and matrix metalloproteinase-degraded vimentin) biomarker were associated with response to anti-TNF treatment in patients with CD. Methods: Serum VICM levels were measured by ELISA in 2 independent cohorts of CD patients (n=42) treated with anti-TNF (infliximab or adalimumab). Response was determined by achieving clinical remission (Harvey Bradshaw Index<5). Results: Compared with baseline, VICM serum levels were reduced by anti-TNF in the infliximab cohort (week 6 and 14) and in the adalimumab cohort (week 8). VICM was lower in the responders compared with the nonresponders [infliximab: Week 6, P<0.05; area under the curve (AUC)=0.90; adalimumab: Week 1, P<0.01 (AUC=0.91), and week 8, P<0.05 (AUC=0.86)], and were able to predict response to treatment after 1 week of treatment with an odds ratio of 42.5. Conclusions: The VICM biomarker was time dependently reduced in CD patients responding to anti-TNF treatment. We suggest that VICM may be used as a marker for monitoring early response to anti-TNF in patients with CD

PA-6 inhibits inward rectifier currents carried by V93I and D172N gain-of-function KIR2.1 channels, but increases channel protein expression

Background: The inward rectifier potassium current IK1 contributes to a stable resting membrane potential and phase 3 repolarization of the cardiac action potential. KCNJ2 gain-of function mutations V93I and D172N associate with increased IK1, short QT syndrome type 3 and congenital atrial fibrillation. Pentamidine-Analogue 6 (PA-6) is an efficient (IC50 = 14 nM with inside-out patch clamp methodology) and specific IK1 inhibitor that interacts with the cytoplasmic pore region of the KIR2.1 ion channel, encoded by KCNJ2. At 10 μM, PA-6 increases wild-type (WT) KIR2. 1 expression in HEK293T cells upon chronic treatment. We hypothesized that PA-6 will interact with and inhibit V93I and D172N KIR2.1 channels, whereas impact on channel expression at the plasma membrane requires higher concentrations. Methods: Molecular modelling was performed with the human KIR2.1 closed state homology model using FlexX. WT and mutant KIR2.1 channels were expressed in HEK293 cells. Patch clamp single cell electrophysiology measurements were performed in the whole cell and inside-out mode of the patch clamp method. KIR2.1 expression level and localization were determined by western blot analysis and immunofluorescence microscopy, respectively. Results: PA-6 docking in the V93I/D172N double mutant homology model of KIR2.1 demonstrated that mutations and drug-binding site are >30 Å apart. PA-6 inhibited WT and V93I outward currents with similar potency (IC50 = 35.5 and 43.6 nM at +50 mV for WT and V93I), whereas D172N currents were less sensitive (IC50 = 128.9 nM at +50 mV) using inside-out patch-clamp electrophysiology. In whole cell mode, 1 μM of PA-6 inhibited outward IK1 at −50 mV by 28 ± 36%, 18 ± 20% and 10 ± 6%, for WT, V93I and D172N channels respectively. Western blot analysis demonstrated that PA-6 (5 μM, 24 h) increased KIR2.1 expression levels of WT (6.3 ± 1.5 fold), and V93I (3.9 ± 0.9) and D172N (4.8 ± 2.0) mutants. Immunofluorescent microscopy demonstrated dose-dependent intracellular KIR2.1 accumulation following chronic PA-6 application (24 h, 1 and 5 μM). Conclusions: 1) KCNJ2 gain-of-function mutations V93I and D172N in the KIR2.1 ion channel do not impair PA-6 mediated inhibition of IK1, 2) PA-6 elevates KIR2.1 protein expression and induces intracellular KIR2.1 accumulation, 3) PA-6 is a strong candidate for further preclinical evaluation in treatment of congenital SQT3 and AF