Simulations of the tidal interaction and mass transfer of a star in an eccentric orbit around an intermediate-mass black hole: the case of HLX-1

The X-ray source HLX-1 near the spiral galaxy ESO 243-49 is currently the best intermediate-mass black hole candidate. It has a peak bolometric luminosity of $10^{42}$ erg s$^{-1}$, which implies a mass inflow rate of $\sim10^{-4}$ MSun yr$^{-1}$, but the origin of this mass is unknown. It has been proposed that there is a star on an eccentric orbit around the black hole which transfers mass at pericentre. To investigate the orbital evolution of this system, we perform stellar evolution simulations using mesa and SPH simulations of a stellar orbit around an intermediate-mass black hole using fi. We run and couple these simulations using the amuse framework. We find that mass is lost through both the first and second Lagrange points and that there is a delay of up to 10 days between the pericentre passage and the peak mass loss event. The orbital evolution timescales we find in our simulations are larger than what is predicted by analytical models, but these models fall within the errors of our results. Despite the fast orbital evolution, we are unable to reproduce the observed change in outburst period. We conclude that the change in the stellar orbit with the system parameters investigated here is unable to account for all observed features of HLX-1.Comment: accepted for publication in mnra

Simulating stellar winds in AMUSE

We present stellar_wind.py, a module that provides multiple methods of simulating stellar winds using smoothed particle hydrodynamics codes (SPH) within the astrophysical multipurpose software environment (AMUSE) framework. With the simple wind mode, we create SPH wind particles in a spherically symmetric shell. We inject the wind particles with a velocity equal to their terminal velocity. The accelerating wind mode is similar, but with this method particles can be injected with a lower initial velocity than the terminal velocity and they are accelerated away from the star according to an acceleration function. With the heating wind mode, SPH particles are created with zero initial velocity with respect to the star, but instead wind particles are given an internal energy based on the integrated mechanical luminosity of the star. This mode is designed to be used on longer timescales and larger spatial scales compared to the other two modes and assumes that the star is embedded in a gas cloud. For fast winds, we find that both the simple and accelerating mode can reproduce the desired velocity, density and temperature profiles. For slow winds, the simple wind mode is insufficient due to dominant hydrodynamical effects that change the wind velocities. The accelerating mode, with additional options to account for these hydrodynamical effects, can still reproduce the desired wind profiles. We test the heating mode by simulating both a normal wind and a supernova explosion of a single star in a uniform density medium. The stellar wind simulation results matches the analytical solution for an expanding wind bubble. The supernova simulation gives qualitatively correct results, but the simulated bubble expands faster than the analytical solution predicts. We conclude with an example of a triple star system which includes the colliding winds of all three stars.Comment: Accepted for publication in A&

TP53 and lacZ mutagenesis induced by 3-nitrobenzanthrone in Xpa-deficient human TP53 knock-in mouse embryo fibroblasts

Abstract3-Nitrobenzanthrone (3-NBA) is a highly mutagenic compound and possible human carcinogen found in diesel exhaust. 3-NBA forms bulky DNA adducts following metabolic activation and induces predominantly G:C>T:A transversions in a variety of experimental systems. Here we investigated the influence of nucleotide excision repair (NER) on 3-NBA-induced mutagenesis of the human tumour suppressor gene TP53 and the reporter gene lacZ. To this end we utilised Xpa -knockout (Xpa-Null) human TP53 knock-in (Hupki) embryo fibroblasts (HUFs). As Xpa is essential for NER of bulky DNA adducts, we hypothesized that DNA adducts induced by 3-NBA would persist in the genomes of Xpa-Null cells and lead to an increased frequency of mutation. The HUF immortalisation assay was used to select for cells harbouring TP53 mutations following mutagen exposure. We found that Xpa-Null Hupki mice and HUFs were more sensitive to 3-NBA treatment than their wild-type (Xpa-WT) counterparts. However, following 3-NBA treatment and immortalisation, a similar frequency of TP53-mutant clones arose from Xpa-WT and Xpa-Null HUF cultures. In cells from both Xpa genotypes G:C>T:A transversion was the predominant TP53 mutation type and mutations exhibited bias towards the non-transcribed strand. Thirty-two percent of 3-NBA-induced TP53 mutations occurred at CpG sites, all of which are hotspots for mutation in smokers’ lung cancer (codons 157, 158, 175, 245, 248, 273, 282). We also examined 3-NBA-induced mutagenesis of an integrated lacZ reporter gene in HUFs, where we again observed a similar mutant frequency in Xpa-WT and Xpa-Null cells. Our findings suggest that 3-NBA-DNA adducts may evade removal by global genomic NER; the persistence of 3-NBA adducts in DNA may be an important factor in its mutagenicity

An inter-laboratory effort to harmonize the cell-delivered in vitro dose of aerosolized materials

Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ12) and titanium dioxide nanoparticles (TiO2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM). Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation (CV)): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ12 and TiO2 NM-105 particles showed good linearity (R2 > 0.95) between particle concentration of the aerosolized suspension and QCM-determined insert-delivered particle dose. The VITROCELL® Cloud 12 performance for DQ12 particles was identical to that for fluorescein-spiked salt, i.e., the ratio of measured and salt-predicted dose was 1.0 (29%). On the other hand, a ca. 2-fold reduced dose was observed for TiO2 NM-105 (0.54 (41%)), which was likely due to partial retention of TiO2 NM-105 agglomerates in the vibrating mesh nebulizer of the VITROCELL® Cloud12. This inter-laboratory comparison demonstrates that the QCM integrated in the VITROCELL® Cloud 12 is a reliable tool for dosimetry, which accounts for potential variations of the transwell insert-delivered dose due to device-, handling- and/or material-specific effects. With the detailed protocol presented herein, all seven partner laboratories were able to demonstrate dose-controlled aerosolization of material suspensions using the VITROCELL® Cloud12 exposure system at dose levels relevant for observing in vitro hazard responses. This is an important step towards regulatory approved implementation of ALI lung cell cultures for in vitro hazard assessment of aerosolized materials

An Air-liquid Interface Bronchial Epithelial Model for Realistic, Repeated Inhalation Exposure to Airborne Particles for Toxicity Testing.

For toxicity testing of airborne particles, air-liquid interface (ALI) exposure systems have been developed for in vitro tests in order to mimic realistic exposure conditions. This puts specific demands on the cell culture models. Many cell types are negatively affected by exposure to air (e.g., drying out) and only remain viable for a few days. This limits the exposure conditions that can be used in these models: usually relatively high concentrations are applied as a cloud (i.e., droplets containing particles, which settle down rapidly) within a short period of time. Such experimental conditions do not reflect realistic long-term exposure to low concentrations of particles. To overcome these limitations the use of a human bronchial epithelial cell line, Calu-3 was investigated. These cells can be cultured at ALI conditions for several weeks while retaining a healthy morphology and a stable monolayer with tight junctions. In addition, this bronchial model is suitable for testing the effects of repeated exposures to low, realistic concentrations of airborne particles using an ALI exposure system. This system uses a continuous airflow in contrast to other ALI exposure systems that use a single nebulization producing a cloud. Therefore, the continuous flow system is suitable for repeated and prolonged exposure to airborne particles while continuously monitoring the particle characteristics, exposure concentration, and delivered dose. Taken together, this bronchial model, in combination with the continuous flow exposure system, is able to mimic realistic, repeated inhalation exposure conditions that can be used for toxicity testing

The fundamental left-right asymmetry in the Germanic verb cluster

Cinque (2005, 2009, 2014a) observes that there is an asymmetry in the possible ordering of dependents of a lexical head before versus after the head. A reflection on some of the concepts needed to develop Cinque’s ideas into a theory of neutral word order reveals that dependents need to be treated separately by class. The resulting system is applied to the problem of word order in the Germanic verb cluster. It is shown that there is an extremely close match between theoretically derived expectations for clusters made up of auxiliaries, modals, causative ‘let’, a main verb, and verbal particles. The facts point to the action of Cinque’s fundamental left-right asymmetry in language in the realm of the verb cluster. At the same time, not all verb clusters fall under Cinque’s generalization, which, therefore, argues against treating all cases of restructuring uniformly