We present our measurements of the amplitude of photometric and spectroscopic variability due to clumping in the wind of Wolf-Rayet (WR) stars. Photometric variability was assessed using TESS light-curves, while spectroscopic variations were obtained from almost 20 years of monitoring of nearly 100 classical (presumably single) stars. Our results show an apparent dependence of the variability amplitude with the stars’ surface temperature and/or terminal velocity. Our interpretation is that it supports the idea that the dominating driver of the clumps in WR winds is a sub-surface convection region.

We present the results of our analysis of 122 light-curves from 50 Wolf-Rayet (WR) stars using a red+white noise analysis, where we compare the fitted red noise features with stellar parameters to assess the presence of correlations with stellar parameters. A significant correlation between the amplitude of variability α0 and v∞ was found for the whole sample, along with several other correlations satisfying the Spearman-Rank p<0.001 criterion for both He-burning and WNh stars. Our results are compatible with several plausible processes that can have an influence on the level of variability in the winds of these stars, including a subsurface convection zone and core-generated internal gravity waves.

Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.

Eta Carinae is the most massive active binary within 10,000 light-years. While famous for the largest non-terminal stellar explosion ever recorded, observations reveal a supermassive (∼120 M⊙) binary consisting of an LBV and either a WR or extreme O star in a very eccentric orbit (e=0.9) with a 5.54-year period. Dramatic changes across multiple wavelengths are routinely observed as the stars move about in their highly elliptical orbits, especially around periastron when the hot (∼40 kK) companion star delves deep into the denser and much cooler (∼15 kK) extended wind photosphere of the LBV primary. Many of these changes are due to a dynamic wind-wind collision region (WWCR) that forms between the stars, plus expanding radiation-illuminated fossil WWCRs formed one, two, and three 5.54-year orbital cycles ago. These fossil WWCRs have been spatially and spectrally resolved by the Hubble Space Telescope/Space Telescope Imaging Spectrograph (HST/STIS) at multiple epochs, resulting in data cubes that spatially map Eta Carinae’s innermost WWCRs and follow temporal changes in several forbidden emission lines (e.g. [Fe iii] 4659 Å, [Fe ii] 4815 Å) across the 5.54-year cycle. We present initial results of 3D time-dependent hydrodynamical and radiative-transfer simulations of the Eta Carinae binary and its WWCRs with the goal of producing synthetic data cubes of forbidden emission lines for comparison to the available HST/STIS observations. Comparison of the theoretical models to the observations reveals important details about the binary’s orbital motion, photoionization properties, and recent (5–15year) mass loss history. Such an analysis also provides a baseline for following future changes in Eta Carinae, essential for understanding the late-stage evolution of a nearby supernova progenitor. Our modeling methods can also be adapted to a number of other colliding wind binary systems (e.g. WR 140) that are scheduled to be studied with future observatories (e.g. the James Webb Space Telescope).

The stellar winds of hot stars have an important impact on both stellar and galactic evolution, yet their structure and internal processes are not fully understood in detail. One of the best nearby laboratories for studying such massive stellar winds is the O4I(n)fp star ζ Pup. After briefly discussing existing X-ray observations from Chandra and XMM, we present a simulation of X-ray emission line profile measurements for the upcoming 840 kilosecond Chandra HETGS observation. This simulation indicates that the increased S/N of this new observation will allow several major steps forward in the understanding of massive stellar winds. By measuring X-ray emission line strengths and profiles, we should be able to differentiate between various stellar wind models and map the entire wind structure in temperature and density. This legacy X-ray spectrum of ζ Pup will be a useful benchmark for future X-ray missions.

Classical Wolf-Rayet stars are evolved, hydrogen depleted massive stars that exhibit strong mass-loss. In theory, these stars can form either by intrinsic mass loss (stellar winds or eruptions), or via mass-removal in binaries. The Wolf-Rayet stars in the Magellanic Clouds are often thought to have originated through binary interaction due to the low ambient metallicity and, correspondingly, reduced wind mass-loss. We performed a complete spectral analysis of all known WR binaries of the nitrogen sequence in the Small and Large Magellanic Clouds, as well as additional orbital analyses, and constrained the evolutionary histories of these stars. We find that the bulk of Wolf-Rayet stars are luminous enough to be explained by single-star evolution. In contrast to prediction, we do not find clear evidence for a large population of low-luminosity Wolf-Rayet stars that could only form via binary interaction, suggesting a discrepancy between predictions and observations.

Eta Carinae is one of the most massive observable binaries. Yet determination of its orbital and physical parameters is hampered by obscuring winds. However the effects of the strong, colliding winds changes with phase due to the high orbital eccentricity. We wanted to improve measures of the orbital parameters and to determine the mechanisms that produce the relatively brief, phase-locked minimum as detected throughout the electromagnetic spectrum. We conducted intense monitoring of the He ii λ4686 line in η Carinae for 10 months in the year 2014, gathering ~300 high S/N spectra with ground- and space-based telescopes. We also used published spectra at the FOS4 SE polar region of the Homunculus, which views the minimum from a different direction. We used a model in which the He ii λ4686 emission is produced by two mechanisms: a) one linked to the intensity of the wind-wind collision which occurs along the whole orbit and is proportional to the inverse square of the separation between the companion stars; and b) the other produced by the ‘bore hole’ effect which occurs at phases across the periastron passage. The opacity (computed from 3D SPH simulations) as convolved with the emission reproduces the behavior of equivalent widths both for direct and reflected light. Our main results are: a) a demonstration that the He ii λ4686 light curve is exquisitely repeatable from cycle to cycle, contrary to previous claims for large changes; b) an accurate determination of the longitude of periastron, indicating that the secondary star is ‘behind’ the primary at periastron, a dispute extended over the past decade; c) a determination of the time of periastron passage, at ~4 days after the onset of the deep light curve minimum; and d) show that the minimum is simultaneous for observers at different lines of sight, indicating that it is not caused by an eclipse of the secondary star, but rather by the immersion of the wind-wind collision interior to the inner wind of the primary.

The objective is to determine the nature of the unseen companion of the single-lined spectroscopic binary, WR 148 (= WN7h+?). The absence of companion lines supports a compact companion (cc) scenario. The lack of hard X-rays favours a non-compact companion scenario. Is WR 148 a commonplace WR+OB binary or a rare WR+cc binary?

We analyzed spectra of all Wolf-Rayet stars in the Small Magellanic Cloud (SMC). We find that, unlike predicted, mass-transfer in binaries is not needed to explain their formation.

ι Orionis is a massive binary system consisting of O9III + B1 III/IV stars. Though the system has been well studied, much about its fundamental properties have been difficult to determine. In this paper we report on the discovery of the heartbeat phenomenon in ι Orionis making it the most massive heartbeat system currently known. Using this phenomenon we have found empirical values for the masses and radii of both components. Moreover, we report the detection of tidally induced oscillations in an O-type star for the first time. These discoveries open a new avenue for exploring asteroseismology in massive stars.

Despite aggressive multimodal therapy, human glioblastoma (hGBM), a highly malignant grade IV astrocytic tumour, remains incurable and inevitably relapses. Recent data has implicated intratumoral heterogeneity as the driver of therapy resistance and tumour relapse in hGBM. Thus models that capture the evolving hGBM biology in response to chemoradiotherapy will allow for the identification of cellular pathways that govern GBM therapy failure. In this study, we have developed a novel model to profile the clonal evolution of treatment naïve brain tumour initiating cell (BTIC) enriched hGBMs through chemoradiotherapy using: stem cell assays, BTIC marker expression and transcriptome analysis, immunohistochemistry, and cellular DNA barcoding technology. We report that treatment of hGBM BTICs leads to increased self-renewal capacity and higher transcript expression of stem cell genes Bmi1 and Sox2. Based on global transcriptome analysis of the in vitro treated hGBM, we also identify a hyper-aggressive form of glioma. Using our therapy-adapted hGBM-mouse xenograft model, we discover that despite tumour regression and increased mouse survival post-therapy, tumour relapse remains inevitable. The treatment-refractory cells again have increased self-renewal capacity and higher expression of Bmi1 and Sox2. Furthermore, by combining cellular DNA barcoding technology, which barcodes hGBM at single cell resolution, with our novel in vitro and in vivo therapy models, we are able to determine whether a pre-existing or a therapy driven subpopulation(s) seeds hGBM tumour relapse. Profiling the dynamic nature of heterogeneous hGBM subpopulations through disease progression and treatment may lead to the identification of novel therapeutic targets for the treatment of recurrent hGBM.

Glioblastoma (GBM), an aggressive primary adult brain tumor, is feared for its near uniformly fatal prognosis. Despite the use of aggressive treatment including surgical resection, radiotherapy and chemotherapy, the outcome of patients with GBM has failed to improve significantly. Numerous studies have implicated CD133+GBM subpopulation as driver of chemo- and radio-resistance. CD133 expression correlates with disease progression, recurrence, and poor overall survival of GBM patients. Here, we describe the preclinical evaluation of a recombinant CD133xCD3 bispecific T-cell engager (BiTE) antibody that redirects human polyclonal T cells to CD133+GBM cells, inducing very potent anti-tumor response. CD133-specific BiTE was constructed; with one arm recognizing the tumor antigen (CD133) while the second is specific to CD3 antigen. Using CD133high and CD133low primary GBM lines, we validated the binding of BiTEs to CD133+GBMs and CD3+T cells. In order to test the ability of BiTEs to functionally elicit CD133-specific cytotoxic responses in vitro, we performed killing assays. We observed CD133-specific BiTE mediated T cell activation and redirection to kill CD133-expressing GBM cells in a co-culture of T cells and GBM cells. The killing was more efficient in CD133high GBMs compared to CD133low GBMs, validating its specificity to target CD133+BTICs. Treatment with BiTEs yielded significant reductions in brain tumor burden in vivo. These data offers compelling evidence that BiTE-mediated cytotoxicity against treatment-resistant CD133+GBMs could provide a very potent, specific and can be a novel therapeutic strategy for GBM patients.

Brain Metastases (BM) represent a leading cause of cancer mortality. While metastatic lesions contain subclones derived from their primary lesion, their functional characterization has been limited by a paucity of preclinical models accurately recapitulating the stages of metastasis. This work describes the isolation of a unique subset of metastatic stem-like cells from primary human patient samples of BM, termed brain metastasis initiating cells (BMICs). Utilizing these BMICs we have established a novel patient-derived xenograft (PDX) model of BM that recapitulates the entire metastatic cascade, from primary tumor initiation to micro-metastasis and macro-metastasis formation in the brain. We then comprehensively interrogated human BM to identify genetic regulators of BMICs using in vitro and in vivo RNA interference screens, and validated hits using both our novel PDX model as well as primary clinical BM specimens. We identified SPOCK1 and TWIST2 as novel BMIC regulators, where in our model SPOCK1 regulated BMIC self-renewal and tumor initiation, and TWIST2 specifically regulated cell migration from lung to brain. A prospective cohort of primary lung cancer specimens was used to establish that SPOCK1 and TWIST2 were only expressed in patients who ultimately developed BM, thus establishing both clinical and functional utility for these gene products. This work offers the first comprehensive preclinical model of human brain metastasis for further characterization of therapeutic targets, identification of predictive biomarkers, and subsequent prophylactic treatment of patients most likely to develop BM. By blocking this process, metastatic lung cancer would effectively become a localized, more manageable disease.

BRITE-Constellation (where BRITE stands for BRIght Target Explorer) is an international nanosatellite mission to monitor photometrically, in two colours, brightness and temperature variations of stars brighter than V ≈ 4, with precision and time coverage not possible from the ground. The current mission design consists of three pairs of 7 kg nanosats (hence “Constellation”) from Austria, Canada and Poland carrying optical telescopes (3 cm aperture) and CCDs. One instrument in each pair is equipped with a blue filter; the other, a red filter. The first two nanosats (funded by Austria) are UniBRITE, designed and built by UTIAS-SFL (University of Toronto Institute for Aerospace Studies-Space Flight Laboratory) and its twin, BRITE-Austria, built by the Technical University Graz (TUG) with support of UTIAS-SFL. They were launched on 25 February 2013 by the Indian Space Agency, under contract to the Canadian Space Agency.

Each BRITE instrument has a wide field of view (≈ 24 degrees), so up to 15 bright stars can be observed simultaneously in 32 × 32 sub-rasters. Photometry (with reduced precision but thorough time sampling) of additional fainter targets will be possible through on-board data processing. A critical technical element of the BRITE mission is the three-axis attitude control system to stabilize a nanosat with very low inertia. The pointing stability is better than 1.5 arcminutes rms, a significant advance by UTIAS-SFL over any previous nanosatellite.

BRITE-Constellation will primarily measure p- and g-mode pulsations to probe the interiors and ages of stars through asteroseismology. The BRITE sample of many of the brightest stars in the night sky is dominated by the most intrinsically luminous stars: massive stars seen at all evolutionary stages, and evolved medium-mass stars at the very end of their nuclear burning phases (cool giants and AGB stars). The Hertzsprung-Russell diagram for stars brighter than mag V=4 from which the BRITE-Constellation sample will be selected is shown in Fig. 1. This sample falls into two principal classes of stars:

(1) Hot luminous H-burning stars (O to F stars). Analyses of OB star variability have the potential to help solve two outstanding problems: the sizes of convective (mixed) cores in massive stars and the influence of rapid rotation on their structure and evolution.

(2) Cool luminous stars (AGB stars, cool giants and cool supergiants). Measurements of the time scales involved in surface granulation and differential rotation will constrain turbulent convection models.

Mass loss from these stars (especially the massive supernova progenitors) is a major contributor to the evolution of the interstellar medium, so in a sense, this sample dominates cosmic “ecology” in terms of future generations of star formation. The massive stars are believed to share many characteristics of the lower mass range of the first generation of stars ever formed (although the original examples are of course long gone).

BRITE observations will also be used to detect some Jupiter- and even Neptune-sized planets around bright host stars via transits, as expected on the basis of statistics from the Kepler exoplanet mission. Detecting planets around such very bright stars will greatly facilitate their subsequent characterization. BRITE will also use surface spots to investigate stellar rotation.

The following Table summarizes launch and orbit parameters of BRITE-Constellation components.

The full version of this paper describing in more detail BRITE-Constellation will be published separately in a journal. The symposium presentation is available at http://iaus301.astro.uni.wroc.pl/program.php