Time resolved spectroscopy of BD+46 442: gas streams and jet creation in a newly discovered evolved binary with a disk

Previous studies have shown that many post-AGB stars with dusty disks are associated with single-lined binary stars. To verify the binarity hypothesis on a larger sample, we started a high-resolution spectral monitoring of about 40 field giants, whose binarity was suspected based on either a light curve, an infrared excess, or a peculiar chemical composition. Here we report on the discovery of the periodic RV variations in BD+46 442, a high-latitude F giant with a disk. We interpret the variations due to the motion around a faint companion, and deduce the following orbital parameters: Porb = 140.77 d, e = 0.083, asini=0.31 AU. We find it to be a moderately metal-poor star ([M/H]=-0.7) without a strong depletion pattern in the photospheric abundances. Interestingly, many lines show periodic changes with the orbital phase: Halpha switches between a double-peak emission and a PCyg-like profiles, while strong metal lines appear split during the maximum redshift. Similar effects are likely visible in the spectra of other post-AGB binaries, but their regularity is not always realized due to sporadic observations. We propose that these features result from an ongoing mass transfer from the evolved giant to the companion. In particular, the blue-shifted absorption in Halpha, which occurs only at superior conjunction, may result from a jet originating in the accretion disk around the companion and seen in absorption towards the luminous primary.Comment: 16 pages, accepted in A&

The 21 micron and 30 micron circumstellar dust features in evolved C-rich objects

The 21micron and 30micron bands are the strongest dust emission features detected in evolved low- and intermediate-mass C-rich stars (i.e. asymptotic giant branch [AGB] stars, proto-planetary nebulae [PPN], and planetary nebulae [PN]). While the 21micron feature is rare and exists only in the transient PPN phase, the 30micron feature is more common and seen in the entire late stage of stellar evolution, from AGB to PPN and PN phases, as well as in the low-metallicity galaxies: the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC). The carriers of these features remain unidentified. Eleven of the twelve well-identified 21micron sources also emit in the 30micron band, suggesting that their carriers may be somewhat related.Comment: 7 pages, 1 figure, uses eps.cls. Accepted for publication in "Earth, Planets and Space" (special issue on Cosmic Dust

Post conjunction detection of β\beta Pictoris b with VLT/SPHERE

With an orbital distance comparable to that of Saturn in the solar system, \bpic b is the closest (semi-major axis $\simeq$\,9\,au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to \bpic have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters. We aimed at further constraining \bpic b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit. We used SPHERE at the VLT to precisely monitor the orbital motion of beta \bpic b since first light of the instrument in 2014. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6\,au) and prevented further detection. We redetected \bpic b on the northeast side of the disk at a separation of 139\,mas and a PA of 30$^{\circ}$ in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of $a = 9.0 \pm 0.5$ au (1 $\sigma$), it definitely excludes previously reported possible long orbital periods, and excludes \bpic b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.Comment: accepted by A&

SPHERE: the exoplanet imager for the Very Large Telescope

Observations of circumstellar environments to look for the direct signal of exoplanets and the scattered light from disks has significant instrumental implications. In the past 15 years, major developments in adaptive optics, coronagraphy, optical manufacturing, wavefront sensing and data processing, together with a consistent global system analysis have enabled a new generation of high-contrast imagers and spectrographs on large ground-based telescopes with much better performance. One of the most productive is the Spectro-Polarimetic High contrast imager for Exoplanets REsearch (SPHERE) designed and built for the ESO Very Large Telescope (VLT) in Chile. SPHERE includes an extreme adaptive optics system, a highly stable common path interface, several types of coronagraphs and three science instruments. Two of them, the Integral Field Spectrograph (IFS) and the Infra-Red Dual-band Imager and Spectrograph (IRDIS), are designed to efficiently cover the near-infrared (NIR) range in a single observation for efficient young planet search. The third one, ZIMPOL, is designed for visible (VIR) polarimetric observation to look for the reflected light of exoplanets and the light scattered by debris disks. This suite of three science instruments enables to study circumstellar environments at unprecedented angular resolution both in the visible and the near-infrared. In this work, we present the complete instrument and its on-sky performance after 4 years of operations at the VLT.Comment: Final version accepted for publication in A&

SPHERE view of Wolf-Rayet 104. Direct detection of the Pinwheel and the link with the nearby star

Context. WR104 is an emblematic dusty Wolf-Rayet star and the prototypical member of a sub-group hosting spirals that are mainly observable with high-angular resolution techniques. Previous aperture masking observations showed that WR104 is likely to be an interacting binary star at the end of its life. However, several aspects of the system are still unknown. This includes the opening angle of the spiral, the dust formation locus, and the link between the central binary star and a candidate companion star detected with the Hubble Space Telescope (HST) at 1′′. Aims. Our aim was to directly image the dusty spiral or “pinwheel” structure around WR104 for the first time and determine its physical properties at large spatial scales. We also wanted to address the characteristics of the candidate companion detected by the HST. Methods. For this purpose, we used SPHERE and VISIR at the Very Large Telescope to image the system in the near- and mid-infrared, respectively. Both instruments furnished an excellent view of the system at the highest angular resolution a single, ground-based telescope can provide. Based on these direct images, we then used analytical and radiative transfer models to determine several physical properties of the system. Results. Employing a different technique than previously used, our new images have allowed us to confirm the presence of the dust pinwheel around the central star. We have also detected up to five revolutions of the spiral pattern of WR104 in the K band for the first time. The circumstellar dust extends up to 2 arcsec from the central binary star in the N band, corresponding to the past 20 yr of mass loss. Moreover, we found no clear evidence of a shadow of the first spiral coil onto the subsequent ones, which likely points to a dusty environment less massive than inferred in previous studies. We have also confirmed that the stellar candidate companion previously detected by the HST is gravitationally bound to WR104 and herein provide information about its nature and orbital elements

The Phenotypic Radiation Resistance of CD44+/CD24−or low Breast Cancer Cells Is Mediated through the Enhanced Activation of ATM Signaling

Cancer initiating cells (CIC) are stem-like cells. CIC may contribute not only to the initiation of cancer but also to cancer recurrence because of the resistance of CIC both to chemotherapy and radiation therapy. From the MCF-7 and MDA-MB231 breast cancer cell lines and primary culture of patient breast cancer cells, we isolated by flow cytometry a CIC subset of cells with the CD44+/CD24−or low phenotype. The CD44+/CD24−or low subset showed increased sphere formation and resistance to radiation compared to the non- CD44+/CD24−or low subset. The increased radiation resistance was not dependent on the result of altered non-homologous end joining (NHEJ) DNA repair activity as both NHEJ activity and expression of the various proteins involved in NHEJ were not significantly different between the CD44+/CD24−or low and non- CD44+/CD24−or low subsets. However, activation of ATM signaling was significantly increased in CD44+/CD24−or low cells compared to non- CD44+/CD24−or low cells in both from breast cancer cell lines and primary human breast cancer cells. Application of an ATM inhibitor effectively decreased the radiation resistance of CD44+/CD24−or low subset, suggesting that targeting ATM signaling may provide a new tool to eradicate stem-like CIC and abolish the radiation resistance of breast cancer

Novel transcripts reveal a complex structure of the human TRKA gene and imply the presence of multiple protein isoforms

Publisher Copyright: © 2015 Luberg et al.Background: Tropomyosin-related kinase A (TRKA) is a nerve growth factor (NGF) receptor that belongs to the tyrosine kinase receptor family. It is critical for the correct development of many types of neurons including pain-mediating sensory neurons and also controls proliferation, differentiation and survival of many neuronal and non-neuronal cells. TRKA (also known as NTRK1) gene is a target of alternative splicing which can result in several different protein isoforms. Presently, three human isoforms (TRKAI, TRKAII and TRKAIII) and two rat isoforms (TRKA L0 and TRKA L1) have been described. Results: We show here that human TRKA gene is overlapped by two genes and spans 67 kb-almost three times the size that has been previously described. Numerous transcription initiation sites from eight different 5' exons and a sophisticated splicing pattern among exons encoding the extracellular part of TRKA receptor indicate that there might be a large variety of alternative protein isoforms. TrkA genes in rat and mouse appear to be considerably shorter, are not overlapped by other genes and display more straightforward splicing patterns. We describe the expression profile of alternatively spliced TRKA transcripts in different tissues of human, rat and mouse, as well as analyze putative endogenous TRKA protein isoforms in human SH-SY5Y and rat PC12 cells. We also characterize a selection of novel putative protein isoforms by portraying their phosphorylation, glycosylation and intracellular localization patterns. Our findings show that an isoform comprising mainly of TRKA kinase domain is capable of entering the nucleus. Conclusions: Results obtained in this study refer to the existence of a multitude of TRKA mRNA and protein isoforms, with some putative proteins possessing very distinct properties.publishersversionPeer reviewe

Recasting the cancer stem cell hypothesis: Unification using a continuum model of microenvironmental forces

Purpose of review Here, we identify shortcomings of standard compartment-based mathematical models of cancer stem-cells, and propose a continuous formalism which includes the tumor microenvironment. Recent findings Stem-cell models of tumor growth have provided explanations for various phenomena in oncology including, metastasis, drug- and radio-resistance, and functional heterogeneity in the face of genetic homogeneity. While some of the newer models allow for plasticity, or de-differentiation, there is no consensus on the mechanisms driving this. Recent experimental evidence suggests that tumor microenvironment factors like hypoxia, acidosis, and nutrient deprivation have causative roles. Summary To settle the dissonance between the mounting experimental evidence surrounding the effects of the microenvironment on tumor stemness, we propose a continuous mathematical model where we model microenvironmental perturbations like forces, which then shape the distribution of stemness within the tumor. We propose methods by which to systematically measure and characterize these forces, and show results of a simple experiment which support our claims

Pharmacological targeting of NF-κB potentiates the effect of the topoisomerase inhibitor CPT-11 on colon cancer cells

NF-κB interferes with the effect of most anti-cancer drugs through induction of anti-apoptotic genes. Targeting NF-κB is therefore expected to potentiate conventional treatments in adjuvant strategies. Here we used a pharmacological inhibitor of the IKK2 kinase (AS602868) to block NF-κB activation. In human colon cancer cells, inhibition of NF-κB using 10 μM AS602868 induced a 30–50% growth inhibitory effect and strongly enhanced the action of SN-38, the topoisomerase I inhibitor and CPT-11 active metabolite. AS602868 also potentiated the cytotoxic effect of two other antineoplasic drugs: 5-fluorouracil and etoposide. In xenografts experiments, inhibition of NF-κB potentiated the antitumoural effect of CPT-11 in a dose-dependent manner. Eighty-five and 75% decreases in tumour size were observed when mice were treated with, respectively, 20 or 5 mg kg−1 AS602868 associated with 30 mg kg−1 CPT-11 compared to 47% with CPT-11 alone. Ex vivo tumour analyses as well as in vitro studies showed that AS602868 impaired CPT-11-induced NF-κB activation, and enhanced tumour cell cycle arrest and apoptosis. AS602868 also enhanced the apoptotic potential of TNFα on HT-29 cells. This study is the first demonstration that a pharmacological inhibitor of the IKK2 kinase can potentiate the therapeutic efficiency of antineoplasic drugs on solid tumours