A search for line intensity enhancements in the far-UV spectra of active late-type stars arising from opacity

Context. Radiative transfer calculations have predicted intensity enhancements for optically thick emission lines, as opposed to the normal intensity reductions, for astrophysical plasmas under certain conditions. In particular, the results are predicted to be dependent both on the geometry of the emitting plasma and the orientation of the observer. Hence in principle the detection of intensity enhancement may provide a way of determining the geometry of an unresolved astronomical source.
Aims. To investigate such enhancements we have analysed a sample of active late-type stars observed in the far ultraviolet spectral region.
Methods. Emission lines of O vi in the FUSE satellite spectra of ϵ Eri, II Peg and Prox Cen were searched for intensity enhancements due to opacity.
Results. We have found strong evidence for line intensity enhancements due to opacity during active or flare-like activity for all three stars. The O vi 1032/1038 line intensity ratios, predicted to have a value of 2.0 in the optically thin case, are found to be up to ~30% larger during several orbital phases.
Conclusions. Our measurements, combined with radiative transfer models, allow us to constrain both the geometry of the O vi emitting regions in our stellar sources and the orientation of the observer. A spherical emitting plasma can be ruled out, as this would lead to no intensity enhancement. In addition, the theory tells us that the line-of-sight to the plasma must be close to perpendicular to its surface, as observations at small angles to the surface lead to either no intensity enhancement or the usual line intensity decrease over the optically thin value. For the future, we outline a laboratory experiment, that could be undertaken with current facilities, which would provide an unequivocal test of predictions of line intensity enhancement due to opacity, in particular the dependence on plasma geometry.

The VLT-FLAMES survey of massive stars: Nitrogen abundances for Be-type stars in the Magellanic Clouds

Aims. We compare the predictions of evolutionary models for early-type stars with atmospheric parameters, projected rotational velocities and nitrogen abundances estimated for a sample of Be-type stars. Our targets are located in 4 fields centred on the Large Magellanic Cloud cluster: NGC 2004 and the N 11 region as well as the Small Magellanic Cloud clusters: NGC 330 and NGC 346.

The empirical metallicity dependence of the mass-loss rate of O- and early B-type stars

We present a comprehensive study of the observational dependence of the mass-loss rate in stationary stellar winds of hot massive stars on the metal content of their atmospheres. The metal content of stars in the Magellanic Clouds is discussed, and a critical assessment is given of state-of-the-art mass-loss determinations of OB stars in these two satellite systems and the Milky-Way. Assuming a power-law dependence of mass loss on metal content,. M. Z(m), and adopting a theoretical relation between the terminal flow velocity and metal content, v(infinity). Z(0.13) (Leitherer et al. 1992, ApJ, 401, 596), we find m = 0.83 +/- 0.16 for non-clumped outflows from an analysis of the wind momentum luminosity relation (WLR) for stars more luminous than 105.2 L circle dot. Within the errors, this result is in agreement with the prediction m = 0.69 +/- 0.10 by Vink et al. (2001, A& A, 369, 574). Absolute empirical values for the mass loss, based on Ha and ultraviolet (UV) wind lines, are found to be a factor of two higher than predictions in this high luminosity regime. If this difference is attributed to inhomogeneities in the wind, and this clumping does not impact the predictions, this would imply that luminous O and early-B stars have clumping factors in their Ha and UV line forming regions of about a factor of four. For lower luminosity stars, the winds are so weak that their strengths can generally no longer be derived from optical spectral lines (essentially Ha) and one must currently rely on the analysis of UV lines. We confirm that in this low-luminosity domain the observed Galactic WLR is found to be much steeper than expected from theory (although the specific sample is rather small), leading to a discrepancy between UV mass-loss rates and the predictions by a factor 100 at luminosities of L similar to 10(4.75) L circle dot, the origin of which is unknown. We emphasize that even if the current mass-loss rates of hot luminous stars would turn out to be overestimated as a result of wind clumping, but the degree of clumping would be rather independent of metallicity, the scalings derived in this study are expected to remain correct.

The VLT-FLAMES survey of massive stars: observations centered on the Magellanic Cloud clusters NGC 330, NGC 346, NGC 2004, and the N11 region

We present new observations of 470 stars using the Fibre Large Array Multi-Element Spectrograph ( FLAMES) instrument in fields centered on the clusters NGC330 and NGC346 in the Small Magellanic Cloud (SMC), and NGC2004 and the N11 region in the Large Magellanic Cloud (LMC). A further 14 stars were observed in the N11 and NGC330 fields using the Ultraviolet and Visual Echelle Spectrograph (UVES) for a separate programme. Spectral classifications and stellar radial velocities are given for each target, with careful attention to checks for binarity. In particular, we have investigated previously unexplored regions around the central LH9/LH10 complex of N11, finding similar to 25 new O-type stars from our spectroscopy. We have observed a relatively large number of Be-type stars that display permitted Fe II emission lines. These are primarily not in the cluster cores and appear to be associated with classical Be-type stars, rather than pre main-sequence objects. The presence of the Fe II emission, as compared to the equivalent width of Ha, is not obviously dependent on metallicity. We have also explored the relative fraction of Be- to normal B-type stars in the field-regions near to NGC330 and NGC2004, finding no strong evidence of a trend with metallicity when compared to Galactic results. A consequence of service observations is that we have reasonable time-sampling in three of our FLAMES fields. We find lower limits to the binary fraction of O- and early B-type stars of 23 to 36%. One of our targets (NGC346-013) is especially interesting with a massive, apparently hotter, less luminous secondary component.

The WR content of IC10 - first detection of WC9 stars in a low metallicity environment?

We present deep, narrow-hand photometry of the Local Group starburst galaxy IC10. Our dedicated photometric system provides detection of 13 new Wolf-Rayet (WR) stars and allows spectral subtypes to be assigned. Three of these new stars appear to be WC9 subtypes. If confirmed, these would be the very first WC9 stars ever detected in a low metallicity environment, hence putting strong new constraints on the formation and evolution models of massive stars. Eight of the new WR stars are of the WC subtype, which does not significantly modify the anomalously high WC/WN ratio in IC10. However it is likely that a number of Wolf-Rayet stars of the WNE and WC spectral subtypes are still to be discovered in the heart of the galaxy.

The Type VI secretion system of Burkholderia cenocepacia affects multiple Rho family GTPases disrupting the actin cytoskeleton and the assembly of NADPH oxidase complex in macrophages

Burkholderia cenocepacia is a Gram-negative opportunistic pathogen of patients with cystic fibrosis and chronic granulomatous disease. The bacterium survives intracellularly in macrophages within a membrane-bound vacuole (BcCV) that precludes the fusion with lysosomes. The underlying cellular mechanisms and bacterial molecules mediating these phenotypes are unknown. Here, we show that intracellular B. cenocepacia expressing a type VI secretion system (T6SS) affects the activation of the Rac1 and Cdc42 RhoGTPase by reducing the cellular pool of GTP-bound Rac1 and Cdc42. The T6SS also increases the cellular pool of GTP-bound RhoA and decreases cofilin activity. These effects lead to abnormal actin polymerization causing collapse of lamellipodia and failure to retract the uropod. The T6SS also prevents the recruitment of soluble subunits of the NADPH oxidase complex including Rac1 to the BcCV membrane, but is not involved in the BcCV maturation arrest. Therefore, T6SS-mediated deregulation of Rho family GTPases is a common mechanism linking disruption of the actin cytoskeleton and delayed NADPH oxidase activation in macrophages infected with B. cenocepacia.

Heat shock protein 90 inhibition is cytotoxic to primary AML cells expressing mutant FLT3 and results in altered downstream signalling

Activating mutations of the FMS-like tyrosine kinase 3 gene (FLT3) occur in approximately one-third of patients with acute myeloid leukaemia (AML) and predict for a poor outcome. Heat shock protein 90 (Hsp90) is a molecular chaperone that is frequently used by cancer cells to stabilise mutant oncoproteins. Mutant FLT3 is chaperoned by Hsp90 in primary AML blasts whereas unmutated FLT3 is not, making Hsp90 inhibitors potentially useful therapeutically. The present study showed that inhibition of Hsp90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) was cytotoxic to primary AML cells expressing mutant FLT3. Inhibition of Hsp90 results in altered downstream signalling effects in primary AML cells with disruption of Janus kinase-signal transducer and activator of transcription (JAK-STAT), mitogen-activated protein kinase and phosphatidylinositol 3/AKT signalling pathways. Co-treatment of blasts with 17-AAG and cytarabine resulted in a synergistic or additive effect in approximately 50% of AML cases tested. Our results confirm that Hsp90 is a valid molecular target in the therapy of AML. Inhibition of Hsp90 in parallel with conventional AML therapies may have particular benefit in those patients with the poor prognostic FLT3 mutant disease.

Potentiation of Inflammatory CXCL8 Signalling Sustains Cell Survival in PTEN-deficient Prostate Carcinoma

Background: Inflammation and genetic instability are enabling characteristics of prostate carcinoma (PCa). Inactivation of the tumour suppressor gene phosphatase and tensin homolog (PTEN) is prevalent in early PCa. The relationship of PTEN deficiency to inflammatory signalling remains to be characterised.

Objective: To determine how loss of PTEN functionality modulates expression and efficacy of clinically relevant, proinflammatory chemokines in PCa.

Design, setting and participants: Experiments were performed in established cell-based PCa models, supported by pathologic analysis of chemokine expression in prostate tissue harvested from PTEN heterozygous (Pten(+/-)) mice harbouring inactivation of one PTEN allele.

Interventions: Small interfering RNA (siRNA)- or small hairpin RNA (shRNA)-directed strategies were used to repress PTEN expression and resultant interleukin-8 (CXCL8) signalling, determined under normal and hypoxic culture conditions.

Outcome measurements and statistical analysis: Changes in chemokine expression in PCa cells and tissue were analysed by real-time polymerase chain reaction (PCR), immunoblotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry; effects of chemokine signalling on cell function were assessed by cell cycle analysis, apoptosis, and survival assays.

Results and limitations: Transient (siRNA) or prolonged (shRNA) PTEN repression increased expression of CXCL8 and its receptors, chemokine (C-X-C motif) receptor (CXCR) 1 and CXCR2, in PCa cells. Hypoxia-induced increases in CXCL8, CXCR1, and CXCR2 expression were greater in magnitude and duration in PTEN-depleted cells. Autocrine CXCL8 signalling was more efficacious in PTEN-depleted cells, inducing hypoxia-inducible factor-1 (HIF-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) transcription and regulating genes involved in survival and angiogenesis. Increased expression of the orthologous chemokine KC was observed in regions displaying atypical cytologic features in Pten(+/-) murine prostate tissue relative to normal epithelium in wild-type PTEN (Pten(WT)) glands. Attenuation of CXCL8 signalling decreased viability of PCa cells harbouring partial or complete PTEN loss through promotion of G1 cell cycle arrest and apoptosis. The current absence of clinical validation is a limitation of the study.

Conclusions: PTEN loss induces a selective upregulation of CXCL8 signalling that sustains the growth and survival of PTEN-deficient prostate epithelium.

The VLT-FLAMES Tarantula Survey XI. A census of the hot luminous stars and their feedback in 30 Doradus

Context. The VLT-FLAMES Tarantula Survey has an extensive view of the copious number of massive stars in the 30 Doradus (30 Dor) star forming region of the Large Magellanic Cloud. These stars play a crucial role in our understanding of the stellar feedback in more distant, unresolved star forming regions. Aims. The first comprehensive census of hot luminous stars in 30 Dor is compiled within a 10 arcmin (150 pc) radius of its central cluster, R136. We investigate the stellar content and spectroscopic completeness of the early type stars. Estimates were made for both the integrated ionising luminosity and stellar wind luminosity. These values were used to re-assess the star formation rate (SFR) of the region and determine the ionising photon escape fraction. Methods. Stars were selected photometrically and combined with the latest spectral classifications. Spectral types were estimated for stars lacking spectroscopy and corrections were made for binary systems, where possible. Stellar calibrations were applied to obtain their physical parameters and wind properties. Their integrated properties were then compared to global observations from ultraviolet (UV) to far-infrared (FIR) imaging as well as the population synthesis code, Starburst99. Results. Our census identified 1145 candidate hot luminous stars within 150 pc of R136 of which >700 were considered to be genuine early type stars and contribute to feedback. We assess the survey to be spectroscopically complete to 85% in the outer regions (>5 pc) but only 35% complete in the region of the R136 cluster, giving a total of 500 hot luminous stars in the census which had spectroscopy. Only 31 were found to be Wolf-Rayet (W-R) or Of/WN stars, but their contribution to the integrated ionising luminosity and wind luminosity was ~ 40% and ~ 50%, respectively. Similarly, stars with M > 100 M (mostly H-rich WN stars) also showed high contributions to the global feedback, ~ 25% in both cases. Such massive stars are not accounted for by the current Starburst99 code, which was found to underestimate the integrated ionising luminosity of R136 by a factor ~ 2 and the wind luminosity by a factor ~ 9. The census inferred a SFR for 30 Dor of 0.073 ± 0.04 M yr . This was generally higher than that obtained from some popular SFR calibrations but still showed good consistency with the far-UV luminosity tracer as well as the combined Hα and mid-infrared tracer, but only after correcting for Hα extinction. The global ionising output was also found to exceed that measured from the associated gas and dust, suggesting that ~6 % of the ionising photons escape the region. Conclusions. When studying the most luminous star forming regions, it is essential to include their most massive stars if one is to determine a reliable energy budget. Photon leakage becomes more likely after including their large contributions to the ionising output. If 30 Dor is typical of other massive star forming regions, estimates of the SFR will be underpredicted if this escape fraction is not accounted for.

Photodissociation and chemistry of N2 in the circumstellar envelope of carbon-rich AGB stars

The envelopes of AGB stars are irradiated externally by ultraviolet photons; hence, the chemistry is sensitive to the photodissociation of N$_2$ and CO, which are major reservoirs of nitrogen and carbon, respectively. The photodissociation of N$_2$ has recently been quantified by laboratory and theoretical studies. Improvements have also been made for CO photodissociation. For the first time, we use accurate N$_2$ and CO photodissociation rates and shielding functions in a model of the circumstellar envelope of the carbon-rich AGB star, IRC +10216. We use a state-of-the-art chemical model of an AGB envelope, the latest CO and N$_2$ photodissociation data, and a new method for implementing molecular shielding functions in full spherical geometry with isotropic incident radiation. We compare computed column densities and radial distributions of molecules with observations. The transition of N$_2$ $\to$ N (also, CO $\to$ C $\to$ C$^+$) is shifted towards the outer envelope relative to previous models. This leads to different column densities and radial distributions of N-bearing species, especially those species whose formation/destruction processes largely depend on the availability of atomic or molecular nitrogen, for example, C$_n$N ($n$=1, 3, 5), C$_n$N$^-$ ($n$=1, 3, 5), HC$_n$N ($n$=1, 3, 5, 7, 9), H$_2$CN and CH$_2$CN. The chemistry of many species is directly or indirectly affected by the photodissociation of N$_2$ and CO, especially in the outer shell of AGB stars where photodissociation is important. Thus, it is important to include N$_2$ and CO shielding in astrochemical models of AGB envelopes and other irradiated environments. In general, while differences remain between our model of IRC +10216 and the observed molecular column densities, better agreement is found between the calculated and observed radii of peak abundance.

p63 drives invasion in keratinocytes expressing HPV16 E6/E7 genes through regulation of Src-FAK signalling

Using microarray information from oro-pharyngeal data sets and results from primary human foreskin keratinocytes (HFK) expressing Human Papilloma Virus (HPV)-16 E6/E7 proteins, we show that p63 expression regulates signalling molecules which initiate cell migration such as Src and focal adhesion kinase (FAK) and induce invasion in 3D-organotypic rafts; a phenotype that can be reversed by depletion of p63. Knockdown of Src or FAK in the invasive cells restored focal adhesion protein paxillin at cell periphery and impaired the cell migration. In addition, specific inhibition of FAK (PF573228) or Src (dasatinib) activities mitigated invasion and attenuated the expression/activity of matrix metalloproteinase 14 (MMP14), a pivotal MMP in the MMP activation cascade. Expression of constitutively active Src in non-invasive HFK expressing E6/E7 proteins upregulated the activity of c-Jun and MMP14, and induced invasion in rafts. Depletion of Src, FAK or AKT in the invasive cells normalised the expression/activity of c-Jun and MMP14, thus implicating the Src-FAK/AKT/AP-1 signalling in MMP14-mediated extra-cellular matrix remodelling. Up-regulation of Src, AP-1, MMP14 and p63 expression was confirmed in oro-pharyngeal cancer. Since p63 transcriptionally regulated expression of many of the genes in this signalling pathway, it suggests that it has a central role in cancer progression.

Observational Constraints on the Progenitors of Core-Collapse Supernovae: The Case for Missing High-Mass Stars

Over the last 15 years, the supernova community has endeavoured to directly identify progenitor stars for core-collapse supernovae discovered in nearby galaxies. These precursors are often visible as resolved stars in high-resolution images from space-and ground-based telescopes. The discovery rate of progenitor stars is limited by the local supernova rate and the availability and depth of archive images of galaxies, with 18 detections of precursor objects and 27 upper limits. This review compiles these results (from 1999 to 2013) in a distance-limited sample and discusses the implications of the findings. The vast majority of the detections of progenitor stars are of type II-P, II-L, or IIb with one type Ib progenitor system detected and many more upper limits for progenitors of Ibc supernovae (14 in all). The data for these 45 supernovae progenitors illustrate a remarkable deficit of high-luminosity stars above an apparent limit of log L/L-circle dot similar or equal to 5.1 dex. For a typical Salpeter initial mass function, one would expect to have found 13 high-luminosity and high-mass progenitors by now. There is, possibly, only one object in this time-and volume-limited sample that is unambiguously high-mass (the progenitor of SN2009ip) although the nature of that supernovae is still debated. The possible biases due to the influence of circumstellar dust, the luminosity analysis, and sample selection methods are reviewed. It does not appear likely that these can explain the missing high-mass progenitor stars. This review concludes that the community's work to date shows that the observed populations of supernovae in the local Universe are not, on the whole, produced by high-mass (M greater than or similar to 18 M-circle dot) stars. Theoretical explosions of model stars also predict that black hole formation and failed supernovae tend to occur above an initial mass of M similar or equal to 18 M-circle dot. The models also suggest there is no simple single mass division for neutron star or black-hole formation and that there are islands of explodability for stars in the 8-120 M-circle dot range. The observational constraints are quite consistent with the bulk of stars above M similar or equal to 18 M-circle dot collapsing to form black holes with no visible supernovae.

Massive stars exploding in a He-rich circumstellar medium - VI. Observations of two distant Type Ibn supernova candidates discovered by La Silla-QUEST

We present optical observations of the peculiar stripped-envelope supernovae (SNe) LSQ12btw and LSQ13ccw discovered by the La Silla-QUEST survey. LSQ12btw reaches an absolute peak magnitude of M-g = -19.3 +/- 0.2, and shows an asymmetric light curve. Stringent pre-discovery limits constrain its rise time to maximum light to less than 4 d, with a slower post-peak luminosity decline, similar to that experienced by the prototypical SN Ibn 2006jc. LSQ13ccw is somewhat different: while it also exhibits a very fast rise to maximum, it reaches a fainter absolute peak magnitude (M-g =-18.4 +/- 0.2), and experiences an extremely rapid post-peak decline similar to that observed in the peculiar SN Ib 2002bj. A stringent pre-discovery limit and an early marginal detection of LSQ13ccw allow us to determine the explosion time with an uncertainty of +/- 1 d. The spectra of LSQ12btw show the typical narrow He I emission lines characterizing Type Ibn SNe, suggesting that the SN ejecta are interacting with He-rich circumstellar material. The He I lines in the spectra of LSQ13ccw exhibit weak narrow emissions superposed on broad components. An unresolved H alpha line is also detected, suggesting a tentative Type Ibn/IIn classification. As for other SNe Ibn, we argue that LSQ12btw and LSQ13ccw likely result from the explosions of Wolf-Rayet stars that experienced instability phases prior to core collapse. We inspect the host galaxies of SNe Ibn, and we show that all of them but one are hosted in spiral galaxies, likely in environments spanning a wide metallicity range.

Chemistry and Distribution of Daughter Species in the Circumstellar Envelopes of O-Rich AGB Stars

Context. Thanks to the advent of Herschel and ALMA, new high-quality observations of molecules present in the circumstellar envelopes of asymptotic giant branch (AGB) stars are being reported that reveal large differences from the existing chemical models. New molecular data and more comprehensive models of the chemistry in circumstellar envelopes are now available.
Aims: The aims are to determine and study the important formation and destruction pathways in the envelopes of O-rich AGB stars and to provide more reliable predictions of abundances, column densities, and radial distributions for potentially detectable species with physical conditions applicable to the envelope surrounding IK Tau.
Methods: We use a large gas-phase chemical model of an AGB envelope including the effects of CO and N2 self-shielding in a spherical geometry and a newly compiled list of inner-circumstellar envelope parent species derived from detailed modeling and observations. We trace the dominant chemistry in the expanding envelope and investigate the chemistry as a probe for the physics of the AGB phase by studying variations of abundances with mass-loss rates and expansion velocities.
Results: We find a pattern of daughter molecules forming from the photodissociation products of parent species with contributions from ion-neutral abstraction and dissociative recombination. The chemistry in the outer zones differs from that in traditional PDRs in that photoionization of daughter species plays a significant role. With the proper treatment of self-shielding, the N → N2 and C+→ CO transitions are shifted outward by factors of 7 and 2, respectively, compared with earlier models. An upper limit on the abundance of CH4 as a parent species of (≲2.5 × 10-6 with respect to H2) is found for IK Tau, and several potentially observable molecules with relatively simple chemical links to other parent species are determined. The assumed stellar mass-loss rate, in particular, has an impact on the calculated abundances of cations and the peak-abundance radius of both cations and neutrals: as the mass-loss rate increases, the peak abundance of cations generally decreases and the peak-abundance radius of all species moves outwards. The effects of varying the envelope expansion velocity and cosmic-ray ionization rate are not as significant.

The VLT-FLAMES Tarantula Survey XXII. Multiplicity properties of the B-type stars

We investigate the multiplicity properties of 408 B-type stars observed in the 30 Doradus region of the Large Magellanic Cloud with multi-epoch spectroscopy from the VLT-FLAMES Tarantula Survey (VFTS). We use a cross-correlation method to estimate relative radial velocities from the helium and metal absorption lines for each of our targets. Objects with significant radial-velocity variations (and with an amplitude larger than 16 km s^-1) are classified as spectroscopic binaries. We find an observed spectroscopic binary fraction (defined by periods of <10^3.5 d and mass ratios >0.1) for the B-type stars, f<inf>B</inf>(obs) = 0.25 ± 0.02, which appears constant across the field of view, except for the two older clusters (Hodge 301 and SL 639). These two clusters have significantly lower binary fractions of 0.08 ± 0.08 and 0.10 ± 0.09, respectively. Using synthetic populations and a model of our observed epochs and their potential biases, we constrain the intrinsic multiplicity properties of the dwarf and giant (i.e. relatively unevolved) B-type stars in 30 Dor. We obtain a present-day binary fraction f<inf>B</inf>(true) = 0.58 ± 0.11, with a flat period distribution. Within the uncertainties, the multiplicity properties of the B-type stars agree with those for the O stars in 30 Dor from the VFTS.