ALBERT

Description: We present a new technique for the statistical evaluation of the Tully–Fisher relation (TFR) using spectral line stacking. This technique has the potential to extend TFR observations to lower masses and higher redshifts than possible through a galaxy-by-galaxy analysis. It further avoids the need for individual galaxy inclination measurements. To quantify the properties of stacked H i emission lines, we consider a simplistic model of galactic discs with analytically expressible line profiles. Using this model, we compare the widths of stacked profiles with those of individual galaxies. We then follow the same procedure using more realistic mock galaxies drawn from the S 3 -SAX model (a derivative of the Millennium simulation). Remarkably, when stacking the apparent H i lines of galaxies with similar absolute magnitude and random inclinations, the width of the stack is very similar to the width of the deprojected (= corrected for inclination) and dedispersed (= after removal of velocity dispersion) input lines. Therefore, the ratio between the widths of the stack and the deprojected/dedispersed input lines is approximately constant – about 0.93 – with very little dependence on the gas dispersion, galaxy mass, galaxy morphology and shape of the rotation curve. Finally, we apply our technique to construct a stacked TFR using H i Parkes All-Sky Survey (HIPASS) data which already has a well-defined TFR based on individual detections. We obtain a B -band TFR with a slope of –8.5 ± 0.4 and a K -band relation with a slope of –11.7 ± 0.6 for the HIPASS data set which is consistent with the existing results.

Description: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. While improved multi-agent chemotherapy regimens with individualized risk stratification have led to increased survival rates of approximately 80 percent, 20 percent of patients respond poorly to therapy or relapse. Therefore, novel therapeutic avenues are urgently needed to improve treatment outcome, overcome resistance and reduce side effects. Failure to undergo cell death represents a key survival mechanism of cancer cells and results in drug resistance and clonal escape. Since inhibitor of apoptosis proteins (IAPs) are often overexpressed in malignant cells and their overexpression correlates with inferior survival rates, they provide an attractive molecular target for therapeutic intervention. Small molecule inhibitors have been developed that act as SMAC mimetics (SMs) to counteract the cell death inhibitory function of IAPs. SMs can activate and/or modulate cell death pathways, and are currently being evaluated in clinical trials. Their successful therapeutic implementation requires identification of patients who could benefit from a SM-based treatment regimen ideally before start of therapy. Here, we analyzed the intrinsic activity of two monovalent (AT406 and LCL161) and two bivalent (Birinapant or BV6) SMs on 29 unselected patient-derived pediatric precursor B-cell (BCP)-ALL samples and identified a subset of BCP-ALL primografts to be sensitive to SM treatment (n=8). When we compared gene expression of SM-sensitive (n=8) and SM-insensitive (n=6) patient-derived BCP-ALL samples, we identified a characteristic gene expression signature with 127 differentially regulated genes, amongst them upregulation of TNFRSF1A (TNFR1) in the SM-sensitive subset. In line with previous reports, we confirmed a critical role of the TNF/TNFR1-axis for SM-induced cell death in BCP-ALL by functional analysis. Expression of TNFRSF1A alone, however, did not correlate with sensitivity to SM-induced cell death indicating that TNFR1 is not the only factor regulating cell fate decisions in response to SM treatment. To identify potential biomarker genes for prediction of patient response to SM monotherapy in BCP-ALL, we compared differentially regulated genes of SM responders and non-responders from our cohort with data from a published cohort. Interestingly, we found 4 genes to overlap between these two cohorts. Of these 4 genes TSPAN7, FAM69C, and TNFRSF1A were upregulated whereas MTX2 was downregulated in SM-sensitive samples. The signature identified may reflect a particular TNF network. Analysis of expression levels of these 4 genes in BCP-ALL cell lines (Nalm6, Reh, UoCB6 and RS4;11) revealed that Reh cells, sensitive to SM-induced cell death, exhibited the biomarker profile of primograft sensitivity, i.e. upregulation of TSPAN7, FAM69C, TNFRSF1A and downregulation of MTX2. Nalm6 cells resembled the expression pattern of SM-insensitive samples with a downregulation of TSPAN7, FAM69C, TNFRSF1A and an upregulation of MTX2 and were resistant to SM-induced cell death. RS4;11 and UoCB6 cells showed no pattern. Based on these findings we hypothesized that the respective expression patterns of TSPAN7, FAM69C, TNFRSF1A and MTX2 could predict sensitivity to SMs. An extended screen of additional primary BCP-ALL samples for their expression levels of TSPAN7, FAM69C, TNFRSF1A and MTX2 and response to SMs substantiated this hypothesis. In summary, the subset of primary BCP-ALL samples with sensitivity to SMs is characterized by a gene signature with MTX2 low and TSPAN7, FAM69C and TNFRSF1A high. By using this expression profile, sensitivity to SMs in BCP-ALL could be identified in cell lines and additional primografts. Based on these results, we suggest the identified gene expression pattern as a biomarker for selecting patients to be treated by SM monotherapy in clinical trials. Disclosures No relevant conflicts of interest to declare.

Description: We use a new, improved version of the H i Parkes All-Sky Survey to search for H i emission from nine new, ultrafaint Milky Way satellite galaxy candidates recently discovered in data from the Dark Energy Survey. None of the candidates is detected in H i , implying upper limits for their H i masses of typically several hundred to a few thousand solar masses. The resulting upper limits on $M_{\rm H\small {I}} / L_{\rm V}$ and $M_{\rm H\small {I}} / M_{\star }$ suggest that at least some of the new galaxy candidates are H i deficient. This finding is consistent with the general H i deficiency of satellite galaxies located within the Milky Way's virial radius and supports the hypothesis that gas is being removed from satellites by tidal and ram-pressure forces during perigalactic passages. In addition, some of the objects may be embedded in, and interacting with, the extended neutral and ionized gas filaments of the Magellanic Stream.

Description: We examine the properties of galaxies in the Galaxies and Mass Assembly (GAMA) survey located in voids with radii 〉10 h –1  Mpc. Utilizing the GAMA equatorial survey, 592 void galaxies are identified out to z   0.1 brighter than M r  = –18.4, our magnitude completeness limit. Using the W Hα versus [N  ii ]/Hα (WHAN) line strength diagnostic diagram, we classify their spectra as star forming, AGN, or dominated by old stellar populations. For objects more massive than 5  x  10 9 M , we identify a sample of 26 void galaxies with old stellar populations classed as passive and retired galaxies in the WHAN diagnostic diagram, else they lack any emission lines in their spectra. When matched to Wide-field Infrared Survey Explorer mid-IR photometry, these passive and retired galaxies exhibit a range of mid-IR colour, with a number of void galaxies exhibiting [4.6] – [12] colours inconsistent with completely quenched stellar populations, with a similar spread in colour seen for a randomly drawn non-void comparison sample. We hypothesize that a number of these galaxies host obscured star formation, else they are star forming outside of their central regions targeted for single-fibre spectroscopy. When matched to a randomly drawn sample of non-void galaxies, the void and non-void galaxies exhibit similar properties in terms of optical and mid-IR colour, morphology, and star formation activity, suggesting comparable mass assembly and quenching histories. A trend in mid-IR [4.6] – [12] colour is seen, such that both void and non-void galaxies with quenched/passive colours 〈1.5 typically have masses higher than 10 10 M , where internally driven processes play an increasingly important role in galaxy evolution.

Description: We report the discovery of a low-mass companion to the nearby ( d = 47 pc) F7V star HD 984. The companion is detected 0.19 arcsec away from its host star in the L ' band with the Apodized Phase Plate on NaCo/Very Large Telescope and was recovered by L '-band non-coronagraphic imaging data taken a few days later. We confirm the companion is comoving with the star with SINFONI integral field spectrograph H + K data. We present the first published data obtained with SINFONI in pupil-tracking mode. HD 984 has been argued to be a kinematic member of the 30 Myr-old Columba group, and its HR diagram position is not altogether inconsistent with being a zero-age main sequence star of this age. By consolidating different age indicators, including isochronal age, coronal X-ray emission, and stellar rotation, we independently estimate a main-sequence age of 115 ± 85 Myr (95 per cent CL) which does not rely on this kinematic association. The mass of directly imaged companions are usually inferred from theoretical evolutionary tracks, which are highly dependent on the age of the star. Based on the age extrema, we demonstrate that with our photometric data alone, the companion's mass is highly uncertain: between 33 and 96 M Jup (0.03–0.09 M ) using the COND evolutionary models. We compare the companion's SINFONI spectrum with field dwarf spectra to break this degeneracy. Based on the slope and shape of the spectrum in the H band, we conclude that the companion is an M6.0 ± 0.5 dwarf. The age of the system is not further constrained by the companion, as M dwarfs are poorly fit on low-mass evolutionary tracks. This discovery emphasizes the importance of obtaining a spectrum to spectral type companions around F-stars.

Description: We report the results of a direct imaging survey of A- and F-type main-sequence stars searching for giant planets. A/F stars are often the targets of surveys, as they are thought to have more massive giant planets relative to solar-type stars. However, most imaging is only sensitive to orbital separations 〉30 au, where it has been demonstrated that giant planets are rare. In this survey, we take advantage of the high-contrast capabilities of the Apodizing Phase Plate coronagraph on NACO at the Very Large Telescope. Combined with optimized principal component analysis post-processing, we are sensitive to planetary-mass companions (2–12 M Jup ) at Solar system scales (≤30 au). We obtained data on 13 stars in the L ' band and detected one new companion as part of this survey: an M6.0 ± 0.5 dwarf companion around HD 984. We re-detect low-mass companions around HD 12894 and HD 20385, both reported shortly after the completion of this survey. We use Monte Carlo simulations to determine new constraints on the low-mass (〈80 M Jup ) companion frequency, as a function of mass and separation. Assuming solar-type planet mass and separation distributions, normalized to the planet frequency appropriate for A-stars, and the observed companion mass-ratio distribution for stellar companions extrapolated to planetary masses, we derive a truncation radius for the planetary mass companion surface density of 〈135 au at 95 per cent confidence.

Description: Gene regulatory networks (GRN) are central to developmental processes. They are composed of transcription factors and signaling molecules orchestrating gene expression modules that tightly regulate the development of organisms. The neural crest (NC) is a multipotent cell population that is considered a key innovation of vertebrates. Its derivatives contribute to shaping the astounding morphological diversity of jaws, teeth, head skeleton, or pigmentation. Here, we study the molecular evolution of the NC GRN by analyzing patterns of molecular divergence for a total of 36 genes in 16 species of bony fishes. Analyses of nonsynonymous to synonymous substitution rate ratios (d N /d S ) support patterns of variable selective pressures among genes deployed at different stages of NC development, consistent with the developmental hourglass model. Model-based clustering techniques of sequence features support the notion of extreme conservation of NC-genes across the entire network. Our data show that most genes are under strong purifying selection that is maintained throughout ray-finned fish evolution. Late NC development genes reveal a pattern of increased constraints in more recent lineages. Additionally, seven of the NC-genes showed signs of relaxation of purifying selection in the famously species-rich lineage of cichlid fishes. This suggests that NC genes might have played a role in the adaptive radiation of cichlids by granting flexibility in the development of NC-derived traits—suggesting an important role for NC network architecture during the diversification in vertebrates.

Description: On average, mutations are deleterious to proteins. Mutations conferring new function to a protein often come at the expense of protein folding or stability, reducing overall activity. Over the years, a panel of T7 RNA polymerases have been designed or evolved to accept nucleotides with modified ribose moieties. These modified RNAs have proven useful, especially in vivo , but the transcriptional yields tend to be quite low. Here we show that mutations previously shown to increase the thermal tolerance of T7 RNA polymerase can increase the activity of mutants with expanded substrate range. The resulting polymerase mutants can be used to generate 2' -O- methyl modified RNA with yields much higher than enzymes currently employed.