The morphology of the Milky Way - I. Reconstructing CO maps from simulations in fixed potentials

PublishedJournal ArticleWe present an investigation into the morphological features of the MilkyWay.We use smoothed particle hydrodynamics (SPH) to simulate the interstellar medium (ISM) in the Milky Way under the effect of a number of different gravitational potentials representing spiral arms and bars, assuming that the Milky Way is a grand design spiral in nature. The gas is subject to ISM cooling and chemistry, enabling us to track the evolution of molecular gas. We use a 3D radiative transfer code to simulate the emission from the SPH output, allowing for the construction of synthetic longitude-velocity (l-v) emission maps as viewed from the Earth. By comparing these maps with the observed emission in CO from the Milky Way, we infer the arm/bar geometry that provides a best fit to our Galaxy. We find that it is possible to reproduce nearly all features of the l-v diagram in CO emission. There is no model, however, that satisfactorily reproduces all of the features simultaneously. Models with two arms cannot reproduce all the observed arm features, while four armed models produce too bright local emission in the inner Galaxy. Our best-fitting models favour a bar pattern speed within 50-60 km s-1 kpc-1 and an arm pattern speed of approximately 20 km s-1 kpc-1, with a bar orientation of approximately 45° and arm pitch angle between 10°-15°.We thank an anonymous referee, whose comments and suggestions improved the paper. We also thank Tom Dame for providing access to the CO longitude–velocity data. The calculations for this paper were performed on the DiRAC Complexity machine, jointly funded by STFC and the Large Facilities Capital Fund of BIS, and the University of Exeter Supercomputer, a DiRAC Facility jointly funded by STFC, the Large Facilities Capital Fund of BIS and the University of Exeter. ARP is supported by an STFC-funded post-graduate studentship. CLD acknowledges funding from the European Research Council for the FP7 ERC starting grant project LOCALSTAR. DJP is supported by a Future Fellowship funded by the Australian Research Council (FT130100034). Figures showing SPH particle density were rendered using SPLASH (Price 2007). Datasets used in this paper are available at: http://hdl.handle.net/10871/15057

The changing GMC population in galaxy interactions

This is the final version. Available from OUP via the DOI in this recordWith the advent of modern observational efforts providing extensive giant molecular cloud catalogues, understanding the evolution of such clouds in a galactic context is of prime importance. While numerous previous numerical and theoretical works have focused on the cloud properties in isolated discs, few have looked into the cloud population in an interacting disc system. We present results of the first study investigating the evolution of the cloud population in galaxy experiencing an M51-like tidal fly-by using numerical simulations including star formation, interstellar medium cooling, and stellar feedback. We see the cloud population shift to large unbound clouds in the wake of the companion passage, with the largest clouds appearing as fleeting short-lived agglomerations of smaller clouds within the tidal spiral arms, brought together by large-scale streaming motions. These are then sheared apart as they leave the protection of the spiral arms. Clouds appear to lead diverse lives, even within similar environments, with some being born from gas shocked by filaments streaming into the spiral arms, and others from effectively isolated smaller colliding pairs. Overall, this cloud population produces a shallower mass function than the disc in isolation, especially in the arms compared to the inter-arm regions. Direct comparisons to M51 observations show similarities between cloud populations, though models tailored to the mass and orbital models of M51 appear necessary to precisely reproduce the cloud population

Loss of MIR15A and MIR16-1 at 13q14 is associated with increased TP53 mRNA, de-repression of BCL2 and adverse outcome in chronic lymphocytic leukaemia.

This study was conducted to investigate the possibility that TP53 mRNA is variably expressed in chronic lymphocytic leukaemia (CLL) and that under-expression is associated with TP53 dysfunction and adverse outcome. Although TP53 mRNA levels did indeed vary among the 104 CLL samples examined, this variability resulted primarily from over-expression of TP53 mRNA in 18 samples, all of which lacked TP53 deletion/mutation. These patients had higher lymphocyte counts and shorter overall and treatment-free survival times compared to cases with low TP53 mRNA expression and no TP53 deletion/mutation. Furthermore, TP53 mRNA levels did not correlate with levels of TP53 protein or its transcriptional target CDKN1A. We speculated that the adverse outcome associated with TP53 mRNA over-expression might reflect variation in levels of MIR15A and MIR16-1, which are encoded on chromosome 13q14 and target TP53 and some oncogenes including BCL2. In keeping with our hypothesis, 13q14 copy number and levels of MIR15A/MIR16-1 correlated positively with one another but negatively with levels of TP53 mRNA and BCL2 mRNA. Our findings support a model in which loss of MIR15A/MIR16-1 at chromosome 13q14 results in adverse outcome due to de-repression of oncogenes such as BCL2, and up-regulation of TP53 mRNA as a bystander effect

Star cluster formation and feedback in different environments of a Milky Way-like galaxy

This is the author accepted manuscriptData availability: The data underlying this paper will be shared on reasonable request to the corresponding author.It remains unclear how galactic environment affects star formation and stellar cluster properties. This is difficult to address in Milky Way-mass galaxy simulations because of limited resolution and less accurate feedback compared to cloud-scale models. We carry out zoom-in simulations to re-simulate 100–300 pc regions of a Milky Way-like galaxy using smoothed particle hydrodynamics, including finer resolution (0.4 M⊙ per particle), cluster-sink particles, ray-traced photoionization from O stars, H2/CO chemistry, and ISM heating/cooling. We select ∼106 M⊙ cloud complexes from a galactic bar, inner spiral arm, outer arm, and inter-arm region (in order of galactocentric radius), retaining the original galactic potentials. The surface densities of star formation rate and neutral gas follow ΣSFR ∝ Σ 1.3 gas, with the bar lying higher up the relation than the other regions. However, the inter-arm region forms stars 2–3x less efficiently than the arm models at the same Σgas. The bar produces the most massive cluster, the inner arm the second, and the inter-arm the third. Almost all clusters in the bar and inner arm are small (radii < 5 pc), while 30-50 per cent of clusters in the outer arm and inter-arm have larger radii more like associations. Bar and inner arm clusters rotate at least twice as fast, on average, than clusters in the outer arm and inter-arm regions. The degree of spatial clustering also decreases from bar to inter-arm. Our results indicate that young massive clusters, potentially progenitors of globular clusters, may preferentially form near the bar/inner arm compared to outer arm/inter-arm regions.European Commissio

Delineating the distinct role of AKT in mediating cell survival and proliferation induced by CD154 and IL-4/IL-21 in chronic lymphocytic leukemia

The functional significance of AKT in chronic lymphocytic leukemia (CLL) remains unclear. Given the importance of non-malignant T cells in regulating clonal expansion in CLL, we investigated the role of AKT in T cell-mediated cytoprotection and proliferation using an established co-culture system in which primary CLL cells were incubated on a monolayer of transfected mouse fibroblasts expressing human CD40L (CD154). Stimulation of CLL cells via CD40 induced activation of AKT, which was closely associated with downregulation of its negative regulator PTEN, and protected CLL cells from killing by bendamustine. This cytoprotective effect of CD40 stimulation was prevented by a selective inhibitor of AKT. Stimulation of CLL cells with CD154 + IL-4 or IL-21 induced proliferation detected as reduced fluorescence of cells pre-stained with CFSE. AKT inhibition produced a significant, consistent reduction in proliferation induced by CD154 + IL-4 and a reduction in proliferation induced by CD154 + IL-21 in most but not all cases. In contrast, AKT inhibition had no effect on the proliferation of normal B cells induced by CD154 + IL-4 or IL-21. These findings indicate that AKT contributes in a significant way to T-cell mediated survival and proliferation signalling in CLL and support the clinical evaluation of AKT inhibitors in this disease

How do different spiral arm models impact the ISM and GMC population?

This is the final version. Available from Oxford University Press via the DOI in this recordData availability: The data underlying this article will be shared on reasonable request to the corresponding author.The nature of galactic spiral arms in disc galaxies remains elusive. Regardless of the spiral model, arms are expected to play a role in sculpting the star-forming interstellar medium (ISM). As such, different arm models may result in differences in the structure of the ISM and molecular cloud properties. In this study, we present simulations of galactic discs subject to spiral arm perturbations of different natures. We find very little difference in how the cloud population or gas kinematics vary between the different grand design spirals, indicating that the ISM on cloud scales cares little about where spiral arms come from. We do, however, see a difference in the interarm/arm mass spectra, and minor differences in tails of the distributions of cloud properties (as well as radial variations in the stellar/gaseous velocity dispersions). These features can be attributed to differences in the radial dependence of the pattern speeds between the different spiral models, and could act as a metric of the nature of spiral structure in observational studies.Japanese Society for the Promotion of Science (JSPS)European Union Horizon 2020Deutsche Forschungsgemeinschaft (DFG)Royal SocietyHeising-Simons FoundationNational Science Foundatio

Borderline gestational diabetes mellitus and pregnancy outcomes

Background: The impact of borderline gestational diabetes mellitus (BGDM), defined as a positive oral glucose challenge test (OGCT) and normal oral glucose tolerance test (OGTT), on maternal and infant health is unclear. We assessed maternal and infant health outcomes in women with BGDM and compared these to women who had a normal OGCT screen for gestational diabetes. Methods: We compared demographic, obstetric and neonatal outcomes between women participating in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS) who had BGDM and who screened negative on OGCT. Results: Women who had BGDM were older (mean difference 1.3 years, [95% confidence interval (CI) 0.3, 2.2], p = 0.01) and more likely to be obese (27.1% vs 14.1%, relative risk (RR) 1.92, [95% CI 1.41, 2.62], p &lt; 0.0001) than women who screened negative on OGCT. The risk of adverse maternal outcome overall was higher (12.9% vs 8.1%, RR 1.59, [95% CI 1.00, 2.52], p = 0.05) in women with BGDM compared with women with a normal OGCT. Women with BGDM were more likely to develop pregnancy induced hypertension (17.9% vs 11.8%, RR 1.51, [95% CI 1.03, 2.20], p = 0.03), have a caesarean for fetal distress (17.1% vs 10.5%, RR 1.63, [95% CI 1.10, 2.41], p = 0.01), and require a longer postnatal hospital stay (mean difference 0.4 day, [95% CI 0.1, 0.7], p = 0.01) than those with a normal glucose tolerance. Infants born to BGDM mothers were more likely to be born preterm (10.7% vs 6.4%, RR 1.68, [95% CI 1.00, 2.80], p = 0.05), have macrosomia (birthweight ≥4.5 kg) (4.3% vs 1.7%, RR 2.53, [95% CI 1.06, 6.03], p = 0.04), be admitted to the neonatal intensive care unit (NICU) (6.5% vs 3.0%, RR 2.18, [95% CI 1.09, 4.36], p = 0.03) or the neonatal nursery (40.3% vs 28.4%, RR 1.42, [95% CI 1.14, 1.76], p = 0.002), and have a longer hospital stay (p = 0.001). More infants in the BGDM group had Sarnat stage 2 or 3 neonatal encephalopathy (12.9% vs 7.8%, RR 1.65, [95% CI 1.04, 2.63], p = 0.03). Conclusion: Women with BGDM and their infants had an increased risk of adverse health outcomes compared with women with a negative OGCT. Intervention strategies to reduce the risks for these women and their infants need evaluation. Trial registration: Current Controlled Trials ISRCTN00416244Hong Ju, Alice R. Rumbold, Kristyn J. Willson and Caroline A. Crowthe

Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.

The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom's 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia