We compare the mean mass assembly histories of compact and fossil galaxy groups in the Millennium Dark Matter Simulation and an associated semi-analytic galaxy formation model. Tracing the halo mass ...of compact groups (CGs) from z = 0 to z = 1 shows that, on average, 55% of the halo mass in CGs is assembled since , compared to 40% of the halo mass in fossil groups (FGs) on the same time interval, indicating that compared to FGs, CGs are relatively younger galaxy systems. At z = 0, for a given halo mass, FGs tend to have a larger concentration than CGs. Investigating the evolution of CG's parameters reveals that they become more compact with time. CGs at z = 0.5 see their magnitude gaps increase exponentially, but it takes ∼10 Gyr for them to reach a magnitude gap of 2 mag. The slow growth of the magnitude gap leads to only a minority (∼41%) of CGs selected at z = 0.5 turning into a FG by z = 0. Also, while three-quarters of FGs go through a compact phase, most fail to meet the CG isolation criterion, leaving only ∼30% of FGs fully satisfying the CG selection criteria. Therefore, there is no strong link of CGs turning into FGs or FGs originating from CGs. The relation between CGs and FGs is thus more complex, and in most cases, FGs and CGs follow different evolutionary tracks.
Breast cancers are complex ecosystems of malignant cells and the tumour microenvironment
. The composition of these tumour ecosystems and interactions within them contribute to responses to cytotoxic ...therapy
. Efforts to build response predictors have not incorporated this knowledge. We collected clinical, digital pathology, genomic and transcriptomic profiles of pre-treatment biopsies of breast tumours from 168 patients treated with chemotherapy with or without HER2 (encoded by ERBB2)-targeted therapy before surgery. Pathology end points (complete response or residual disease) at surgery
were then correlated with multi-omic features in these diagnostic biopsies. Here we show that response to treatment is modulated by the pre-treated tumour ecosystem, and its multi-omics landscape can be integrated in predictive models using machine learning. The degree of residual disease following therapy is monotonically associated with pre-therapy features, including tumour mutational and copy number landscapes, tumour proliferation, immune infiltration and T cell dysfunction and exclusion. Combining these features into a multi-omic machine learning model predicted a pathological complete response in an external validation cohort (75 patients) with an area under the curve of 0.87. In conclusion, response to therapy is determined by the baseline characteristics of the totality of the tumour ecosystem captured through data integration and machine learning. This approach could be used to develop predictors for other cancers.
DNA methylation is aberrant in cancer, but the dynamics, regulatory role and clinical implications of such epigenetic changes are still poorly understood. Here, reduced representation bisulfite ...sequencing (RRBS) profiles of 1538 breast tumors and 244 normal breast tissues from the METABRIC cohort are reported, facilitating detailed analysis of DNA methylation within a rich context of genomic, transcriptional, and clinical data. Tumor methylation from immune and stromal signatures are deconvoluted leading to the discovery of a tumor replication-linked clock with genome-wide methylation loss in non-CpG island sites. Unexpectedly, methylation in most tumor CpG islands follows two replication-independent processes of gain (MG) or loss (ML) that we term epigenomic instability. Epigenomic instability is correlated with tumor grade and stage, TP53 mutations and poorer prognosis. After controlling for these global trans-acting trends, as well as for X-linked dosage compensation effects, cis-specific methylation and expression correlations are uncovered at hundreds of promoters and over a thousand distal elements. Some of these targeted known tumor suppressors and oncogenes. In conclusion, this study demonstrates that global epigenetic instability can erode cancer methylomes and expose them to localized methylation aberrations in-cis resulting in transcriptional changes seen in tumors.
We study the stellar populations of the brightest group galaxies (BGGs) in groups with different dynamical states, using Galaxy And Mass Assembly survey data. We use two independent, ...luminosity-dependent indicators to probe the relaxedness of their groups: the magnitude gap between the two most luminous galaxies (ΔM12), and the offset between BGGs and the luminosity center (Doffset) of the group. Combined, these two indicators were previously found useful for identifying relaxed and unrelaxed groups. We find that the BGGs of unrelaxed groups have significantly bluer near-ultraviolet-r colors than in relaxed groups. This is also true at the fixed sersic index. We find the bluer colors cannot be explained away by differing dust fraction, suggesting there are real differences in their stellar populations. Star formation rates derived from spectral energy distribution (SED) fitting tend to be higher in unrelaxed systems. This is in part because of a greater fraction of BGGs with non-elliptical morphology, but also because unrelaxed systems have larger numbers of mergers, some of which may bring fuel for star formation. The SED-fitted stellar metallicities of BGGs in unrelaxed systems also tend to be higher by around 0.05 dex, perhaps because their building blocks were more massive. We find that the ΔM12 parameter is the most important parameter behind the observed differences in the relaxed/unrelaxed groups, in contrast with the previous study of Trevisan et al. We also find that groups selected to be unrelaxed using our criteria tend to have higher velocity offsets between the BGG and their group.
We investigate the dynamical evolution of galaxies in groups with different formation epochs. Galaxy groups have been selected to be in different dynamical states, namely dynamically old and ...dynamically young, which reflect their early and late formation times, respectively, based on their halo mass assembly. The brightest galaxies in dynamically young groups have suffered their last major galaxy merger typically ∼2 Gyr more recently than their counterparts in dynamically old groups. Furthermore, we study the evolution of velocity dispersion in these two classes and compare them with the analytic models of isolated halos. The velocity dispersion of dwarf galaxies in high-mass, dynamically young groups increases slowly in time, while the analogous dispersion in dynamically old, high-mass groups is constant. In contrast, the velocity dispersion of giant galaxies in low-mass groups decreases rapidly at late times. This increasing velocity bias is caused by dynamical friction, and starts much earlier in the dynamically old groups. The recent Radio-SAGE model of galaxy formation suggests that radio luminosities of central galaxies, considered to be tracers of AGN activity, are enhanced in halos that assembled more recently, independent of the time since the last major merger.
Understanding the interaction between galaxies and their surroundings is central to building a coherent picture of galaxy evolution. Here we use Galaxy Evolution Explorer imaging of a statistically ...representative sample of 23 galaxy groups at z approximately 0.06 to explore how local and global group environments affect the UV properties and dust-corrected star formation rates (SFRs) of their member galaxies. The data provide SFRs out to beyond 2R sub(200) in all groups, down to a completeness limit and limiting galaxy stellar mass of 0.06 M sub(middot in circle) yr super(-1) and 1 x 10 super(8) M sub(middot in circle), respectively. At fixed galaxy stellar mass, we find that the fraction of star-forming group members is suppressed relative to the field out to an average radius of R approximately 1.5 Mpc approximately 2R sub(200), mirroring results for massive clusters. For the first time, we also report a similar suppression of the specific SFR within such galaxies, on average by 40% relative to the field, thus directly revealing the impact of the group environment in quenching star formation within infalling galaxies. At fixed galaxy density and stellar mass, this suppression is stronger in more massive groups, implying that both local and global group environments play a role in quenching. The results favor an average quenching timescale of gap2 Gyr and strongly suggest that a combination of tidal interactions and starvation is responsible. Despite their past and ongoing quenching, galaxy groups with more than four members still account for at least ~25% of the total UV output in the nearby universe.
There have been a number of studies dedicated to identification of fossil galaxy groups, arguably groups with a relatively old formation epoch. Most of such studies identify fossil groups, primarily ...based on a large luminosity gap, which is the magnitude gap between the two most luminous galaxies in the group. Studies of these types of groups in the millennium cosmological simulations show that, although they have accumulated a significant fraction of their mass, relatively earlier than groups with a small luminosity gap, this parameter alone is not highly efficient in fully discriminating between the ‘old’ and ‘young’ galaxy groups, a label assigned based on halo mass accumulation history. We study galaxies drawn from the semi-analytic models of Guo et al., based on the Millennium Simulation. We establish a set of four observationally measurable parameters which can be used in combination, to identify a subset of galaxy groups which are old, with a very high probability. We thus argue that a sample of fossil groups selected based on luminosity gap will result in a contaminated sample of old galaxy groups. By adding constraints on the luminosity of the brightest galaxy, and its offset from the group luminosity centroid, we can considerably improve the age dating.
The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry ...(BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.
We investigate the assembly of groups and clusters of galaxies using the Millennium dark matter simulation and the associated Millennium gas simulations, and semi-analytic catalogues of galaxies. In ...particular, in order to find an observable quantity that could be used to identify early-formed groups, we study the development of the difference in magnitude between their brightest galaxies to assess the use of magnitude gaps as possible indicators. We select galaxy groups and clusters at redshift z= 1 with dark matter halo mass M(R200) ≥ 1013 h−1 M⊙, and trace their properties until the present time (z= 0). We consider only the systems with X-ray luminosity LX,bol≥ 0.25 × 1042 h−2 erg s−1 at redshift z= 0. While it is true that a large magnitude gap between the two brightest galaxies of a particular group often indicates that a large fraction of its mass was assembled at an early epoch, it is not a necessary condition. More than 90 per cent of fossil groups defined on the basis of their magnitude gaps (at any epoch between 0 < z < 1) cease to be fossils within 4 Gyr, mostly because other massive galaxies are assembled within their cores, even though most of the mass in their haloes might have been assembled at early times. We show that compared to the conventional definition of fossil galaxy groups based on the magnitude gap Δm12≥ 2 (in the R-band, within 0.5 R200 of the centre of the group), an alternative criterion Δm14≥ 2.5 (within the same radius) finds 50 per cent more early-formed systems, and those that on average retain their fossil phase longer. However, the conventional criterion performs marginally better at finding early-formed groups at the high-mass end of groups. Nevertheless, both criteria fail to identify a majority of the early-formed systems.
We analyze the role played by shear in regulating star formation in the Galaxy on the scale of individual molecular clouds. The clouds are selected from the super(13)CO J = 1-0 line of the Galactic ...Ring Survey. For each cloud, we estimate the shear parameter which describes the ability of density perturbations to grow within the cloud. We find that for almost all molecular clouds considered, there is no evidence that shear is playing a significant role in opposing the effects of self-gravity. We also find that the shear parameter of the clouds does not depend on their position in the Galaxy. Furthermore, we find no correlations between the shear parameter of the clouds with several indicators of their star formation activity. No significant correlation is found between the shear parameter and the star formation efficiency of the clouds which is measured using the ratio of the massive young stellar objects luminosities, measured in the Red MSX survey, to the cloud mass. There are also no significant correlations between the shear parameter and the fraction of their mass that is found in denser clumps which is a proxy for their clump formation efficiency, nor with their level of fragmentation expressed in the number of clumps per unit mass. Our results strongly suggest that shear is playing only a minor role in affecting the rates and efficiencies at which molecular clouds convert their gas into dense cores and thereafter into stars.
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