Galaxy And Mass Assembly (GAMA): testing galaxy formation models through the most massive galaxies in the Universe

We have analysed the growth of Brightest Group Galaxies and Brightest Cluster Galaxies (BGGs/BCGs) over the last 3 billion years using a large sample of 883 galaxies from the Galaxy And Mass Assembly survey. By comparing the stellar mass of BGGs and BCGs in groups and clusters of similar dynamical masses, we find no significant growth between redshift z = 0.27 and 0.09. We also examine the number of BGGs/BCGs that have line emission, finding that approximately 65 per cent of BGGs/BCGs show Hα in emission. From the galaxies where the necessary spectroscopic lines were accurately recovered (54 per cent of the sample), we find that half of this (i.e. 27 per cent of the sample) harbour ongoing star formation with rates up to 10 M⊙ yr−1, and the other half (i.e. 27 per cent of the sample) have an active nucleus (AGN) at the centre. BGGs are more likely to have ongoing star formation, while BCGs show a higher fraction of AGN activity. By examining the position of the BGGs/BCGs with respect to their host dark matter halo, we find that around 13 per cent of them do not lie at the centre of the dark matter halo. This could be an indicator of recent cluster–cluster mergers. We conclude that BGGs and BCGs acquired their stellar mass rapidly at higher redshifts as predicted by semi-analytic models, mildly slowing down at low redshifts

Heterogeneity of luminal breast cancer characterised by immunohistochemical expression of basal markers

Background: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours. Methods: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))− and EGFR−) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case–case comparison was performed using unconditional logistic regression. Results: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index. Conclusions: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations

SPECTRA OF YOUNG GALAXIES

Invited review, Ringberg conference on "Galaxies in the Young Universe" (Sept94)Comment: 12 pages, uuencoded compressed Postscript fil

The SAMI Galaxy Survey: Spatially resolving the environmental quenching of star formation in GAMA galaxies

We use data from the Sydney-AAO Multi-Object Integral Field Spectrograph (SAMI) Galaxy Survey and the Galaxy And Mass Assembly (GAMA) survey to investigate the spatially-resolved signatures of the environmental quenching of star formation in galaxies. Using dust-corrected measurements of the distribution of Hα emission we measure the radial profiles of star formation in a sample of 201 star-forming galaxies covering three orders of magnitude in stellar mass (M∗M∗; 108.1-1010.95 M⊙) and in 5th nearest neighbour local environment density (Σ5; 10−1.3- 102.1 Mpc−2). We show that star formation rate gradients in galaxies are steeper in dense (log10(Σ5/Mpc2) > 0.5) environments by 0.58 ± 0.29 dex re−1 in galaxies with stellar masses in the range 1010 1.0). These lines of evidence strongly suggest that with increasing local environment density the star formation in galaxies is suppressed, and that this starts in their outskirts such that quenching occurs in an outside-in fashion in dense environments and is not instantaneous

Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer

Background: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. Methods: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. Findings: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. Interpretation: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input

Stellar population synthesis at the resolution of 2003

We present a new model for computing the spectral evolution of stellar populations at ages between 100,000 yr and 20 Gyr at a resolution of 3 A across the whole wavelength range from 3200 to 9500 A for a wide range of metallicities. These predictions are based on a newly available library of observed stellar spectra. We also compute the spectral evolution across a larger wavelength range, from 91 A to 160 micron, at lower resolution. The model incorporates recent progress in stellar evolution theory and an observationally motivated prescription for thermally-pulsing stars on the asymptotic giant branch. The latter is supported by observations of surface brightness fluctuations in nearby stellar populations. We show that this model reproduces well the observed optical and near-infrared colour-magnitude diagrams of Galactic star clusters of various ages and metallicities. Stochastic fluctuations in the numbers of stars in different evolutionary phases can account for the full range of observed integrated colours of star clusters in the Magellanic Clouds. The model reproduces in detail typical galaxy spectra from the Early Data Release (EDR) of the Sloan Digital Sky Survey (SDSS). We exemplify how this type of spectral fit can constrain physical parameters such as the star formation history, metallicity and dust content of galaxies. Our model is the first to enable accurate studies of absorption-line strengths in galaxies containing stars over the full range of ages. Using the highest-quality spectra of the SDSS EDR, we show that this model can reproduce simultaneously the observed strengths of those Lick indices that do not depend strongly on element abundance ratios [abridged].Comment: 35 pages, 22 figures, to appear in MNRAS; version with full resolution figures available at http://www.iap.fr/~charlot/bc2003/pape

High-throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium (BCAC)

Automated methods are needed to facilitate high-throughput and reproducible scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in large-scale studies. To address this need, we developed an automated protocol for Ki67 scoring and evaluated its performanc

Cosmology with clusters of galaxies

In this Chapter I review the role that galaxy clusters play as tools to constrain cosmological parameters. I will concentrate mostly on the application of the mass function of galaxy clusters, while other methods, such as that based on the baryon fraction, are covered by other Chapters of the book. Since most of the cosmological applications of galaxy clusters rely on precise measurements of their masses, a substantial part of my Lectures concentrates on the different methods that have been applied so far to weight galaxy clusters. I provide in Section 2 a short introduction to the basics of cosmic structure formation. In Section 3 I describe the Press--Schechter (PS) formalism to derive the cosmological mass function, then discussing extensions of the PS approach and the most recent calibrations from N--body simulations. In Section 4 I review the methods to build samples of galaxy clusters at different wavelengths. Section 5 is devoted to the discussion of different methods to derive cluster masses. In Section 6 I describe the cosmological constraints, which have been obtained so far by tracing the cluster mass function with a variety of methods. Finally, I describe in Section 7 the future perspectives for cosmology with galaxy clusters and the challenges for clusters to keep playing an important role in the era of precision cosmology.Comment: 49 pages, 19 figures, Lectures for 2005 Guillermo Haro Summer School on Clusters, to appear in "Lecture notes in Physics" (Springer

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-