Fine-Scale mapping of the 11q13 breast cancer susceptibility locus

The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799–121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000–120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Perallelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08–1.13, $\small \textit{P}$ = 1.49 x 10$^{-21}$). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity $\small \textit{P}$ $\leq$ 8.41 x 10$^{-5}$). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.Cancer Research UK (Grant IDs: C1287/A10118, C1287/A12014, C490/A10124, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), European Community's Seventh Framework Programme (Grant ID: HEALTH-F2-2009-223175), National Institutes of Health (Grant IDs: CA128978, CA116167, CA176785, CA116201, CA63464, CA54281, CA098758, CA132839, R01CA100374, R01CA64277, R01CA148667, R37CA70867, R01CA092447), National Institute for Health Research. See also Table K via http://dx.doi.org/10.1371/journal.pone.0160316.s003This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pone.016031

Galaxy and Mass Assembly (GAMA): merging galaxies and their properties

We derive the close pair fractions and volume merger rates for galaxies in the Galaxy and Mass Assembly (GAMA) survey with -23 &lt; M-r &lt; -17 (Omega(M) = 0.27, Omega(A) = 0.73, H-0 = 100 km s(-1) Mpc(-1)) at 0.01 &lt; z &lt; 0.22 (look-back time of &lt; 2 Gyr). The merger fraction is approximately 1.5 per cent Gyr(-1) at all luminosities (assuming 50 per cent of pairs merge) and the volume merger rate is approximate to 3.5 x 10(-4) Mpc(-3) Gyr(-1). We examine how the merger rate varies by luminosity and morphology. Dry mergers (between red/spheroidal galaxies) are found to be uncommon and to decrease with decreasing luminosity. Fainter mergers are wet, between blue/discy galaxies. Damp mergers (one of each type) follow the average of dry and wetmergers. In the brighter luminosity bin (-23 &lt; M-r &lt; -20), the merger rate evolution is flat, irrespective of colour or morphology, out to z similar to 0.2. The makeup of the merging population does not appear to change over this redshift range. Galaxy growth by major mergers appears comparatively unimportant and dry mergers are unlikely to be significant in the buildup of the red sequence over the past 2 Gyr. We compare the colour, morphology, environmental density and degree of activity (BPT class, Baldwin, Phillips &amp; Terlevich) of galaxies in pairs to those of more isolated objects in the same volume. Galaxies in close pairs tend to be both redder and slightly more spheroid dominated than the comparison sample. We suggest that this may be due to &#39;harassment&#39; in multiple previous passes prior to the current close interaction. Galaxy pairs do not appear to prefer significantly denser environments. There is no evidence of an enhancement in the AGN fraction in pairs, compared to other galaxies in the same volume.</p

Galaxy And Mass Assembly (GAMA): A forensic SED reconstruction of the cosmic star-formation history and metallicity evolution by galaxy type

We apply the spectral energy distribution-fitting code ProSpect to multiwavelength imaging for $\sim$7,000 galaxies from the GAMA survey at $z<0.06$, in order to extract their star-formation histories. We combine a parametric description of the star formation history with a closed-box evolution of metallicity where the present-day gas-phase metallicity of the galaxy is a free parameter. We show with this approach that we are able to recover the observationally-determined cosmic star formation history (CSFH), an indication that stars are being formed in the correct epoch of the Universe, on average, for the manner in which we are conducting SED fitting. We also show the contribution to the CSFH of galaxies of different present-day visual morphologies, and stellar masses. This analysis suggests that half of the mass in present-day elliptical galaxies was in place 11 Gyr ago, whereas in other morphological types the stellar mass formed later, up to 6 Gyr ago for present-day irregular galaxies. Similarly, the most massive galaxies in our sample were shown to have formed half their stellar mass by 10.5 Gyr ago, whereas the least massive galaxies formed half their stellar mass as late as 4 Gyr ago (the well-known effect of "galaxy downsizing"). Finally, our metallicity approach allows us to follow the average evolution in gas-phase metallicity for populations of galaxies, and extract the evolution of the cosmic metal mass density in stars and in gas, producing results in broad agreement with observations of metal densities in the Universe

Modulating attentional load affects numerosity estimation: evidence against a pre-attentive subitizing mechanism

Traditionally, the visual enumeration of a small number of items (1 to about 4), referred to as subitizing, has been thought of as a parallel and pre-attentive process and functionally different from the serial attentive enumeration of larger numerosities. We tested this hypothesis by employing a dual task paradigm that systematically manipulated the attentional resources available to an enumeration task. Enumeration accuracy for small numerosities was severely decreased as more attentional resources were taken away from the numerical task, challenging the traditionally held notion of subitizing as a pre-attentive, capacity-independent process. Judgement of larger numerosities was also affected by dual task conditions and attentional load. These results challenge the proposal that small numerosities are enumerated by a mechanism separate from large numerosities and support the idea of a single, attention-demanding enumeration mechanism

Galaxy And Mass Assembly (GAMA): the unimodal nature of the dwarf galaxy population

In this paper we aim to (i) test the number of statistically distinct classes required to classify the local galaxy population, and, (ii) identify the differences in the physical and star formation properties of visually-distinct galaxies. To accomplish this, we analyse the structural parameters (effective radius (Reff ), effective surface brightness within Reff (hμie), central surface brightness (μ0), and S´ersic index (n)), obtained by fitting the light profile of 432 galaxies (0.002 < z 6 0.02; Viking Z-band), and their spectral energy distribution using multi-band photometry in 18 broadbands to obtain the stellar mass (M ), the star formation rate (SFR), the specific SFR (sSFR) and the dust mass (Mdust), respectively. We show that visually distinct, star-forming dwarf galaxies (irregulars, blue spheroids and low surface brightness galaxies) form a unimodal population in a parameter space mapped by hμie, μ0, n, Reff , SFR, sSFR, M , Mdust and (g − i). The SFR and sSFR distribution of passively evolving (dwarf) ellipticals on the other hand, statistically distinguish them from other galaxies with similar luminosity, while the giant galaxies clearly segregate into starforming spirals and passive lenticulars. We therefore suggest that the morphology classification scheme(s) used in literature for dwarf galaxies only reflect the observational differences based on luminosity and surface brightness among the apparent distinct classes, rather than any physical differences between them

Galaxy And Mass Assembly (GAMA): the unimodal nature of the dwarf galaxy population

In this paper we aim to (i) test the number of statistically distinct classes required to classify the local galaxy population, and, (ii) identify the differences in the physical and star formation properties of visually-distinct galaxies. To accomplish this, we analyse the structural parameters (effective radius (Reff ), effective surface brightness within Reff (hμie), central surface brightness (μ0), and S´ersic index (n)), obtained by fitting the light profile of 432 galaxies (0.002 < z 6 0.02; Viking Z-band), and their spectral energy distribution using multi-band photometry in 18 broadbands to obtain the stellar mass (M ), the star formation rate (SFR), the specific SFR (sSFR) and the dust mass (Mdust), respectively. We show that visually distinct, star-forming dwarf galaxies (irregulars, blue spheroids and low surface brightness galaxies) form a unimodal population in a parameter space mapped by hμie, μ0, n, Reff , SFR, sSFR, M , Mdust and (g − i). The SFR and sSFR distribution of passively evolving (dwarf) ellipticals on the other hand, statistically distinguish them from other galaxies with similar luminosity, while the giant galaxies clearly segregate into starforming spirals and passive lenticulars. We therefore suggest that the morphology classification scheme(s) used in literature for dwarf galaxies only reflect the observational differences based on luminosity and surface brightness among the apparent distinct classes, rather than any physical differences between them

Deceptive body movements reverse spatial cueing in soccer

This article has been made available through the Brunel Open Access Publishing Fund.The purpose of the experiments was to analyse the spatial cueing effects of the movements of soccer players executing normal and deceptive (step-over) turns with the ball. Stimuli comprised normal resolution or point-light video clips of soccer players dribbling a football towards the observer then turning right or left with the ball. Clips were curtailed before or on the turn (-160, -80, 0 or +80 ms) to examine the time course of direction prediction and spatial cueing effects. Participants were divided into higher-skilled (HS) and lower-skilled (LS) groups according to soccer experience. In experiment 1, accuracy on full video clips was higher than on point-light but results followed the same overall pattern. Both HS and LS groups correctly identified direction on normal moves at all occlusion levels. For deceptive moves, LS participants were significantly worse than chance and HS participants were somewhat more accurate but nevertheless substantially impaired. In experiment 2, point-light clips were used to cue a lateral target. HS and LS groups showed faster reaction times to targets that were congruent with the direction of normal turns, and to targets incongruent with the direction of deceptive turns. The reversed cueing by deceptive moves coincided with earlier kinematic events than cueing by normal moves. It is concluded that the body kinematics of soccer players generate spatial cueing effects when viewed from an opponent's perspective. This could create a reaction time advantage when anticipating the direction of a normal move. A deceptive move is designed to turn this cueing advantage into a disadvantage. Acting on the basis of advance information, the presence of deceptive moves primes responses in the wrong direction, which may be only partly mitigated by delaying a response until veridical cues emerge

Respirable antisense oligonucleotides: a new drug class for respiratory disease

Respirable antisense oligonucleotides (RASONs), which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery

Galaxy And Mass Assembly (GAMA): The absence of stellar mass segregation in galaxy groups and consistent predictions from GALFORM and EAGLE simulations

We investigate the contentious issue of the presence, or lack thereof, of satellites mass segregation in galaxy groups using the Galaxy And Mass Assembly (GAMA) survey, the GALFORM semi-analytic and the EAGLE cosmological hydrodynamical simulation catalogues of galaxy groups. We select groups with halo mass $12 \leqslant \log(M_{\text{halo}}/h^{-1}M_\odot) <14.5$ and redshift $z \leqslant 0.32$ and probe the radial distribution of stellar mass out to twice the group virial radius. All the samples are carefully constructed to be complete in stellar mass at each redshift range and efforts are made to regularise the analysis for all the data. Our study shows negligible mass segregation in galaxy group environments with absolute gradients of $\lesssim0.08$ dex and also shows a lack of any redshift evolution. Moreover, we find that our results at least for the GAMA data are robust to different halo mass and group centre estimates. Furthermore, the EAGLE data allows us to probe much fainter luminosities ($r$-band magnitude of 22) as well as investigate the three-dimensional spatial distribution with intrinsic halo properties, beyond what the current observational data can offer. In both cases we find that the fainter EAGLE data show a very mild spatial mass segregation at $z \leqslant 0.22$, which is again not apparent at higher redshift. Interestingly, our results are in contrast to some earlier findings using the Sloan Digital Sky Survey. We investigate the source of the disagreement and suggest that subtle differences between the group finding algorithms could be the root cause

Chronos: A NIR spectroscopic galaxy survey to probe the most fundamental stages of galaxy evolution

We propose a dedicated, ultra-deep spectroscopic survey in the near infrared (NIR), that will target a mass-limited sample of galaxies during two of the most fundamental epochs of cosmic evolution: the formation of the first galaxies (at z ≳ 6; comsmic dawn), and at the peak of galaxy formation activity (at redshift z∼1–3; cosmic noon). By way of NIR observations (λ= 0.8–2μ m), it is possible to study the UV Lyman-α region in the former, and the optical rest-frame in the latter, allowing us to extract fundamental observables such as gas and stellar kinematics, chemical abundances, and ages, providing a unique legacy database covering these two crucial stages of cosmic evolution. The need to work in the NIR at extremely low flux levels makes a ground-based approach unfeasible due to atmospheric emission and absorption. Only with the largest facilities of the future (e.g. ELT) will be possible to observe a reduced set of targets, comprising at most of order thousands of galaxies. Likewise, from space, the small field of view of JWST and its use as a general purpose facility will yield a rather small set of high quality NIR spectra of distant galaxies (in the thousands, at best). Our project (codename Chronos) aims to produce ∼1 million high quality spectra, with a high S/N in the continuum, where information about the underlying stellar populations is encoded. The main science drivers are: - The connection between the star formation history and the mass assembly history. - The role of AGN and supernova feedback in shaping the formation histories of galaxies, with a quantitative estimate of quenching timescales. - The formation of the first galaxies. - The source of reionization. - Evolution of the metallicity-mass relation, including [α/Fe] and individual abundances. - Precision cosmology through detailed studies of the “baryon physics” of galaxy formation, probing the power spectrum over scales k∼1 Mpc− 1