A Seven-Marker Signature and Clinical Outcome in Malignant Melanoma: A Large-Scale Tissue-Microarray Study with Two Independent Patient Cohorts

Current staging methods such as tumor thickness, ulceration and invasion of the sentinel node are known to be prognostic parameters in patients with malignant melanoma (MM). However, predictive molecular marker profiles for risk stratification and therapy optimization are not yet available for routine clinical assessment.; Using tissue microarrays, we retrospectively analyzed samples from 364 patients with primary MM. We investigated a panel of 70 immunohistochemical (IHC) antibodies for cell cycle, apoptosis, DNA mismatch repair, differentiation, proliferation, cell adhesion, signaling and metabolism. A marker selection procedure based on univariate Cox regression and multiple testing correction was employed to correlate the IHC expression data with the clinical follow-up (overall and recurrence-free survival). The model was thoroughly evaluated with two different cross validation experiments, a permutation test and a multivariate Cox regression analysis. In addition, the predictive power of the identified marker signature was validated on a second independent external test cohort (n?=?225). A signature of seven biomarkers (Bax, Bcl-X, PTEN, COX-2, loss of ?-Catenin, loss of MTAP, and presence of CD20 positive B-lymphocytes) was found to be an independent negative predictor for overall and recurrence-free survival in patients with MM. The seven-marker signature could also predict a high risk of disease recurrence in patients with localized primary MM stage pT1-2 (tumor thickness ?2.00 mm). In particular, three of these markers (MTAP, COX-2, Bcl-X) were shown to offer direct therapeutic implications.; The seven-marker signature might serve as a prognostic tool enabling physicians to selectively triage, at the time of diagnosis, the subset of high recurrence risk stage I-II patients for adjuvant therapy. Selective treatment of those patients that are more likely to develop distant metastatic disease could potentially lower the burden of untreatable metastatic melanoma and revolutionize the therapeutic management of MM

Rubin-Euclid Derived Data Products:Initial Recommendations

This report is the result of a joint discussion between the Rubin and Euclid scientific communities. The work presented in this report was focused on designing and recommending an initial set of Derived Data products (DDPs) that could realize the science goals enabled by joint processing. All interested Rubin and Euclid data rights holders were invited to contribute via an online discussion forum and a series of virtual meetings. Strong interest in enhancing science with joint DDPs emerged from across a wide range of astrophysical domains: Solar System, the Galaxy, the Local Volume, from the nearby to the primaeval Universe, and cosmology

The Wide-field Spectroscopic Telescope (WST) Science White Paper

The Wide-field Spectroscopic Telescope (WST) is proposed as a new facility dedicated to the efficient delivery of spectroscopic surveys. This white paper summarises the initial concept as well as the corresponding science cases. WST will feature simultaneous operation of a large field-of-view (3 sq. degree), a high multiplex (20,000) multi-object spectrograph (MOS) and a giant 3x3 sq. arcmin integral field spectrograph (IFS). In scientific capability these requirements place WST far ahead of existing and planned facilities. Given the current investment in deep imaging surveys and noting the diagnostic power of spectroscopy, WST will fill a crucial gap in astronomical capability and work synergistically with future ground and space-based facilities. This white paper shows that WST can address outstanding scientific questions in the areas of cosmology; galaxy assembly, evolution, and enrichment, including our own Milky Way; origin of stars and planets; time domain and multi-messenger astrophysics. WST's uniquely rich dataset will deliver unforeseen discoveries in many of these areas. The WST Science Team (already including more than 500 scientists worldwide) is open to the all astronomical community. To register in the WST Science Team please visit https://www.wstelescope.com/for-scientists/participat

Extended fast action minimization method: Application to SDSS-DR12 combined sample

We present the first application of the extended Fast Action Minimization method (eFAM) to a real data set, the SDSS-DR12 Combined Sample, to reconstruct galaxies orbits back-in-time, their two-point correlation function (2PCF) in real-space, and enhance the baryon acoustic oscillation (BAO) peak. For this purpose, we introduce a new implementation of eFAM that accounts for selection effects, survey footprint, and galaxy bias. We use the reconstructed BAO peak to measure the angular diameter distance, D A(z)r fid s/r s, and the Hubble parameter, H(z)r s/r fid s}, normalized to the sound horizon scale for a fiducial cosmology r fid} s}, at the mean redshift of the sample z = 0.38, obtaining D A(z=0.38)r fid s/r s=1090pm 29(Mpc)-1, and H(z=0.38)r s/r fid s=83pm 3(km s-1 Mpc-1), in agreement with previous measurements on the same data set. The validation tests, performed using 400 publicly available SDSS-DR12 mock catalogues, reveal that eFAM performs well in reconstructing the 2PCF down to separations of 3c25h-1Mpc, i.e. well into the non-linear regime. Besides, eFAM successfully removes the anisotropies due to redshift-space distortion (RSD) at all redshifts including that of the survey, allowing us to decrease the number of free parameters in the model and fit the full-shape of the back-in-time reconstructed 2PCF well beyond the BAO peak. Recovering the real-space 2PCF, eFAM improves the precision on the estimates of the fitting parameters. When compared with the no-reconstruction case, eFAM reduces the uncertainty of the Alcock-Paczynski distortion parameters \u3b1 and \u3b1\u3c0 of about 40 per cent and that on the non-linear damping scale \u3c2\u3c0 of about 70 per cent. These results show that eFAM can be successfully applied to existing redshift galaxy catalogues and should be considered as a reconstruction tool for next-generation surveys alternative to popular methods based on the Zel'dovich approximation

BAO reconstruction: a swift numerical action method for massive spectroscopic surveys

none4A new fully non-linear reconstruction algorithm for the accurate recovery of the baryonic acoustic oscillations (BAO) scale in two-point correlation functions is proposed, based on the least action principle and extending the Fast Action Minimisation method by Nusser & Branchini (2000). Especially designed for massive spectroscopic surveys, it is tested on dark matter halo catalogues extracted from the DEUS-FUR Lambda cold dark matter simulation (Reverdy et al. 2015) to trace the trajectories of up to {˜ }207 000 haloes backward in time, well beyond the first-order Lagrangian approximation. The new algorithm successfully recovers the BAO feature in real and redshift space in both the monopole and the anisotropic two-point correlation function, also for anomalous samples showing misplaced or absent signature of BAO. In redshift space, the non-linear displacement parameter ΣNL is reduced from 11.8± 0.3 h^{-1} Mpc at redshift z = 0 to 4.0± 0.5 h^{-1} Mpc at z ≃ 37 after reconstruction. A comparison with the first-order Lagrangian reconstruction is presented, showing that these techniques outperform the linear approximation in recovering an unbiased measurement of the acoustic scale.mixedSarpa, E; Schimd, C; Branchini, E; Matarrese, SSarpa, E; Schimd, C; Branchini, E; Matarrese,

The GALEX Ultraviolet Virgo Cluster Survey (GUViCS): VIII. Diffuse dust in the Virgo intra-cluster space

International audienceAims. We present the first detection of diffuse dust in the intra-cluster medium of the Virgo cluster out to ∼0.4 virial radii, and study the radial variation of its properties on a radial scale of the virial radius.Methods. Analysing near-UV – i colours for a sample of ∼12 000 background galaxies with redshifts 0.02 <  z <  0.8, we find significant colour reddening and relate it to variation in E(B − V) values.Results. The E(B − V) mean profile shows a dust component characterised by an average reddening E(B − V) ∼ 0.042 ± 0.004 mag within 1.5 degrees (∼0.3 rvir) from the cluster centre. Assuming a Large Magellanic Cloud extinction law, we derive an average visual extinction AV = 0.14 ± 0.01 for a total dust mass, Md = 2.5 ± 0.2 × 109 M⊙, hence a dust-to-gas mass ratio Md/Mg = 3.0 ± 0.3 × 10−4. Based on the upper limits on the flux density I250μm = 0.1 MJy sr−1 derived from Herschel data, we estimate an upper limit for the dust temperature of Td ∼ 10 K. However, similar densities can be obtained with dust at higher temperatures with lower emissivities.Conclusions. The Virgo cluster has diffuse dust in its intra-cluster medium characterised by different physical properties as those characterising the Milky Way dust. The diffuse dust in Virgo is transported into the cluster space through similar phenomena (stripping) as those building up the optical intra-cluster light, and it constitutes an additional cooling agent of the cluster gas

Genetic Rescue of Glycosylation-deficient Fgf23 in the Galnt3 Knockout Mouse

Fibroblast growth factor 23 (FGF23) is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. The FGF23 subtilisin-like proprotein convertase recognition sequence ((176)RHTR(179)↓) is protected by O-glycosylation through ppGalNAc-T3 (GALNT3) activity. Thus, inactivating GALNT3 mutations render FGF23 susceptible to proteolysis, thereby reducing circulating intact hormone levels and leading to hyperphosphatemic familial tumoral calcinosis. To further delineate the role of glycosylation in the Fgf23 function, we generated an inducible FGF23 transgenic mouse expressing human mutant FGF23 (R176Q and R179Q) found in patients with autosomal dominant hypophosphatemic rickets (ADHR) and bred this animal to Galnt3 knockout mice, a model of familial tumoral calcinosis. Due to the low intact Fgf23 level, Galnt3 knockout mice with wild-type Fgf23 alleles were hyperphosphatemic. In contrast, carriers of the mutant FGF23 transgene, regardless of Galnt3 mutation status, had significantly higher serum intact FGF23, resulting in severe hypophosphatemia. Importantly, serum phosphorus and FGF23 were comparable between transgenic mice with or without normal Galnt3 alleles. To determine whether the presence of the ADHR mutation could improve biochemical and skeletal abnormalities in Galnt3-null mice, these mice were also mated to Fgf23 knock-in mice, carrying heterozygous or homozygous R176Q ADHR Fgf23 mutations. The knock-in mice with functional Galnt3 had normal Fgf23 but were slightly hypophosphatemic. The stabilized Fgf23 ADHR allele reversed the Galnt3-null phenotype and normalized total Fgf23, serum phosphorus, and bone Fgf23 mRNA. However, the skeletal phenotype was unaffected. In summary, these data demonstrate that O-glycosylation by ppGaINAc-T3 is only necessary for proper secretion of intact Fgf23 and, once secreted, does not affect Fgf23 function. Furthermore, the more stable Fgf23 ADHR mutant protein could normalize serum phosphorus in Galnt3 knockout mice

Euclid preparation. TBD. Galaxy power spectrum modelling in real space

We investigate the accuracy of the perturbative galaxy bias expansion in view of the forthcoming analysis of the Euclid spectroscopic galaxy samples. We compare the performance of an Eulerian galaxy bias expansion, using state-of-art prescriptions from the effective field theory of large-scale structure (EFTofLSS), against a hybrid approach based on Lagrangian perturbation theory and high-resolution simulations. These models are benchmarked against comoving snapshots of the Flagship I N-body simulation at $z=(0.9,1.2,1.5,1.8)$, which have been populated with H$\alpha$ galaxies leading to catalogues of millions of objects within a volume of about $58\,h^{-3}\,{\rm Gpc}^3$. Our analysis suggests that both models can be used to provide a robust inference of the parameters $(h, \omega_{\rm c})$ in the redshift range under consideration, with comparable constraining power. We additionally determine the range of validity of the EFTofLSS model in terms of scale cuts and model degrees of freedom. From these tests, it emerges that the standard third-order Eulerian bias expansion can accurately describe the full shape of the real-space galaxy power spectrum up to the maximum wavenumber $k_{\rm max}=0.45\,h\,{\rm Mpc}^{-1}$, even with a measurement precision well below the percent level. In particular, this is true for a configuration with six free nuisance parameters, including local and non-local bias parameters, a matter counterterm, and a correction to the shot-noise contribution. Fixing either tidal bias parameters to physically-motivated relations still leads to unbiased cosmological constraints. We finally repeat our analysis assuming a volume that matches the expected footprint of Euclid, but without considering observational effects, as purity and completeness, showing that we can get consistent cosmological constraints over this range of scales and redshifts

Euclid preparation. TBD. Galaxy power spectrum modelling in real space

We investigate the accuracy of the perturbative galaxy bias expansion in view of the forthcoming analysis of the Euclid spectroscopic galaxy samples. We compare the performance of an Eulerian galaxy bias expansion, using state-of-art prescriptions from the effective field theory of large-scale structure (EFTofLSS), against a hybrid approach based on Lagrangian perturbation theory and high-resolution simulations. These models are benchmarked against comoving snapshots of the Flagship I N-body simulation at $z=(0.9,1.2,1.5,1.8)$, which have been populated with H$\alpha$ galaxies leading to catalogues of millions of objects within a volume of about $58\,h^{-3}\,{\rm Gpc}^3$. Our analysis suggests that both models can be used to provide a robust inference of the parameters $(h, \omega_{\rm c})$ in the redshift range under consideration, with comparable constraining power. We additionally determine the range of validity of the EFTofLSS model in terms of scale cuts and model degrees of freedom. From these tests, it emerges that the standard third-order Eulerian bias expansion can accurately describe the full shape of the real-space galaxy power spectrum up to the maximum wavenumber $k_{\rm max}=0.45\,h\,{\rm Mpc}^{-1}$, even with a measurement precision well below the percent level. In particular, this is true for a configuration with six free nuisance parameters, including local and non-local bias parameters, a matter counterterm, and a correction to the shot-noise contribution. Fixing either tidal bias parameters to physically-motivated relations still leads to unbiased cosmological constraints. We finally repeat our analysis assuming a volume that matches the expected footprint of Euclid, but without considering observational effects, as purity and completeness, showing that we can get consistent cosmological constraints over this range of scales and redshifts

A Virgo Environmental Survey Tracing Ionised Gas Emission (VESTIGE): VII. Bridging the cluster-ICM-galaxy evolution at small scales

International audienceAims. We measure far-infrared (FIR) emission from tails of stripped dust following the ionised and atomic gas components in galaxies undergoing ram pressure stripping. We study the dust-to-gas relative distribution and mass ratio in the stripped interstellar medium and relate them to those of the intra-cluster medium (ICM), thus linking the cluster-ICM-galaxy evolution at small-scales. The galaxy sample consists of three Scd Virgo galaxies with stellar masses in the range of 109 ≲ M* ≲ 1010 M⊙ and within 1 Mpc from the cluster centre, namely NGC 4330, NGC 4522, and NGC 4654.Methods. Through the analysis of Virgo Environmental Survey Tracing Ionised Gas Emission (VESTIGE) Hα, Herschel SPIRE FIR, and VLA Imaging of Virgo in Atomic gas HI data, we trace the spatial distribution of the tails and infer the dust and gas masses from the measured FIR 250 μm and HI flux densities. Dust-to-gas mass ratios in the tails are analysed as a function of the galaxy mass, metallicity, and dust temperature.Results. Along the stripped component, the dust distribution closely follows the HI and Hα emitting gas, which extend beyond the optical disc (defined by the B-band 25th magnitude isophote). In these regions, the dust-to-gas mass ratios are 2.0 ± 0.6 × 10−3, 0.7 ± 0.1 × 10−3, and 0.4 ± 0.03 × 10−3 for NGC 4330, NGC 4522, and NGC 4654, respectively. Thus, dust is widespread in the stripped material with a lower dust-to-gas mass ratio (up to a factor of 15) than the one measured in the main body of nearby galaxies. We also find a negative trend in the dust-to-gas mass ratio as a function of the metallicity that can be explained in terms of a dust component more centrally concentrated in more metal-rich systems. Together with the finding that the stripped dust is cold, Td ≲ 25 K, our results can be interpreted as a consequence of an outside-in stripping of the galaxy interstellar medium.Conclusions. Gas and dust in galaxies are perturbed in a similar fashion by the cluster environment, although their relative contribution differs from the one measured in the main body of the galaxies. When this value is considered, ram pressure stripping is consistent with being one of the key mechanisms in building up the Virgo intra-cluster component, injecting dust grains into the ICM, thus contributing to its metal enrichment