We describe the public ESO near-IR variability survey (VVV) scanning the Milky Way bulge and an adjacent section of the mid-plane where star formation activity is high. The survey will take 1929 h of observations with the 4-m VISTA telescope during 5 years (2010-2014), covering ˜109 point sources across an area of 520 deg2, including 33 known globular clusters and ˜350 open clusters. The final product will be a deep near-IR atlas in five passbands (0.9-2.5 μm) and a catalogue of more than 106 variable point sources. Unlike single-epoch surveys that, in most cases, only produce 2-D maps, the VVV variable star survey will enable the construction of a 3-D map of the surveyed region using well-understood distance indicators such as RR Lyrae stars, and Cepheids. It will yield important information on the ages of the populations. The observations will be combined with data from MACHO, OGLE, EROS, VST, Spitzer, HST, Chandra, INTEGRAL, WISE, Fermi LAT, XMM-Newton, GAIA and ALMA for a complete understanding of the variable sources in the inner Milky Way. This public survey will provide data available to the whole community and therefore will enable further studies of the history of the Milky Way, its globular cluster evolution, and the population census of the Galactic Bulge and center, as well as the investigations of the star forming regions in the disk. The combined variable star catalogues will have important implications for theoretical investigations of pulsation properties of stars

In the era of precision cosmology, it is essential to empirically determine the Hubble constant with an accuracy of one per cent or better 1 . At present, the uncertainty on this constant is dominated by the uncertainty in the calibration of the Cepheid period -luminosity relationship 2, 3 (also known as Leavitt Law). The Large Magellanic Cloud has traditionally served as the best galaxy with which to calibrate Cepheid period-luminosity relations, and as a result has become the best anchor point for the cosmic distance scale 4,5 . Eclipsing binary systems composed of late-type stars offer the most precise and accurate way to measure the distance to the Large Magellanic Cloud. Currently the limit of the precision attainable with this technique is about two per cent, and is set by the precision of the existing calibrations of the surface brightness -colour relation 5,6 . Here we report the calibration of the surface brightness-colour relation with a precision of 0.8 per cent. We use this calibration to determine the geometrical distance to the Large Magellanic Cloud that is precise to 1 per cent based on 20 eclipsing binary systems. The final distane is 49.59 ± 0.09 (statistical) ± 0.54 (systematic) kiloparsecs.All data are available upon request from G.P. Extended DataFig.1. Comparison of our relation with the relation of Di Benedetto obtained for giant stars 6 . Top panel, comparison of relations: data points show our results, with the fitted line shown in blue. The blue shaded area represents our obtained r.m.s. scatter of 0.018 mag. The green line is from ref. 6 . Very good agreement is demonstrated. Both S V and (V − K) 0 are in magnitudes. S V physically corresponds to the V band magnitude of a red giant star whose angular diameter is 1 mas. The error bars correspond to 1σ errors. Bottom panel, observed minus calculated values. Extended Data Fig.2. Observed minus calculated surface brightness versus metallicity 6 , [Fe/H]. In a relatively large range of metallicities (about 1 dex) no correlation is found. A formal linear fit gives O − C = 0.0009[Fe/H] -0.002 dex with coefficient of determination R 2 = 0.0001. Fig.3. Example of Monte Carlo simulations for one of our objects, ECL-12669. We computed 10,000 models with the JKTEBOP code 77 from which we obtained statistical uncertainties on the radii R 1 and R 2 , the orbital inclination i, the phase shift φ, the surface brightness ratio j 21 , radial velocity semi-amplitudes K 1 and K 2 , and the systemic velocities γ 1 and γ 2 . For every model we computed the distance modulus converting j 21 into temperature ratio T 2 /T 1 by using Popper's calibration 78 and our original solution with the Wilson-Devinney code 79 . We plot the number of calculated models versus distance modulus (m − M). The dashed line is the best fitted Gaussian and the blue line is the distance determined for this object. The intrinsic (V − K) 0 colours used to estimate the angular diameters of the components were computed using a temperature-colour calibration 28 . Extended DataExtended Data...

We present a distance determination to the Small Magellanic Cloud (SMC) based on an analysis of four detached, long period, late type eclipsing binaries discovered by the OGLE Survey. The components of the binaries show negligible intrinsic variability. A consistent set of stellar parameters was derived with low statistical and systematic uncertainty. The absolute dimensions of the stars are calculated with a precision of better than 3%.The surface brightness -infrared color relation was used to derive the distance to each binary. The four systems clump around a distance modulus of (m − M ) = 18.99 with a dispersion of only 0.05 mag. Combining these results with the distance published by Graczyk et al. for the eclipsing binary OGLE SMC113.3 4007 we obtain a mean distance modulus to the SMC of 18.965 ± 0.025 (stat.) ± 0.048 (syst.) mag. This corresponds to a distance of 62.1 ± 1.9 kpc, where the error includes both uncertainties. Taking into account other recent published determinations of the SMC distance we calculated the distance modulus difference between the SMC and the LMC equal to 0.458 ± 0.068 mag. Finally we advocate µ SMC = 18.95 ± 0.07 as a new "canonical" value of the distance modulus to this galaxy.

We present new Period-Age (PA) and Period-Age-Color (PAC) relations for fundamental and first overtone classical Cepheids. Current predictions rely on homogeneous sets of evolutionary and pulsation models covering a broad range of stellar masses and chemical compositions. We found that PA and PAC relations present a mild dependence upon metal content. Moreover, the use of different PA and PAC relation for fundamental and first overtone Cepheids improves the accuracy of age estimates in the short-period (log P < 1) range (old Cepheids), because they present smaller intrinsic dispersions. At the same time, the use of the PAC relations improves the accuracy in the long-period (log P ≥ 1) range (young Cepheids), since they account for the position of individual objects inside the instability strip.We performed a detailed comparison between evolutionary and pulsation ages for a sizable sample of LMC (15) and SMC (12) clusters which host at least two Cepheids. In order to avoid deceptive uncertainties in the photometric absolute zero-point, we adopted the homogeneous set of B,V,I data for clusters and Cepheids collected by OGLE. We also adopted the same reddening scale. The different age estimates agree at the level of 20% for LMC clusters and of 10% for SMC clusters. We also performed the same comparison for two Galactic clusters (NGC6067, NGC7790) and the difference in age is smaller than 20%.These findings support the use of PA and PAC relations to supply accurate estimates of individual stellar ages in the Galaxy and in external Galaxies. The main advantage of this approach is its independence from the distance.

Aims. We determine period-luminosity relations for Milky Way Cepheids in the optical and near-IR bands. These relations can be used directly as reference for extra-galactic distance determination to Cepheid populations with solar metallicity, and they form the basis for a direct comparison with relations obtained in exactly the same manner for stars in the Magellanic Clouds, presented in an accompanying paper. In that paper we show that the metallicity effect is very small and consistent with a null effect, particularly in the near-IR bands, and we combine here all 111 Cepheids from the Milky Way, the LMC and SMC to form a best relation. Methods. We employ the near-IR surface brightness (IRSB) method to determine direct distances to the individual Cepheids after we have recalibrated the projection factor using the recent parallax measurements to ten Galactic Cepheids and the constraint that Cepheid distances to the LMC should be independent of pulsation period. Results. We confirm our earlier finding that the projection factor for converting radial velocity to pulsational velocity depends quite steeply on pulsation period, p = 1.550− 0.186 log(P) in disagrement with recent theoretical predictions. We find PL relations based on 70 Milky Way fundamental mode Cepheids of M K = −3.33(±0.09)(log(P) − 1.0) − 5.66(±0.03), W VI = −3.26(±0.11)(log(P) − 1.0) − 5.96(±0.04). Combining the 70 Cepheids presented here with the results for 41 Magellanic Cloud Cepheids which are presented in an accompanying paper, we find M K = −3.30(±0.06)(log(P) − 1.0) − 5.65(±0.02), W VI = −3.32(±0.08)(log(P) − 1.0) − 5.92(±0.03). Conclusions. We delineate the Cepheid PL relation using 111 Cepheids with direct distances from the IRSB analysis. The relations are by construction in agreement with the recent HST parallax distances to Cepheids and slopes are in excellent agreement with the slopes of apparent magnitudes versus period observed in the LMC.

Many advanced tumors overexpress and secrete the S100A4 protein that is known to promote angiogenesis and metastasis development. The mechanisms of this effect and the endothelial receptor for S100A4 are both still unknown. Here we report that extracellular S100A4 interacts with annexin II, an endothelial plasminogen co-receptor. Co-localization and direct binding of S100A4 and annexin II were demonstrated, and the binding site was identified in the N-terminal region of annexin II. S100A4 alone or in a complex with annexin II accelerated tissue plasminogen activator-mediated plasminogen activation in solution and on the endothelial cell surface through interaction of the S100A4 Cterminal lysines with the lysine-binding domains of plasminogen. A synthetic peptide corresponding to the N terminus of annexin II prevented S100A4-induced plasmin formation in the endothelial cell culture. Local plasmin formation induced by circulating S100A4 could contribute to tumor-induced angiogenesis and metastasis formation that makes this protein an attractive target for new anti-cancer and anti-angiogenic therapies.

We present the first example of binary microlensing for which the parameter measurements can be verified (or contradicted) by future Doppler observations. This test is made possible by a confluence of two relatively unusual circumstances. First, the binary lens is bright enough (I = 15.6) to permit Doppler measurements. Second, we measure not only the usual seven binary-lens parameters, but also the "microlens parallax" (which yields the binary mass) and two components of the instantaneous orbital velocity. Thus, we measure, effectively, six "Kepler+1" parameters (two instantaneous positions, two instantaneous velocities, the binary total mass, and the mass ratio). Since Doppler observations of the brighter binary component determine five Kepler parameters (period, velocity amplitude, eccentricity, phase, and position of periapsis), while the same spectroscopy yields the mass of the primary, the combined Doppler + microlensing observations would be overconstrained by 6 + (5 + 1) − (7 + 1) = 4 degrees of freedom. This makes possible an extremely strong test of the microlensing solution. We also introduce a uniform microlensing notation for single and binary lenses, define conventions, summarize all known microlensing degeneracies, and extend a set of parameters to describe full Keplerian motion of the binary lenses.

In this fourth part of the series presenting the Optical Gravitational Lensing Experiment (OGLE) microlensing studies of the dark matter halo compact objects (MACHOs), we describe results of the OGLE‐III monitoring of the Small Magellanic Cloud (SMC). Three sound candidates for microlensing events were found and yielded the optical depth τSMC‐OIII= 1.30 ± 1.01 × 10−7, consistent with the expected contribution from Galactic disc and SMC self‐lensing. We report that event OGLE‐SMC‐03 is most likely a thick‐disc lens candidate, the first of such type found towards the SMC. In this paper we also combined all OGLE Large Magellanic Cloud and SMC microlensing results in order to refine the conclusions on MACHOs. All but one of the OGLE events are most likely caused by the lensing by known populations of stars; therefore, we concluded that there is no need for introducing any special dark matter compact objects in order to explain the observed event rates. Potential black hole event indicates that similar lenses can contribute only about 2 per cent to the total mass of the halo, which is still in agreement with the expected number of such objects.