Early vessel destabilization mediated by Angiopoietin-2 and subsequent vessel maturation via Angiopoietin-1 induce functional neovasculature after ischemia.

We assessed whether Angiopoietin-2 (Ang2), a Tie2 ligand and partial antagonist of Angiopoietin-1 (Ang1), is required for early vessel destabilization during postischemic angiogenesis, when combined with vascular growth factors. In vitro, matrigel co-cultures assessed endothelial-cell tube formation and pericyte recruitment after stimulation of VEGF-A, Apelin (APLN), Ang1 with or without Ang2. In a murine hindlimb ischemia model, adeno-associated virus (rAAV, 3×10(12) virusparticles) transduction of VEGF-A, APLN and Ang1 with or without Ang2 (continuous or early expression d0-3) was performed intramuscularly (d-14). Femoral artery ligation was performed at d0, followed by laser doppler perfusion meassurements (LDI) 7 and 14. At d7 (early timepoint) and d14 (late timepoint), histological analysis of capillary/muscle fiber ratio (CMF-R, PECAM-1) and pericyte/capillary ratio (PC-R, NG2) was performed. In vitro, VEGF-A, APLN and Ang1 induced ring formation, but only APLN and Ang1 recruited pericytes. Ang2 did not affect tube formation by APLN, but reduced pericyte recruitment after APLN or Ang1 overexpression. In vivo, rAAV.VEGF-A did not alter LDI-perfusion at d14, consistent with an impaired PC-R despite a rise in CMF-R. rAAV.APLN improved perfusion at d14, with or without continuous Ang2, increasing CMF-R and PC-R. rAAV.Ang1 improved perfusion at d14, when combined with rAAV.Ang2 (d0-3), accompanied by an increased CMF-R and PC-R. The combination of early vessel destabilization (Ang2 d0-3) and continuous Ang1 overexpression improves hindlimb perfusion, pointing to the importance of early vessel destabilization and subsequent vessel maturation for enhanced therapeutic neovascularization

Evolution of strigolactone receptors by gradual neofunctionalization of KAI2 paralogues

Background: Strigolactones (SLs) are a class of plant hormones that control many aspects of plant growth. The SL signalling mechanism is homologous to that of karrikins (KARs), smoke-derived compounds that stimulate seed germination. In angiosperms, the SL receptor is an a/p hydrolase known as DWARF14 (D14); its close homologue, KARRIKIN INSENSITIVE2 (KAI2), functions as a KAR receptor, and likely recognizes an uncharacterized, endogenous signal (‘KL’). Previous phylogenetic analyses have suggested that the KAI2 lineage is ancestral in land plants, and that canonical D14-type SL receptors only arose in seed plants; this is paradoxical, however, as nonvascular plants synthesize and respond to SLs. Results: We have used a combination of phylogenetic and structural approaches to re-assess the evolution of the D14/KAI2 family in land plants. We analyzed 339 members of the D14/KAI2 family from land plants and charophyte algae. Our phylogenetic analyses show that the divergence between the eu-KAI2 lineage and the DDK (D14/DLK2/KAI2) lineage that includes D14 occurred very early in land plant evolution. We show that eu-KAI2 proteins are highly conserved, and have unique features not found in DDK proteins. Conversely, we show that DDK proteins show considerable sequence and structural variation to each other, and lack clearly definable characteristics. We use homology modelling to show that the earliest members of the DDK lineage structurally resemble KAI2, and that SL receptors in non-seed plants likely do not have D14-like structure. We also show that certain groups of DDK proteins lack the otherwise conserved MAX2-interface, and may thus function independently of MAX2, which we show is highly conserved throughout land plant evolution. Conclusions: Our results suggest D14-like structure is not required for SL perception, and that SL perception has relatively relaxed structural requirements compared to KAI2-mediated signalling. We suggest that SL perception gradually evolved by neo-functionalization within the DDK lineage, and that the transition from KAI2-like to D14-like protein may have been driven by interactions with protein partners, rather than being required for SL perception per se

Final report on the evaluation of RRM/CRRM algorithms

Deliverable public del projecte EVERESTThis deliverable provides a definition and a complete evaluation of the RRM/CRRM algorithms selected in D11 and D15, and evolved and refined on an iterative process. The evaluation will be carried out by means of simulations using the simulators provided at D07, and D14.Preprin

Question Answering with Subgraph Embeddings

This paper presents a system which learns to answer questions on a broad range of topics from a knowledge base using few hand-crafted features. Our model learns low-dimensional embeddings of words and knowledge base constituents; these representations are used to score natural language questions against candidate answers. Training our system using pairs of questions and structured representations of their answers, and pairs of question paraphrases, yields competitive results on a competitive benchmark of the literature

Short GRBs at the dawn of the gravitational wave era

We derive the luminosity function and redshift distribution of short Gamma Ray Bursts (SGRBs) using (i) all the available observer-frame constraints (i.e. peak flux, fluence, peak energy and duration distributions) of the large population of Fermi SGRBs and (ii) the rest-frame properties of a complete sample of Swift SGRBs. We show that a steep $\phi(L)\propto L^{-a}$ with a>2.0 is excluded if the full set of constraints is considered. We implement a Monte Carlo Markov Chain method to derive the $\phi(L)$ and $\psi(z)$ functions assuming intrinsic Ep-Liso and Ep-Eiso correlations or independent distributions of intrinsic peak energy, luminosity and duration. To make our results independent from assumptions on the progenitor (NS-NS binary mergers or other channels) and from uncertainties on the star formation history, we assume a parametric form for the redshift distribution of SGRBs. We find that a relatively flat luminosity function with slope ~0.5 below a characteristic break luminosity ~3$\times10^{52}$ erg/s and a redshift distribution of SGRBs peaking at z~1.5-2 satisfy all our constraints. These results hold also if no Ep-Liso and Ep-Eiso correlations are assumed. We estimate that, within ~200 Mpc (i.e. the design aLIGO range for the detection of GW produced by NS-NS merger events), 0.007-0.03 SGRBs yr$^{-1}$ should be detectable as gamma-ray events. Assuming current estimates of NS-NS merger rates and that all NS-NS mergers lead to a SGRB event, we derive a conservative estimate of the average opening angle of SGRBs: $\theta_{jet}$~3-6 deg. Our luminosity function implies an average luminosity L~1.5$\times 10^{52}$ erg/s, nearly two orders of magnitude higher than previous findings, which greatly enhances the chance of observing SGRB "orphan" afterglows. Efforts should go in the direction of finding and identifying such orphan afterglows as counterparts of GW events.Comment: 13 pages, 5 figures, 2 tables. Accepted for publication in Astronomy & Astrophysics. Figure 5 and angle ranges corrected in revised versio

A Bayesian blind survey for cold molecular gas in the Universe

A new Bayesian method for performing an image domain search for line-emitting galaxies is presented. The method uses both spatial and spectral information to robustly determine the source properties, employing either simple Gaussian, or other physically motivated models whilst using the evidence to determine the probability that the source is real. In this paper, we describe the method, and its application to both a simulated data set, and a blind survey for cold molecular gas using observations of the Hubble Deep Field North taken with the Plateau de Bure Interferometer. We make a total of 6 robust detections in the survey, 5 of which have counterparts in other observing bands. We identify the most secure detections found in a previous investigation, while finding one new probable line source with an optical ID not seen in the previous analysis. This study acts as a pilot application of Bayesian statistics to future searches to be carried out both for low-$J$ CO transitions of high redshift galaxies using the JVLA, and at millimeter wavelengths with ALMA, enabling the inference of robust scientific conclusions about the history of the molecular gas properties of star-forming galaxies in the Universe through cosmic time.Comment: 12 pages, 4 Figures, 5 Table

Push it to the limit: Local Group constraints on high-redshift stellar mass functions for Mstar > 10^5 Msun

We constrain the evolution of the galaxy stellar mass function from 2 < z < 5 for galaxies with stellar masses as low as 10^5 Msun by combining star formation histories of Milky Way satellite galaxies derived from deep Hubble Space Telescope observations with merger trees from the ELVIS suite of N-body simulations. This approach extends our understanding more than two orders of magnitude lower in stellar mass than is currently possible by direct imaging. We find the faint end slopes of the mass functions to be alpha= -1.42(+0.07/-0.05) at z = 2 and alpha = -1.57^(+0.06/-0.06) at z = 5, and show the slope only weakly evolves from z = 5 to z = 0. Our findings are in stark contrast to a number of direct detection studies that suggest slopes as steep as alpha = -1.9 at these epochs. Such a steep slope would result in an order of magnitude too many luminous Milky Way satellites in a mass regime that is observationally complete (Mstar > 2*10^5 Msun at z = 0). The most recent studies from ZFOURGE and CANDELS also suggest flatter faint end slopes that are consistent with our results, but with a lower degree of precision. This work illustrates the strong connections between low and high-z observations when viewed through the lens of LCDM numerical simulations