Pepducin-mediated cardioprotection via β-arrestin-biased β2-adrenergic receptor-specific signaling

Reperfusion as a therapeutic intervention for acute myocardial infarction-induced cardiac injury itself induces further cardiomyocyte death. β-arrestin (βarr)-biased β-adrenergic receptor (βAR) activation promotes survival signaling responses in vitro; thus, we hypothesize that this pathway can mitigate cardiomyocyte death at the time of reperfusion to better preserve function. However, a lack of efficacious βarr-biased orthosteric small molecules has prevented investigation into whether this pathway relays protection against ischemic injury in vivo. We recently demonstrated that the pepducin ICL1-9, a small lipidated peptide fragment designed from the first intracellular loop of β2AR, allosterically engaged pro-survival signaling cascades in a βarr-dependent manner in vitro. Thus, in this study we tested whether ICL1-9 relays cardioprotection against ischemia/reperfusion (I/R)-induced injury in vivo. Methods: Wild-type (WT) C57BL/6, β2AR knockout (KO), βarr1KO and βarr2KO mice received intracardiac injections of either ICL1-9 or a scrambled control pepducin (Scr) at the time of ischemia (30 min) followed by reperfusion for either 24 h, to assess infarct size and cardiomyocyte death, or 4 weeks, to monitor the impact of ICL1-9 on long-term cardiac structure and function. Neonatal rat ventricular myocytes (NRVM) were used to assess the impact of ICL1-9 versus Scr pepducin on cardiomyocyte survival and mitochondrial superoxide formation in response to either serum deprivation or hypoxia/reoxygenation (H/R) in vitro and to investigate the associated mechanism(s). Results: Intramyocardial injection of ICL1-9 at the time of I/R reduced infarct size, cardiomyocyte death and improved cardiac function in a β2AR- and βarr-dependent manner, which led to improved contractile function early and less fibrotic remodeling over time. Mechanistically, ICL1-9 attenuated mitochondrial superoxide production and promoted cardiomyocyte survival in a RhoA/ROCK-dependent manner. RhoA activation could be detected in cardiomyocytes and whole heart up to 24 h post-treatment, demonstrating the stability of ICL1-9 effects on βarr-dependent β2AR signaling. Conclusion: Pepducin-based allosteric modulation of βarr-dependent β2AR signaling represents a novel therapeutic approach to reduce reperfusion-induced cardiac injury and relay long-term cardiac remodeling benefits

The VIMOS-VLT Deep Survey: Dependence of galaxy clustering on stellar mass

We have investigated the dependence of galaxy clustering on their stellar mass at z~1, using the data from the VIMOS-VLT Deep Survey (VVDS). We have measured the projected two-point correlation function of galaxies, wp(rp) for a set of stellar mass selected samples at an effective redshift =0.85. We have control and quantify all effects on galaxy clustering due to the incompleteness of our low mass samples. We find that more massive galaxies are more clustered. When compared to similar results at z~0.1 in the SDSS, we observed no evolution of the projected correlation function for massive galaxies. These objects present a stronger linear bias at z~1 with respect to low mass galaxies. As expected, massive objects at high redshift are found in the highest pics of the dark matter density field.Comment: 4 pages, 2 figures, 43rd Rencontres de Moriond - March 15-22, 2008 - La Thuile (Val d'Aosta, Italy

Comparison of the VIMOS-VLT Deep Survey with the Munich semi-analytical model. II. The colour-density relation up to z=1.5

[Abridged] We perform on galaxy mock catalogues the same colour-density analysis made by Cucciati et al. (2006) on a 5 Mpc/h scale using the VVDS-Deep survey, and compare the results from mocks with observed data. We use mocks with the same flux limits (I=24) as the VVDS (CMOCKS), built using the semi- analytic model by De Lucia & Blaizot (2007) applied to the Millennium Simulation. From CMOCKS, we extracted samples of galaxies mimicking the VVDS observational strategy (OMOCKS). We computed the B-band Luminosity Function LF and the colour-density relation (CDR) in the mocks. We find that the LF in mocks roughly agrees with the observed LF, but at z<0.8 the faint-end slope of the model LF is steeper than the VVDS one. Computing the LF for early and late type galaxies, we show that mocks have an excess of faint early-type and of bright late-type galaxies with respect to data. We find that the CDR in OMOCKS is in excellent agreement with the one in CMOCKS. At z~0.7, the CDR in mocks agrees with the VVDS one (red galaxies reside mainly in high densities). Yet, the strength of the CDR in mocks does not vary within 0.2<z<1.5, while the observed relation flattens with increasing z and possibly inverts at z=1.3. We argue that the lack of evolution in the CDR in mocks is not due only to inaccurate prescriptions for satellite galaxies, but that also the treatment of central galaxies has to be revised. The reversal of the CDR can be explained by wet mergers between young galaxies, producing a starburst event. This should be seen on group scales. A residual of this is found in observations at z=1.5 on larger scales, but not in the mocks, suggesting that the treatment of physical processes affecting satellites and central galaxies in models should be revised.Comment: 15 pages, 12 figures, accepted for publication in A&

The wave nature of biomolecules and fluorofullerenes

We demonstrate quantum interference for tetraphenylporphyrin, the first biomolecule exhibiting wave nature, and for the fluorofullerene C60F48 using a near-field Talbot-Lau interferometer. For the porphyrins, which are distinguished by their low symmetry and their abundant occurence in organic systems, we find the theoretically expected maximal interference contrast and its expected dependence on the de Broglie wavelength. For C60F48 the observed fringe visibility is below the expected value, but the high contrast still provides good evidence for the quantum character of the observed fringe pattern. The fluorofullerenes therefore set the new mark in complexity and mass (1632 amu) for de Broglie wave experiments, exceeding the previous mass record by a factor of two.Comment: 5 pages, 4 figure

The Millimeter- and Submillimeter-Wave Spectrum of Ethylene Oxide (c-C2H4O)

The cyclic molecule ethylene oxide (c-C_2 H_4 O) has recently been detected in the interstellar source Sgr B2N. Previous laboratory work on the rotational spectrum of this molecule extends only to a frequency of 123 GHz. We report here the extension of the laboratory rotational spectrum of this species through the frequency range 262-358 GHz using a new fast scan spectrometer (FASSST). The newly measured lines have been combined with previous data at lower frequencies to form a data set consisting of 662 lines that has been assigned and fitted via a standard semirigid asymmetric top analysis. The spectral constants obtained from the fit have allowed us to predict the frequencies of many additional lines

The Frontier Fields Lens Modeling Comparison Project

Gravitational lensing by clusters of galaxies offers a powerful probe of their structure and mass distribution. Deriving a lens magnification map for a galaxy cluster is a classic inversion problem and many methods have been developed over the past two decades to solve it. Several research groups have developed techniques independently to map the predominantly dark matter distribution in cluster lenses. While these methods have all provided remarkably high precision mass maps, particularly with exquisite imaging data from the Hubble Space Telescope (HST), the reconstructions themselves have never been directly compared. In this paper, we report the results of comparing various independent lens modeling techniques employed by individual research groups in the community. Here we present for the first time a detailed and robust comparison of methodologies for fidelity, accuracy and precision. For this collaborative exercise, the lens modeling community was provided simulated cluster images -- of two clusters Ares and Hera -- that mimic the depth and resolution of the ongoing HST Frontier Fields. The results of the submitted reconstructions with the un-blinded true mass profile of these two clusters are presented here. Parametric, free-form and hybrid techniques have been deployed by the participating groups and we detail the strengths and trade-offs in accuracy and systematics that arise for each methodology. We note in conclusion that lensing reconstruction methods produce reliable mass distributions that enable the use of clusters as extremely valuable astrophysical laboratories and cosmological probes.Comment: 38 pages, 25 figures, submitted to MNRAS, version with full resolution images can be found at http://pico.bo.astro.it/~massimo/papers/FFsims.pd

The bright galaxy population of five medium redshift clusters. I. Color-Magnitude Relation, Blue Fractions and Visual Morphology

Using data of five clusters of galaxies within the redshift range 0.15 $\leq$ z $\leq$ 0.25, imaged with the Nordic Optical Telescope (NOT) in the central $\approx$ 1 Mpc$^2$ in very good seeing conditions, we have performed an exhaustive inspection of their bright galaxy population. That range of redshift, where only a small amount of data with the required resolution and quality is available, is particularly important for the understanding of the formation and evolution of clusters of galaxies. We have inspected the color-magnitude relation (CMR) for those clusters and measured the blue fraction of galaxies in their cores to check for evidence of evolution as found in other works. Moreover, the visual classification of the galaxy morphology has been performed and the morphology-radius relation has been examined We have not found signs of evolution neither in the slope of the CMR nor in the blue fraction of galaxies. A diversity of situations regarding those parameters and in the morphological mixing has been noticed, with two out of five clusters containing a dominant late-type core population. The cluster A1878 stands out as some of its properties differ from those of the other clusters in the sample. No clear signs of evolution appear in our analysis. The data support the view that the morphology and the stellar content of the galaxies in our clusters have been already settled at z $\sim$ 0.2. Only the fraction of interacting galaxies in the clusters appear to be larger than in clusters like Coma although the number of clusters in the sample is small to give a definitive conclusion.Comment: 16 pages, 8 figures, 4 tables, 1 longtable The paper has been already accepted but still not publishe

The VIMOS Public Extragalactic Redshift Survey (VIPERS). Exploring the dependence of the three-point correlation function on stellar mass and luminosity at 0.5<z<1.1

The three-point correlation function (3PCF) is a powerful probe to investigate the clustering of matter in the Universe in a complementary way with respect to lower-order statistics, providing additional information with respect to the two-point correlation function and allowing us to shed light on biasing, nonlinear processes, and deviations from Gaussian statistics. In this paper, we analyse the first data release of the VIMOS Public Extragalactic Redshift Survey (VIPERS), determining the dependence of the three-point correlation function on luminosity and stellar mass at $z=[0.5,1.1]$. We exploit the VIPERS Public Data Release 1, consisting of more than 50,000 galaxies with B-band magnitudes in the range $-21.6\lesssim M_{\rm B}-5\log(h)\lesssim-19.9$ and stellar masses in the range $9.8\lesssim\log(M_\star[h^{-2}\,M_\odot])\lesssim 10.7$. We measure both the connected 3PCF and the reduced 3PCF in redshift space, probing different configurations and scales, in the range $2.5<r\,$[Mpc/h]$<20$. We find a significant dependence of the reduced 3PCF on scales and triangle shapes, with stronger anisotropy at larger scales ($r\sim10$ Mpc/h) and an almost flat trend at smaller scales, $r\sim2.5$ Mpc/h. Massive and luminous galaxies present a larger connected 3PCF, while the reduced 3PCF is remarkably insensitive to magnitude and stellar masses in the range we explored. These trends, already observed at low redshifts, are confirmed for the first time to be still valid up to $z=1.1$, providing support to the hierarchical scenario for which massive and bright systems are expected to be more clustered. The possibility of using the measured 3PCF to provide independent constraints on the linear galaxy bias $b$ has also been explored, showing promising results in agreement with other probes.Comment: 12 pages, 11 figures, 2 tables, accepted for publication in A&

The galaxy-halo connection from a joint lensing, clustering and abundance analysis in the CFHTLenS/VIPERS field

We present new constraints on the relationship between galaxies and their host dark matter halos, measured from the location of the peak of the stellar-to-halo mass ratio (SHMR), up to the most massive galaxy clusters at redshift $z\sim0.8$ and over a volume of nearly 0.1~Gpc$^3$. We use a unique combination of deep observations in the CFHTLenS/VIPERS field from the near-UV to the near-IR, supplemented by $\sim60\,000$ secure spectroscopic redshifts, analysing galaxy clustering, galaxy-galaxy lensing and the stellar mass function. We interpret our measurements within the halo occupation distribution (HOD) framework, separating the contributions from central and satellite galaxies. We find that the SHMR for the central galaxies peaks at $M_{\rm h, peak} = 1.9^{+0.2}_{-0.1}\times10^{12} M_{\odot}$ with an amplitude of $0.025$, which decreases to $\sim0.001$ for massive halos ($M_{\rm h} > 10^{14} M_{\odot}$). Compared to central galaxies only, the total SHMR (including satellites) is boosted by a factor 10 in the high-mass regime (cluster-size halos), a result consistent with cluster analyses from the literature based on fully independent methods. After properly accounting for differences in modelling, we have compared our results with a large number of results from the literature up to $z=1$: we find good general agreement, independently of the method used, within the typical stellar-mass systematic errors at low to intermediate mass (${M}_{\star} < 10^{11} M_{\odot}$) and the statistical errors above. We have also compared our SHMR results to semi-analytic simulations and found that the SHMR is tilted compared to our measurements in such a way that they over- (under-) predict star formation efficiency in central (satellite) galaxies.Comment: 31 pages, 18 figures, 4 table. Accepted for publication in MNRAS. Online material available at http://www.cfhtlens.or