Targeting kinases with anilinopyrimidines: Discovery of N-phenyl-N'-[4-(pyrimidin-4-ylamino)phenyl]urea derivatives as selective inhibitors of class III receptor tyrosine kinase subfamily

Kinase inhibitors are attractive drugs/drug candidates for the treatment of cancer. The most recent literature has highlighted the importance of multi target kinase inhibitors, although a correct balance between specificity and non-specificity is required. In this view, the discovery of multityrosine kinase inhibitors with subfamily selectivity is a challenging goal. Herein we present the synthesis and the preliminary kinase profiling of a set of novel 4-anilinopyrimidines. Among the synthesized compounds, the N-phenyl-N\u2019-[4-(pyrimidin-4-ylamino)phenyl]urea derivatives selectively targeted some members of class III receptor tyrosine kinase family. Starting from the structure of hit compound 19 we synthesized a further compound with an improved affinity toward the class III receptor tyrosine kinase members and endowed with a promising antitumor activity both in vitro and in vivo in a murine solid tumor model. Molecular modeling simulations were used in order to rationalize the behavior of the title compounds

The Next Generation Virgo Cluster Survey XVI. The Angular Momentum of Dwarf Early-Type Galaxies from Globular Cluster Satellites

We analyze the kinematics of six Virgo cluster dwarf early-type galaxies (dEs) from their globular cluster (GC) systems. We present new Keck/DEIMOS spectroscopy for three of them and reanalyze the data found in the literature for the remaining three. We use two independent methods to estimate the rotation amplitude (Vmax) and velocity dispersion (sigma_GC) of the GC systems and evaluate their statistical significance by simulating non-rotating GC systems with the same number of GC satellites and velocity uncertainties. Our measured kinematics agree with the published values for the three galaxies from the literature and, in all cases, some rotation is measured. However, our simulations show that the null hypothesis of being non-rotating GC systems cannot be ruled out. In the case of VCC1861, the measured Vmax and the simulations indicate that it is not rotating. In the case of VCC1528, the null hypothesis can be marginally ruled out, thus, it might be rotating although further confirmation is needed. In our analysis, we find that, in general, the measured Vmax tends to be overestimated and the measured sigma_GC tends to be underestimated by amounts that depend on the intrinsic Vmax/sigma_GC, the number of observed GCs (N_GC), and the velocity uncertainties. The bias is negligible when N_GC>~20. In those cases where a large N_GC is not available, it is imperative to obtain data with small velocity uncertainties. For instance, errors of <2km/s lead to Vmax<10km/s for a system that is intrinsically not rotating.Comment: ApJ in press. 20 pages, 17 figures, 5 table

The GALEX Ultraviolet Virgo Cluster Survey (GUViCS) III. The Ultraviolet Source Catalogs

In this paper we introduce the deepest and most extensive ultraviolet extragalactic source catalogs of the Virgo Cluster area to date. Archival and targeted GALEX imaging is compiled and combined to provide the deepest possible coverage over ~120 deg^2 in the NUV (lambda_eff=2316 angstroms) and ~40 deg^2 in the FUV (lambda_eff=1539 angstroms) between 180 deg <= R.A. <= 195 deg and 0 deg <= Decl. <= 20 deg. We measure the integrated photometry of 1770 extended UV sources of all galaxy types and use GALEX pipeline photometry for 1,230,855 point-like sources in the foreground, within, and behind the cluster. Extended source magnitudes are reliable to m_UV ~22, showing ~0.01 sigma difference from their asymptotic magnitudes. Point-like source magnitudes have a 1 sigma standard deviation within ~0.2 mag down to m_uv ~23. The point-like source catalog is cross-matched with large optical databases and surveys including the SDSS DR9 (> 1 million Virgo Cluster sources), the Next Generation Virgo Cluster Survey (NGVS; >13 million Virgo Cluster sources), and the NED (~30,000 sources in the Virgo Cluster). We find 69% of the entire UV point-like source catalog has a unique optical counterpart, 11% of which are stars and 129 are Virgo cluster members neither in the VCC nor part of the bright CGCG galaxy catalog (i.e., m_pg < 14.5). These data are collected in four catalogs containing the UV extended sources, the UV point-like sources, and two catalogs each containing the most relevant optical parameters of UV-optically matched point-like sources for further studies from SDSS and NGVS. The GUViCS catalogs provide a unique set of data for future works on UV and multiwavelength studies in the cluster and background environments.Comment: 35 pages, 24 figures, 15 tables, Accepted for publication in A&

Transabdominal pre-peritoneal mesh in inguinal hernia repair in elderly: end point of our experience

BACKGROUND: Aim of this study is to present our standardized laparoscopic transabdominal preperitoneal hernia repair (TAPP) technique, and to study our experience in the elderly as far as concerns preoperative and postoperative variables. METHODS: We described our standardized TAPP technique according with Stuttgart technique [1], and we evalutated our team's experience in TAPP inguinal hernia repair in elderly (> 65 yrs) and in young patients (< 65 yrs). RESULTS: We retrospectively reviewed our Surgery Division's experience about TAPP; we included in our study 185 patients. The sample was subdivided in two groups: TAPP Group (< 65 years patients) and TAPPe Group (> 65 years patients). TAPP Group was composed by 154 patients and TAPPe Group of 31 patients. According with literature, in this subgroup recurrence rate (3,2%), early and delayed complications and mean operative time (86 min). There were no major vascular or intestinal complications. At the moment follow-up is 31 months. There were no incisional hernias on umbilical trocar. Mean satisfaction rate was excellent also in elderly patients. CONCLUSIONS: According with literature, in our experience TAPP technique is a safe and feasible procedure, even in elderly patients

Selection bias in dynamically measured supermassive black hole samples : its consequences and the quest for the most fundamental relation

We compare the set of local galaxies having dynamically measured black holes with a large, unbiased sample of galaxies extracted from the Sloan Digital Sky Survey. We confirm earlier work showing that the majority of black hole hosts have significantly higher velocity dispersions sigma than local galaxies of similar stellar mass. We use Monte Carlo simulations to illustrate the effect on black hole scaling relations if this bias arises from the requirement that the black hole sphere of influence must be resolved to measure black hole masses with spatially resolved kinematics. We find that this selection effect artificially increases the normalization of the M-bh-sigma relation by a factor of at least similar to 3; the bias for the M-bh-M-star relation is even larger. Our Monte Carlo simulations and analysis of the residuals from scaling relations both indicate that sigma is more fundamental than M-star or effective radius. In particular, the M-bh-M-star relation is mostly a consequence of the M-bh-sigma and sigma-M-star relations, and is heavily biased by up to a factor of 50 at small masses. This helps resolve the discrepancy between dynamically based black hole-galaxy scaling relations versus those of active galaxies. Our simulations also disfavour broad distributions of black hole masses at fixed sigma. Correcting for this bias suggests that the calibration factor used to estimate black hole masses in active galaxies should be reduced to values of f(vir) similar to 1. Black hole mass densities should also be proportionally smaller, perhaps implying significantly higher radiative efficiencies/black hole spins. Reducing black hole masses also reduces the gravitational wave signal expected from black hole mergers.Peer reviewe

The Next Generation Virgo Cluster Survey. X. Properties of Ultra-Compact Dwarfs in the M87, M49 and M60 Regions

We use imaging from the Next Generation Virgo cluster Survey (NGVS) to present a comparative study of ultra-compact dwarf (UCD) galaxies associated with three prominent Virgo sub-clusters: those centered on the massive, red-sequence galaxies M87, M49 and M60. We show how UCDs can be selected with high completeness using a combination of half-light radius and location in color-color diagrams ($u^*iK_s$ or $u^*gz$). Although the central galaxies in each of these sub-clusters have nearly identical luminosities and stellar masses, we find large differences in the sizes of their UCD populations, with M87 containing ~3.5 and 7.8 times more UCDs than M49 and M60, respectively. The relative abundance of UCDs in the three regions scales in proportion to sub-cluster mass, as traced by X-ray gas mass, total gravitating mass, number of globular clusters, and number of nearby galaxies. We find that the UCDs are predominantly blue in color, with ~85% of the UCDs having colors similar to blue GCs and stellar nuclei of dwarf galaxies. We present evidence that UCDs surrounding M87 and M49 may follow a morphological sequence ordered by the prominence of their outer, low surface brightness envelope, ultimately merging with the sequence of nucleated low-mass galaxies, and that envelope prominence correlates with distance from either galaxy. Our analysis provides evidence that tidal stripping of nucleated galaxies is an important process in the formation of UCDs.Comment: 37 pages, 40 figures. To appear in The Astrophysical Journa

The Next Generation Virgo Cluster Survey. VIII. The Spatial Distribution of Globular Clusters in the Virgo Cluster

We report on a large-scale study of the distribution of globular clusters (GCs) throughout the Virgo cluster, based on photometry from the Next Generation Virgo Cluster Survey, a large imaging survey covering Virgo's primary subclusters to their virial radii. Using the g', (g'-i') color-magnitude diagram of unresolved and marginally-resolved sources, we constructed 2-D maps of the GC distribution. We present the clearest evidence to date showing the difference in concentration between red and blue GCs over the extent of the cluster, where the red (metal-rich) GCs are largely located around the massive early-type galaxies, whilst the blue (metal-poor) GCs have a more extended spatial distribution, with significant populations present beyond 83' (215 kpc) along the major axes of M49 and M87. The GC distribution around M87 and M49 shows remarkable agreement with the shape, ellipticity and boxiness of the diffuse light surrounding both galaxies. We find evidence for spatial enhancements of GCs surrounding M87 that may be indicative of recent interactions or an ongoing merger history. We compare the GC map to the locations of Virgo galaxies and the intracluster X-ray gas, and find good agreement between these baryonic structures. The Virgo cluster contains a total population of 67300$\pm$14400 GCs, of which 35% are located in M87 and M49 alone. We compute a cluster-wide specific frequency S_N,CL=$2.8\pm0.7$, including Virgo's diffuse light. The GC-to-baryonic mass fraction is e_b=$5.7\pm1.1\times10^{-4}$and the GC-to-total cluster mass formation efficiency is e_t=$2.9\pm0.5\times10^{-5}$, values slightly lower than, but consistent with, those derived for individual galactic halos. Our results show that the production of the complex structures in the unrelaxed Virgo cluster core (including the diffuse intracluster light) is an ongoing process.(abridged)Comment: 23 pages, 17 figures. Accepted for publication in the Astrophysical Journal. Figure 1 has reduced resolution. Revised version with updated references, corrected typos -- no changes to result