Sintesi e studi <i>SAR</i> di nuove piattaforme tricicliche a struttura pirazolo-isochinolinica e pirazolo-naftiridinica come inibitori dell’enzima fosfodiesterasi 10A (<i>PDE10A</i>)

A new class of pyrazolo[5,1-a]isoquinolines, pyrazolo[5,1-f][1,6]naphthyridines, pyrazolo[5,1-a][2,6]naphthyridines, pyrazolo[5,1-a][2,7]naphthyridines and pyrazolo[1,5-h][1,7]naphthyridines were designed as bioisosteres of pyrazolo[1,5-c]quinazolines, described as potent inhibitors of PDE10A enzyme. In fact, bioisosteric modifications of the tricyclic core of the above known molecules might offer new templates that could provide optimized interactions with the PDE10A enzyme and desiderable pharmacokinetic properties. This work allowed to synthesize a small library of compounds incorporating a bi-substituted tricyclic pyrazole-based platform. A reproducible and efficient one-pot synthesis was achieved for the above-mentioned compounds

Intravitreal Dexamethasone in Patients with Wet Age-Related Macular Degeneration Resistant to Anti-VEGF: A Prospective Pilot Study

Purpose. To evaluate the efficacy and safety of a single intravitreal dexamethasone implant (DXI) combined with intravitreal antivascular endothelial growth factor (anti-VEGF) therapy, in patients with neovascular age-related macular degeneration (wet-AMD) resistant to conventional treatment. Methods. In this randomized, controlled pilot study, 16 eyes of 15 patients, unresponsive to anti-VEGF therapy, were enrolled and randomly assigned to two groups: DXI + anti-VEGF (treatment group: 11 eyes) and monthly anti-VEGF alone (control group: 5 eyes). Patients were treated at baseline and followed for 6 months. Best corrected visual acuity (BCVA), optical coherence tomography (OCT) parameters, and fluorescein angiography (FA) were evaluated. Results. Eight eyes (72.7%) in the treatment group and 2 eyes in the control group (40%) showed complete retinal fluid resorption (p=0.049). BCVA showed no significant change from baseline in both the treatment group and the control group (p=0.40 and p=0.29, respectively). Both median central foveal thickness (CFT) and median macular volume showed a greater reduction from baseline in the treatment group. Conclusion. In patients showing an incomplete response to anti-VEGF therapy, DXI combined with intravitreal anti-VEGF seems to improve retinal fluid resorption without functional advantage. This trial is registered with ACTRN12618001102268

Precursors of the RNA-world in space: Detection of (ZZ)-1,2-ethenediol in the interstellar medium, a key intermediate in sugar formation

We present the first detection of ($Z$)-1,2-ethenediol, (CHOH)$_2$, the enol form of glycolaldehyde, in the interstellar medium towards the G+0.693-0.027 molecular cloud located in the Galactic Center. We have derived a column density of (1.8$\pm$0.1)$\times$10$^{13}$ cm$^{-2}$, which translates into a molecular abundance with respect to molecular hydrogen of 1.3$\times$10$^{-10}$. The abundance ratio between glycolaldehyde and ($Z$)-1,2-ethenediol is $\sim$5.2. We discuss several viable formation routes through chemical reactions from precursors such as HCO, H$_2$CO, CHOH or CH$_2$CHOH. We also propose that this species might be an important precursor in the formation of glyceraldehyde (HOCH$_2$CHOHCHO) in the interstellar medium through combination with the hydroxymethylene (CHOH) radical.Comment: Accepted for publication in The Astrophysical Journal Letter

Parameterizing the Effect of Dark Energy Perturbations on the Growth of Structures

We present an analytical fit to the growth function of the dark matter perturbations when dark energy perturbations are present. The growth index depends upon the dark energy equation of state w, the speed of sound of the dark energy fluctuations, the dark matter abundance and the observed comoving scale. The growth index changes by ~5% for small speed of sound and large deviations of w from -1 with respect to its value in the limit of no dark energy perturbations.Comment: 18 LaTex pages, 7 figures. Typo correcte

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed

Ocean acidification along the 24.5°N section in the subtropical North Atlantic

9 páginas, 4 figuras.-- Proyecto CarbochangeOcean acidification is directly related to increasing atmospheric CO2 levels due to human activities and the active role of the global ocean in absorbing part of this anthropogenic CO2. Here we present an assessment of the pH changes that have occurred along 24.5°N in the subtropical North Atlantic through comparison of pH observations conducted in 1992 and 2011. It reveals an overall decline in pH values in the first 1000 dbar of the water column. The deconvolution of the temporal pH differences into anthropogenic and nonanthropogenic components reveals that natural variability, mostly owed to a decrease in oxygen levels in particular regions of the section, explains the vertical distribution of the larger pH decreases (up to −0.05 pH units), which are found within the permanent thermocline. The detection of long-term trends in dissolved oxygen in the studied region gains importance for future pH projections, as these changes modulate the anthropogenically derived acidification. The anthropogenic forcing explains significant acidification deeper than 1000 dbar in the western basin, within the Deep Western Boundary Current.We acknowledge funding from the Spanish Ministry of Economy and Competitiveness through grants CSD2008-00077 (Circumnavigation Expedition MALASPINA 2010 Project), CTM2009-08849 (ACDC Project), and CTM2012-32017 (MANIFEST Project) and from the Seventh Framework Programme FP7 CARBOCHANGE (grant agreement 264879). E.F. Guallart was funded by CSIC through a JAE-Pre grant.Peer reviewe