A novel cyclosporin a aqueous formulation for dry eye treatment: in vitro and in vivo evaluation.

PURPOSE: The aim of the present study was the in vitro and in vivo evaluation of a novel aqueous formulation based on polymeric micelles for the topical delivery of cyclosporine A for dry eye treatment. METHODS: In vitro experiments were carried out on primary rabbit corneal cells, which were characterized by immunocytochemistry using fluorescein-labeled lectin I/isolectin B4 for the endothelial cells and mouse monoclonal antibody to cytokeratin 3+12 for the epithelial ones. Living cells were incubated for 1 hour or 24 hours with a fluorescently labeled micelle formulation and analyzed by fluorescence microscopy. In vivo evaluations were done by Schirmer test, osmolarity measurement, CyA kinetics in tears, and CyA ocular distribution after topical instillation. A 0.05% CyA micelle formulation was compared to a marketed emulsion (Restasis). RESULTS: The in vitro experiments showed the internalization of micelles in the living cells. The Schirmer test and osmolarity measurements demonstrated that micelles did not alter the ocular surface properties. The evaluation of the tear fluid gave similar CyA kinetics values: AUC = 2339 ± 1032 min*μg/mL and 2321 ± 881.63; Cmax = 478 ± 111 μg/mL and 451 ± 74; half-life = 36 ± 9 min and 28 ± 9 for the micelle formulation and Restasis, respectively. The ocular distribution investigation revealed that the novel formulation delivered 1540 ± 400 ng CyA/g tissue to the cornea. CONCLUSIONS: The micelle formulation delivered active CyA into the cornea without evident negative influence on the ocular surface properties. This formulation could be applied for immune-related ocular surface diseases

The coronal line regions of planetary nebulae NGC6302 and NGC6537: 3-13um grating and echelle spectroscopy

We report on advances in the study of the cores of NGC6302 and NGC6537 using infrared grating and echelle spectroscopy. In NGC6302, emission lines from species spanning a large range of ionization potential, and in particular [SiIX]3.934um, are interpreted using photoionization models (including CLOUDY), which allow us to reestimate the central star's temperature to be about 250000K. All of the detected lines are consistent with this value, except for [AlV] and [AlVI]. Aluminium is found to be depleted to one hundredth of the solar abundance, which provides further evidence for some dust being mixed with the highly ionized gas (with photons harder than 154eV). A similar depletion pattern is observed in NGC6537. Echelle spectroscopy of IR coronal ions in NGC6302 reveals a stratified structure in ionization potential, which confirms photoionization to be the dominant ionization mechanism. The lines are narrow (< 22km/s FWHM), with no evidence of the broad wings found in optical lines from species with similar ionization potentials, such as [NeV]3426A. We note the absence of a hot bubble, or a wind blown bipolar cavity filled with a hot plasma, at least on 1'' and 10km/s scales. We also provide accurate new wavelengths for several of the infrared coronal lines observed with the echelle.Comment: Accepted for publication in MNRA

The Chemical Composition of the 30 Doradus Nebula Derived from VLT Echelle Spectrophotometry

Echelle spectrophotometry of the 30 Doradus nebula in the LMC is presented. The data consists of VLT UVES observations in the 3100 to 10350 A range. The intensities of 366 emission lines have been measured, including 269 identified permitted lines of H 0, He 0, C 0, C+, N+, N++, O 0, O+, Ne 0, Ne+, S+, S++, Si 0 , Si+, Si++, Ar+, and Mg+. Electron temperatures and densities have been determined using different line intensity ratios. The He+, C++, O+, and O++ ionic abundances have been derived from recombination lines, these abundances are almost independent of the temperature structure of the nebula. Alternatively abundances from collisionally excited lines have been derived for a large number of ions of different elements, these abundances depend strongly on the temperature structure. Accurate t^2 values have been derived from the Balmer continuum, and by comparing the C++, O+, and O++ ionic abundances obtained from collisionally excited and recombination lines. The chemical composition of 30 Doradus is compared with those of Galactic and extragalactic HII regions. The values of Delta Y / Delta O, Delta Y / Delta Z, and Yp are also discussed.Comment: 37 pages, 2 figures, submitted to the Astrophysical Journa

Fermi Discovery of Gamma-Ray Emission from NGC 1275

We report the discovery of high-energy (E>100 MeV) gamma-ray emission from NGC 1275, a giant elliptical galaxy lying at the center of the Perseus cluster of galaxies, based on observations made with the Large Area Telescope (LAT) of the Fermi Gamma ray Space Telescope. The positional center of the gamma-ray source is only ~3' away from the NGC 1275 nucleus, well within the 95% LAT error circle of ~5'.The spatial distribution of gamma-ray photons is consistent with a point source. The average flux and power-law photon index measured with the LAT from 2008 August 4 to 2008 December 5 are F_gamma = (2.10+-0.23)x 10^{-7} ph (>100 MeV) cm^{-2} s^{-1} and Gamma = 2.17+-0.05, respectively. The measurements are statistically consistent with constant flux during the four-month LAT observing period.Previous EGRET observations gave an upper limit of F_gamma 100 MeV) cm^{-2} s^{-1} to the gamma-ray flux from NGC 1275. This indicates that the source is variable on timescales of years to decades, and therefore restricts the fraction of emission that can be produced in extended regions of the galaxy cluster. Contemporaneous and historical radio observations are also reported. The broadband spectrum of NGC 1275 is modeled with a simple one-zone synchrotron/synchrotron self-Compton model and a model with a decelerating jet flow.Comment: 27 pages, 7 figures, Accepted for publication in the Astrophysical Journa

A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279

It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight. The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and gamma-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10^5 gravitational radii.Comment: Published in Nature issued on 18 February 2010. Corresponding authors: Masaaki Hayashida and Greg Madejsk

The Spectral Energy Distribution of Fermi bright blazars

(Abridged) We have conducted a detailed investigation of the broad-band spectral properties of the \gamma-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi gamma-ray spectra with Swift, radio, infra-red, optical and other hard X-ray/gamma-ray data, collected within three months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous Spectral Energy Distributions (SED) for 48 LBAS blazars.The SED of these gamma-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual Log $\nu$ - Log $\nu$ F$_\nu$ representation, the typical broad-band spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SEDs to characterize the peak intensity of both the low and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broad-band colors (i.e. the radio to optical and optical to X-ray spectral slopes) and from the gamma-ray spectral index. Our data show that the synchrotron peak frequency $\nu_p^S$ is positioned between 10$^{12.5}$ and 10$^{14.5}$ Hz in broad-lined FSRQs and between $10^{13}$ and $10^{17}$ Hz in featureless BL Lacertae objects.We find that the gamma-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron - inverse Compton scenarios. However, simple homogeneous, one-zone, Synchrotron Self Compton (SSC) models cannot explain most of our SEDs, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. (...)Comment: 85 pages, 38 figures, submitted to Ap

The 2009 multiwavelength campaign on Mrk 421: Variability and correlation studies

We performed a 4.5-month multi-instrument campaign (from radio to VHE gamma rays) on Mrk421 between January 2009 and June 2009, which included VLBA, F-GAMMA, GASP-WEBT, Swift, RXTE, Fermi-LAT, MAGIC, and Whipple, among other instruments and collaborations. Mrk421 was found in its typical (non-flaring) activity state, with a VHE flux of about half that of the Crab Nebula, yet the light curves show significant variability at all wavelengths, the highest variability being in the X-rays. We determined the power spectral densities (PSD) at most wavelengths and found that all PSDs can be described by power-laws without a break, and with indices consistent with pink/red-noise behavior. We observed a harder-when-brighter behavior in the X-ray spectra and measured a positive correlation between VHE and X-ray fluxes with zero time lag. Such characteristics have been reported many times during flaring activity, but here they are reported for the first time in the non-flaring state. We also observed an overall anti-correlation between optical/UV and X-rays extending over the duration of the campaign. The harder-when-brighter behavior in the X-ray spectra and the measured positive X-ray/VHE correlation during the 2009 multi-wavelength campaign suggests that the physical processes dominating the emission during non-flaring states have similarities with those occurring during flaring activity. In particular, this observation supports leptonic scenarios as being responsible for the emission of Mrk421 during non-flaring activity. Such a temporally extended X-ray/VHE correlation is not driven by any single flaring event, and hence is difficult to explain within the standard hadronic scenarios. The highest variability is observed in the X-ray band, which, within the one-zone synchrotron self-Compton scenario, indicates that the electron energy distribution is most variable at the highest energies.Comment: Accepted for publication in A&A, 18 pages, 14 figures (v2 has a small modification in the acknowledgments, and also corrects a typo in the field "author" in the metadata

PKS 1502+106: a new and distant gamma-ray blazar in outburst discovered by the Fermi Large Area Telescope

The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope discovered a rapid (about 5 days duration), high-energy (E >100 MeV) gamma-ray outburst from a source identified with the blazar PKS 1502+106 (OR 103, S3 1502+10, z=1.839) starting on August 05, 2008 and followed by bright and variable flux over the next few months. Results on the gamma-ray localization and identification, as well as spectral and temporal behavior during the first months of the Fermi all-sky survey are reported here in conjunction with a multi-waveband characterization as a result of one of the first Fermi multi-frequency campaigns. The campaign included a Swift ToO (followed up by 16-day observations on August 07-22, MJD 54685-54700), VLBA (within the MOJAVE program), Owens Valley (OVRO) 40m, Effelsberg-100m, Metsahovi-14m, RATAN-600 and Kanata-Hiroshima radio/optical observations. Results from the analysis of archival observations by INTEGRAL, XMM-Newton and Spitzer space telescopes are reported for a more complete picture of this new gamma-ray blazar.Comment: 17 pages, 11 figures, accepted for The Astrophysical Journa

Supermassive black holes, pseudobulges, and the narrow-line Seyfert 1 galaxies

We present HST/ACS observations of ten galaxies that host narrow-line Seyfert 1 (NLS1) nuclei, believed to contain relatively smaller mass black holes accreting at high Eddington ratios. We deconvolve each ACS image into a nuclear point source (AGN), a bulge, and a disk, and fitted the bulge with a Sersic profile and the disk with an exponential profile. We find that at least five galaxies can be classified as having pseudobulges. All ten galaxies lie below the \mbh--L$_{bulge}$ relation, confirming earlier results. Their locus is similar to that occupied by pseudobulges. This leads us to conclude that the growth of BHs in NLS1s is governed by secular processes rather than merger-driven. Active galaxies in pseudobulges point to an alternative track of black hole--galaxy co-evolution. Because of the intrinsic scatter in black hole mass--bulge properties scaling relations caused by a combination of factors such as the galaxy morphology, orientation, and redshift evolution, application of scaling relations to determine BH masses may not be as straightforward as has been hoped.Comment: Replaced with accepted versio

Coordinated Multiwavelength Observations of BL Lacertae in 2000

BL Lacertae was the target of an extensive multiwavelength monitoring campaign in the second half of 2000. Simultaneous or quasi-simultaneous observations were taken at radio (UMRAO and Metsaehovi) and optical(WEBT collaboration) frequencies, in X-rays (BeppoSAX and RXTE), and at VHE gamma-rays (HEGRA). The WEBT optical campaign achieved an unprecedented time coverage, virtually continuous over several 10 - 20 hour segments. It revealed intraday variability on time scales of ~ 1.5 hours and evidence for spectral hardening associated with increasing optical flux. During the campaign, BL Lacertae underwent a major transition from a rather quiescent state prior to September 2000, to a flaring state for the rest of the year. This was also evident in the X-ray activity of the source. BeppoSAX observations on July 26/27 revealed a rather low X-ray flux and a hard spectrum, while a BeppoSAX pointing on Oct. 31 - Nov. 2, 2000, indicated significant variability on time scales of < a few hours, and provided evidence for the synchrotron spectrum extending out to ~ 10 keV during that time. During the July 26/27 observation, there is a tantalizing, though not statistically significant, indication of a time delay of ~ 4 - 5 hr between the BeppoSAX and the R-band light curve. Also, a low-significance detection of a time delay of 15 d between the 14.5 GHz and the 22 GHz radio light curves is reported. Several independent methods to estimate the co-moving magnetic field in the source are presented, suggesting a value of ~ 2 e_B^{2/7} G, where e_B is the magnetic-field equipartition factor w.r.t. the electron energy density in the jet.Comment: Accepted for publication in Ap