High Energy gamma-rays From FR I Jets

Thanks to Hubble and Chandra telescopes, some of the large scale jets in extragalactic radio sources are now being observed at optical and X-ray frequencies. For the FR I objects the synchrotron nature of this emission is surely established, although a lot of uncertainties - connected for example with the particle acceleration processes involved - remain. In this paper we study production of high energy gamma-rays in FR I kiloparsec-scale jets by inverse-Compton emission of the synchrotron-emitting electrons. We consider different origin of seed photons contributing to the inverse-Compton scattering, including nuclear jet radiation as well as ambient, stellar and circumstellar emission of the host galaxies. We discuss how future detections or non-detections of the evaluated gamma-ray fluxes can provide constraints on the unknown large scale jet parameters, i.e. the magnetic field intensity and the jet Doppler factor. For the nearby sources Centaurus A and M 87, we find measurable fluxes of TeV photons resulting from synchrotron self-Compton process and from comptonisation of the galactic photon fields, respectively. In the case of Centaurus A, we also find a relatively strong emission component due to comptonisation of the nuclear blazar photons, which could be easily observed by GLAST at energy ~10 GeV, providing important test for the unification of FR I sources with BL Lac objects.Comment: 39 pages, 6 figures included. Modified version, accepted for publication in Astrophysical Journa

Spectropolarimetry of the 3.4 micron absorption feature in NGC 1068

In order to test the silicate-core/organic-mantle model of galactic interstellar dust, we have performed spectropolarimetry of the 3.4 micron C-H bond stretch that is characteristic of aliphatic hydrocarbons, using the nucleus of the Seyfert 2 galaxy, NGC 1068, as a bright, dusty background source. Polarization calculations show that, if the grains in NGC 1068 had the properties assigned by the core-mantle model to dust in the galactic diffuse ISM, they would cause a detectable rise in polarization over the 3.4 micron feature. No such increase is observed. We discuss modifications to the basic core-mantle model, such as changes in grain size or the existence of additional non-hydrocarbon aligned grain populations, which could better fit the observational evidence. However, we emphasize that the absence of polarization over the 3.4 micron band in NGC 1068 - and, indeed, in every line of sight examined to date - can be readily explained by a population of small, unaligned carbonaceous grains with no physical connection to the silicates.Comment: ApJ, accepte

Synthesis of Carboxamides Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors for AML

Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues containing a carboxamide at the 4-position of the aryl ring and novel carbamates. These compounds were potent submicromolar LSD1 inhibitors in enzyme assays and were anti-proliferative against a panel of AML cell lines. LSD1 target engagement in cells was demonstrated through the effects on H3K4me2 protein expression, CD86, CD11b and CD14 levels

T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice.

Chronic lymphocytic leukaemia (CLL) cells require microenvironmental support for their proliferation. This can be recapitulated in highly immunocompromised hosts in the presence of T cells and other supporting cells. Current primary CLL xenograft models suffer from limited duration of tumour cell engraftment coupled with gradual T-cell outgrowth. Thus, a greater understanding of the interaction between CLL and T cells could improve their utility. In this study, using two distinct mouse xenograft models, we investigated whether xenografts recapitulate CLL biology, including natural environmental interactions with B-cell receptors and T cells, and whether manipulation of autologous T cells can expand the duration of CLL engraftment. We observed that primary CLL xenografts recapitulated both the tumour phenotype and T-cell repertoire observed in patients and that engraftment was significantly shorter for progressive tumours. A reduction in the number of patient T cells that were injected into the mice to 2-5% of the initial number or specific depletion of CD8+ cells extended the limited xenograft duration of progressive cases to that characteristic of indolent disease. We conclude that manipulation of T cells can enhance current CLL xenograft models and thus expand their utility for investigation of tumour biology and pre-clinical drug assessment

Unveiling the Active Nucleus of Centaurus A

We report new HST WFPC2 and NICMOS observations of the center of the nearest radio galaxy Centaurus A (NGC 5128) and discuss their implications for our understanding of the active nucleus and jet. We detect the active nucleus in the near-IR (K and H) and, for the first time, in the optical (I and V), deriving the spectral energy distribution of the nucleus from the radio to X-rays. The optical and part of the near-IR emission can be explained by the extrapolation of the X-ray power law reddened by A_V~14mag, a value consistent with other independent estimates. The 20pc-scale nuclear disk discovered by Schreier et al. (1998) is detected in the [FeII] 1.64mic line and presents a morphology similar to that observed in Pa alpha with a [FeII]/Pa alpha ratio typical of low ionization Seyfert galaxies and LINERs. NICMOS 3 Pa alpha observations in a 50"x50" circumnuclear region suggest enhanced star formation (~0.3Msun/yr) at the edges of the putative bar seen with ISO, perhaps due to shocks driven into the gas. The light profile, reconstructed from V, H and K observations, shows that Centaurus A has a core profile with a resolved break at ~4" and suggests a black--hole mass of ~10^9 Msun. A linear blue structure aligned with the radio/X-ray jet may indicate a channel of relatively low reddening in which dust has been swept away by the jet.Comment: 19 pages, 13 figures, Astrophysical Journal, in press. High quality figures available at http://www.arcetri.astro.it/~marconi/colpic.htm

Resolving the complex structure of the dust torus in the active nucleus of the Circinus galaxy

To test the dust torus model for active galactic nuclei directly, we study the extent and morphology of the nuclear dust distribution in the Circinus galaxy using high resolution interferometric observations in the mid-infrared with the MIDI instrument at the Very Large Telescope Interferometer. We find that the dust distribution in the nucleus of Circinus can be explained by two components, a dense and warm disk-like component of 0.4 pc size and a slightly cooler, geometrically thick torus component with a size of 2.0 pc. The disk component is oriented perpendicular to the ionisation cone and outflow and seems to show the silicate feature at 10 micron in emission. It coincides with a nuclear maser disk in orientation and size. From the energy needed to heat the dust, we infer a luminosity of the accretion disk corresponding to 20% of the Eddington luminosity of the nuclear black hole. We find that the interferometric data are inconsistent with a simple, smooth and axisymmetric dust emission. The irregular behaviour of the visibilities and the shallow decrease of the dust temperature with radius provide strong evidence for a clumpy or filamentary dust structure. We see no evidence for dust reprocessing, as the silicate absorption profile is consistent with that of standard galactic dust. We argue that the collimation of the ionising radiation must originate in the geometrically thick torus component. Our findings confirm the presence of a geometrically thick, torus-like dust distribution in the nucleus of Circinus, as required in unified schemes of Seyfert galaxies. Several aspects of our data require that this torus is irregular, or "clumpy".Comment: 20 pages, 16 figures, accepted for publication by A&

Resolved Mid-IR Emission in the Narrow Line Region of NGC 4151

We present subarcsecond resolution mid infrared images of NGC 4151 at 10.8 micron and 18.2 micron. These images were taken with the University of Florida mid-IR camera/spectrometer OSCIR at the Gemini North 8-m telescope. We resolve emission at both 10.8 micron and 18.2 micron extending ~ 3.5" across at a P.A. of ~ 60 degrees. This coincides with the the narrow line region of NGC 4151 as observed in [OIII] by the Hubble Space Telescope. The most likely explanation for this extended mid-IR emission is dust in the narrow line region heated by a central engine. We find no extended emission associated with the proposed torus and place an upper limit on its mid-IR size of less than or equal to ~ 35 pc.Comment: accepted for publication in the Astrophysical Journal, 19 pages including 5 figure

Tracing PAHs and Warm Dust Emission in the Seyfert Galaxy NGC 1068

We present a study of the nearby Seyfert galaxy NGC 1068 using mid- and far- infrared data acquired with the IRAC, IRS, and MIPS instruments aboard the Spitzer Space Telescope. The images show extensive 8 um and 24 um emission coinciding with star formation in the inner spiral approximately 15" (1 kpc) from the nucleus, and a bright complex of star formation 47" (3 kpc) SW of the nucleus. The brightest 8 um PAH emission regions coincide remarkably well with knots observed in an Halpha image. Strong PAH features at 6.2, 7.7, 8.6, and 11.3 um are detected in IRS spectra measured at numerous locations inside, within, and outside the inner spiral. The IRAC colors and IRS spectra of these regions rule out dust heated by the AGN as the primary emission source; the SEDs are dominated by starlight and PAH emission. The equivalent widths and flux ratios of the PAH features in the inner spiral are generally consistent with conditions in a typical spiral galaxy ISM. Interior to the inner spiral, the influence of the AGN on the ISM is evident via PAH flux ratios indicative of a higher ionization parameter and a significantly smaller mean equivalent width than observed in the inner spiral. The brightest 8 and 24 um emission peaks in the disk of the galaxy, even at distances beyond the inner spiral, are located within the ionization cones traced by [O III]/Hbeta, and they are also remarkably well aligned with the axis of the radio jets. Although it is possible that radiation from the AGN may directly enhance PAH excitation or trigger the formation of OB stars that subsequently excite PAH emission at these locations in the inner spiral, the orientation of collimated radiation from the AGN and star formation knots in the inner spiral could be coincidental. (abridged)Comment: 20 pages, 11 figures; AJ, accepted; full resolution version available at http://spider.ipac.caltech.edu/staff/jhhowell/astro/howelln1068.pd

A randomized placebo-controlled trial of methotrexate in psoriatic arthritis.

OBJECTIVE: MTX is widely used to treat synovitis in PsA without supporting trial evidence. The aim of our study was to test the value of MTX in the first large randomized placebo-controlled trial (RCT) in PsA. METHODS: A 6-month double-blind RCT compared MTX (15 mg/week) with placebo in active PsA. The primary outcome was PsA response criteria (PsARC). Other outcomes included ACR20, DAS-28 and their individual components. Missing data were imputed using multiple imputation methods. Treatments were compared using logistic regression analysis (adjusted for age, sex, disease duration and, where appropriate, individual baseline scores). RESULTS: Four hundred and sixty-two patients were screened and 221 recruited. One hundred and nine patients received MTX and 112 received placebo. Forty-four patients were lost to follow-up (21 MTX, 23 placebo). Twenty-six patients discontinued treatment (14 MTX, 12 placebo). Comparing MTX with placebo in all randomized patients at 6 months showed no significant effect on PsARC [odds ratio (OR) 1.77, 95% CI 0.97, 3.23], ACR20 (OR 2.00, 95% CI 0.65, 6.22) or DAS-28 (OR 1.70, 95% CI 0.90, 3.17). There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ and pain. The only benefits of MTX were reductions in patient and assessor global scores and skin scores at 6 months (P = 0.03, P < 0.001 and P = 0.02, respectively). There were no unexpected adverse events. CONCLUSIONS: This trial of active PsA found no evidence for MTX improving synovitis and consequently raises questions about its classification as a disease-modifying drug in PsA. Trial registration. Current Controlled Trials, www.controlled-trials.com, ISRCTN:54376151