Reverberation Mapping and the Physics of Active Galactic Nuclei

Reverberation-mapping campaigns have revolutionized our understanding of AGN. They have allowed the direct determination of the broad-line region size, enabled mapping of the gas distribution around the central black hole, and are starting to resolve the continuum source structure. This review describes the recent and successful campaigns of the International AGN Watch consortium, outlines the theoretical background of reverberation mapping and the calculation of transfer functions, and addresses the fundamental difficulties of such experiments. It shows that such large-scale experiments have resulted in a ``new BLR'' which is considerably different from the one we knew just ten years ago. We discuss in some detail the more important new results, including the luminosity-size-mass relationship for AGN, and suggest ways to proceed in the near future.Comment: Review article to appear in Astronomical Time Series, Proceedings of the Wise Observatory 25th Ann. Symposium. 24 pages including 7 figure

Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy

The development of methods for specific delivery of drugs is an important issue for many cancer therapy approaches. Most of macromolecular drugs are taken into the cell through endocytosis and, being unable to escape from endocytic vesicles, eventually are degraded there, which hinders their therapeutic usefulness. We have developed a method, called photochemical internalization, based on light-induced photochemical reactions, disrupting endocytic vesicles specifically within illuminated sites e.g. tumours. Here we present a new drug delivery concept based on photochemical internalization-principle – photochemical disruption of endocytic vesicles before delivery of macromolecules, leading to an instant endosomal release instead of detrimental stay of the molecules in endocytic vesicles. Previously we have shown that illumination applied after the treatment with macromolecules substantially improved their biological effect both in vitro and in vivo. Here we demonstrate that exposure to light before delivery of protein toxin gelonin improves gelonin effect in vitro much more than light after. However, in vitro transfection with reporter genes delivered by non-viral and adenoviral vectors is increased more than 10- and six-fold, respectively, by both photochemical internalization strategies. The possible cellular mechanisms involved, and the potential of this new method for practical application of photochemical internalization concept in cancer therapy are discussed

Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research

<p>Abstract</p> <p>Background</p> <p><it>Viscum album </it>L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment.</p> <p>Methods</p> <p>Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality.</p> <p>Results</p> <p>19 randomized (RCT), 16 non-randomized (non-RCT) controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse); 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL) and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival and tumour remission especially in mice, while application in rats as well as application of VAE compounds had mixed results. <it>In vitro </it>VAE and its compounds have strong cytotoxic effects on cancer cells.</p> <p>Conclusion</p> <p>VAE shows some positive effects in breast and gynaecological cancer. More research into clinical efficacy is warranted.</p

The BeppoSAX observation of IRAS 20210+1121

We have obtained a hard X-ray spectrum of the ultraluminous infrared galaxy IRAS 20210+1121 (z=0.056), whose optical spectrum is that of a Seyfert 2. The most significant feature is a strong Fe K line at 6.7 (6.5-7.0) keV in the lest-frame with equivalent width about 1 keV. This suggests that the observed X-ray continuum is scattered emission from a completely blocked AGN, a situation similar to that in NGC 1068. However, IRAS 20210+1121 has an observed 2-10 keV luminosity of 4 x 10(42) erg s(-1) (assuming H-0 = 50km s(-1) Mpc(-1)), about ten times higher than NGC 1068. If the scattering efficiencies of NGC 1068 and IRAS 20210 are similar, then this implies the presence of an extremely luminous X-ray source in IRAS 20210

BeppoSAX observations of luminous IRAS galaxies

We have obtained hard X-ray spectra of four luminous IRAS galaxies, which were selected on the basis of their optical polarized broad lines. We have found prominent Fe K line emission from IRAS 20210+1121, suggesting that its observed X-ray continuum is scattered emission from a completely blocked AGN. The X-ray-[OIII]lambda 5007 ratios of our sources are in the range of moderately or heavily absorbed Seyfert 2s. (C) 2000 COSPAR. Published by Elsevier Science Ltd

BeppoSAX observations of Narrow-Line Seyfert 1 galaxies - II. Ionized iron features in Arakelian 564

The BeppoSAX observations of the bright Narrow-Line Seyfert I galaxy Ark 564 are presented along with a high quality optical spectrum taken at the 1.5 m telescope at La Silla. The 0.1-10 keV X-ray spectrum is characterized by a strong soft; component which is best described by blackbody-like emission with a temperature of similar to 160 eV. At higher energies a steep (Gamma similar or equal to 2.4) power-law tail is present. There is evidence of an ionized reflector in the form of an iron line and edge. We do not find significant evidence of soft X-ray features if the spectrum is modelled with a two component continuum. The optical and X-ray spectral properties support the hypothesis of a high accretion rate onto a low mass black hole

1H0419-577: a "two-state" soft X-ray Seyfert galaxy

In this paper we report on the first simultaneous optical and X-ray (Beppo-SAX) observations of the radio-quiet AGN 1H0419-577. The optical spectrum clearly leads us to classify this source as a Seyfert I. The X-ray spectrum is, however, somewhat at odds with this classification: a simple flat (Gamma similar to 1.55) and featureless power-law is a good description of the whole 1.8-40 keV spectrum, even if the upper limit to a broad iron line is not very tight. An analysis of a still unpublished ROSAT observation of the same target reveals that the soft X-ray spectrum has undergone a transition from a steep (Gamma = 2.5) to a flat (Gamma = 1.55) state, at least in the 0.7-2 keV band. If this difference is due to a remarkably variable soft excess, it is unlikely that a single component is responsible for the optical/UV/soft X-ray spectral distribution. The hypothesis that the difference is due to a change in the primary X-ray continuum and its implications for current Comptonization models are discussed

BeppoSAX observations of narrow-line Seyfert 1 galaxies

We report on the first spectrum up to 10 keV of the bright narrow-line Seyfert 1 galaxy Ton S 180, obtained with the imaging instruments onboard BeppoSAX. This is the first observed source in a sample of a dozen narrow-line Seyfert 1 galaxies in the BeppoSAX Core Program, We also present and discuss a high quality optical spectrum taken at the 1.5 m telescope at La Silla two months before the BeppoSAX observation. The X-ray spectrum shows a clear hardening above about 2 keV, where a power law with Gamma similar or equal to 2.3 plus an iron line provide a good description of the data. This slope is significantly steeper than the typical one for classical Seyfert 1's and quasars. The best fit line energy is suggestive of highly ionized iron, which would support the idea that the high accretion rate is (one of) the fundamental parameter(s) characterizing the Narrow Line Seyfert 1 phenomenon