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

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer

BACKGROUND:In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed.METHODS:A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70Gy (62.4-75Gy).RESULTS:At a median follow-up of 14months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications.CONCLUSIONS:IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Kinetic regulation of multi-ligand binding proteins

Background: Second messengers, such as calcium, regulate the activity of multisite binding proteins in a concentration-dependent manner. For example, calcium binding has been shown to induce conformational transitions in the calcium-dependent protein calmodulin, under steady state conditions. However, intracellular concentrations of these second messengers are often subject to rapid change. The mechanisms underlying dynamic ligand-dependent regulation of multisite proteins require further elucidation. Results: In this study, a computational analysis of multisite protein kinetics in response to rapid changes in ligand concentrations is presented. Two major physiological scenarios are investigated: i) Ligand concentration is abundant and the ligand-multisite protein binding does not affect free ligand concentration, ii) Ligand concentration is of the same order of magnitude as the interacting multisite protein concentration and does not change. Therefore, buffering effects significantly influence the amounts of free ligands. For each of these scenarios the influence of the number of binding sites, the temporal effects on intermediate apo- and fully saturated conformations and the multisite regulatory effects on target proteins are investigated. Conclusions: The developed models allow for a novel and accurate interpretation of concentration and pressure jump-dependent kinetic experiments. The presented model makes predictions for the temporal distribution of multisite protein conformations in complex with variable numbers of ligands. Furthermore, it derives the characteristic time and the dynamics for the kinetic responses elicited by a ligand concentration change as a function of ligand concentration and the number of ligand binding sites. Effector proteins regulated by multisite ligand binding are shown to depend on ligand concentration in a highly nonlinear fashion

The spectral energy distribution of PKS 2004-447: a compact steep-spectrum source and possible radio-loud narrow-line Seyfert 1 galaxy

(abridged) The spectral energy distribution (SED) of the compact steep spectrum (CSS) source and possible radio-loud narrow-line Seyfert 1 galaxy (NLS1), PKS2004-447, is presented. Five out of six well studied RL NLS1 share this dual classification (optically defined as a NLS1 with radio definition of a CSS or giga-hertz peaked spectrum (GPS) source). The SED is created from simultaneous observations at radio (ATCA), optical/NIR (Siding Spring) and UV/X-ray (XMM-Newton) wavelengths. The X-ray data show evidence of short-term variability, a possible soft excess, and negligible absorption. Together with the rest of the SED, the X-ray emission is excessive in comparison to synchrotron plus synchrotron self-Compton (SSC) models. The SED can be described with a two component model consisting of extended synchrotron/SSC emission with Comptonisation in the X-rays, though SSC models with a very high electron-to-magnetic energy density ratio cannot be excluded either. The peak emission in the SED appears to be in the near infrared, which can be attributed to thermal emission from a dusty torus. Analysis of a non-contemporaneous, low resolution optical spectrum suggests that the narrow-line region (NLR) is much more reddened than the X-ray emitting region suggesting that the gas-to-dust ratio in PKS2004-447 may be very different then in our own Galaxy. Long-term radio monitoring of PKS2004-447 shows a rather constant light curve over nearly a six month period with the exception of one outburst when the 6.65GHz flux increased by ~35% over 19 days. In comparison to general samples of GPS sources, which appear to be X-ray weak, NLS1-CSS/GPS sources possess stronger X-ray emission relative to radio, and lower intrinsic absorption than GPS sources of similar X-ray luminosity.Comment: 10 pages, 8 figures. Accepted for publication in MNRA

Mutations that permit residual CFTR function delay acquisition of multiple respiratory pathogens in CF patients

<p>Abstract</p> <p>Background</p> <p>Lung infection by various organisms is a characteristic feature of cystic fibrosis (CF). <it>CFTR </it>genotype effects acquisition of <it>Pseudomonas aeruginosa (Pa)</it>, however the effect on acquisition of other infectious organisms that frequently precede <it>Pa </it>is relatively unknown. Understanding the role of CFTR in the acquisition of organisms first detected in patients may help guide symptomatic and molecular-based treatment for CF.</p> <p>Methods</p> <p>Lung infection, defined as a single positive respiratory tract culture, was assessed for 13 organisms in 1,381 individuals with CF. Subjects were divided by predicted CFTR function: 'Residual': carrying at least one partial function <it>CFTR </it>mutation (class IV or V) and 'Minimal' those who do not carry a partial function mutation. Kaplan-Meier estimates were created to assess <it>CFTR </it>effect on age of acquisition for each organism. Cox proportional hazard models were performed to control for possible cofactors. A separate Cox regression was used to determine whether defining infection with <it>Pa</it>, mucoid <it>Pa </it>or <it>Aspergillus (Asp) </it>using alternative criteria affected the results. The influence of severity of lung disease at the time of acquisition was evaluated using stratified Cox regression methods by lung disease categories.</p> <p>Results</p> <p>Subjects with 'Minimal' CFTR function had a higher hazard than patients with 'Residual' function for acquisition of 9 of 13 organisms studied (HR ranging from 1.7 to 3.78 based on the organism studied). Subjects with minimal CFTR function acquired infection at a younger age than those with residual function for 12 of 13 organisms (p-values ranging: < 0.001 to 0.017). Minimal CFTR function also associated with younger age of infection when 3 alternative definitions of infection with <it>Pa</it>, mucoid <it>Pa </it>or <it>Asp </it>were employed. Risk of infection is correlated with CFTR function for 8 of 9 organisms in patients with good lung function (>90%ile) but only 1 of 9 organisms in those with poorer lung function (<50%ile).</p> <p>Conclusions</p> <p>Residual CFTR function correlates with later onset of respiratory tract infection by a wide spectrum of organisms frequently cultured from CF patients. The protective effect conferred by residual CFTR function is diminished in CF patients with more advanced lung disease.</p

Continuing the conversation about public health ethics: education for public health professionals in Europe

An important related question is why we should teach public health ethics. Fundamentally, we must teach public health ethics because ethical practice creates and maintains public trust and public health cannot function without public trust. To serve the public—whether through controlling an outbreak of an infectious disease, preparing for or responding to public health emergencies, or reducing the impact of non-communicable diseases—communities and individuals must trust our decisions and actions. This trust grows in large part from past successes, transparent and participatory decision making, and ethical management of the inevitable moral tensions that arise in our work.S

Detailed maps of interstellar clouds in front of omega Centauri: Small-scale structures in the Galactic Disc-Halo interface

We used the multiplex capabilities of the AAOmega spectrograph at the Anglo-Australian Telescope to create a half-square-degree map of the neutral and low-ionized ISM in front of the nearby (~5 kpc), most massive Galactic globular cluster, omega Centauri. Its redshifted, metal-poor and hot horizontal branch stars probe the medium-strong Ca II K and Na I D2 line absorption, and weak absorption in the lambda5780 and lambda5797 Diffuse Interstellar Bands (DIBs), on scales around a parsec. The kinematical and thermodynamical picture emerging from these data is that we predominantly probe the warm neutral medium and weakly-ionized medium of the Galactic Disc-Halo interface, ~0.3-1 kpc above the mid-plane. A comparison with Spitzer Space Telescope 24-micron and DIRBE/IRAS maps of the warm and cold dust emission confirms that both Na I and Ca II trace the overall column density of the warm neutral and weakly-ionized medium. Clear signatures are seen of the depletion of calcium atoms from the gas phase into dust grains. Curiously, the coarse DIRBE/IRAS map is a more reliable representation of the relative reddening between sightlines than the Na I and Ca II absorption-line measurements, most likely because the latter are sensitive to fluctuations in the local ionization conditions. The behaviour of the DIBs is consistent with the lambda5780 band being stronger than the lambda5797 band in regions where the ultraviolet radiation level is relatively high, as in the Disc-Halo interface. This region corresponds to a sigma-type cloud. In all, our maps and simple analytical model calculations show in unprecedented detail that small-scale density and/or ionization structures exist in the extra-planar gas of a spiral galaxy. (abridged)Comment: Accepted for publication in MNRA

The Schnitzler syndrome

The Schnitzler syndrome is a rare and underdiagnosed entity which is considered today as being a paradigm of an acquired/late onset auto-inflammatory disease. It associates a chronic urticarial skin rash, corresponding from the clinico-pathological viewpoint to a neutrophilic urticarial dermatosis, a monoclonal IgM component and at least 2 of the following signs: fever, joint and/or bone pain, enlarged lymph nodes, spleen and/or liver, increased ESR, increased neutrophil count, abnormal bone imaging findings. It is a chronic disease with only one known case of spontaneous remission. Except of the severe alteration of quality of life related mainly to the rash, fever and pain, complications include severe inflammatory anemia and AA amyloidosis. About 20% of patients will develop a lymphoproliferative disorder, mainly Waldenström disease and lymphoma, a percentage close to other patients with IgM MGUS. It was exceedingly difficult to treat patients with this syndrome until the IL-1 receptor antagonist anakinra became available. Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections