Obscuring Material around Seyfert Nuclei with Starbursts

The structure of obscuring matter in the environment of active galactic nuclei with associated nuclear starbursts is investigated using 3-D hydrodynamical simulations. Simple analytical estimates suggest that the obscuring matter with energy feedback from supernovae has a torus-like structure with a radius of several tens of parsecs and a scale height of about 10 pc. These estimates are confirmed by the fully non-linear numerical simulations, in which the multi-phase inhomogeneous interstellar matter and its interaction with the supernovae are consistently followed. The globally stable, torus-like structure is highly inhomogeneous and turbulent. To achieve the high column densities (> 10^{24} cm^{-2}) as suggested by observations of some Seyfert 2 galaxies with nuclear starbursts, the viewing angle should be larger than about 70 degree from the pole-on for a 10^8 solar mass massive black hole. Due to the inhomogeneous internal structure of the torus, the observed column density is sensitive to the line-of-sight, and it fluctuates by a factor of order 100. The covering fraction for N > 10^{23} cm^{-2} is about 0.4. The average accretion rate toward R < 1 pc is 0.4 solar mass/yr, which is boosted to twice that in the model without the energy feedback.Comment: ApJL in press (4 pages, 3 figures) A gziped ps file with high resolution figures is available at http://th.nao.ac.jp/~wada/AGN

The Global Structure and Evolution of a Self-Gravitating Multi-phase Interstellar Medium in a Galactic Disk

Using high resolution, two-dimensional hydrodynamical simulations, we investigate the evolution of a self-gravitating multi-phase interstellar medium in the central kiloparsec region of a galactic disk. We find that a gravitationally and thermally unstable disk evolves, in a self-stabilizing manner, into a globally quasi-stable disk that consists of cold (T < 100 K), dense clumps and filaments surrounded by hot (T > 10^4 K), diffuse medium. The quasi-stationary, filamentary structure of the cold gas is remarkable. The hot gas, characterized by low-density holes and voids, is produced by shock heating. The shocks derive their energy from differential rotation and gravitational perturbations due to the formation of cold dense clumps. In the quasi-stable phase where cold and dense clouds are formed, the effective stability parameter, Q, has a value in the range 2-5. The dynamic range of our multi-phase calculations is 10^6 - 10^7 in both density and temperature. Phase diagrams for this turbulent medium are analyzed and discussed.Comment: 10 pages, 3 figures, ApJ Letters in press (vol. 516

MEN 2A: Update on the Northern Ireland and Australian Family

The Northern Ireland/Australian family with multiple endocrine neoplasia type 2A (MEN 2A) originally described in 1987 is presented with a revised and enlarged pedigree. Four members of the first generation studied have died. A seventh member of the second generation studied has developed medullary thyroid carcinoma and has progressed to surgery. None of the third generation members studied has shown any conclusive abnormality in metabolic screening tests. Each member of the third and fourth generations has had genetic counseling and (if appropriate) DNA analysis with gene probes close to the MEN 2A gene locus on chromosome 10. All members of this highly penetrant family have remained asymptomatic for their disease

Targeting metastatic colorectal cancer with immune oncological therapies

Metastatic colorectal cancer carries poor prognosis, and current therapeutic regimes convey limited improvements in survival and high rates of detrimental side effects in patients that may not stand to benefit. Immunotherapy has revolutionised cancer treatment by restoring antitumoural mechanisms. However, the efficacy in metastatic colorectal cancer, is limited. A literature search was performed using Pubmed (Medline), Web of Knowledge, and Embase. Search terms included combinations of immunotherapy and metastatic colorectal cancer, primarily focusing on clinical trials in humans. Analysis of these studies included status of MMR/MSS, presence of combination strategies, and disease control rate and median overall survival. Evidence shows that immune checkpoint inhibitors, such as anti-PD1 and anti-PD-L1, show efficacy in less than 10% of patients with microsatellite stable, MMR proficient colorectal cancer. In the small subset of patients with microsatellite unstable, MMR deficient cancers, response rates were 40–50%. Combination strategies with immunotherapy are under investigation but have not yet restored antitumoural mechanisms to permit durable disease regression. Immunotherapy provides the potential to offer additional strategies to established chemotherapeutic regimes in metastatic colorectal cancer. Further research needs to establish which adjuncts to immune checkpoint inhibition can unpick resistance, and better predict which patients are likely to respond to individualised therapies to not just improve response rates but to temper unwarranted side effects

Progressing the care, husbandry and management of ageing mice used in scientific studies

Driven by the longer lifespans of humans, particularly in Westernised societies, and the need to know more about ‘healthy ageing’, ageing mice are being used increasingly in scientific research. Many departments and institutes involved with ageing research have developed their own systems to determine intervention points for potential refinements and to identify humane end points. Several good systems are in use, but variations between them could contribute to poor reproducibility of the science achieved. Working with scientific and regulatory communities in the UK, we have reviewed the clinical signs observed in ageing mice and developed recommendations for enhanced monitoring, behaviour assessment, husbandry and veterinary interventions. We advocate that the default time point for enhanced monitoring should be 15 months of age, unless prior information is available. Importantly, the enhanced monitoring should cause no additional harms to the animals. Where a mouse strain is well characterised, the onset of age-related enhanced monitoring may be modified based on knowledge of the onset of an expected age-related clinical sign. In progeroid models where ageing is accelerated, enhanced monitoring may need to be brought forward. Information on the background strain must be considered, as it influences the onset of age-related clinical signs. The range of ageing models currently used means that there will be no ‘one-size fits all’ solution. Increased awareness of the issues will lead to more refined and consistent husbandry of ageing mice, and application of humane end points will help to reduce the numbers of animals maintained for longer than is scientifically justified

The Evolution of Cuspy Triaxial Galaxies Harboring Central Black Holes

We use numerical simulations to study the evolution of triaxial elliptical galaxies with central black holes. In contrast to earlier numerical studies which used galaxy models with central density ``cores,'' our galaxies have steep central cusps, like those observed in real ellipticals. As a black hole grows in these cuspy triaxial galaxies, the inner regions become rounder owing to chaos induced in the orbit families which populate the model. At larger radii, however, the models maintain their triaxiality, and orbital analyses show that centrophilic orbits there resist stochasticity over many dynamical times. While black hole induced evolution is strong in the inner regions of these galaxies, and reaches out beyond the nominal ``sphere of influence'' of a black hole, our simulations do not show evidence for a rapid {\it global} transformation of the host. The triaxiality of observed elliptical galaxies is therefore not inconsistent with the presence of supermassive black holes at their centers.Comment: 15 pages, 7 figures (1 color). Accepted for publication in Ap

Detection of the Entropy of the Intergalactic Medium: Accretion Shocks in Clusters, Adiabatic Cores in Groups

The thermodynamics of the diffuse, X-ray emitting gas in clusters of galaxies is linked to the entropy level of the intra cluster medium. In particular, models that successfully reproduce the properties of local X-ray clusters and groups require the presence of a minimum value for the entropy in the center of X-ray halos. Such a minimum entropy is most likely generated by non-gravitational processes, in order to produce the observed break in self-similarity of the scaling relations of X-ray halos. At present there is no consensus on the level, the source or the time evolution of this excess entropy. In this paper we describe a strategy to investigate the physics of the heating processes acting in groups and clusters. We show that the best way to extract information from the local data is the observation of the entropy profile at large radii in nearby X-ray halos (z~0.1), both at the upper and lower extremes of the cluster mass scale. The spatially and spectrally resolved observation of such X-ray halos provides information on the mechanism of the heating. We demonstrate how measurements of the size of constant entropy (adiabatic) cores in clusters and groups can directly constrain heating models, and the minimum entropy value. We also consider two specific experiments: the detection of the shock fronts expected at the virial boundary of rich clusters, and the detection of the isentropic, low surface-brightness emission extending to radii larger than the virial ones in low mass clusters and groups. Such observations will be a crucial probe of both the physics of clusters and the relationship of non-gravitational processes to the thermodynamics of the intergalactic medium.Comment: ApJ accepted, 31 pages including 8 figures. Important material added; references update

Sequential Electrostatic Assembly of a Polymer Surfactant Corona Increases Activity of the Phosphotriesterase arPTE

We present a new methodology for the generation of discrete molecularly dispersed enzyme–polymer–surfactant bioconjugates. Significantly, we demonstrate that &gt;3-fold increase in the catalytic efficiency of the diffusion-limited phosphotriesterase arPTE can be achieved through sequential electrostatic addition of cationic and anionic polymer surfactants, respectively. Here, the polymer surfactants assemble on the surface of the enzyme via ion exchange to yield a compact corona. The observed rate enhancement is consistent with a mechanism whereby the polymer–surfactant corona gives rise to a decrease in the dielectric constant in the vicinity of the active site of the enzyme, accelerating the rate-determining product diffusion step. The facile methodology has significant potential for increasing the efficiency of enzymes and could therefore have a substantially positive impact for industrial enzymology

Evolution of the Lyman-alpha Halos around High-Redshift Radio Galaxies

We have obtained the first constraints on extended Ly-alpha emission at z ~ 1 in a sample of five radio galaxies. We detect Ly-alpha emission from four of the five galaxies. The Ly-alpha luminosities range from 0.1 - 4 times 10^43 erg/s and are much smaller than those observed for halos around higher redshift radio galaxies. If the z ~ 1 radio galaxies are the descendents the z >~ 2 radio galaxies, then their Ly-alpha luminosities evolve strongly with redshift as ~(1+z)^5. There do not appear to be strong correlations between other parameters, such as radio power, suggesting that this observed evolution is real and not an observational artifact or secondary correlation. We speculate that this evolution of luminous halos may be due to gas depletion (as gas cools, settles, and forms stars) accompanied by an overall rise in the mean gas temperature and a decrease in specific star-formation rate in and around these massive galaxies.Comment: 5 pages, 4 figures, published in ApJ Letters, 694, L31-35 March 20 200