A self-consistent hybrid Comptonization model for broad-band spectra of accreting supermassive black holes

The nature of the broad-band spectra of supermassive accreting black holes in active galactic nuclei (AGNs) is still unknown. The hard X-ray spectra of Seyferts as well as of Galactic stellar-mass black holes (GBHs) are well represented by thermal Comptonization, but the origin of the seed photons is less certain. The MeV tails observed in GBHs provide evidence in favour of non-thermal electron tails and it is possible that such electrons are also present in the X-ray emitting regions of AGNs. Using simulations with the kinetic code that self-consistently models electron and photon distributions, we find that the power-law-like X-ray spectra in AGNs can be explained in terms of the synchrotron self-Compton radiation of hybrid thermal/non-thermal electrons, similarly to the hard/low state of GBHs. Under a very broad range of parameters the model predicts a rather narrow distribution of photon spectral slopes consistent with that observed from LINERs and Seyferts at luminosities less than 3 per cent of the Eddington luminosity. The entire infrared to X-ray spectrum of these objects can be described in terms of our model, suggesting a tight correlation between the two energy bands. We show that the recently found correlation between slope and the Eddington ratio at higher luminosities can be described by the increasing fraction of disc photons in the emitting region, which may be associated with the decreasing inner radius of the optically thick accretion disc. The increasing flux of soft photons is also responsible for the transformation of the electron distribution from nearly thermal to almost completely non-thermal. The softer X-ray spectra observed in narrow-line Seyfert galaxies may correspond to non-thermal Comptonization of the disc photons, predicting that no cutoff should be observed up to MeV energies in these sources, similarly to the soft-state GBHs.Comment: MNRAS publishe

A celestial gamma-ray foreground due to the albedo of small solar system bodies and a remote probe of the interstellar cosmic ray spectrum

We calculate the gamma-ray albedo flux from cosmic-ray (CR) interactions with the solid rock and ice in Main Belt asteroids (MBAs), Jovian and Neptunian Trojan asteroids, and Kuiper Belt objects (KBOs) using the Moon as a template. We show that the gamma-ray albedo for the Main Belt, Trojans, and Kuiper Belt strongly depends on the small-body size distribution of each system. Based on an analysis of the Energetic Gamma Ray Experiment Telescope (EGRET) data we infer that the diffuse emission from the MBAs, Trojans, and KBOs has an integrated flux of less than ~6x10^{-6} cm^{-2} s^{-1} (100-500 MeV), which corresponds to ~12 times the Lunar albedo, and may be detectable by the forthcoming Gamma Ray Large Area Space Telescope (GLAST). If detected by GLAST, it can provide unique direct information about the number of small bodies in each system that is difficult to assess by any other method. Additionally, the KBO albedo flux can be used to probe the spectrum of CR nuclei at close-to-interstellar conditions. The orbits of MBAs, Trojans, and KBOs are distributed near the ecliptic, which passes through the Galactic center and high Galactic latitudes. Therefore, the asteroid gamma-ray albedo has to be taken into account when analyzing weak gamma-ray sources close to the ecliptic, especially near the Galactic center and for signals at high Galactic latitudes, such as the extragalactic gamma-ray emission. The asteroid albedo spectrum also exhibits a 511 keV line due to secondary positrons annihilating in the rock. This may be an important and previously unrecognized celestial foreground for the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) observations of the Galactic 511 keV line emission including the direction of the Galactic center.Comment: 10 pages, 5 figures, 1 table, emulateapj.cls; ApJ in press. Calculations extended to include Jovian and Neptunian Trojan groups, and Centaurs, in addition to Main Belt Asteroids and Kuiper Belt Objects. Many other considerable change

Elevated intracellular cAMP concentration mediates growth suppression in glioma cells.

Supressed levels of intracellular cAMP have been associated with malignancy. Thus, elevating cAMP through activation of adenylyl cyclase (AC) or by inhibition of phosphodiesterase (PDE) may be therapeutically beneficial. Here, we demonstrate that elevated cAMP levels suppress growth in C6 cells (a model of glioma) through treatment with forskolin, an AC activator, or a range of small molecule PDE inhibitors with differing selectivity profiles. Forskolin suppressed cell growth in a PKA-dependent manner by inducing a G2/M phase cell cycle arrest. In contrast, trequinsin (a non-selective PDE2/3/7 inhibitor), not only inhibited cell growth via PKA, but also stimulated (independent of PKA) caspase-3/-7 and induced an aneuploidy phenotype. Interestingly, a cocktail of individual PDE 2,3,7 inhibitors suppressed cell growth in a manner analogous to forskolin but not trequinsin. Finally, we demonstrate that concomitant targeting of both AC and PDEs synergistically elevated intracellular cAMP levels thereby potentiating their antiproliferative actions

Soft X-ray spectral variations of the narrow line Seyfert l galaxy Markarian 766

The X-ray variability of the narrow-line Seyfert 1 galaxy Markarian 766 is studied using nine ROSAT PSPC data sets. The spectrum is well described by a power law combined with a blackbody (kT ∼ 70 eV) soft excess. Examination of flux ratio changes and variability amplitude in three X-ray bands shows that the power-law component varies continuously on time-scales of ∼ 5000 s and is steeper when it is brighter. In contrast, variability of the soft excess is not detected. Spectral modelling of 31 spectra from different observations and at a range of count rates is also consistent with a picture in which the power law is steeper when it is brighter, and in which the soft-excess component does not vary. The power-law variability can be explained if the power law is produced by variable thermal or non-thermal Comptonization of soft photons. This behaviour is similar to that of Galactic black hole candidates in the low state. The X-ray and multiwavelength properties of Markarian 766 are shown to be very similar to those of other narrow-line Seyfert 1s. This may mean that the rapid X-ray variability seen in other narrow-line Seyfert 1s may also not originate in their strong soft-excess components

Determinants of medication adherence to antihypertensive medications among a Chinese population using Morisky medication adherence scale

<b>Background and objectives</b> Poor adherence to medications is one of the major public health challenges. Only one-third of the population reported successful control of blood pressure, mostly caused by poor drug adherence. However, there are relatively few reports studying the adherence levels and their associated factors among Chinese patients. This study aimed to study the adherence profiles and the factors associated with antihypertensive drug adherence among Chinese patients.<p></p> <b>Methods</b> A cross-sectional study was conducted in an outpatient clinic located in the New Territories Region of Hong Kong. Adult patients who were currently taking at least one antihypertensive drug were invited to complete a self-administered questionnaire, consisting of basic socio-demographic profile, self-perceived health status, and self-reported medication adherence. The outcome measure was the Morisky Medication Adherence Scale (MMAS-8). Good adherence was defined as MMAS scores greater than 6 points (out of a total score of 8 points).<p></p> <b>Results</b> From 1114 patients, 725 (65.1%) had good adherence to antihypertensive agents. Binary logistic regression analysis was conducted. Younger age, shorter duration of antihypertensive agents used, job status being employed, and poor or very poor self-perceived health status were negatively associated with drug adherence.<p></p> <b>Conclusion</b> This study reported a high proportion of poor medication adherence among hypertensive subjects. Patients with factors associated with poor adherence should be more closely monitored to optimize their drug taking behavior

Interrogation of modern and ancient genomes reveals the complex domestic history of cattle

The analysis of mitochondrial and nuclear DNA sequence polymorphisms from modern cattle populations has had a profound impact on our understanding of the events surrounding the domestication of cattle. From these studies, it has been possible to distinguish between pre- and post-domestic genetic differentiation, supporting previous assertions from archaeological studies and, in some cases, revealing novel aspects of the demographic history of cattle. Analyses of genetic material retrieved from the remains of extinct ancestral wild cattle have also added valuable layers of information pertaining to cattle domestic origins; however, information from these investigations have, in general, been limited to small, variable portions of the mitochondrial genome owing to technical challenges associated with the retrieval and amplification of ancient DNA. In recent years, however, new high-throughput, massively parallel genomics technology platforms, such as single-nucleotide polymorphism (SNP) genotyping arrays and next-generation sequencing (NGS), have provided a new impetus to the studies of genetic variation in extant and ancient cattle. Arrays of SNP have facilitated high-resolution genetic surveys of global cattle populations and detection of ancient and recent genomic selective sweeps. Next-generation sequencing analyses of modern and ancient cattle hold great promise for identifying and cataloging of pre- and post-domestication patterns of genomic variation and correlating this with natural and artificial selection processes

Transcriptional Regulation of Proteoglycans and Glycosaminoglycan Chain-synthesizing Glycosyltransferases by UV Irradiation in Cultured Human Dermal Fibroblasts

Various kinds of glycosaminoglycans (GAGs) and proteoglycans (PGs) have been known to be involved in structural and space-filling functions, as well as many physiological regulations in skin. To investigate ultraviolet (UV) radiation-mediated regulation of GAGs and PGs in cultured human dermal fibroblasts, transcriptional changes of many types of PGs and GAG chain-synthesizing enzymes at 18 hr after 75 mJ/cm2 of UV irradiation were examined using quantitative real-time polymerase chain reaction methods. Hyaluronic acid synthase (HAS)-1, -2, and -3 and hyaluronidase-2 mRNA expressions were significantly increased by UV irradiation. Expressions of lumican, fibromodulin, osteoglycin, syndecan-2, perlecan, agrin, versican, decorin, and biglycan were significantly decreased by UV irradiation, while syndecan-1 was increased. Expressions of GAG chain-synthesizing glycosyltransferases, xylosyltransferase-1, β1,3-glucuronyltransferase-1, β1,4-galactosyltransferase-2, -4, exostosin-1, chondroitin polymerizing factor, and chondroitin sulfate synthase-3 were significantly reduced, whereas those of β1,3-galactosyltransferase-6, β1,4-galactosyltransferase-3, -7, β-1,3-N-acetylglucosaminyltran sferase-2, and -7 were increased by UV irradiation. Heparanase-1 mRNA expression was increased, but that of heparanase-2 was reduced by UV irradiation. Time-course investigation of representative genes showed consistent results. In conclusion, UV irradiation may increase hyaluronic acid production through HAS induction, and decrease other GAG productions through downregulation of PG core proteins and GAG chain-synthesizing glycosyltransferases in cultured human dermal fibroblasts

Bee Venom Induces Unfolded Protein Response in A172 Glioblastoma Cell Line

Background: Glioblastoma is a type of brain tumor with poor response to available therapies, and shows high rate of mortality. Despite remarkable advancements in our knowledge about cytogenetic and pathophysiologic features of glioblastoma, current treatment strategies are mainly based on cytotoxic drugs; however, these therapeutic approaches are facing progressive failure because of the resistant nature of glioblastomas. In the recent years, however, promising results have emerged owing to targeted therapies toward molecular pathways within cancerous cells. Unfolded Protein Response (UPR) is a remarkable signaling pathway that triggers both apoptosis and survival pathways within cells, and therefore induces UPR-related apoptotic pathways in cancer cells by ER stress inducers. Objectives: Recently, the role of Bee venom (Bv), which contains powerful bioactive peptides, in inducing UPR-related apoptosis was revealed in cancer cell lines. Nevertheless, currently there are no reports of Bv potential ability in induction of UPR apoptotic routes in glioblastoma. The aim of current study was to evaluate possible role of Bee venome in inducing of UPR pathway within A172 glioblastoma cell line. Materials and Methods: We treated the A172 glioblastoma cell line with different Bv doses, and assessed UPR-related genes expression by real-time Polymerase Chain Reaction (PCR). Results: The IC50 of Bv for the studied cell line was 28 μg/mL. Furthermore, we observed that Bv can induce UPR target genes (Grp94 and Gadd153) over-expression through a dose-dependent mechanism. Conclusions: Our results suggest the potential role of Bv as a therapeutic agent for glioblastomas. Keywords: Glioblastoma; A172 Cell Line; Unfolded Protein Response; Bee Veno