Monte Carlo radiation hydrodynamics:Methods, tests and application to Type Ia supernova ejecta

In astrophysical systems, radiation-matter interactions are important in transferring energy and momentum between the radiation field and the surrounding material. This coupling often makes it necessary to consider the role of radiation when modelling the dynamics of astrophysical fluids. During the last few years, there have been rapid developments in the use of Monte Carlo methods for numerical radiative transfer simulations. Here, we present an approach to radiation hydrodynamics that is based on coupling Monte Carlo radiative transfer techniques with finite-volume hydrodynamical methods in an operator-split manner. In particular, we adopt an indivisible packet formalism to discretize the radiation field into an ensemble of Monte Carlo packets and employ volume-based estimators to reconstruct the radiation field characteristics. In this paper the numerical tools of this method are presented and their accuracy is verified in a series of test calculations. Finally, as a practical example, we use our approach to study the influence of the radiation-matter coupling on the homologous expansion phase and the bolometric light curve of Type Ia supernova explosions. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.

Multidimensional simulations of radiative transfer in Type Ia supernovae

A three-dimensional Monte Carlo code for modelling radiation transport in Type Ia supernovae is described. In addition to tracking Monte Carlo quanta to follow the emission, scattering and deposition of radiative energy, a scheme involving volume-based Monte Carlo estimators is used to allow properties of the emergent radiation field to be extracted for specific viewing angles in a multidimensional structure. This eliminates the need to compute spectra or light curves by angular binning of emergent quanta. The code is applied to two test problems to illustrate consequences of multidimensional structure on the modelling of light curves. First, elliptical models are used to quantify how large-scale asphericity can introduce angular dependence to light curves. Secondly, a model which incorporates complex structural inhomogeneity, as predicted by modern explosion models, is used to investigate how such structure may affect light-curve properties. © 2006 RAS.

Synthetic X-ray spectra for simulations of the dynamics of an accretion flow irradiated by a quasar

Ultraviolet and X-ray observations show evidence of outflowing gas around many active galactic nuclei. It has been proposed that some of these outflows are driven off gas infalling towards the central supermassive black hole. We perform radiative transfer calculations to compute the gas ionization state and the emergent X-ray spectra for both two- and three-dimensional (3D) hydrodynamical simulations of this outflow-from-inflow scenario. By comparison with observations, our results can be used to test the theoretical models and guide future numerical simulations. We predict both absorption and emission features, most of which are formed in a polar funnel of relatively dense (10 -10 g cm ) outflowing gas. This outflow causes strong absorption for observer orientation angles of ?35°. Particularly in 3D, the strength of this absorption varies significantly for different lines of sight owing to the fragmentary structure of the gas flow. Although infalling material occupies a large fraction of the simulation volume, we do not find that it imprints strong absorption features in the X-ray spectra since the ionization state is predicted to be very high. Thus, an absence of observed inflow absorption features does not exclude the models. The main spectroscopic consequence of the infalling gas is a Compton-scattered continuum component that partially re-fills the absorption features caused by the outflowing polar funnel. Fluorescence and scattering in the outflow are predicted to give rise to several emission features including a multicomponent Fe Ka emission complex for all observer orientations. For the hydrodynamical simulations considered, we predict both ionization states and column densities for the outflowing gas that are too high to be quantitatively consistent with well-observed X-ray absorption systems. Nevertheless, our results are qualitatively encouraging and further exploration of the model parameter space is warranted. Higher resolution hydrodynamic simulations are needed to determine whether the outflows fragment on scales unresolved in our current study, which may yield the denser lower ionization material that could reconcile the models and the observations. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.

nero- a post-maximum supernova radiation transport code

The interpretation of supernova (SN) spectra is essential for deriving SN ejecta properties such as density and composition, which in turn can tell us about their progenitors and the explosion mechanism. A very large number of atomic processes are important for spectrum formation. Several tools for calculating SN spectra exist, but they mainly focus on the very early or late epochs. The intermediate phase, which requires a non-local thermodynamic equilibrium (NLTE) treatment of radiation transport has rarely been studied. In this paper, we present a new SN radiation transport code, nero, which can look at those epochs. All the atomic processes are treated in full NLTE, under a steady-state assumption. This is a valid approach between roughly 50 and 500days after the explosion depending on SN type. This covers the post-maximum photospheric and the early and the intermediate nebular phase. As a test, we compare nero to the radiation transport code of Jerkstrand, Fransson & Kozma and to the nebular code of Mazzali et al. All three codes have been developed independently and a comparison provides a valuable opportunity to investigate their reliability. Currently, nero is one-dimensional and can be used for predicting spectra of synthetic explosion models or for deriving SN properties by spectral modelling. To demonstrate this, we study the spectra of the 'normal' Type Ia supernova (SN Ia) 2005cf between 50 and 350 days after the explosion and identify most of the common SN Ia line features at post-maximum epochs. © 2011 The Authors Monthly Notices of the Royal Astronomical Society © 2011 RAS.

Multidimensional modelling of X-ray spectra for AGN accretion disc outflows - II

Highly ionized fast accretion disc winds have been suggested as an explanation for a variety of observed absorption and emission features in the X-ray spectra of active galactic nuclei. Simple estimates have suggested that these flows may be massive enough to carry away a significant fraction of the accretion energy and could be involved in creating the link between supermassive black holes and their host galaxies. However, testing these hypotheses, and quantifying the outflow signatures, requires high-quality theoretical spectra for comparison with observations. Here, we describe extensions of our Monte Carlo radiative transfer code that allow us to generate realistic theoretical spectra for a much wider variety of disc wind models than that was possible in our previous work. In particular, we have expanded the range of atomic physics simulated by the code so that L- and M-shell ions can now be included. We have also substantially improved our treatment of both ionization and radiative heating such that we are now able to compute spectra for outflows containing far more diverse plasma conditions. We present example calculations that illustrate the variety of spectral features predicted by parametrized outflow models and demonstrate their applicability to the interpretation of data by comparison with observations of the bright quasar PG1211+143. We find that the major features in the observed 2-10 keV spectrum of this object can be well reproduced by our spectra, confirming that it likely hosts a massive outflow. © 2010 The Authors. Journal compilation © 2010 RAS.

Late-time supernova light curves:The effect of internal conversion and auger electrons

Energy release from radioactive decays contributes significantly to supernova light curves. Previous works, which considered the energy deposited by ?-rays and positrons produced by Ni, Co, Ni, Co, Ti and Sc, have been quite successful in explaining the light curves of both core collapse and thermonuclear supernovae. We point out that Auger and internal conversion electrons, together with the associated X-ray cascade, constitute an additional heat source. When a supernova is transparent to ?-rays, these electrons can contribute significantly to light curves for reasonable nucleosynthetic yields. In particular, the electrons emitted in the decay of Co, which are largely due to internal conversion from a fortuitously low-lying 3/2 state in the daughter Fe, constitute an additional significant energy-deposition channel. We show that when the heating by these electrons is accounted for, a slow-down in the light curve of SN 1998bw is naturally obtained for typical hypernova nucleosynthetic yields. Additionally, we show that for generic Type Ia supernova yields, the Auger electrons emitted in the ground-state to ground-state electron capture decay of Fe exceed the energy released by the Ti decay chain for many years after the explosion. © 2009 RAS.

Nebular emission-line profiles of Type Ib/c supernovae - Probing the ejecta asphericity

In order to assess qualitatively the ejecta geometry of stripped-envelope core-collapse supernovae (SNe), we investigate 98 late-time spectra of 39 objects, many of them previously unpublished. We perform a Gauss-fitting of the [O ] ??6300, 6364 feature in all spectra, with the position, full width at half maximum and intensity of the ?6300 Gaussian as free parameters, and the ?6364 Gaussian added appropriately to account for the doublet nature of the [O ] feature. On the basis of the best-fitting parameters, the objects are organized into morphological classes, and we conclude that at least half of all Type Ib/c SNe must be aspherical. Bipolar jet models do not seem to be universally applicable, as we find too few symmetric double-peaked [O ] profiles. In some objects, the [O ] line exhibits a variety of shifted secondary peaks or shoulders, interpreted as blobs of matter ejected at high velocity and possibly accompanied by neutron-star kicks to assure momentum conservation. At phases earlier than ~200 d, a systematic blueshift of the [O ] ??6300, 6364 line centroids can be discerned. Residual opacity provides the most convincing explanation of this phenomenon, photons emitted on the rear side of the SN being scattered or absorbed on their way through the ejecta. Once modified to account for the doublet nature of the oxygen feature, the profile of Mg i] ?4571 at sufficiently late phases generally resembles that of [O ] ??6300, 6364, suggesting negligible contamination from other lines and confirming that O and Mg are similarly distributed within the ejecta. © 2009 RAS.

On the relativistic iron line and soft excess in the Seyfert 1 galaxy Markarian 335

We report a 133-ks XMM-Newton observation of the Seyfert 1 galaxy Markarian 335. The 0.4-12 keV spectrum contains an underlying power-law continuum, a soft excess below 2 keV, and a double-peaked iron emission feature in the 6-7 keV range. We investigate the possibility that the double-peaked emission might represent the characteristic signature of the accretion disc. Detailed investigations show that a moderately broad accretion disc line is most likely present, but that the peaks may be due to narrower components from more distant material. The peaks at 6.4 and 7 keV can be identified, respectively, with the molecular torus in active galactic nucleus unification schemes, and very highly ionized, optically thin gas filling the torus. The X-ray variability spectra on both long (~100 ks) and short (~1 ks) time-scales do not support the recent suggestion that the soft excess is an artefact of variable, moderately ionized absorption. © 2007 The Authors. Journal compilation © 2007 RAS.

HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells

Reendothelialization involves endothelial progenitor cell (EPC) homing, proliferation, and differentiation, which may be influenced by fluid shear stress and local flow pattern. This study aims to elucidate the role of laminar flow on embryonic stem (ES) cell differentiation and the underlying mechanism. We demonstrated that laminar flow enhanced ES cell-derived progenitor cell proliferation and differentiation into endothelial cells (ECs). Laminar flow stabilized and activated histone deacetylase 3 (HDAC3) through the Flk-1-PI3K-Akt pathway, which in turn deacetylated p53, leading to p21 activation. A similar signal pathway was detected in vascular endothelial growth factor-induced EC differentiation. HDAC3 and p21 were detected in blood vessels during embryogenesis. Local transfer of ES cell-derived EPC incorporated into injured femoral artery and reduced neointima formation in a mouse model. These data suggest that shear stress is a key regulator for stem cell differentiation into EC, especially in EPC differentiation, which can be used for vascular repair, and that the Flk-1-PI3K-Akt-HDAC3-p53-p21 pathway is crucial in such a process.

The Caspase-Related Protease Separase (EXTRA SPINDLE POLES) Regulates Cell Polarity and Cytokinesis in Arabidopsis

Vesicle trafficking plays an important role in cell division, establishment of cell polarity, and translation of environmental cues to developmental responses. However, the molecular mechanisms regulating vesicle trafficking remain poorly understood. Here, we report that the evolutionarily conserved caspase-related protease separase (EXTRA SPINDLE POLES [ESP]) is required for the establishment of cell polarity and cytokinesis in Arabidopsis thaliana. At the cellular level, separase colocalizes with microtubules and RabA2a (for RAS GENES FROM RAT BRAINA2a) GTPase-positive structures. Separase facilitates polar targeting of the auxin efflux carrier PIN-FORMED2 (PIN2) to the rootward side of the root cortex cells. Plants with the radially swollen4 (rsw4) allele with compromised separase activity, in addition to mitotic failure, display isotropic cell growth, perturbation of auxin gradient formation, slower gravitropic response in roots, and cytokinetic failure. Measurements of the dynamics of vesicle markers on the cell plate revealed an overall reduction of the delivery rates of KNOLLE and RabA2a GTPase in separase-deficient roots. Furthermore, dissociation of the clathrin light chain, a protein that plays major role in the formation of coated vesicles, was slower in rsw4 than in the control. Our results demonstrate that separase is a key regulator of vesicle trafficking, which is indispensable for cytokinesis and the establishment of cell polarity.

RUNX3 downregulation in human lung adenocarcinoma is independent of p53, EGFR or KRAS status

RUNX3 aberrations play a pivotal role in the oncogenesis of breast, gastric, colon, skin and lung tissues. The aim of this study was to characterize further the expression of RUNX3 in lung cancers. To achieve this, a lung cancer tissue microarray (TMA), frozen lung cancer tissues and lung cell lines were examined for RUNX3 expression by immunohistochemistry, while the TMA was also examined for EGFR and p53 expression. RUNX3 promoter methylation status, and EGFR and KRAS mutation status were also investigated. Inactivation of RUNX3 was observed in 70% of the adenocarcinoma samples, and this was associated with promoter hypermethylation but not biased to EGFR/KRAS mutations. Our results suggest a central role of RUNX3 downregulation in pulmonary adenocarcinoma, which may not be dependent of other established cancer-causing pathways and may have important diagnostic and screening implications.

Coexpressing shRNA with fluorescence tags for quantification of cell migration studies

Understanding migration of cells has many implications in human physiology; some examples include developmental biology, healing, immune responses and tissue remodeling. On the other hand, invasive migration by tumor cells is pathological and is a major cause of mortality amongst cancer sufferers. Cell migration assays have been widely used to quantify potentially metastatic genes. In recent years, the use of RNAi has significantly increased the tools available in cell migration research due to its specific gene targeting for knockdown. The inability to ensure 100% transfection/transduction efficiency reduces the sensitivity of cell migration assays because cells not successfully transfected/transduced with the RNAi are also included in the calculations. This study introduces a different experimental setup mathematically expressed in our named normalized relative infected cell count (N-RICC) that analyses cell migration assays by co-expressing retrovirally transduced shRNA with fluorescence tags from a single vector. Vectors transduced into cells are visible under fluorescence, thus alleviating the problems involved with transduction efficiency by individually identifying cells with targeted genes. Designed shRNAs were targeted against a list of potentially metastatic genes in a highly migratory breast cancer cell line model, MDA-MB-231. We have successfully applied N-RICC analysis to show greater sensitivity of integrin alpha5 (ITGA5) and Ras homologue A (RhoA) in cell metastasis over conventional methods in scratch-wound assays and migration chambers assays.

Overexpression of neurone glial-related cell adhesion molecule is an independent predictor of poor prognosis in advanced colorectal cancer

A downstream target of the Wnt pathway, neurone glial-related cell adhesion molecule (Nr-CAM) has recently been implicated in human cancer development. However, its role in colorectal cancer (CRC) pathobiology and clinical relevance remains unknown. In this study, we examined the clinical significance of Nr-CAM protein expression in a retrospective series of 428 CRCs using immunohistochemistry and tissue microarrays. Cox proportional hazards regression was used to calculate hazard ratios (HR) of mortality according to various clinicopathological features and molecular markers. All CRC samples were immunoreactive for Nr-CAM protein expression, compared to 10 / 245 (4%) matched normal tissue (P <0.0001). Of 428 CRC samples, 97 (23%) showed Nr-CAM overexpression, which was significantly associated with nodal (P = 0.012) and distant (P = 0.039) metastasis, but not with extent of local invasion or tumor size. Additionally, Nr-CAM overexpression was associated with vascular invasion (P = 0.0029), p53 expression (P = 0.036), and peritoneal metastasis at diagnosis (P = 0.013). In a multivariate model adjusted for other clinicopathological predictors of survival, Nr-CAM overexpression correlated with a significant increase in disease-specific (HR 1.66; 95% confidence interval 1.11-2.47; P = 0.014) and overall mortality (HR 1.57; 95% confidence interval 1.07-2.30; P = 0.023) in advanced but not early stage disease. Notably, 5-fluorouracil-based chemotherapy conferred significant survival benefit to patients with tumors negative for Nr-CAM overexpression but not to those with Nr-CAM overexpressed tumors. In conclusion, Nr-CAM protein expression is upregulated in CRC tissues. Nr-CAM overexpression is an independent marker of poor prognosis among advanced CRC patients, and is a possible predictive marker for non-beneficence to 5-fluorouracil- based chemotherapy.

Identification of RBCK1 as a novel regulator of FKBPL: implications for tumor growth and response to tamoxifen

FKBPL has been implicated in processes associated with cancer, including regulation of tumor growth and angiogenesis with high levels of FKBPL prognosticating for improved patient survival. Understanding how FKBPL levels are controlled within the cell is therefore critical. We have identifed a novel role for RBCK1 as an FKBPL-interacting protein, which regulates FKBPL stability at the post-translational level via ubiquitination. Both RBCK1 and FKBPL are upregulated by 17-b-estradiol and interact within heat shock protein 90 chaperone complexes, together with estrogen receptor-a (ERa). Furthermore, FKBPL and RBCK1 associate with ERa at the promoter of the estrogen responsive gene, pS2, and regulate pS2 levels. MCF-7 clones stably overexpressing RBCK1 were shown to have reduced proliferation and increased levels of FKBPL and p21. Furthermore, these clones were resistant to tamoxifen therapy, suggesting that RBCK1 could be a predictive marker of response to endocrine therapy. RBCK1 knockdown using targeted small interfering RNA resulted in increased proliferation and increased sensitivity to tamoxifen treatment. Moreover, in support of our in vitro data, analysis of mRNA microarray data sets demonstrated that high levels of FKBPL and RBCK1 correlated with increased patient survival, whereas high RBCK1 predicted for a poor response to tamoxifen. Our findings support a role for RBCK1 in the regulation of FKBPL with important implications for estrogen receptor signaling, cell proliferation and response to endocrine therapy.

Validation of Next Generation Sequencing Technologies in Comparison to Current Diagnostic Gold Standards for BRAF, EGFR and KRAS Mutational Analysis

Next Generation Sequencing (NGS) has the potential of becoming an important tool in clinical diagnosis and therapeutic decision-making in oncology owing to its enhanced sensitivity in DNA mutation detection, fast-turnaround of samples in comparison to current gold standard methods and the potential to sequence a large number of cancer-driving genes at the one time. We aim to test the diagnostic accuracy of current NGS technology in the analysis of mutations that represent current standard-of-care, and its reliability to generate concomitant information on other key genes in human oncogenesis. Thirteen clinical samples (8 lung adenocarcinomas, 3 colon carcinomas and 2 malignant melanomas) already genotyped for EGFR, KRAS and BRAF mutations by current standard-of-care methods (Sanger Sequencing and q-PCR), were analysed for detection of mutations in the same three genes using two NGS platforms and an additional 43 genes with one of these platforms. The results were analysed using closed platform-specific proprietary bioinformatics software as well as open third party applications. Our results indicate that the existing format of the NGS technology performed well in detecting the clinically relevant mutations stated above but may not be reliable for a broader unsupervised analysis of the wider genome in its current design. Our study represents a diagnostically lead validation of the major strengths and weaknesses of this technology before consideration for diagnostic use.