A Comprehensive Radio and Optical Study of Abell 2256: Activity from an Infalling Group

Abell 2256 is a nearby (z~0.06), rich cluster of galaxies with fascinating observed properties across a range of wavelengths. Long believed to represent a cluster merger, recent X-ray and optical results have suggested that in addition to the primary cluster and subcluster there is evidence for a third, poorer system. We present wide-field, high sensitivity 1.4 GHz VLA radio observations of Abell 2256 in conjunction with optical imaging and additional spectroscopy. Over 40 cluster radio galaxies are identified, with optical spectroscopy indicating the emission source (star formation or AGN) for most of them. While the overall fraction of galaxies exhibiting radio emission is consistent with a large sample of other nearby clusters, we find an increase in the activity level of galaxies belonging to the third system (hereafter, the ``Group''). Specifically, the Group has relatively more star formation than both the primary cluster and main subcluster. The position of the Group is also coincident with the observed cluster radio relic. We suggest that the Group recently (~0.3 Gyr) merged with the primary cluster and that this merger, not the ongoing merger of the primary and the main subcluster, might be responsible for many of the unusual radio properties of Abell 2256. Furthermore, the greater star formation activity of the Group suggests that the infall of groups is an important driver of galaxy evolution in clusters.Comment: 21 pages plus 13 JPEG figures; to appear in the Astronomical Journa

Combined inhibition of TGF-beta 1-induced EMT and PD-L1 silencing re-sensitizes hepatocellular carcinoma to sorafenib treatment

Hepatocellular carcinoma (HCC) is the most common type of primary hepatic malignancy. HCC is one of the leading causes of cancer deaths worldwide. The oral multi-tyrosine kinase inhibitor Sorafenib is the standard first-line therapy in patients with advanced unresectable HCC. Despite the significant survival benefit in HCC patients post treatment with Sorafenib, many patients had progressive disease as a result of acquiring drug resistance. Circumventing resistance to Sorafenib by exploring and targeting possible molecular mechanisms and pathways is an area of active investigation worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process allowing epithelial cells to assume mesenchymal traits. HCC tumour cells undergo EMT to become immune evasive and develop resistance to Sorafenib treatment. Immune checkpoint molecules control immune escape in many tumours, including HCC. The aim of this study is to investigate whether combined inhibition of EMT and immune checkpoints can re-sensitise HCC to Sorafenib treatment. Post treatment with Sorafenib, HCC cells PLC/PRF/5 and Hep3B were monitored for induction of EMT and immune checkpoint molecules using quantitative reverse transcriptase (qRT)- PCR, western blot, immunofluorescence, and motility assays. The effect of combination treatment with SB431542, a specific inhibitor of the transforming growth factor (TGF)-β receptor kinase, and siRNA mediated knockdown of programmed cell death protein ligand-1 (PD-L1) on Sorafenib resistance was examined using a cell viability assay. We found that three days of Sorafenib treatment activated EMT with overexpression of TGF-β1 in both HCC cell lines. Following Sorafenib exposure, increase in the expression of PD-L1 and other immune checkpoints was observed. SB431542 blocked the TGF-β1-mediated EMT in HCC cells and also repressed PD-L1 expression. Likewise, knockdown of PD-L1 inhibited EMT. Moreover, the sensitivity of HCC cells to Sorafenib was enhanced by combining a blockade of EMT with SB431542 and knockdown of PD-L1 expression. Sorafenib-induced motility was attenuated with the combined treatment of SB431542 and PD-L1 knockdown. Our findings indicate that treatment with Sorafenib induces EMT and expression of immune checkpoint molecules, which contributes to Sorafenib resistance in HCC cells. Thus, the combination treatment strategy of inhibiting EMT and immune checkpoint molecules can re-sensitise HCC cells to Sorafenib

Cosmological parameters in the noncommutative inflation

We investigate how the uncertainty of noncommutative spacetime could explain the WMAP data. For this purpose, the spectrum is divided into the IR and UV region. We introduce a noncommutative parameter of $\gamma_0$ in the IR region and a noncommutative parameter of $\mu_0$ in the UV region. We calculate cosmological parameters using the slow-roll expansion in the UV region and a perturbation method in the IR region. The power-law inflation is chosen to obtain explicit forms for the power spectrum, spectral index, and running spectral index. Further, these are used to fit the data.Comment: 13 pages, version to appear in PL

Cosmological Systematics Beyond Nuisance Parameters : Form Filling Functions

In the absence of any compelling physical model, cosmological systematics are often misrepresented as statistical effects and the approach of marginalising over extra nuisance systematic parameters is used to gauge the effect of the systematic. In this article we argue that such an approach is risky at best since the key choice of function can have a large effect on the resultant cosmological errors. As an alternative we present a functional form filling technique in which an unknown, residual, systematic is treated as such. Since the underlying function is unknown we evaluate the effect of every functional form allowed by the information available (either a hard boundary or some data). Using a simple toy model we introduce the formalism of functional form filling. We show that parameter errors can be dramatically affected by the choice of function in the case of marginalising over a systematic, but that in contrast the functional form filling approach is independent of the choice of basis set. We then apply the technique to cosmic shear shape measurement systematics and show that a shear calibration bias of |m(z)|< 0.001(1+z)^0.7 is required for a future all-sky photometric survey to yield unbiased cosmological parameter constraints to percent accuracy. A module associated with the work in this paper is available through the open source iCosmo code available at http://www.icosmo.org .Comment: 24 pages, 18 figures, accepted to MNRA

Heterozygous Hfe gene deletion leads to impaired glucose homeostasis, but not liver injury in mice fed a high-calorie diet

Heterozygous mutations of the Hfe gene have been proposed as cofactors in the development and progression of nonalcoholic fatty liver disease (NAFLD). Homozygous Hfe deletion previously has been shown to lead to dysregulated hepatic lipid metabolism and accentuated liver injury in a dietary mouse model of NAFLD. We sought to establish whether heterozygous deletion of Hfe is sufficient to promote liver injury when mice are exposed to a high-calorie diet (HCD). Eight-week-old wild-type and Hfe mice received 8\ua0weeks of a control diet or HCD. Liver histology and pathways of lipid and iron metabolism were analyzed. Liver histology demonstrated that mice fed a HCD had increased NAFLD activity score (NAS), steatosis, and hepatocyte ballooning. However, liver injury was unaffected by Hfe genotype. Hepatic iron concentration (HIC) was increased in Hfe mice of both dietary groups. HCD resulted in a hepcidin-independent reduction in HIC. Hfe mice demonstrated raised fasting serum glucose concentrations and HOMA-IR score, despite unaltered serum adiponectin concentrations. Downstream regulators of hepatic de novo lipogenesis (pAKT, SREBP-1, Fas, Scd1) and fatty acid oxidation (AdipoR2, Pparα, Cpt1) were largely unaffected by genotype. In summary, heterozygous Hfe gene deletion is associated with impaired iron and glucose metabolism. However, unlike homozygous Hfe deletion, heterozygous gene deletion did not affect lipid metabolism pathways or liver injury in this model

Clusters of Galaxies: magnetic fields and nonthermal emission

The nonthermal particle content of galaxy clusters should in part have a cosmological component generated during the early starburst phase of the member galaxies. This is reviewed in the framework of a simple cluster formation model suggested previously. It implies a nonthermal energy fraction of about 10 percent for the Intracluster gas. We also propose a mechanism for the early generation of Intracluster magnetic fields in terms of Galactic Winds. It results in typical field strengths of about 0.1 microGauss. Such comparatively weak fields are consistent with an inverse Compton origin of the excess EUV and hard X-ray emission of the Coma cluster, given the radio synchrotron emission. The required relativistic electrons must have been accelerated rather recently, less than a few billion years ago, presumably in cluster accretion shocks. This is in contrast to the hadronic nonthermal component which accumulates on cosmological time scales, and whose pion-decay TeV gamma-ray emission is expected to be larger, or of the same order as the inverse Compton TeV emission. This gamma-radiation characterizes the energetic history of cluster formation and should be observable with future arrays of imaging atmospheric Cherenkov telescopes.Comment: 16 pages, 8 figures; invited talk presented at the VERITAS Workshop on TeV Astrophysics of Extragalactic Sources, submitted to Astroparticle Physic

Clinical practice guidelines on hemochromatosis: Asian Pacific Association for the Study of the Liver

Hereditary hemochromatosis is the result of pathogenic variants in multiple genes that can result in increased body iron stores with excess iron deposited in various organs, including the liver, pancreas, and heart. The two most important advances in the field over the past 30 years have been the identification of the HFE gene (and the associated p.Cys282Tyr substitution), and the discovery of the hormone hepcidin, which is inappropriately low in this condition and is the pathophysiological basis of the increased iron absorption. The identification of mutations in the HFE gene and subsequent studies have reshaped diagnostic algorithms resulting in a marked reduction in the need for liver biopsy. The discovery of hepcidin has resulted in many studies that have dramatically improved our understanding of iron metabolism with clear potential therapeutic implications. The variable clinical expression of hemochromatosis has puzzled clinicians and scientists, and our understanding of the factors that influence the phenotype has increased over recent years. Nevertheless, increased clinician and patient awareness, early diagnosis, and therapeutic phlebotomy to restore normal life expectancy are still the cornerstones of management. The classic triad of cirrhosis, diabetes, and skin pigmentation is now uncommon, and many patients are diagnosed with minimal or no symptoms

Second-order corrections to slow-roll inflation in the brane cosmology

We calculate the power spectrum, spectral index, and running spectral index for the RS-II brane inflation in the high-energy regime using the slow-roll expansion. There exist several modifications. As an example, we take the power-law inflation by choosing an inverse power-law potential. When comparing these with those arisen in the standard inflation, we find that the power spectrum is enhanced and the spectral index is suppressed, while the running spectral index becomes zero as in the standard inflation. However, since second-order corrections are rather small, these could not play a role of distinguishing between standard and brane inflations.Comment: 6 page

The removal of shear-ellipticity correlations from the cosmic shear signal: Influence of photometric redshift errors on the nulling technique

Cosmic shear is regarded one of the most powerful probes to reveal the properties of dark matter and dark energy. To fully utilize its potential, one has to be able to control systematic effects down to below the level of the statistical parameter errors. Particularly worrisome in this respect is intrinsic alignment, causing considerable parameter biases via correlations between the intrinsic ellipticities of galaxies and the gravitational shear, which mimic lensing. In an earlier work we have proposed a nulling technique that downweights this systematic, only making use of its well-known redshift dependence. We assess the practicability of nulling, given realistic conditions on photometric redshift information. For several simplified intrinsic alignment models and a wide range of photometric redshift characteristics we calculate an average bias before and after nulling. Modifications of the technique are introduced to optimize the bias removal and minimize the information loss by nulling. We demonstrate that one of the presented versions is close to optimal in terms of bias removal, given high quality of photometric redshifts. For excellent photometric redshift information, i.e. at least 10 bins with a small dispersion, a negligible fraction of catastrophic outliers, and precise knowledge about the redshift distributions, one version of nulling is capable of reducing the shear-intrinsic ellipticity contamination by at least a factor of 100. Alternatively, we describe a robust nulling variant which suppresses the systematic signal by about 10 for a very broad range of photometric redshift configurations. Irrespective of the photometric redshift quality, a loss of statistical power is inherent to nulling, which amounts to a decrease of the order 50% in terms of our figure of merit.Comment: 26 pages, including 16 figures; minor changes to match accepted version; published in Astronomy and Astrophysic

Second-order corrections to noncommutative spacetime inflation

We investigate how the uncertainty of noncommutative spacetime affects on inflation. For this purpose, the noncommutative parameter $\mu_0$ is taken to be a zeroth order slow-roll parameter. We calculate the noncommutative power spectrum up to second order using the slow-roll expansion. We find corrections arisen from a change of the pivot scale and the presence of a variable noncommutative parameter, when comparing with the commutative power spectrum. The power-law inflation is chosen to obtain explicit forms for the power spectrum, spectral index, and running spectral index. In cases of the power spectrum and spectral index, the noncommutative effect of higher-order corrections compensates for a loss of higher-order corrections in the commutative case. However, for the running spectral index, all higher-order corrections to the commutative case always provide negative spectral indexes, which could explain the recent WMAP data.Comment: 15 pages, no figure, version published in PR