The mRNA expression of SETD2 in human breast cancer: Correlation with clinico-athological parameters

BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). CONCLUSION: This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer

Probing the faint end of the quasar luminosity function at z ~ 4 in the COSMOS field

We searched for quasars that are ~ 3 mag fainter than the SDSS quasars in the redshift range 3.7 < z < 4.7 in the COSMOS field to constrain the faint end of the quasar luminosity function. Using optical photometric data, we selected 31 quasar candidates with 22 < i' < 24 at z ~ 4. We obtained optical spectra for most of these candidates using FOCAS on the Subaru telescope, and identified 8 low-luminosity quasars at z ~ 4. In order to derive the quasar luminosity function (QLF) based on our spectroscopic follow-up campaign, we estimated the photometric completeness of our quasar survey through detailed Monte Carlo simulations. Our QLF at z ~ 4 has a much shallower faint-end slope beta = -1.67^{+0.11}_{-0.17} than that obtained by other recent surveys in the same redshift. Our result is consistent with the scenario of downsizing evolution of active galactic nuclei inferred by recent optical and X-ray quasar surveys at lower redshifts.Comment: 13 pages, 4 figure, Accepted for publication in ApJ

Multiple large shareholders, excess leverage and tunneling: evidence from an emerging market

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Manuscript Type: Empirical Research Question/Issue: Past empirical efforts in corporate governance have examined the effects of large shareholders with the excess control rights on tunneling activities. However, no study has systematically investigated the effects of multiple large shareholders on excess leverage policies and tunneling in an emerging country environment where minority rights protection is weak. In this study, we examine the role of multiple large shareholders and the effects of control contestability of multiple large shareholders on firm excess leverage decision and tunneling by controlling shareholders. Research Findings/Insights: Using a sample of 2,341 Chinese firms for the years 2001 to 2013, we document that the contestability of multiple non-controlling large shareholders relative to controlling shareholders reduces the adoption of excess leverage policies, tunneling and enhances capital investment. Another intriguing finding is that the government as a controlling shareholder exerts significant influence and reduces the monitoring effectiveness of multiple larger shareholders. Theoretical/Academic Implications: By addressing the role of multiple large shareholders on excess leverage decisions, this study makes an important contribution to the corporate governance literature. We extend the recent developments in agency theory regarding the role of multiple large shareholders in constraining expropriation of controlling shareholders with excess control rights and their effect on firm leverage decisions. Our results support the theoretical models which indicate that the presence of multiple large shareholders is an important and efficient internal governance mechanism that mitigates a firm’s agency costs, particularly, in an emerging market environment where corporate governance is weak and inadequate to curb tunneling problem. JEL classification: G15; G34; G3

Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection.

HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRRs) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRRs and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of Toll-like receptor 4 (TLR4) and TLR8 was downmodulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early antiretroviral therapy led to viral suppression but only partial maintenance of gut PRRs and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes, and ineffective viral clearance

On growth rate and contact homology

It is a conjecture of Colin and Honda that the number of Reeb periodic orbits of universally tight contact structures on hyperbolic manifolds grows exponentially with the period, and they speculate further that the growth rate of contact homology is polynomial on non-hyperbolic geometries. Along the line of the conjecture, for manifolds with a hyperbolic component that fibers on the circle, we prove that there are infinitely many non-isomorphic contact structures for which the number of Reeb periodic orbits of any non-degenerate Reeb vector field grows exponentially. Our result hinges on the exponential growth of contact homology which we derive as well. We also compute contact homology in some non-hyperbolic cases that exhibit polynomial growth, namely those of universally tight contact structures non-transverse to the fibers on a circle bundle

Tools for computing the AGN feedback: radio-loudness distribution and the kinetic luminosity function

We studied the Active Galactic Nuclei (AGN) radio emission from a compilation of hard X-ray selected samples, all observed in the 1.4 GHz band. A total of more than 1600 AGN with 2-10 keV de-absorbed luminosities higher than 10^42 erg/s were used. For a sub-sample of about 50 z\lsim 0.1 AGN it was possible to reach a ~80% fraction of radio detections and therefore, for the first time, it was possible to almost completely measure the probability distribution function of the ratio between the radio and the X-ray luminosity Rx=log[L(1.4)/Lx]. The probability distribution function of Rx was functionally fitted as dependent on the X-ray luminosity and redshift, P(Rx|Lx,z). It roughly spans over 6 decades (-7<Rx<-1), and does not show any sign of bi-modality. It resulted that the probability of finding large values of the Rx ratio increases with decreasing X-ray luminosities and (possibly) with increasing redshift. No statistical significant difference was found between the radio properties of the X-ray absorbed and unabsorbed AGN. The measure of the probability distribution function of Rx allowed us to compute the kinetic luminosity function and the kinetic energy density which, at variance with what assumed in many galaxy evolution models, is observed to decrease of about a factor of five at redshift below 0.5. About half of the kinetic energy density results to be produced by the more radio quiet (Rx<-4) AGN. In agreement with previous estimates, the AGN efficiency in converting the accreted mass energy into kinetic power is, on average, ~5x10-3.Comment: 13 pages, ApJsty; ApJ in pres

Surface Photometry and Radial Color Gradients of Nearby Luminous Early-type Galaxies in SDSS Stripe 82

We make use of the images from the Sloan Digital Sky Survey Stripe 82 to present an analysis of r band surface brightness profiles and radial color gradients (g - r, u - r) in 111 nearby early-type galaxies (ETGs). With Stripe 82 images, we are able to pay special attentions to the low-surface-brightness areas (LSB areas) of the galaxies. The LSB areas make a difference to the Sersic fittings and concentration indices, making both the indices less than the typical values for ETGs. There are about 60% negative color gradients (red-core) within 1.5Re , much more than the approximately 10% positive ones (blue-core) within the same radius. However, taking into account of the LSB areas, we find that the color gradients are not necessarily monotonic: about one third of the red-core (or blue-core) galaxies have positive (or negative) color gradients in the outer areas. So LSB areas not only make ETGs' Sersic profiles deviate from de Vaucouleur ones and shift to the disk end, but also reveal that quite a number of ETGs have opposite color gradients in inner and outer areas. These outcomes remind us the necessity of double-Sersic fitting. These LSB phenomena may be interpreted by mergers and thus different metallicity in the outer areas. Isophotal parameters are also discussed briefly in this paper: more disky nearby ETGs are spotted than boxy ones.Comment: 14 pages, 12 figure

Hawking radiation as tunneling from charged black holes in 0A string theory

There has been much work on explaining Hawking radiation as a quantum tunneling process through horizons. Basically, this intuitive picture requires the calculation of the imaginary part of the action for outgoing particle. And two ways are known for achieving this goal: the null-geodesic method and the Hamilton-Jacobi method. We apply these methods to the charged black holes in 2D dilaton gravity which is originated from the low energy effective theory of type 0A string theory. We derive the correct Hawking temperature of the black holes including the effect of the back reaction of the radiation, and obtain the entropy by using the 1st law of black hole thermodynamics. For fixed-charge ensemble, the 0A black holes are free of phase transition and thermodynamically stable regardless of mass-charge ratio. We show this by interpreting the back reaction term as the inverse of the heat capacity of the black holes. Finally, the possibility of the phase transition in the fixed-potential ensemble is discussed.Comment: 12 pages; v2: references added, revised with some changes in formula and unaltered conclusions, to be published in Phys. Lett.