Hawking radiation as tunneling from a Vaidya black hole in noncommutative gravity

In the context of a noncommutative model of coordinate coherent states, we present a Schwarzschild-like metric for a Vaidya solution instead of the standard Eddington-Finkelstein metric. This leads to the appearance of an exact $(t - r)$ dependent case of the metric. We analyze the resulting metric in three possible causal structures. In this setup, we find a zero remnant mass in the long-time limit, i.e. an instable black hole remnant. We also study the tunneling process across the quantum horizon of such a Vaidya black hole. The tunneling probability including the time-dependent part is obtained by using the tunneling method proposed by Parikh and Wilczek in terms of the noncommutative parameter $\sigma$. After that, we calculate the entropy associated to this noncommutative black hole solution. However the corrections are fundamentally trifling; one could respect this as a consequence of quantum inspection at the level of semiclassical quantum gravity.Comment: 19 pages, 5 figure

DISSECTING THE ROLE OF HISTONE DEACETYLASE 3 (HDAC3) IN LEUKEMOGENESIS

Histone deacetylases (HDACs) are epigenetic enzymes that modulate chromatin structure through the deacetylation of lysine residues in histones, playing a crucial role in cell viability, cell cycle progression and tumorigenesis. Yet the role of individual HDACs in these biological processes remains enigmatic. Inappropriate recruitment of HDACs is involved in the pathogenesis of several forms of leukemia and several lines of evidence point to a role for HDACs in tumor progression, consistent with the anti-proliferative and apoptotic effects of HDAC inhibitors (HDACi). In this regard, HDACs are considered promising targets for development of new molecules for cancer therapy. To date, some HDACi which have a broad antitumor activity and low toxicity towards normal cells, such as Romidepsin (Depsipeptide or FK228) and SAHA have been approved by U.S. food and drug administration (FDA) for the treatment of cutaneous T-cell lymphoma (CTCL). Moreover, HDACi are undergoing clinical trials for the treatment of hematological malignancies as well as for solid tumors. Most of the HDACi available at the moment are not isoform specific, being active on more than one HDAC. Thus, to design more selective HDACi for cancer therapy it is important to elucidate the role of individual HDACs. Acute Promyelocytic Leukemia (APL) is the first model disease in which the involvement of HDACs has been documented. APL is a subtype of Acute Myeloid Leukemia (AML), a cancer of blood and bone marrow, which is characterized by hyperproliferation of immature granulocytes blocked at the promyelocytic stage. It is genetically associated with a chromosomal translocation t(15;17)(q22;q21), which encodes the oncogenic fusion protein PML-RAR\u3b1 found in more than 90% of APL patients. In murine models of APL that recapitulate the human disease, PML-RAR\u3b1 induces a \u201cpre-leukemic\u201d stage with long latency and without an overtly dramatic phenotype before full leukemic transformation. In fact, for this reason it is assumed that in addition to this oncogenic fusion protein, other genetic hits are required for clonal expansion of leukemic blasts. This fusion protein recruits a number of chromatin modifier enzymes such as HDACs and DNA methyltransferases (DNMTs) to the promoter of retinoic acid (RA) target genes and transcriptionally silence them, leading to the myeloid differentiation block. Furthermore, PML-RAR\u3b1 causes the impairment of p53 pathway by deacetylation and degradation of p53 through the recruitment of HDAC- containing complexes. HDACs from class I (HDACs 1, 2 and 3) have been found associated with PML-RAR\u3b1 paving the way for the use of HDACi for APL treatment. Recently, a study on APL, which has been conducted by Santoro et al., showed that among class I HDACs, HDAC1 and to a lesser extent HDAC2 have a dual role in APL development and maintenance. In fact, while they behave as oncosuppressors at the early stages, they function as oncogenes in established tumor cells. Since inhibition of HDAC1 and HDAC2 in pre-leukemic stage leads to the acceleration of the disease in murine models of leukemia, it suggests caution in the clinical utility of epidrugs that target any of these two HDAC isoforms. Moreover, it has been shown that the expression of HDAC3, which associates with nuclear hormone corepressor and silencing mediator of retinoid hormone (NCoR/SMRT) complex, is frequently increased in tumors, while Hdac3 downregulation results in reduced proliferation and survival of tumor cells. In view of these observations, in this study we functionally assessed the role of HDAC3 in the development and maintenance of APL. To achieve our goal, we have dissected the role of HDAC3 in two different phases of the disease: pre-leukemic phase and full-established leukemia. The murine model of APL, which we used, is the mCGPR/PR mouse model in which PML-RAR\u3b1 is expressed under the control of the cathepsin G promoter. The mice show a very long latency (the pre-leukemic phase) associated with high penetrance (more than 90% of the mice develop APL). We characterized the role of HDAC3 through a functional knock-down approach, assessing its impact on cellular differentiation, proliferation and the ability to influence the transplantation of HSCs and APL cells. Indeed, Hdac3-KD in vitro reduced the proliferative potential of both pre-leukemic and full leukemic cells and boosted their differentiation, suggesting that HDAC3 plays the role of an oncogene in APL initiation and progression. These results were not restricted to APL, because lymphoma driven by c-myc overexpression and leukemia driven by MLL-AF9, were both impaired in cell growth upon Hdac3-KD. In vivo, inoculation of Hdac3-KD pre-leukemic cells into lethally irradiated recipient mice or inoculation of Hdac3-KD APL cells into the recipient mice did not result in leukemia development or progression, respectively. These results suggest that HDAC3 can be considered as a target for epidrugs in the treatment of hematological malignancies. Thus, we assessed this hypothesis with the treatment of pre-leukemic and leukemic cells with the HDAC3 selective inhibitor, RGFP966. Indeed, inhibition of HDAC3 enzymatic activity with RGFP966, phenocopied Hdac3-KD phenotypes in pre-leukemic and leukemic cells confirming the putative oncogenic role of HDAC3. In conclusion, my PhD project has expanded our comprehension about the role of HDAC3 in hematological malignancies and is beginning to unravel alternative views on the targets of epidrugs for the treatment of leukemic patients

Tunneling of massive and charged particles from noncommutative Reissner-Nordstr\"{o}m black hole

Massive charged and uncharged particles tunneling from commutative Reissner-Nordstrom black hole horizon has been studied with details in literature. Here, by adopting the coherent state picture of spacetime noncommutativity, we study tunneling of massive and charged particles from a noncommutative inspired Reissner-Nordstrom black hole horizon. We show that Hawking radiation in this case is not purely thermal and there are correlations between emitted modes. These correlations may provide a solution to the information loss problem. We also study thermodynamics of noncommutative horizon in this setup.Comment: 10 pages, 2 figure

Entropic force approach in a noncommutative charged black hole and the equivalence principle

Recently, Verlinde has suggested a novel model of duality between thermodynamics and gravity which leads to an emergent phenomenon for the origin of gravity and general relativity. In this paper, we investigate some features of this model in the presence of noncommutative charged black hole by performing the method of coordinate coherent states representing smeared structures. We derive several quantities, e.g. temperature, energy and entropic force. Our approach clearly exhibits that the entropic force on a smallest fundamental cell of holographic surface with radius $r_0$ is halted. Accordingly, we can conclude that the black hole remnants are absolutely inert without gravitational interactions. So, the equivalence principle of general relativity is contravened due to the fact that it is now possible to find a difference between the gravitational and inertial mass. In other words, the gravitational mass in the remnant size does not emit any gravitational field, therefore it is experienced to be zero, contrary to the inertial mass. This phenomenon illustrates a good example for a feasible experimental confirmation to the entropic picture of Newton's Second law in very short distances.Comment: 11 pages, 2 figure

Black Hole Evaporation in a Noncommutative Charged Vaidya Model

The aim of this paper is to study the black hole evaporation and Hawking radiation for a noncommutative charged Vaidya black hole. For this purpose, we determine spherically symmetric charged Vaidya model and then formulate a noncommutative Reissner-Nordstr$\ddot{o}$m-like solution of this model which leads to an exact $(t-r)$ dependent metric. The behavior of temporal component of this metric and the corresponding Hawking temperature is investigated. The results are shown in the form of graphs. Further, we examine the tunneling process of the charged massive particles through the quantum horizon. It is found that the tunneling amplitude is modified due to noncommutativity. Also, it turns out that black hole evaporates completely in the limits of large time and horizon radius. The effect of charge is to reduce the temperature from maximum value to zero. It is mentioned here that the final stage of black hole evaporation turns out to be a naked singularity.Comment: 25 pages, 36 figures, accepted for publication in J. Exp. Theor. Phy

Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families

Background: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age. Methods: Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression. Results: The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients ≤ 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples. No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen. Conclusion: The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (≤ 40 years) and this may have therapeutic implications in the context of hTR targeting strategies

Evaluating equality in prescribing Novel Oral Anticoagulants (NOACs) in England: the protocol of a Bayesian small area analysis

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 1.6% of the population in England. Novel oral anticoagulants (NOACs) are approved AF treatments that reduce stroke risk. In this study, we estimate the equality in individual NOAC prescriptions with high spatial resolution in Clinical Commissioning Groups (CCGs) across England from 2014 to 2019. Methods A Bayesian spatio-temporal model will be used to estimate and predict the individual NOAC prescription trend on ‘prescription data’ as an indicator of health services utilisation, using a small area analysis methodology. The main dataset in this study is the “Practice Level Prescribing in England,” which contains four individual NOACs prescribed by all registered GP practices in England. We will use the defined daily dose (DDD) equivalent methodology, as recommended by the World Health Organization (WHO), to compare across space and time. Four licensed NOACs datasets will be summed per 1,000 patients at the CCG-level over time. We will also adjust for CCG-level covariates, such as demographic data, Multiple Deprivation Index, and rural-urban classification. We aim to employ the extended BYM2 model (space-time model) using the RStan package. Discussion This study suggests a new statistical modelling approach to link prescription and socioeconomic data to model pharmacoepidemiologic data. Quantifying space and time differences will allow for the evaluation of inequalities in the prescription of NOACs. The methodology will help develop geographically targeted public health interventions, campaigns, audits, or guidelines to improve areas of low prescription. This approach can be used for other medications, especially those used for chronic diseases that must be monitored over time

Multiwavelength campaign on Mrk 509 XII. Broad band spectral analysis

(Abridged) The simultaneous UV to X-rays/gamma rays data obtained during the multi-wavelength XMM/INTEGRAL campaign on the Seyfert 1 Mrk 509 are used in this paper and tested against physically motivated broad band models. Each observation has been fitted with a realistic thermal comptonisation model for the continuum emission. Prompted by the correlation between the UV and soft X-ray flux, we use a thermal comptonisation component for the soft X-ray excess. The UV to X-rays/gamma-rays emission of Mrk 509 can be well fitted by these components. The presence of a relatively hard high-energy spectrum points to the existence of a hot (kT~100 keV), optically-thin (tau~0.5) corona producing the primary continuum. On the contrary, the soft X-ray component requires a warm (kT~1 keV), optically-thick (tau~15) plasma. Estimates of the amplification ratio for this warm plasma support a configuration close to the "theoretical" configuration of a slab corona above a passive disk. An interesting consequence is the weak luminosity-dependence of its emission, a possible explanation of the roughly constant spectral shape of the soft X-ray excess seen in AGNs. The temperature (~ 3 eV) and flux of the soft-photon field entering and cooling the warm plasma suggests that it covers the accretion disk down to a transition radius $R_{tr}$ of 10-20 $R_g$. This plasma could be the warm upper layer of the accretion disk. On the contrary the hot corona has a more photon-starved geometry. The high temperature ($\sim$ 100 eV) of the soft-photon field entering and cooling it favors a localization of the hot corona in the inner flow. This soft-photon field could be part of the comptonised emission produced by the warm plasma. In this framework, the change in the geometry (i.e. $R_{tr}$) could explain most of the observed flux and spectral variability.Comment: 19 pages, 14 figures. Accepted for publication in A&

The Swift-UVOT ultraviolet and visible grism calibration

We present the calibration of the Swift UVOT grisms, of which there are two, providing low-resolution field spectroscopy in the ultraviolet and optical bands respectively. The UV grism covers the range 1700-5000 Angstrom with a spectral resolution of 75 at 2600 Angstrom for source magnitudes of u=10-16 mag, while the visible grism covers the range 2850-6600 Angstrom with a spectral resolution of 100 at 4000 Angstrom for source magnitudes of b=12-17 mag. This calibration extends over all detector positions, for all modes used during operations. The wavelength accuracy (1-sigma) is 9 Angstrom in the UV grism clocked mode, 17 Angstrom in the UV grism nominal mode and 22 Angstrom in the visible grism. The range below 2740 Angstrom in the UV grism and 5200 Angstrom in the visible grism never suffers from overlapping by higher spectral orders. The flux calibration of the grisms includes a correction we developed for coincidence loss in the detector. The error in the coincidence loss correction is less than 20%. The position of the spectrum on the detector only affects the effective area (sensitivity) by a few percent in the nominal modes, but varies substantially in the clocked modes. The error in the effective area is from 9% in the UV grism clocked mode to 15% in the visible grism clocked mode .Comment: 27 pages, 31 figures; MNRAS accepted 23 February 201

Multiwavelength campaign on Mrk 509: testing realistic comptonization models

Mrk 509 was observed by XMM-Newton and INTEGRAL in October/November 2009, with one observation every four days for a total of ten observations. Each observation has been fitted with a realistic thermal Comptonization model for the continuum emission. Prompted by the correlation between the UV and soft X-ray flux, we used a thermal Comptonization component for the soft X-ray excess. The UV to X-ray/gamma-ray emission of Mrk 509 can be well fitted by these components, pointing to the existence of a hot (kT ∼ 100 keV), optically-thin (τ ∼ 0.5) corona producing the primary continuum. In contrast, the soft X-ray component requires a warm (kT ∼ 1 keV), optically-thick (τ ∼ 10-20) plasma. Estimates of the amplification ratio for this warm plasma support a configuration relatively close to the “theoretical” configuration of a slab corona above a passive disk. This plasma could be the warm upper layer of the accretion disk. In contrast, the hot corona has a more photon-starved geometry. The high temperature (∼ 100 eV) of the soft-photon field entering and cooling it favors a localization of the hot corona in the inner flow. This soft-photon field could be part of the comptonized emission produced by the warm plasma