Ab initio simulations of accretion disks instability

We show that accretion disks, both in the subcritical and supercritical accretion rate regime, may exhibit significant amplitude luminosity oscillations. The luminosity time behavior has been obtained by performing a set of time-dependent 2D SPH simulations of accretion disks with different values of alpha and accretion rate. In this study, to avoid any influence of the initial disk configuration, we produced the disks injecting matter from an outer edge far from the central object. The period of oscillations is 2 - 50 s respectively for the two cases, and the variation amplitude of the disc luminosity is 10^38 - 10^39 erg/s. An explanation of this luminosity behavior is proposed in terms of limit cycle instability: the disk oscillates between a radiation pressure dominated configuration (with a high luminosity value) and a gas pressure dominated one (with a low luminosity value). The origin of this instability is the difference between the heat produced by viscosity and the energy emitted as radiation from the disk surface (the well-known thermal instability mechanism). We support this hypothesis showing that the limit cycle behavior produces a sequence of collapsing and refilling states of the innermost disk region.Comment: 11 pages, 15 Postscript figures, uses natbib.sty, accepted for publication in MNRA

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SPH simulations of Shakura-Sunyaev instability at intermediate accretion rates

We show that a standard Shakura-Sunyaev accretion disc around a black hole with an accretion rate lower than the critical Eddington limit does show the instability in the radiation pressure dominated zone. We obtain this result performing time-dependent simulations of accretion disks for a set of values of the viscosity parameter and accretion rate. In particular we always find the occurrence of the collapse of the disc: the instability develops always towards a collapsed gas pressure dominated disc and not towards the expansion. This result is valid for all initial configurations we tested. We find significant convective heat flux that increases the instability development time, but is not strong enough to inhibit the disc collapse. A physical explanation of the lack of the expansion phase is proposed considering the role of the radial heat advection. Our finding is relevant since it excludes the formation of the hot comptonizing corona -often suggested to be present- around the central object by the mechanism of the Shakura-Sunyaev instability. We also show that, in the parameters range we simulated, accretion disks are crossed by significant amplitude acoustic waves.Comment: 8 pages, 12 Postscript figures, uses natbib.sty, accepted for publication in MNRA

Radiative Shocks in Rotating Accretion Flows around Black Holes

It is well known that the rotating inviscid accretion flows with adequate injection parameters around black holes could form shock waves close to the black holes, after the flow passes through the outer sonic point and can be virtually stopped by the centrifugal force. We examine numerically such shock waves in 1D and 2D accretion flows, taking account of cooling and heating of the gas and radiation transport. The numerical results show that the shock location shifts outward compared with that in the adiabatic solutions and that the more rarefied ambient density leads to the more outward shock location. In the 2D-flow, we find an intermediate frequency QPO behavior of the shock location as is observed in the black hole candidate GRS 1915+105.Comment: 11pages, 5 Postscript figures, to appear in PASJ, Vol.56, No.3, 200

Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells

Essential oils from various aromatic plants have been reported to exert chemopreventive and/or antitumor effects. In addition, a number of studies have shown the ability of chemopreventive phytochemicals to increase the sensitivity of cancer cells to conventional anticancer drugs. The success of chemotherapeutic agents is often hindered by the development of drug resistance, with multidrug resistant (MDR) phenotypes reported in a number of tumors, generally involving reduced intracellular drug accumulation due to increased drug efflux by membrane transporters. In the present study, the effects of linalool (LIN), a monoterpene alcohol found in the essential oils from many aromatic plants, on the growth of two human breast adenocarcinoma cell lines, MCF7 WT and multidrug resistant MCF7 AdrR, were investigated, both as a single agent and in combination with doxorubicin (DOX). The results reported here show that LIN only moderately inhibits cell proliferation; interestingly, however, subtoxic concentrations of LIN potentiate DOX-induced cytotoxicity and pro-apoptotic effects in both cell lines. A significant synergism can be observed in MCF7 AdrR cells, which may be due, at least in part, to the ability of LIN to increase DOX accumulation and to induce a decrease in Bcl-xL levels. In summary, the results of the present study suggest that LIN may improve the therapeutic index of anthracyclines in the management of breast cancer, especially in MDR tumors

GSK2801 Reverses Paclitaxel Resistance in Anaplastic Thyroid Cancer Cell Lines through MYCN Downregulation

Anaplastic thyroid cancer (ATC) is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. Treatment with taxanes (such as paclitaxel) is an important approach in counteracting ATC or slowing its progression in tumors without known genetic aberrations or those which are unresponsive to other treatments. Unfortunately, resistance often develops and, for this reason, new therapies that overcome taxane resistance are needed. In this study, effects of inhibition of several bromodomain proteins in paclitaxel-resistant ATC cell lines were investigated. GSK2801, a specific inhibitor of BAZ2A, BAZ2B and BRD9, was effective in resensitizing cells to paclitaxel. In fact, when used in combination with paclitaxel, it was able to reduce cell viability, block the ability to form colonies in an anchor-independent manner, and strongly decrease cell motility. After RNA-seq following treatment with GSK2801, we focused our attention on MYCN. Based on the hypothesis that MYCN was a major downstream player in the biological effects of GSK2801, we tested a specific inhibitor, VPC-70619, which showed effective biological effects when used in association with paclitaxel. This suggests that the functional deficiency of MYCN determines a partial resensitization of the cells examined and, ultimately, that a substantial part of the effect of GSK2801 results from inhibition of MYCN expression

SHORT COMMUNICATION: Urban malaria in Dodoma and Iringa, Tanzania

Cross sectional malaria parasitaemia and entomological surveys were carried out in urban Iringa and Dodoma in Tanzania. A total of 395 and 392 schoolchildren (age range= 6-15 years) were screened for malaria parasites in Iringa and Dodoma, respectively. Plasmodium falciparum was the predominant malaria parasite (Iringa= 100%, Dodoma= 97.8%). Malaria parasitaemia was observed in 14.9% and 12% of the schoolchildren in Iringa and Dodoma, respectively. The geometric mean parasite density for P. falciparum was higher (632 parasites/μl) in Iringa than in Dodoma (74.1 parasites/μl). The average spleen rates were 0.5% and 2% in Iringa and Dodoma, respectively. A slightly higher haemoglobin level was observed among schoolchildren in Dodoma (10.2g/dl) than in Iringa (9.5g/dl). Only a few Anopheles gambiae sensu lato were collected indoors in the two areas. On the average 47.3% and 80% of the children in Iringa and Dodoma, respectively were sleeping under mosquito nets. Although malaria endemicity in the two municipalities is low, unplanned rapid urbanisation is likely to change malaria epidemiology in Tanzania. Continuous malaria and mosquito density surveillance should therefore, form an in integral part of the malaria control strategies in urban areas. Communities should be continuously sensitised to use insecticide-treated mosquito nets and strengthen community-based environmental management to minimise malaria breeding sites. Keywords: urban, malaria, schoolchildren, Tanzania Tanzania Health Research Bulletin Vol. 8 (2) 2006: pp. 115-11

Role of m6A RNA Methylation in Thyroid Cancer Cell Lines

N6-methyladenosine (m6A) is the most abundant internal modification of RNA in eukaryotic cells, and, in recent years, it has gained increasing attention. A good amount of data support the involvement of m6A modification in tumorigenesis, tumor progression, and metastatic dissemination. However, the role of this RNA modification in thyroid cancer still remains poorly investigated. In this study, m6A-related RNA methylation profiles are compared between a normal thyroid cell line and different thyroid cancer cell lines. With this approach, it was possible to identify the different patterns of m6A modification in different thyroid cancer models. Furthermore, by silencing METTL3, which is the main player in the RNA methylation machinery, it was possible to evaluate the impact of m6A modification on gene expression in an anaplastic thyroid cancer model. This experimental approach allowed us to identify DDI2 as a gene specifically controlled by the m6A modification in anaplastic thyroid cancer cell lines. Altogether, these data are a proof of concept that RNA methylation widely occurs in thyroid cancer cell models and open a way forward in the search for new molecular patterns for diagnostic discrimination between benign and malignant lesions

Chronic mild stress-induced alterations of clock gene expression in rat prefrontal cortex: modulatory effects of prolonged lurasidone treatment

Disruptions of biological rhythms are known to be associated with depressive disorders, suggesting that abnormalities in the molecular clock may contribute to the development of these disorders. These mechanisms have been extensively characterized in the suprachiasmatic nucleus, but little is know about the role exerted by individual clock genes in brain structures that are important for depressive disorders. Using the chronic mild stress model we found a significant reduction of BMAL1 and CLOCK protein levels in the nuclear compartment of the prefrontal cortex of CMS rats, which was paralleled by a down-regulation of the expression of several target genes, including Pers and Crys but also Reverb\u3b2 and Ppar\u3b1. Interestingly, chronic treatment with the multi receptor modulator lurasidone (3 mg/kg for 5 weeks) was able to normalize the molecular changes induced by CMS exposure in prefrontal cortex, but it was also able to regulate some of these genes within the hippocampus. We believe that changes in clock genes expression after CMS exposure may contribute to the disturbances associated with depressive disorders and that the ability of chronic lurasidone to normalize such alterations may be relevant for its therapeutic properties in ameliorating functions that are deteriorated in patients with major depression and other stress-related disorders