Frequency of symbol occurrences in simple non-primitive stochastic models

We study the random variable Y-n representing the number of occurrences of a given symbol in a word of length n generated at random. The stochastic model we assume is a simple non-ergodic model defined by the product of two primitive rational formal series, which form two distinct ergodic components. We obtain asymptotic evaluations for the mean and the variance of Y-n and its limit distribution. It turns out that there are two main cases: if one component is dominant and non-degenerate we get a Gaussian limit distribution; if the two components are equipotent and have different leading terms of the mean, we get a uniform limit distribution. Other particular limit distributions are obtained in the case of a degenerate dominant component and in the equipotent case when the leading terms of the expectation values are equal

Frequency of symbol occurrences in bicomponent stochastic models

We give asymptotic estimates of the frequency of occurrences of a symbol in a random word Generated by any bicomponent stochastic model. More precisely, we consider the random variable Y-n representing the number of occurrences of a given symbol in a word of length n generated at random; the stochastic model is defined by a rational formal series r having a linear representation with two primitive components. This model includes the case when r is the product or the sum of two primitive rational formal series. We obtain asymptotic evaluations for the mean value and the variance of Yn and its limit distribution

The transitional millisecond pulsar IGR J18245-2452 during its 2013 outburst at X-rays and soft gamma-rays

IGR~J18245--2452/PSR J1824--2452I is one of the rare transitional accreting millisecond X-ray pulsars, showing direct evidence of switches between states of rotation powered radio pulsations and accretion powered X-ray pulsations, dubbed transitional pulsars. IGR~J18245--2452 is the only transitional pulsar so far to have shown a full accretion episode, reaching an X-ray luminosity of $\sim10^{37}$~erg~s$^{-1}$ permitting its discovery with INTEGRAL in 2013. In this paper, we report on a detailed analysis of the data collected with the IBIS/ISGRI and the two JEM-X monitors on-board INTEGRAL at the time of the 2013 outburst. We make use of some complementary data obtained with the instruments on-board XMM-Newton and Swift in order to perform the averaged broad-band spectral analysis of the source in the energy range 0.4 -- 250~keV. We have found that this spectrum is the hardest among the accreting millisecond X-ray pulsars. We improved the ephemeris, now valid across its full outburst, and report the detection of pulsed emission up to $\sim60$ keV in both the ISGRI ($10.9 \sigma$) and Fermi/GBM ($5.9 \sigma$) bandpass. The alignment of the ISGRI and Fermi GBM 20 -- 60 keV pulse profiles are consistent at a $\sim25\ \mu$s level. We compared the pulse profiles obtained at soft X-rays with \xmm\ with the soft \gr-ray ones, and derived the pulsed fractions of the fundamental and first harmonic, as well as the time lag of the fundamental harmonic, up to $150\ \mu$s, as a function of energy. We report on a thermonuclear X-ray burst detected with \Integ, and using the properties of the previously type-I X-ray burst, we show that all these events are powered primarily by helium ignited at a depth of $y_{\rm ign} \approx 2.7\times10^8$ g cm${}^{-2}$. For such a helium burst the estimated recurrence time of $\Delta t_{\rm rec}\approx5.6$ d is in agreement with the observations.Comment: 10 pages, 6 Figures, 3 Tables Astronomy and Astrophysics Journal, accepted for publication on the 13th of April 201

Interference of dibutylphthalate on human prostate cell viability

Dibutylphthalate (DBP) is an environmental pollutant widely used as plasticizer in a variety of industrial applications worldwide. This agent can be found in personal-care products, children's toy, pharmaceuticals, food products. Exposure to DBP can occur via ingestion and inhalation as well as intravenous or skin contact. DBP belongs to the family of endocrine disrupting chemicals (EDCs) and its effects on reproductive system were demonstrated both in vivo and in vitro. In the present study we evaluated the effects of DBP on human prostate adenocarcinoma epithelial cells (LNCaP) in order to highlight xenoestrogens influence on human prostate. Moreover, we have compared DBP effects with 17β-estradiol action in order to investigate possible mimetical behaviour. We have assessed the effects of both compounds on the cell viability. After then, we have evaluated the expression of genes and proteins involved in cell cycle regulation. Furthermore, we have observed the expression and the cell localization of estrogen (ERs) and androgen (AR) receptors. In conclusion, we have demonstrated that DBP interacts with estrogen hormonal receptor pathway but differently from E2. DBP alters the normal gland physiology and it is involved in the deregulation of prostate cell cycle

Role of the interaction between large T antigen and Rb family members in the oncogenicity of JC virus

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Alkyphenol exposure alters steroidogenesis in male lizard podarcis siculus

Background: Nonylphenol (NP) and Octylphenol (OP) are persistent and non-biodegradable environmental contaminants classified as endocrine disruptor chemicals (EDCs). These compounds are widely used in several industrial applications and present estrogen-like properties, which have extensively been studied in aquatic organisms. The present study aimed to verify the interference of these compounds alone, and in mixture, on the reproductive cycle of the male terrestrial vertebrate Podarcis siculus, focusing mainly on the steroidogenesis process. Methods: Male lizards have been treated with different injections of both NP and OP alone and in mixture, and evaluation has been carried out using a histological approach. Results: Results obtained showed that both substances are able to alter both testis histology and localization of key steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) and P450 aromatase. Moreover, OP exerts a preponderant effect, and the P450 aromatase represents the major target of both chemicals. Conclusions: In conclusion, NP and OP inhibit steroidogenesis, which in turn may reduce the reproductive capacity of the specimens

Nonylphenol induces proliferation of prostate epithelial cell line (PNT1a)

Nonylphenol (NP) belongs to Endocrine Disrupting Chemicals (EDCs) with xenoestrogenic activity, called xenoestrogens, abundantly present in the environment. NP is widely used as surfactants in industrial and agricultural applications and in plastic formulations. Its xenoestrogenic activity was demonstrated both in vitro and in vivo. However, there are only few studies on the NP effects on prostate cell lines. Estrogens play an important role in development and growth of the prostate and may cause some pathologies, including cancer. Since NP mimics endogenous estrogens, it could have a negative influence on prostate physiology. In this study we examined the effects of NP and 17β-estradiol (E2) on the proliferation of non tumorigenic prostate epithelial cell line (PNT1A) and their interaction with estrogen receptors. These effects were also studied in presence of selective estrogen receptor antagonist ICI182,780. We found that both NP and E2 stimulate PNT1A proliferation in a dose-dependent manner, but the NP effects were lower than E2. Immunofluorescence and western blot analyses revealed that both NP and E2 induce cytoplasm-nucleus translocation of ERα. The nuclear localization of ERα by E2 was already shown after 2h of treatment and only after 6h by NP. The inhibition of these effects by adding ICI182,780 was shown. Surprisingly, NP and E2 didn’t affect the localization of ERβ. These results suggest that NP stimulates PNT1A proliferation probably through the interaction with ERα that in turn is involved in the activation of some prostate cell cycle key regulators

Prolyl 3‐hydroxylase 2 is a molecular player of angiogenesis

Prolyl 3‐hydroxylase 2 (P3H2) catalyzes the post‐translational formation of 3‐ hydroxyproline on collagens, mainly on type IV. Its activity has never been directly associated to angiogenesis. Here, we identified P3H2 gene through a deep‐sequencing transcriptome analysis of human umbilical vein endothelial cells (HUVECs) stimulated with vascular endothelial growth factor A (VEGF‐A). Differently from many previous studies we carried out the stimulation not on starved HUVECs, but on cells grown to maintain the best condition for their in vitro survival and propagation. We showed that P3H2 is induced by VEGF‐A in two primary human endothelial cell lines and that its transcription is modulated by VEGF‐A/VEGF receptor 2 (VEGFR‐2) signaling pathway through p38 mitogen‐activated protein kinase (MAPK). Then, we demonstrated that P3H2, through its activity on type IV Collagen, is essential for angiogenesis properties of endothelial cells in vitro by performing experiments of gain‐ and loss‐of‐function. Immunofluorescence studies showed that the overexpression of P3H2 induced a more condensed status of Collagen IV, accompanied by an alignment of the cells along the Collagen IV bundles, so towards an evident pro‐angiogenic status. Finally, we found that P3h2 knockdown prevents pathological angiogenesis in vivo, in the model of laser‐induced choroid neovascularization. Together these findings reveal that P3H2 is a new molecular player involved in new vessels formation and could be considered as a potential target for anti‐angiogenesis therapy

Current understanding of the role and regulation of miRNAs in Burkitt lymphoma.

Since its discovery in 1958, Burkitt lymphoma (BL) has been extensively studied and has become a model for tumorigenesis, but its pathogenesis has not been completely explained and understood yet. The aim of this review was to summarize the current knowledge about BL and, in particular, to discuss the role of miRNAs in its pathogenesis and their possible use as diagnostic and prognostic indicators. The impact of viral-encoded miRNAs is also discussed, with the Epstein-Barr infection being almost invariably detected in the endemic variant of this tumor