Episode-like pulse testosterone supplementation induces tumor senescence and growth arrest down-modulating androgen receptor through modulation of p-ERK1/2, pAR ser81 and CDK1 signaling: biological implications for men treated with testosterone replacement therapy

Despite the growing body of knowledge showing that testosterone (T) may not significantly affect tumor progression in hypogonadal patients treated for prostate cancer (Pca), the use of this hormone in this population still remains controversial. The effects of continuous or pulsed T stimulation were tested in vitro and in vivo on androgen-sensitive Pca cell lines in order to assess the differential biological properties of these two treatment modalities. Pulsed T treatment resulted in a greater inhibition than continuous T supplementation of tumor growth in vitro and in vivo. The effects of pulsed T treatment on tumor growth inhibition, G0/G1 cell cycle arrest, and tumor senescence was more pronounced than those obtained upon continuous T treatments. Mechanistic studies revealed that G0/G1 arrest and tumor senescence upon pulsed T treatment were associated with a marked decrease in cyclin D1, c-Myc and SKp2, CDK4 and p-Rb levels and upregulation of p27 and p-ERK1/2. Pulsed, but not continuous, T supplementation decreased the expression levels of AR, p-AR ser81 and CDK1 in both cellular models. The in vitro results were confirmed in an in vivo xenografts, providing evidence of a greater inhibitory activity of pulsed supraphysiological T supplementation than continuous treatment, both in terms of tumor volume and decreased AR, p-AR ser81 , PSA and CDK1 staining. The rapid cycling from hypogonadal to physiological or supra-physiological T intraprostatic concentrations results in cytostatic and senescence effects in preclinical models of androgen-sensitive Pca. Our preclinical evidence provides relevant new insights in the biology of Pca response to pulsed T supplementation

Stability of nonlinear AR-GARCH models

This paper studies the stability of nonlinear autoregressive models with conditionally heteroskedastic errors. We consider a nonlinear autoregression of order p (AR(p)) with the conditional variance specified as a nonlinear first order generalized autoregressive conditional heteroskedasticity (GARCH(1,1)) model. Conditions under which the model is stable in the sense that its Markov chain representation is geometrically ergodic are provided. This implies the existence of an initial distribution such that the process is strictly stationary and beta-mixing. Conditions under which the stationary distribution has finite moments are also given. The results cover several nonlinear specifications recently proposed for both the conditional mean and conditional variance.-

Parameter Estimation in Nonlinear AR-GARCH Models

This paper develops an asymptotic estimation theory for nonlinear autoregressive models with conditionally heteroskedastic errors. We consider a functional coefficient autoregression of order p (AR(p)) with the conditional variance specified as a general nonlinear first order generalized autoregressive conditional heteroskedasticity (GARCH(1,1)) model. Strong consistency and asymptotic normality of the global Gaussian quasi maximum likelihood (QML) estimator are established under conditions comparable to those recently used in the corresponding linear case. To the best of our knowledge, this paper provides the first results on consistency and asymptotic normality of the QML estimator in nonlinear autoregressive models with GARCH errors.AR-GARCH, asymptotic normality, consistency, nonlinear time series, quasi maximum likelihood estimation

La quarta p[ar]te del Vita Christi Cartuxano [Texto impreso]

Autor y trad. constan en colofónPie de imp. consta en colofónSign.: 3[cristus]8, 3a-3z8, 3[et]8, 3[cum]8, 3[rum]8, 3A-3F-8G10Port. a dos tintas con marca tip.Texto en letra gót. a dos col., fileteado, con inic. adornadas y apostillas marginalesPort. xil. arquitectonica y grab. xil. en h. [cristus]1

A note on the geometric ergodicity of a nonlinear AR–ARCH model

This note studies the geometric ergodicity of nonlinear autoregressive models with conditionally heteroskedastic errors. A nonlinear autoregression of order p (AR(p)) with the conditional variance specified as the conventional linear autoregressive conditional heteroskedasticity model of order q (ARCH(q)) is considered. Conditions under which the Markov chain representation of this nonlinear AR– ARCH model is geometrically ergodic and has moments of known order are provided. The obtained results complement those of Liebscher [Journal of Time Series Analysis, 26 (2005), 669–689] by showing how his approach based on the concept of the joint spectral radius of a set of matrices can be extended to establish geometric ergodicity in nonlinear autoregressions with conventional ARCH(q) errors.Nonlinear Autoregression, Autoregressive Conditional Heteroskedasticity, Nonlinear Time Series Models, Geometric Ergodicity, Mixing, Strict Stationarity, Existence of Moments, Markov Models

Parameter estimation in nonlinear AR–GARCH models

This paper develops an asymptotic estimation theory for nonlinear autoregressive models with conditionally heteroskedastic errors. We consider a general nonlinear autoregression of order p (AR(p)) with the conditional variance specified as a general nonlinear first order generalized autoregressive conditional heteroskedasticity (GARCH(1,1)) model. We do not require the rescaled errors to be independent, but instead only to form a stationary and ergodic martingale difference sequence. Strong consistency and asymptotic normality of the global Gaussian quasi maximum likelihood (QML) estimator are established under conditions comparable to those recently used in the corresponding linear case. To the best of our knowledge, this paper provides the first results on consistency and asymptotic normality of the QML estimator in nonlinear autoregressive models with GARCH errors.Nonlinear Autoregression, Generalized Autoregressive Conditional Heteroskedasticity, Nonlinear Time Series Models, Quasi-Maximum Likelihood Estimation, Strong Consistency, Asymptotic Normality

Differential Study of Projectile Coherence Effects on Double Capture Processes in p + Ar Collisions

We have measured differential yields for double capture and double capture accompanied by ionization in 75 keV p + Ar collisions. Data were taken for two different transverse projectile coherence lengths. A small effect of the projectile coherence properties on the yields were found for double capture, but not for double capture plus ionization. The results suggest that multiple projectile-target interactions can lead to a significant weakening of projectile coherence effects

Interstellar abundances in the neutral and ionized gas of NGC604

We present FUSE spectra of the giant HII region NGC604 in the spiral galaxy M33. Chemical abundances are derived from far-UV absorption lines and are compared to those derived from optical emission lines. We derived the column densities of HI, NI, OI, SiII, PII, ArI, and FeII, fitting the line profiles with either a single component or several components. Our net results, assuming a single component, show that N, O, Si, and Ar are apparently underabundant in the neutral phase by a factor of 10 or more with respect to the ionized phase, while Fe is the same. However, we discuss the possibility that the absorption lines are made of individual unresolved components, and find that only PII, ArI, and FeII lines should not be affected by the presence of hidden saturated components, while NI, OI, and SiII might be much more affected. If N, O, and Si are actually underabundant in the neutral gas of NGC604 with respect to the ionized gas, this would confirm earlier results obtained for the blue compact dwarfs. However, a deeper analysis focused on P, Ar, and Fe mitigates the above conclusion and indicates that the neutral gas and ionized gas could have similar abundances.Comment: Accepted for publication in A&