USP2a alters chemotherapeutic response by modulating redox

Cancer cells are characterized by altered ubiquitination of many proteins. The ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme overexpressed in prostate adenocarcinomas, where it exhibits oncogenic behavior in a variety of ways including targeting c-Myc via the miR-34b/c cluster. Here we demonstrate that USP2a induces drug resistance in both immortalized and transformed prostate cells. Specifically, it confers resistance to typically pro-oxidant agents, such as cisplatin (CDDP) and doxorubicin (Doxo), and to taxanes. USP2a overexpression protects from drug-induced oxidative stress by reducing reactive oxygen species (ROS) production and stabilizing the mitochondrial membrane potential (ΔΨ), thus impairing downstream p38 activation and triggering of apoptosis. The molecular mediator of the USP2a protective function is the glutathione (GSH). Through miR-34b/c-driven c-Myc regulation, USP2a increases intracellular GSH content, thus interfering with the oxidative cascade triggered by chemotherapeutic agents. In light of these findings, targeting Myc and/or miR-34b/c might revert chemo-resistance

Validation of a multi-scale simulation strategy based on the Pointwise Strain Superposition Method

This paper details the experimental validation of a multi-scale simulation strategy that we developed for predicting the stresses and distortions induced by Powder Bed Fusion processes. The strategy comprises a meso-scale model, a macro-scale model, and a scaling method named Pointwise Strain Superposition. The first model evaluates the temperature, stress, and strain fields produced by a single scan line. The scaling method transfers the meso-scale results to the macro-scale model, which is then able to simulate the entire manufacturing process with a reasonable computational cost. The simulation strategy was validated by comparing its results with the stresses and distortions measured on several specimens made of selective laser melted Inconel 718. Stresses were measured through the blind hole drilling method on a cylindrical specimen printed with two different scanning strategies, while distortions were measured on a hollow cylinder and on a cantilever-shaped specimen after removing its supports. In both cases, the simulation showed first- or higher-order accuracy despite the significant uncertainties regarding the input parameters and material properties. This robustness, coupled with its computational efficiency, leads us to believe that our simulation strategy could enhance the process optimization and provide a better understanding of the underlying physical phenomena along with their effects on the manufactured parts

Effects of phase transitions in devices actuated by the electromagnetic vacuum force

We study the influence of the electromagnetic vacuum force on the behaviour of a model device based on materials, like germanium tellurides, that undergo fast and reversible metal-insulator transitions on passing from the crystalline to the amorphous phase. The calculations are performed at finite temperature and fully accounting for the behaviour of the material dielectric functions. The results show that the transition can be exploited to extend the distance and energy ranges under which the device can be operated without undergoing stiction phenomena. We discuss the approximation involved in adopting the Casimir expression in simulating nano- and micro- devices at finite temperature

Size quantization effects in thin film Casimir interaction

We investigate the role of size quantization in the vacuum force between metallic films of nanometric thickness. The force is calculated by the Lifshitz formula with the film dielectric tensor derived from the one-electron energies and wavefunctions under the assumption of a constant potential inside the film and a uniform distribution of the positive ion charge. The results show that quantization effects tend to reduce the force with respect to the continuum plasma model. The reduction is more significant at low electron densities and for film size of the order of few nanometers and persists for separation distances up to 10 nm. Comparison with previous work indicates that the softening of the boundary potential is important in determining the amount of the reduction. The calculations are extended to treat Drude intraband absorption. It is shown that the inclusion of relaxation time enhances the size quantization effects in the force calculations

Influência da temperatura de armazenamento na qualidade sensorial do pinhão.

Resumo

Bender-Wu Formula and the Stark Effect in Hydrogen

We discuss a close connection between the formula of Banks, Bender, and Wu for the asymptotics of the Rayleigh-Schrödinger coefficients of the two-dimensional rotationally symmetric anharmonic oscillator and the behavior of resonances of the hydrogen Stark problem in two regimes: small field (Oppenheimer's formula) and large field (where we obtain the new results arg E → −π/3, ∣E∣ ∼α[F(lnF)^(2/3) for F, the electric field strength, going to infinity). We also announce a rigorous proof of Bender-Wu-type formulas

Analysis of Diterpens in Green and Roasted Coffee of Coffea arabica Cultivars Growing in the Same Edapho-Climatic Conditions.

Lipids are important components of coffee beverage flavor and aroma. Coffee oil is rich in diterpens of the kaurane family, mainly cafestol (C20H28O3) and kahweol (C20H26O3), which have increasingly received attention in recent years due to their physiological effects in human health. However, few studies have been conducted on the effects of the genetic variability for those lipids in Coffea arabica. In this work we initiate the characterization of cafestol and kahweol in different cultivars of Coffea arabica, growing in the same edaphoclimatic conditions. Mature coffee fruits from cultivars Catuaí, Icatu and three Catucaí derived the cultivars IPR 100, IPR 102 and IPR 106. They were harvested at the Agricultural Field Station of the Coop COCARI, Mandaguari, Paraná, Brazil, from May to July 2009. Although the time of harvesting was according to the maturation of each cultivar, harvesting and post-harvesting conditions were the same for all cultivars. The five samples were subjected to medium roasting for 8 to 11 minutes at 200-210 °C, until the degree of roasting light/media (L* around 28). The extraction of diterpens was carried out in green or roasted coffee by direct saponification with KOH, extraction with terc-butyl methyl ether, and clean up with water. A reverse-phase HPLC column with isocratic elution with acetonitrile/water (55/45 v/v) was used for detection and quantification of kahweol at 290 nm and cafestol at 220 nm. In green beans, the level of kahweol was higher than cafestol, for all three IPR cultivars. Meanwhile, the inverse was observed for green beans cultivars Catuaí and Icatu, where cafestol levels were higher than kahweol. The higher levels of kahweol in relation to cafestol were again observed in roasted coffee of the three IPR cultivars. In cultivars Icatu the values for kahweol and cafestol were similar (635 and 683 mg/100 g, respectively). The highest levels of kahweol were observed in cultivar IPR 106 (1096 mg/100 g). The cultivar IPR 102 showed the highest level of cafestol (394 mg/100g). Association of this data with gene expression profile can be useful to find genes involved in cafestol and kahweol metabolism as well as to develop molecular markers for diterpens in coffee

Shock Profiles for the Asymmetric Simple Exclusion Process in One Dimension

The asymmetric simple exclusion process (ASEP) on a one-dimensional lattice is a system of particles which jump at rates $p$ and $1-p$ (here $p>1/2$) to adjacent empty sites on their right and left respectively. The system is described on suitable macroscopic spatial and temporal scales by the inviscid Burgers' equation; the latter has shock solutions with a discontinuous jump from left density $\rho_-$ to right density $\rho_+$, $\rho_-<\rho_+$, which travel with velocity $(2p-1)(1-\rho_+-\rho_-)$. In the microscopic system we may track the shock position by introducing a second class particle, which is attracted to and travels with the shock. In this paper we obtain the time invariant measure for this shock solution in the ASEP, as seen from such a particle. The mean density at lattice site $n$, measured from this particle, approaches $\rho_{\pm}$ at an exponential rate as $n\to\pm\infty$, with a characteristic length which becomes independent of $p$ when $p/(1-p)>\sqrt{\rho_+(1-\rho_-)/\rho_-(1-\rho_+)}$. For a special value of the asymmetry, given by $p/(1-p)=\rho_+(1-\rho_-)/\rho_-(1-\rho_+)$, the measure is Bernoulli, with density $\rho_-$ on the left and $\rho_+$ on the right. In the weakly asymmetric limit, $2p-1\to0$, the microscopic width of the shock diverges as $(2p-1)^{-1}$. The stationary measure is then essentially a superposition of Bernoulli measures, corresponding to a convolution of a density profile described by the viscous Burgers equation with a well-defined distribution for the location of the second class particle.Comment: 34 pages, LaTeX, 2 figures are included in the LaTeX file. Email: [email protected], [email protected], [email protected]