Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action,Pharmacology, Safety,and Efficacy

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.     

The Electron–Phonon Interaction of Low-Dimensional and Multi-Dimensional Materials from He Atom Scattering

Atom scattering is becoming recognized as a sensitive probe of the electron–phonon interaction parameter λ at metal and metal-overlayer surfaces. Here, the theory is developed, linking λ to the thermal attenuation of atom scattering spectra (in particular, the Debye–Waller factor), to conducting materials of different dimensions, from quasi-1D systems such as W(110):H(1 × 1) and Bi(114), to quasi-2D layered chalcogenides, and high-dimensional surfaces such as quasicrystalline 2ML-Ba(0001)/Cu(001) and d-AlNiCo(00001). Values of λ obtained using He atoms compare favorably with known values for the bulk materials. The corresponding analysis indicates in addition, the number of layers contributing to the electron–phonon interaction, which is measured in an atom surface collision.     

Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered.     

Passive target detection and tracking from electromagnetic field measurements

This paper presents a novel approach to the localization of moving targets in a complex environment based on the measurement of the perturbations induced by the target presence on an independently‐generated time‐varying electromagnetic field. Field perturbations are measured via a set of sensors deployed over the domain of interest and used to detect and track a possible target by resorting to a particle Bernoulli filter (PBF). To comply with real‐time operation, the PBF works along with an artificial neural network (ANN) model of the environment trained offline via finite elements (FEs). The performance of the proposed algorithm is assessed via simulation experiments.     

The first five responses in the method of constant stimuli.

Examined whether the method of constant stimuli with the standard presented first produces a constant error that depends on adaptation level. 120 university students were shown 5 series of 5 pairs of standard and variable lines. They had to decide whether the standard or the variable was longer or shorter than the preceding variable, or standard, respectively. In order to establish when the constant error occurred, the point of subjective equality was determined for each response. It was found that the 1st response was nearly random. The constant error was present from the 2nd response, and its magnitude did not change in succeeding series, contrary to expectations from adaptation-level theory. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On regular drawn symbolic picture languages

Drawn symbolic pictures are an extension of drawn pictures obtained by associating a symbol from an alphabet to each point of the picture. In the paper we will address some new interesting issues derived from the introduction of the symbols and we will identify the conditions, which ensure the preservation of properties holding for drawn pictures in the setting of the proposed extension.     

On the relationships among latent variables and residuals in PLS path modeling: The formative-reflective scheme

A new approach for the estimation and the validation of a structural equation model with a formative-reflective scheme is presented. The basis of the paper is a proposal for overcoming a potential deficiency of PLS path modeling. In the PLS approach the reflective scheme assumed for the endogenous latent variables (LVs) is inverted; moreover, the model errors are not explicitly taken into account for the estimation of the endogenous LVs. The proposed approach utilizes all the relevant information in the formative manifest variables (MVs) providing solutions which respect the causal structure of the model. The estimation procedure is based on the optimization of the redundancy criterion. The new approach, entitled redundancy analysis approach to path modeling (RA-PM) is compared with both traditional PLS Path Modeling and LISREL methodology, on the basis of real and simulated data.     

Some spatial equilibria in facility investment under uncertain demand

This paper describes the spatial distribution of customer demand, supply of customer services and facility investment, as the outcome of a three-level game-like interaction between customers (e.g., shoppers), suppliers (e.g., retailers) and developers (e.g., landlords). Treating both the suppliers and developers at each centre as competitors, oligopolistic equilibria of the Nash-Stackelberg type are developed, and conditions for their existence and uniqueness established. Uncertain customer demand is specified in probabilistic terms, representing the suppliers' perception of expected customer behaviour.