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.     

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 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.     

Aspects of fetal physiology from 18 to 37 weeks' gestation as assessed by blood sampling

OBJECTIVE: To construct reference ranges for fetal pH, oxygen pressure (PO2), and hematologic and biochemical blood constituents, which can be used to analyze changes with gestation and differences with maternal values, thus elucidating some aspects of fetal biology and the effects of the maternal and placental environments. METHODS: We assayed venous pH, PO2, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatine kinase, triglycerides, and cholesterol concentrations in 157 fetuses and 134 mothers who underwent fetal blood sampling from 18 to 37 weeks' gestation. None of the fetuses was infected or had chromosomal, hematologic, or hormonal abnormalities. RESULTS: All the variables analyzed were similar in fetuses sampled at the placental cord insertion (n = 125) or at the intrahepatic vein (n = 32). Maternal and fetal concentrations of glucose (r = 0.79, P < .001), urea (r = 0.96, P < .001), creatinine (r = 0.83, P < .001), and uric acid (r = 0.94, P < .001) correlated significantly, and their differences exhibited significant changes: the maternal-fetal differences of glucose and urea increased, whereas those of uric acid and creatinine decreased with advancing gestation. Fetal pH and PO2 decreased with gestational age, whereas hematocrit increased, similar to what has been described previously. All of the other variables, with the exception of amylase and cholesterol, changed significantly during the investigated period of pregnancy. Gestational age explained at least 40% of the variance in values of fetal total protein, pseudocholinesterase, alanine aminotransferase, creatine kinase, and triglycerides, but only 3-25% of the variation in the remainder. Most enzymes were higher in the fetus than in the maternal circulation, and all except alkaline phosphatase increased with gestational age. The maternal-fetal glucose difference correlated significantly with hematocrit, pH, and PO2, independent of gestational age and independent of each other. CONCLUSION: With the exception of aspartate aminotransferase, all of the analyzed fetal variables were different from the maternal values, and most changed with gestational age. The mechanisms leading to these fetal specificities remain mostly uncertain, but the provision of reference ranges for several blood constituents may be useful in the differential diagnosis of fetal disease.