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A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH.Pyrimido-pyrimidine derivatives have been developed as rigid merbarone analogues. In a previous study, these compounds showed potent antiproliferative activity and efficiently inhibited topoisomerase IIα. To further extend the structure-activity relationships on pyrimido-pyrimidines, a novel series of analogues was synthesized by a two-step procedure. Analogues 3-6 bear small alky groups at positions 1 and 3 of the pyrimido-pyrimidine scaffold whereas at position 6a (4-chloro)phenyl substituent was inserted. The basic side chains introduced at position 7 were selected on the basis of the previously developed structure-activity relationships. The antiproliferative activity of the novel compounds proved to be affected by both the nature of the basic side chain and the substituents on the pyrimido-pyrimidine moiety. Derivatives 5d and 5e were identified as the most promising molecules still showing reduced antiproliferative activity in comparison with the previously prepared pyrimido-pyrimidine analogues. In topoisomerase IIα-5d docking complex, the ligand would poorly interact with the enzyme and assume a different orientation in comparison with 1d bioactive conformation.

The financial effect of households' out-of-pocket payments (OOP) on access and use of health systems has been extensively studied in the literature, especially in emerging or developing countries. Ziritaxestat molecular weight However, it has been the subject of little research in European countries, and is almost nonexistent after the financial crisis of 2008. The aim of the work is to analyze the incidence and intensity of financial catastrophism derived from Spanish households' out-of-pocket payments associated with health care during the period 2008-2015.

The Household Budget Survey was used and catastrophic measures were estimated, classifying the households into those above the threshold of catastrophe versus below. Three ordered logistic regression models and margins effects were estimated.

The results reveal that, in 2008, 4.42% of Spanish households dedicated more than 40% of their income to financing out-of-pocket payments in health, with an average annual gap of EUR 259.84 (DE EUR 2431.55), which in overall terms amounts to EUR 3939.44 million (0.36% of GDP).

The findings of this study reveal the existence of catastrophic households resulting from OOP payments associated with health care in Spain and the need to design financial protection policies against the financial risk derived from facing these types of costs.

The findings of this study reveal the existence of catastrophic households resulting from OOP payments associated with health care in Spain and the need to design financial protection policies against the financial risk derived from facing these types of costs.Polycrystalline cubic boron nitride (PcBN) are super-hard materials with high hardness and excellent abrasive resistance, widely used in cutting tools for precision machining of automotive and aerospace parts; however, their brittle properties make them prone to premature failure. Coatings are often applied to PcBN to extend their range of applicability and durability. Conventional coating methods are limited to the thickness range of a few hundred nanometres, poor adhesion to the substrate, and limited stability under ambient conditions. To further the properties of PcBN composites, in this paper, we explore the use of ultrasonic bonding to apply thick coatings (30-80 μm) on PcBN cutting tools. For the first time, a multi-walled carbon nanotube (MWCNT) powder is preplaced on a PcBN substrate to allow an unconventional coating technique to take place. The effects of ultrasonic bonding parameters on the change of mechanical properties of the coated tools are investigated through scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), micro-hardness analyses, and white light interferometry. The structure of the carbon nanotubes is investigated through transmission electron microscopy (pre coating) and cross-section of the bonded MWCNTs is studied via focused ion beam milling and SEM to evaluate the bonding between the multi-walled nanotubes. Optimum processing windows (i.e., bonding speed, energy, and pressure) are discovered for coating MWCNTs on PcBN. Focus ion beam milling analyses revealed a relationship between consolidation parameters and porosity of MW(pCNT) bonds. The proposed method paves the way for the novel design of functional coatings with attunable properties (i.e., thickness and hardness) and therefore improved productivity in the machining of aerospace and automotive parts.Single-Sample Face Recognition (SSFR) is a computer vision challenge. In this scenario, there is only one example from each individual on which to train the system, making it difficult to identify persons in unconstrained environments, mainly when dealing with changes in facial expression, posture, lighting, and occlusion. This paper discusses the relevance of an original method for SSFR, called Multi-Block Color-Binarized Statistical Image Features (MB-C-BSIF), which exploits several kinds of features, namely, local, regional, global, and textured-color characteristics. First, the MB-C-BSIF method decomposes a facial image into three channels (e.g., red, green, and blue), then it divides each channel into equal non-overlapping blocks to select the local facial characteristics that are consequently employed in the classification phase. Finally, the identity is determined by calculating the similarities among the characteristic vectors adopting a distance measurement of the K-nearest neighbors (K-NN) classifier. Extensive experiments on several subsets of the unconstrained Alex and Robert (AR) and Labeled Faces in the Wild (LFW) databases show that the MB-C-BSIF achieves superior and competitive results in unconstrained situations when compared to current state-of-the-art methods, especially when dealing with changes in facial expression, lighting, and occlusion. The average classification accuracies are 96.17% and 99% for the AR database with two specific protocols (i.e., Protocols I and II, respectively), and 38.01% for the challenging LFW database. These performances are clearly superior to those obtained by state-of-the-art methods. Furthermore, the proposed method uses algorithms based only on simple and elementary image processing operations that do not imply higher computational costs as in holistic, sparse or deep learning methods, making it ideal for real-time identification.

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