Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.     

Standardization for an innovative world

Standardization is beneficial for society in general and for research and innovation in particular. Standardization bodies as well as policymakers should promote the use of standards as a way of disseminating knowledge, exploiting research results and reducing time to market for the “innovation”.Several examples are presented here with regard to the standardization of research/innovation in the cement field. From cement manufacturing to nanotechnology applied to additives, cement and special concretes, it is possible to find good examples of innovation/research activities linked to standardization.     

A combinatorial auction improves school meals in Chile: a case of OR in developing countries

The Chilean State delivers essential meal services at schools for low‐income students. Junta Nacional de Auxilio Escolar y Becas, the institution in charge of covering 1,300,000 children, leases the meal service to private enterprises. We developed an integer linear programming model to assign the meal contracts, in a process known as combinatorial auctions. The resulting model, which is NP‐hard, led to significant improvements in efficiency and also contributed to making the process more transparent. The results are apparent in substantial improvements in quality and coverage of the service, and important savings to the country, which are equivalent to feeding 300,000 children in addition. We developed techniques to solve the combinatorial models and also to analyze and compare multiple scenarios to find robust solutions. For the objective function of this problem, we analyzed several options to consider different kinds of social benefits. In this paper, we describe the problem, the methodology and the results. We also present empirical results based on 6 years of experience. Finally, we discuss the relevance and impact of using operations research in these central issues in developing countries.     

Tuning of ultraviolet-curable ink printability via in situ ultraviolet irradiation during direct ink write applications

Direct ink write deposition facilitates line-by-line extrusion of inks spanning wide viscoelastic ranges. Following deposition, post processing technologies permit tuning of the extrudate's material property characteristics—ultraviolet (UV) irradiation, facilitating the photopolymerization of UV-reactive catalyst solutions, permits targeted modification of the extrudate's microstructure and in situ tuning of extrudate macrostructure. This report analyzes the morphological, rheological, and microstructural property relationships governing the printability, and processivity, of extruded UV-curable resin inks for delineation of sufficiency and optimization of ink printability utilizing direct ink write technologies. A design-of-experiments approach is implemented to quantify significance regarding an extrudate's dimensional response to extrusion parameter variation and in situ processing parameters, identifying proportionally of nozzle velocity, nozzle height, and UV irradiation exposure with extrudate aspect ratio, reflected by respective maximum extrudate aspect ratio increases of 158% and 109%, regarding 121 and 123K resin inks. Finally, the relationship between extrudate morphology and microstructure variation was assessed via dielectric cure monitoring, whereby an extrudate's ion viscosity was calculated in relation to its rheological modulus, reflecting the relationship between an extrudate's morphology, rheological response, and printability, regarding its microstructural variation.     

Misleading postevent information and memory for events: Arguments and evidence against memory impairment hypotheses.

The claim that a person's memory for an event may be altered by information encountered after the event has been based on studies showing that Ss who are given false or misleading information about a previously witnessed event perform more poorly on tests of memory for the event than Ss who are not misled. It is argued that the available evidence does not imply that misleading postevent information impairs memory for the original event because the procedure used in previous studies is inappropriate for assessing effects of misleading information on memory. A more appropriate procedure is presented that involves a change in the recognition test phase. This procedure was used in 6 experiments with 792 undergraduates. Findings indicate that misleading postevent information had no effect on memory for the original event. Several recent studies that seem to contradict this conclusion are reviewed, and it is shown that the studies do not pose problems for the present authors' position. Findings are also considered in relation to the more general claim that information about an event from various sources are integrated into a single representation of the event. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dental trauma in schoolchildren six to twelve years of age

The prevalence of dental injuries in Spanish children living in an urban area was studied in 4000 schoolchildren ages six to twelve years. A total of 227 children experienced dental injuries. Simple enamel fracture was the predominant injury (46.2 percent). Boys showed a higher prevalence than girls In the majority of cases (74.9 percent), the trauma affected one tooth only. The maxillary central incisor was the most frequently affected tooth (87.9 percent). The most common fracture site was the mesioincisal angle (40.6 percent) followed by distoincisal angle (27.3 percent). Twenty-four percent of the children with dental injuries had an overjet of more than 3 mm.     

Misleading postevent information and the memory impairment hypothesis: Comment on Belli and reply to Tversky and Tuchin.

R. F. Belli (see record 1989-24859-001) and B. Tversky and M. Tuchin (see record 1989-24890-001) used a "Yes"/"No" recognition procedure to explore effects of misleading postevent information on memory for events. We examine the data and arguments presented in these studies, concluding that neither study demonstrates that misleading postevent information impairs memory for the original event. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activation of the uncoupling protein by fatty acids is modulated by mutations in the C-terminal region of the protein

The transport properties of the uncoupling protein (UCP) from brown adipose tissue have been studied in mutants where Cys304 has been replaced by either Gly, Ala, Ser, Thr, Ile or Trp. This position is only two residues away from the C-terminus of the protein, a region that faces the cytosolic side of the mitochondrial inner membrane. Mutant proteins have been expressed in Saccharomyces cerevisiae and their activity determined in situ by comparing yeast growth rates in the presence and absence of 2-bromopalmitate. Their bioenergetic properties have been studied in isolated mitochondria by determining the effects of fatty acids and nucleotides on the proton permeability and NADH oxidation rate. It is revealed that substitution of Cys304 by non-charged residues alters the response of UCP to fatty acids. The most effective substitution is Cys for Gly since it greatly enhances the sensitivity to palmitate, decreasing threefold the concentration required for half-maximal stimulation of respiration. The opposite extreme is the substitution by Ala which increases twofold the half-maximal concentration. We conclude that the C-terminal region participates in the fatty acid regulation of UCP activity. The observed correlation between yeast growth rates in the presence of bromopalmitate and the calculated activation constants for respiration in isolated mitochondria validates growth analysis as a method to screen the in situ activity of UCP mutants.     

Three-Level Converter Topologies With Switch Breakdown Fault-Tolerance Capability

This paper presents some modified topologies of the neutral-point-clamped converter. In all of them, the main change consists of adding a fourth leg, which is based on the flying-capacitor converter structure. The aim of this additional leg is to provide the converter with fault tolerance. Furthermore, during normal operation mode, this leg is able to provide a stiff neutral voltage. Consequently, the low-frequency voltage oscillations that appear at the neutral point of the standard three-level topology in some operating conditions no longer exist. As a result, the modulation strategy of the three main legs of the converter does not have to take care of voltage balance, and it can be designed to either achieve optimal output voltage spectra or improve the efficiency of the converter. Simulation and experimental results are presented to show the viability of this approach both under normal operation mode and in the event of faults.