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.     

Fast computation of minimal elementary decompositions of metabolic flux vectors

The concept of elementary flux vector is valuable in a number of applications of metabolic engineering. For instance, in metabolic flux analysis, each admissible flux vector can be expressed as a non-negative linear combination of a small number of elementary flux vectors. However a critical issue concerns the total number of elementary flux vectors which may be huge because it combinatorially increases with the size of the metabolic network. In this paper we present a fast algorithm that randomly computes a decomposition of admissible flux vectors in a minimal number of elementary flux vectors without explicitly enumerating all of them.     

Resonant and non-resonant microwave absorption in the magnetoelectric YCrO3 through ferro-paraelectric transition

An electron paramagnetic resonance (EPR) study in the polycrystalline magnetoelectric YCrO₃ is carried out at X-band (8.8-9.8 GHz) in the 300-510 K temperature range. For all the temperatures, the EPR spectra show a single broad line attributable to Cr³⁺ (S = 3/2) ions. The onset of the ferro-paraelectric transition has been determined from the temperature dependence of three main parameters deduced from the EPR spectra: the peak-to-peak linewidth (ΔH_pp), the integrated intensity (I_EPR) and the g-factor; these parameters indicate a behavior in agreement with a diffuse phase transition. Low-field microwave absorption (LFMA) is used to give a further knowledge on this material; where this technique also gives evidence of the ferro-paraelectric transition.     

Excitatory amino acid receptors and puberty

Glutamate is an important excitatory signal in the hypothalamus for the steroid-mediated preovulatory gonadotropin surge. Steroids may exert this action by regulating glutamate receptor levels or glutamate release, or both. Work in our laboratory found no changes in NMDA and kainate receptor binding in the hypothalamus of castrated or castrated plus steroid-replaced male and female rats. Likewise, we found that NMDA and kainate binding did not change over the onset of puberty in the female rat. A competitive quantitative RT-PCR assay using exogenous internal standards was used to measure NMDAR1, GluR1, and beta-actin mRNAs levels. NMDAR1 and GluR1 expression was examined in the preoptic hypothalamic area and in the medial basal hypothalamus at Postnatal Days 10, 15, 20, 25, 30, 32, 34, 36, 40, and 63. A transient increase in GluR1 mRNA levels in the preoptic hypothalamic area was observed on Day 20, with all other time points showing comparable levels. NMDAR1 levels in the POA and medial basal hypothalamus did not change significantly at any of the time points; in contrast, however, AMPA receptor binding levels were increased in the hypothalamus at the time of puberty in the female rat. Thus, in addition to the previously reported elevation of glutamate release rates in the hypothalamus at the time of puberty, AMPA receptors may also be elevated and play a role in mediating glutamate regulatory effects on the timing of puberty in the female rat.     

Enzymatic activities related to cherimoya fruit softening and sugar metabolism during short-term controlled-atmosphere treatments

 The effects of short controlled-atmosphere (CA) treatments, involving exposure to 10% O₂ combined with 10%, 15% and 20% CO₂, on a selection of biochemical parameters and related enzymatic activities of cherimoya fruit were studied. A marked increase in the activity of soluble and cell-wall invertases was found in cherimoyas stored in air, but this was inhibited by CA treatment, which also reduced the accumulation of soluble sugar and malic acid. CA had no effect on the citric acid content and enhanced the rise in fumaric acid concentration, which was directly related to the CO₂ level. Differences in the softening of fruit stored in air and in CA were found after 9 days of storage, but the role of the cell-wall hydrolases polygalacturonase and carboxymethyl-cellulase in this behaviour was not elucidated. Received: 25 January 1998 / Revised version: 3 March 1998     

Interactive intraoperative localization during the resection of intraventricular lesions

Mass lesions located in the ventricular system can be surgically challenging. These tumors are often slow growing and reach considerable size before they are diagnosed. These lesions commonly cause multiple obstructions to the circulation of cerebrospinal fluid with subsequent hydrocephalus. They are deeply located in the brain, surrounded by vital neurological and vascular structures, and often have irregular configurations. All these characteristics may pose real problems during surgery in terms of orientation and a optimal resection. For the surgical approach to such intraventricular lesions we are currently using an infrared-based system implemented at Wayne State University that allows intraoperative real-time localization. Three infrared cameras continuously track the position of multiple light-emitting diodes in relation to a predetermined "rigid body". This system can be used with different surgical instruments, and does not interfere with standard neurosurgical techniques. We present our preliminary experience in 18 patients with intraventricular tumors that were operated on between December 1992 and March 1995. Their lesions were located in the lateral ventricles, third ventricle, and pineal region with extension into the posterior aspect of the third ventricle. The use of the interactive infrared-based localizing unit allowed a total resection in 15 cases and a subtotal resection in 3 cases. We report 3 complications, but only one of them was related to the surgical procedure. The postoperative follow-up period ranged from 2 to 24 months. All patients were followed clinically and with postoperative magnetic resonance imaging scans. This interactive infrared system has proven to be a very useful tool, flexible, safe and reliable, increasing surgical efficiency, without a significant increase in the length of resection.     

C–(N)–S–H and N–A–S–H gels: Compositions and solubility data at 25°C and 50°C

Calcium silicate hydrates containing sodium [C–(N)–S–H], and sodium aluminosilicate hydrates [N–A–S–H] are the dominant reaction products that are formed following reaction between a solid aluminosilicate precursor (eg, slags, fly ash, metakaolin) and an alkaline activation agent (eg NaOH) in the presence of water. To gain insights into the thermochemical properties of such compounds, C–(N)–S–H and N–A–S–H gels were synthesized with compositions: 0.8≤Ca/Si≤1.2 for the former, and 0.25≤Al/Si≤0.50 (atomic units) for the latter. The gels were characterized using thermogravimetric analysis (TGA), scanning electron microscopy with energy‐dispersive X‐ray microanalysis (SEM‐EDS), and X‐ray diffraction (XRD). The solubility products (K_S0) of the gels were established at 25°C and 50°C. Self‐consistent solubility data of this nature are key inputs required for calculation of mass and volume balances in alkali‐activated binders (AABs), and to determine the impacts of the precursor chemistry on the hydrated phase distributions; in which, C–(N)–S–H and N–A–S–H compounds dominate the hydrated phase assemblages.     

Using semantic technologies and the OSU ontology for modelling context and activities in multi-sensory surveillance systems

Automatic systems that monitor human behaviour for detecting security problems are a challenge today. Previously, our group defined the Horus framework, which is a modular architecture for the integration of multi-sensor monitoring stages. In this work, structure and technologies required for high-level semantic stages of Horus are proposed, and the associated methodological principles established with the aim of recognising specific behaviours and situations.

Our methodology distinguishes three semantic levels of events: low level (compromised with sensors), medium level (compromised with context), and high level (target behaviours). The ontology for surveillance and ubiquitous computing has been used to integrate ontologies from specific domains and together with semantic technologies have facilitated the modelling and implementation of scenes and situations by reusing components.

A home context and a supermarket context were modelled following this approach, where three suspicious activities were monitored via different virtual sensors. The experiments demonstrate that our proposals facilitate the rapid prototyping of this kind of systems.