Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.     

Development and characterization of an implantable biosensor for telemetric monitoring of ethanol in the brain of freely moving rats

Ethanol is one of the most widespread psychotropic agents in western society. While its psychoactive effects are mainly associated with GABAergic and glutamatergic systems, the positive reinforcing properties of ethanol are related to activation of mesolimbic dopaminergic pathways resulting in a release of dopamine in the nucleus accumbens. Given these neurobiological implications, the detection of ethanol in brain extracellular fluid (ECF) is of great importance. In this study, we describe the development and characterization of an implantable biosensor for the amperometric detection of brain ethanol in real time. Ten different designs were characterized in vitro in terms of Michaelis-Menten kinetics (V(MAX) and K(M)), sensitivity (linear region slope, limit of detection (LOD), and limit of quantification (LOQ)), and electroactive interference blocking. The same parameters were monitored in selected designs up to 28 days after fabrication in order to quantify their stability. Finally, the best performing biosensor design was selected for implantation in the nucleus accumbens and coupled with a previously developed telemetric device for the real-time monitoring of ethanol in freely moving, untethered rats. Ethanol was then administered systemically to animals, either alone or in combination with ranitidine (an alcohol dehydrogenase inhibitor) while the biosensor signal was continuously recorded. The implanted biosensor, integrated in the low-cost telemetry system, was demonstrated to be a reliable device for the short-time monitoring of exogenous ethanol in brain ECF and represents a new generation of analytical tools for studying ethanol toxicokinetics and the effect of drugs on brain ethanol levels.     

State Estimation for the Localization of Harmonic Sources in Electric Distribution Systems

Throughout the last years, with the liberalization of the energy market, the localization of the sources of power quality disturbances has become a nodal point for operators and customers. In the liberalized market, knowledge of the system status, along with the uncertainty affecting the estimated data, is required to operate management and control issues such as energy dispatching and protection coordination. In distribution systems, too many measurement instruments would be needed to obtain a complete observation of the electric quantities. Thus, model-based state-estimation techniques can be implemented to exploit the few real-time measurements from the field and all the other available information to estimate the desired quantities. In this paper, a novel approach to the estimation of the harmonic sources by means of a Bayesian approach is proposed. The procedure also allows the ldquoqualityrdquo of the obtained estimates to be assessed. The theoretical fundamentals of the method are discussed, and results relevant to a simple distribution network are presented.     

Micro-solid-phase extraction (µ-SPE) of organophosphorous pesticides from wheat followed by LC-MS/MS determination

A rapid, selective and effective method of extraction, clean-up and concentration of organophosphorous pesticides from wheat followed by electrospray (ESI) LC-MS/MS analysis was developed. The μ-SPE (micro-solid-phase extraction) procedure resulted in good analytical performance and reduced at the same time matrix effects, analysis time and solvent consumption. Limits of detection (LODs) and quantification (LOQs) were in the range of 0.3–10 and 1–30 μg kg^?1, respectively, with good reproducibility (RSD ≤ 13.8) and recoveries between 75% and 109%. Coefficients of determination (r²) were greater than 0.996 for the studied pesticides. Despite the reduced sorbent bed mass of μ-SPE tips (4.2 mg), the analytical data showed that no saturation phenomena occurs in the tested range of concentration both for single compounds and mixtures. Several real samples were analysed and the concentrations of the selected pesticides were found to be below the respective maximum residue limit (MRLs).     

NATURAL CONVECTION IN CUBICAL ENCLOSURES WITH THERMAL SOURCES ON ADJACENT VERTICAL WALLS

Natural convection in a cubical enclosure with a hot source centered on a vertical wall and with an adjacent, fully cooled vertical wall was numerically investigated for Rayleigh numbers ( Ras ) of 10 3 - 4 2 10 6 . At Ra < 10 5 the heat transfer strongly depends on the hot sector side and its dependence on Ra is weak. Opposite characteristics occur at very high Ra , and there is a long transition between these two regimes. This behavior is caused by a mixing pattern, which, at low Ra , is similar to the one found in side heated cavities, whereas at high Rayleigh numbers lateral mixing is dominant.     

Artificial intelligence in science of measurements: from measurement instruments to perceptive agencies

This paper motivates, from historical, philosophical, and industrial points of view, the adoption of a novel scheme for developing complex measuring systems as perceptive agencies. The general concept of agency, a cooperative multiagent system defined within distributed artificial intelligence and robotics, is discussed together with its particular application to the field of intelligent instruments. An embryonic example of perceptive agency applied to the field of environmental monitoring is reported.