The Inactivation Mechanism of Human Group IIA Phospholipase A2 by Scalaradial

Secretory phospholipases A₂ (sPLA₂s) are implicated in the pathogenesis of several inflammation diseases, such as rheumatoid arthritis, septic shock, psoriasis, and asthma. Thus, an understanding of their inactivation mechanisms could be useful for the development of new classes of chemical selective inhibitors. In the marine environment, several bioactive terpenoids possess interesting anti‐inflammatory activity, often through covalent and/or noncovalent inactivation of sPLA₂. Herein, we report the molecular mechanism of human group IIA phospholipase A₂ (sPLA₂‐IIA) inactivation by Scalaradial (SLD), a marine 1,4‐dialdehyde terpenoid isolated from the sponge Cacospongia mollior and endowed with a significant anti‐inflammatory profile. Our results have been collected by a combination of biochemical approaches, advanced mass spectrometry, surface plasmon resonance, and molecular modeling. These suggest that SLD acts as a competitive inhibitor. Indeed, the sPLA₂‐IIA inactivation process seems to be driven by the noncovalent recognition process of SLD in the enzyme active site and by chelation of the catalytic calcium ion. In contrast, covalent modification of the enzyme by the SLD dialdehyde moiety emerges as only a minor side event in the ligand–enzyme interaction. These results could be helpful for the rational design of new PLA₂ inhibitors that would be able to selectively target the enzyme active site.     

Wetting behaviour and direct observation of thermally responsive polystyrene‐block‐poly(N‐isopropylacrylamide)‐block‐polystyrene electrospun fibres in aqueous environment

Electrospun fibres of thermally responsive triblock copolymer polystyrene‐block‐poly(N‐isopropylacrylamide)‐block‐polystyrene were prepared. Fibre morphology and swelling were studied below and above the lower critical solution temperature of poly(N‐isopropylacrylamide) (PNIPAM) using cryo‐electron microscopy. Cryo‐transmission electron microscopy showed that the fibre diameter increased up to 150% after immersion in water at 20 °C. In contrast, at 45 °C the fibre diameter increased considerably less. The sessile drop technique was used to characterize temperature‐dependent wetting of fibre mats. Contact angle (θ_CA) measurements revealed that a block copolymer fibre mat changed from hydrophobic (θ_CA > 90°) to hydrophilic (θ_CA < 90°) state within seconds after applying a water droplet on it at 20 °C. At 40 °C the initial contact angle was measured to be higher (135°) and it decreased much less than at 20 °C during the first minute of measurement. We observed using scanning electron microscopy that the electrospun fibres of the block copolymer having 77 wt% of PNIPAM lost their cylindrical shape and changed from fibres to thin sheets at both 20 and 40 °C within seconds after applying water on the fibres. Fibres having 55 wt% of PNIPAM were observed to be stable in water at both 20 and 40 °C, which resulted, surprisingly, in fibre mats with the strongest effects on thermally sensitive wetting. We discuss the surprising results and the implications that the evolution of fibre surface roughness has on the long‐term wetting behaviour, demonstrating a self‐adaptable hydrophilicity/hydrophobicity nature of the fibre mats. © 2013 Society of Chemical Industry     

A procedure for assessing the reliability of short circuited concentration photovoltaic systems in outdoor degradation conditions

A procedure for assessing the reliability functions of photovoltaic concentration (CPV) systems, subjected to outdoor degradation, will be described in this work. The evaluation of the concentrator cells failure rate, the understanding of the origin of these degradation modes and how they affect the performances of concentration cells is an essential step to improve their reliability and to accelerate their competitiveness. The reliability evaluation methodology introduced here, as the cells are deployed outdoors and then are subjected to the actual sources of stress (e.g. ambient temperature, solar concentrated irradiance, cells working temperature and the variations of these parameters over days and seasons), will furnish values of failure rates very close to the true ones.     

A harvest and transport cost model for Eucalyptus spp. fast-growing short rotation plantations

This project developed a cost model for the mechanical harvesting of fast-growing Eucalyptus plantations. With such a model, forest managers can check the profitability of a prospective operation under different work conditions and assess the competitiveness of alternative options, which in turn will lead to supply chain optimization. The model is based on mathematical relationships that return machine productivity as a function of operational conditions. These relationships were calculated on data obtained from detailed time studies, conducted on all the main equipment types used in Eucalyptus plantations. Tests were conducted on 11 different machines that harvested a total 2465 oven-dry tonnes over 23 ha on 12 sites in 3 countries. The time study sessions lasted 250 h. Both the Cut-to-Length (CTL) system and the Whole-Tree (WT) system were studied. The model was validated with success and was used to make a number of different simulations. Simulation results show that the WT system allows cheaper harvesting and transport than the CTL system for a range of conditions. Under the conditions of our simulations and in favourable terrain, WT harvesting results in a delivered cost of about 20 euro/green tonne of bark-free pulp chips, whereas CTL harvesting results in a cost between 25 and over 30 euro/green tonne of debarked pulp roundwood.     

Gamma-ray emission gauge for solar salt level in a tank

One of the most investigated heat transfer fluid or heat storage medium in the field of thermal solar conversion is the “solar salt”, a mixture of nitrates NaNO₃/KNO₃, 60/40% by weight, respectively. The content of potassium in this fluid allows exploiting the self activity of the isotope ⁴⁰K to perform measurements useful for control or diagnostics of a solar plant. Here an experimental test on the non-invasive measurement of the salt level in a tank by means of gamma-ray spectrometry is shown.     

Perturbed MEBDF methods

We investigate MEBDF methods of Cash from general linear methods point of view. Some perturbations of these methods are constructed which preserve the order of these formulas and improve their stability properties.     

Amyloid Fibrils form Hybrid Colloidal Gels and Aerogels with Dispersed CaCO3 Nanoparticles

New hybrid colloidal gels are reported formed by amyloid fibrils and CaCO₃ nanoparticles (CaNPs), with Ca²⁺ as charge screening ions and CaNPs as physical crosslinking agents to establish and stabilize the network. The gel is characterized by rheological measurements and diffusing wave spectroscopy, complemented by microscopic observations using transmission and scanning electron microscopy. The hybrid colloidal gels show a two orders of magnitude improved gel strength at significantly shorter gelation times compared to previous calcium ion‐induced amyloid fibril gels. Supercritical CO₂‐dried colloidal aerogels allow demonstrating that amyloid fibrils, combined with smaller (higher specific surface area) CaNPs, constitute a denser fibrils network, resulting in stronger gels. By varying the amyloid fibril concentration and the CaNPs size and concentration, the complete phase diagram is mapped out. This enables identifying the sol–gel phase transition and a window for gel formation, which widens with increasing CaNPs size. Finally pH responsiveness and self‐healing properties of this hybrid colloidal gel are also demonstrated, making these systems a suitable candidate for biological applications.     

Fast magnetic field computation in fusion technology using GPU technology

One of the main issues in the simulation of Tokamaks functioning is the reliable and accurate computation of actual field maps in the plasma chamber. In this paper a tool able to accurately compute magnetic field maps produced by active coils of any 3D shape, wound with high number of conductors, is presented. Under linearity assumption, the coil winding is modeled by means of “sticks”, following each conductor's shape, and the contribution of each stick is computed using high speed Graphic Computing Units (GPU's). Relevant speed enhancements with respect to standard parallel computing environment are achieved in this way.     

Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.