Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Simple SummaryDiabetic nephropathy is one of the most frequent complications of diabetes, resulting from diffuse damage to different kidney cells. The identification of subjects at risk is mandatory to prevent its development and provide appropriate therapies reducing the unmanageable evolution towards end-stage kidney disease. The aim of this work was to identify urinary-derived extracellular vesicles (EVs) miRNA cargo to be used as biomarker of kidney damage in diabetic patients. The miRNA profile was then correlated with the molecular mechanism associated with the glomerular and tubular damage using a diabetic-like model. In patients, miR145 and miR126 in urinary EVs increased together with albuminuria. MiR145 and miR126 increased in parallel in EVs from renal epithelial cells undergoing transition to a fibrotic mesenchymal phenotype. These data unveiled a role for miR126 and miR145 as the biomarkers of damage progression and proteinuria development in diabetic nephropathy. AbstractDiabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney’s physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition.     

Statistical Evaluation of Real-Time PCR Protocols Applied to Quantify Genetically Modified Maize

Real-time PCR (RTi-PCR) is the technique of choice for event-specific quantification of genetically modified organisms (GMOs) by determining the amount of event with respect to a species-specific reference gene. Reference genes can be amplified from the genome extracted from Certified Reference Materials (CRMs) or from ad hoc designed plasmids. In the present study, we statistically evaluate the performance of RTi-PCR protocols for GM maize MON810 event by using both genomic DNA from conventional CRMs and a plasmid containing sequences representative of four maize species-specific reference genes. The significance of simple and interaction effects of several variables included in the experimental design on DNA quantification methods and RTi-PCR were evaluated and discussed. Statistically significant differences on Ct values may have an impact on the GMOs quantification and consequently on the compliance of GM quantification-established legal thresholds. Our results confirm the reliability of the plasmid as alternative calibrant for the calculation of GMOs copy number.     

Reversible Fragmentation and Self‐Assembling of Nematic Liquid Crystal Droplets on Functionalized Pyroelectric Substrates

Investigation on the behavior of nematic liquid crystals on functionalized polar dielectric crystal substrates is accomplished. Very interesting effects can be observed in maneuvering liquid crystal droplets on the substrate surface, driven by electric fields generated by pyroelectric effect. Reversible drops fragmentation and self‐assembling in different configurations can be achieved. The dynamics of the observed phenomena is studied and the repeatability of the process is full assessed.     

Piperazine and methyldiethanolamine interrelationships in CO2 absorption by aqueous amine mixtures. Part II—Saturation rates of mixed reagent solutions

This work is a companion to a previous article, Part I, published in The Canadian Journal of Chemical Engineering, dealing with CO₂ absorption in aqueous solutions containing a single aminic reagent (specifically methyldiethanolamine (MDEA) or piperazine (PZ)). In this second part, different PZ/MDEA mixtures are experimentally studied and their performances are compared with that of the single reagents. It is indeed well known that small quantities of PZ added to MDEA aqueous solutions are sufficient to obtain a significant improvement in the kinetics of the process. PZ is considered an activator or promoter for MDEA, but the mechanism of this synergy has still not been clearly demonstrated. The aim of this study is an attempt to understand how PZ and MDEA can interact by experimentally analyzing this beneficial mutual effect and by explaining it with the help of a suitable yet not complex model. We believe that the involved chemistry is not more complex than that reported in Part I for the single reagents. According to our findings, it is MDEA that enhances the action of PZ, as opposed to what many authors claim. Moreover, our results seem to rule out the existence of any PZ shuttle effect.     

Catalytic olefin polymerisation at short times: Studies using specially adapted reactors

Despite the fact that the very early stages (several tens of seconds) of catalysed olefin polymerisation processes appear negligibly short with respect to the residence time of most industrial reactors, they are critical in terms of catalyst activation, obtaining good particle morphology, and avoiding irreparable problems caused by particle overheating. The different types of reactors that have been used over the course of the past few years are discussed in this feature article. It is shown that despite the difficulties encountered in finding the perfect experimental tool for this purpose, different configurations of stopped flow reactors can be used successfully to explore different aspects of what happens to the catalyst (supported and molecular) during these critical moments of polymerisation. © 2012 Canadian Society for Chemical Engineering     

The Role of Higher Lying Electronic States in Charge Photogeneration in Organic Solar Cells

The role of excess photon energy on charge generation efficiency in bulk heterojunction solar cells is still an open issue for the organic photovoltaic community. Here, the spectral dependence of the internal quantum efficiency (IQE) for a poly[2,6‐(4,4‐bis‐(2‐ethylhexyl)‐4H‐cyclopenta[2,1‐b;3,4‐b]­dithiophene)‐alt‐4,7‐(2,1,3‐benzothiadiazole)]:6,6‐phenyl‐C₆₁‐butyric acid methyl ester (PCPDTBT:PC60BM)‐based solar cell is derived combining accurate optoelectronic characterization and comprehensive optical modeling. This joint approach is shown to be essential to get reliable values of the IQE. Photons with energy higher than the bandgap of the donor material can effectively contribute to enhance the IQE of the solar cell. This holds true independently of the device architecture, reflecting an intrinsic property of the active material. Moreover, the nanomorphology of the bulk heterojunction plays a crucial role in determining the IQE spectral dependence: the coarser and more crystalline, the lesser the gain in IQE upon high energy excitation.     

Fast and air stable near-infrared organic detector based on squaraine dyes

In search for an organic material suitable for the detection of near-infrared electromagnetic radiation and at the same time capable of air stable operation of related devices, so to address the many applications envisaged with this technology (remote control, chemical/biological sensing, optical communication, spectroscopic and medical instruments), we explore the performance of a blend of hydrazone end-capped symmetric squaraines and phenyl C₆₁ butyric acid methyl ester. We succeed in developing air stable solution-processed devices with external quantum efficiency in the NIR as high as 3.5% and response times of few hundreds of nanoseconds. Essential to these achievements has been a detailed characterization of the devices performed by correlating the optoelectronic performances to the morphology of the layers (extracted from AFM measurements) and to the charge carrier mobility (extracted from transistor structures), enabling their optimization at the chemical level, by tailoring the squaraine substitution pattern, and at the device level, by tuning the blend composition. We show that a good balance between holes and electrons mobility is essential for high EQE and fast response speed, and that a smooth morphology is mandatory to achieve long term air stability and operability with no need for encapsulation.     

Ultrafine,fine, and black carbon particle concentrations in California child‐care facilities

Although many U.S. children spend time in child care, little information exists on exposures to airborne particulate matter (PM) in this environment, even though PM may be associated with asthma and other respiratory illness, which is a key concern for young children. To address this data gap, we measured ultrafine particles (UFP), PM_2.5, PM₁₀, and black carbon in 40 California child‐care facilities and examined associations with potential determinants. We also tested a low‐cost optical particle measuring device (Dylos monitor). Median (interquartile range) concentrations for indoor UFP, gravimetric PM_2.5, real‐time PM_2.5, gravimetric PM₁₀, and black carbon over the course of a child‐care day were 14 000 (11 000‐29 000) particles/cm³, 15 (9.6‐21) μg/m³, 15 (11‐23) μg/m³, 48 (33‐73) μg/m³, and 0.43 (0.25‐0.65) ng/m³, respectively. Indoor black carbon concentrations were inversely associated with air exchange rate (Spearman's rho = ?.36) and positively associated with the sum of all Gaussian‐adjusted traffic volume within a one‐kilometer radius (Spearman's rho = .45) (P‐values <.05). Finally, the Dylos may be a valid low‐cost alternative to monitor PM levels indoors in future studies. Overall, results indicate the need for additional studies examining particle levels, potential health risks, and mitigation strategies in child‐care facilities.     

Scaling up effects of Mg hydride in a temperature and pressure-controlled hydrogen storage device

A research program addressed to evaluate the magnesium hydride storage scaling up effects is being developed by CESI RICERCA, Milano, and the Hydrogen Group of Padova University. A storage device containing 500 g of magnesium hydride powder (manufactured by Venezia Tecnologie S.p.A. using high-energy ball milling) has been designed and tested in different operating conditions. A number of absorption and desorption cycles at different temperatures and pressures has been carried out in order to see if the results are comparable with laboratory data obtained on small amounts (fractions of grams) of powder samples. A sensible performance degradation that reduced the overall storage capacity of about 50% has been noticed after 20 cycles, presumably due to local powder heating, fragmentation and subsequent compaction. Further tests on a smaller tank equipped also with a porous baffle gave useful indications for the design of an improved large hydrogen reservoir.