Proprotein Convertase Subtilisin Kexin Type 9 Inhibitors Reduce Platelet Activation Modulating ox-LDL Pathways

Background: Proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) lower LDL-cholesterol and slow atherosclerosis preventing cardiovascular events. While it is known that circulating PCSK9 enhances platelet activation (PA) and that PCSK9i reduce it, the underlying mechanism is not still clarified. Methods: In a multicenter before–after study in 80 heterozygous familial hypercholesterolemia (HeFH) patients on treatment with maximum tolerated statin dose ± ezetimibe, PA, soluble-NOX2-derived peptide (sNOX2-dp), and oxidized-LDL (ox-LDL) were measured before and after six months of PCSK9i treatment. In vitro study investigates the effects of plasma from HeFH patients before and after PCK9i on PA in washed platelets (wPLTs) from healthy subjects. Results: Compared to baseline, PCSK9i reduced the serum levels of LDL-c, ox-LDL, Thromboxane (Tx) B2, sNOX2-dp, and PCSK9 (p < 0.001). The decrease of TxB2 correlates with that of ox-LDL, while ox-LDL reduction correlated with PCSK9 and sNOX2-dp delta. In vitro study demonstrated that wPLTs resuspended in plasma from HeFH after PCSK9i treatment induced lower PA and sNOX2-dp release than those obtained using plasma before PCSK9i treatment. This reduction was vanished by adding ox-LDL. ox-LDL-induced PA was blunted by CD36, LOX1, and NOX2 inhibition. Conclusions: PCSK9i treatment reduces PA modulating NOX2 activity and in turn ox-LDL formation in HeFH patients.     

Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine

In this paper, we report our investigations on five {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties.     

Evaluation of harassment of migrating double-crested cormorants to limit depredation on selected sport fisheries in Michigan

Diverse management techniques have been used to mitigate conflicts between humans and double-crested cormorants (Phalacrocorax auritus) including harassment methods supplemented by lethal take. In this study we evaluated impacts of programs to harass spring migrating cormorants on the walleye (Sander vitreus) fishery in Brevoort Lake and the yellow perch (Perca flavescens) and walleye fisheries at Drummond Island. Cormorant foraging declined significantly (p < 0.05) at both locations subsequent to initiation of harassment programs. Overall harassment deterred 90% of cormorant foraging attempts while taking less than 6% lethally on average at each site. Yellow perch were a predominate prey item in number and biomass at both locations. Walleye made up a small proportion of the diet at both locations. However, both walleye and yellow perch abundance increased significantly (p < 0.05) at Drummond Island. Walleye abundance at age 3 increased to record levels in 2008 following 3 years of cormorant management at Brevoort Lake. The estimated cormorant consumption of age-1 walleye in the absence of management at Brevoort Lake during 2005 would account for 55% of the record 2006 age-1 walleye population. These results support the hypothesis that cormorant predation on spawning aggregations of sportfish was a significant mortality factor and cormorant management reduced sportfish mortality and increased abundance at both locations. Continuation of harassment programs and fishery assessments will determine whether improvement of targeted sport fisheries through control of spring migrating cormorants is sustainable.     

EU carcass classification system: carcass and meat quality in light lambs

Sixty male Apenninica suckling lambs carcasses were studied in order to evaluate the relationship between carcass and meat quality of light lambs as evaluated according to the EU Mediterranean classification system. Increased carcass weight (6–12 kg) was accompanied by greater carcass size and compactness and reduced bone percentage. Moreover the meat quality was similar with the increase of carcass weight in terms of colour, water holding capacity and suitability for domestic storage. No differences for the examined parameters were found between carcasses classified in quality 1 and 2. The EU Mediterranean classification system appears to be unrelated to the quality of the merchandized meat.     

Effect of fluctuating exposures on the acute toxicity of ammonia to rainbow trout (Salmo gairdneri) and cutthroat trout (S. clarki)

Acute toxicity bioassays in which fish were exposed to short-term cyclic fluctuations of ammonia were conducted on rainbow trout (Salmo gairdneri) and on cutthroat trout (S. clarki). Companion tests were also conducted in which test fish were subjected to ammonia at constant concentrations. The tests ranged in duration from 96 h to 4 weeks. Median lethal concentration (LC 50) values in terms of both average and peak concentrations of ammonia for the fluctuating concentration tests were compared with LC 50 values for the constant concentration (conventional) tests. Based on comparisons of total dose exposure, results showed that fish were more tolerant of constant concentrations of ammonia than of fluctuating concentrations. Fish subjected to fluctuating concentrations of ammonia at levels below those acutely toxic were subsequently better able to withstand exposure to higher fluctuating concentrations than fish not previously so acclimated.     

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.     

Tunable frequency-selective surfaces for beam-steering applications

First results from a study on tunable frequency-selective surfaces (FSSs) used for beam-steering applications are reported. In particular, the scattering response of a multilayer passband FSS based on varactorloaded rectangular slots has been investigated. Simulated and measured results show that tunable FSSs can be employed to locally control the phase of the transmitted field with limited amplitude losses.     

安全仪表系统的网络安全考虑：最先还是最后？

对于完整的控制和安全系统，建立强大的防护体系是否是一项可以确保安全仪表系统商业连续性的必要投资？     

Numerical simulation of turbulent gas flames in tubes

Computational fluid dynamics (CFD) is an emerging technique to predict possible consequences of gas explosion and it is often considered a powerful and accurate tool to obtain detailed results. However, systematic analyses of the reliability of this approach to real-scale industrial configurations are still needed. Furthermore, few experimental data are available for comparison and validation.In this work, a set of well documented experimental data related to the flame acceleration obtained within obstacle-filled tubes filled with flammable gas-air mixtures, has been simulated. In these experiments, terminal steady flame speeds corresponding to different propagation regimes were observed, thus, allowing a clear and prompt characterisation of the numerical results with respect to numerical parameters, as grid definition, geometrical parameters, as blockage ratio and to mixture parameters, as mixture reactivity.The CFD code AutoReagas was used for the simulations. Numerical predictions were compared with available experimental data and some insights into the code accuracy were determined. Computational results are satisfactory for the relatively slower turbulent deflagration regimes and became fair when choking regime is observed, whereas transition to quasi-detonation or Chapman-Jogouet (CJ) were never predicted.     

Crossover enhancements in GEFREX

This letter describes some improvements to the crossover operator in the genetic-neuro-fuzzy algorithm called genetic fuzzy rule extractor (GEFREX). Although, the new crossovers studied are very simple, the performance of GEFREX, in terms of learning time, is decidedly improved.