Polarity reversal induced by electrochemically generated thiazol-2-ylidenes: The Stetter reaction

The inversion of the normal reactivity (umpolung) of aldehydes has been induced via N-heterocyclic carbenes (NHCs) thiazol-2-ylidenes 2a or 3a, generated by simple electrolyses of solutions containing thiazolium salt 2 or 3. Accordingly, 1,4-dicarbonyl compounds have been obtained, in mild conditions and in moderate to very high yields, via 1,4-addition of the Breslow intermediates to the suitable Michael acceptor. The procedure has been performed in classical organic solvents (VOCs) as well as in room temperature ionic liquids (RTILs). The different reactivity of aliphatic aldehydes vs the one of aromatic and heteroaromatic aldehydes has been emphasized.     

Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.     

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.     

Relaxation Pathways in Metallic Glasses

At temperatures below the glass transition temperature, physical properties of metallic glasses, such as density, viscosity, electrical resistivity or enthalpy, slowly evolve with time. This is the process of physical aging that occurs among all types of glasses and leads to structural changes at the microscopic level. Even though the relaxation pathways are ruled by thermodynamics as the glass attempts to re-attain thermodynamic equilibrium, they are steered by sluggish kinetics at the microscopic level. Understanding the structural and dynamic pathways of the relaxing glassy state is still one of the grand challenges in materials physics. We review some of the recent experimental advances made in understanding the nature of the relaxation phenomenon in metallic glasses and its implications to the macroscopic and microscopic properties changes of the relaxing glass.     

Effects of alkali treatment on the in-vitro digestibility of proteins and the release of amino acids

Three protein sources, casein, soya bean and rapeseed concentrates, were subjected to alkali treatment (0.2 M, 60° C) for 2 or 6 h. The impact of these treatments on protein digestibility and on release of amino acids, especially lysinoalanine, was evaluated by an in-vitro enzymic digestion method with simultaneous dialysis of digestion products. The impairment of digestibility was higher for casein and soya bean concentrate than for rapeseed concentrate. Whatever the amount of lysinoalanine produced in each protein, it was poorly released by proteolytic enzymes. The rate of release of other amino acids was reduced by the treatments, but to different levels for each protein. Arginine and lysine were particularly affected. As can be inferred from the release of the target amino acids, the hydrolytic capacity of chymotrypsin was not specifically impaired, in contrast to that of trypsin for casein and of elastase for all protein sources. This technique was useful to evaluate quickly the effects of processing on the digestibility of proteins.     

Fictitious domain formulations of unilateral problems: analysis and algorithms

The present article deals with fictitious domain methods for numerical realization of scalar variational inequalities with the Signorini type conditions on the boundary. Two variants are introduced and analyzed. A discretization is done by finite elements. It leads to a system of non-smooth, piecewise linear equations. This system is solved by the semismooth Newton method. Numerical experiments confirm the efficiency of this approach.     

Electrogenerated N-heterocyclic carbene: N-acylation of chiral oxazolidin-2-ones in ionic liquids

An electrochemical procedure for the N-acylation of chiral oxazolidin-2-ones, in the absence of volatile molecular organic solvents, has been set up via electrolyses of ionic liquid [bmim]BF₄ containing oxazolidin-2-ones followed by addition of saturated or unsaturated anhydrides. N-acyloxazolidin-2-ones were isolated in good to elevated yields. The electrochemically induced N-acylation of chiral oxazolidin-2-ones occurs with total retention of the absolute configuration of all the chiral atoms. The electrogenerated carbene (1-butyl-3-methyl-1H-imidazol-2-ylidene) has been indicated as the base involved in the deprotonation of chiral oxazolidin-2-ones.     

Pathogenic Mutations Shift the Equilibria of α‐Synuclein Single Molecules towards Structured Conformers

α‐synuclein (α‐Syn) is an abundant brain protein whose mutations have been linked to early‐onset Parkinson's disease (PD). We recently demonstrated, by means of a single‐molecule force spectroscopy (SMFS) methodology, that the conformational equilibrium of monomeric wild‐type (WT) α‐Syn shifts toward β‐containing structures in several unrelated conditions linked to PD pathogenicity. Herein, we follow the same methodology previously employed for WT α‐Syn to characterize the conformational heterogeneity of pathological α‐Syn mutants A30P, A53T, and E46K. Contrary to the bulk ensemble‐averaged spectroscopies so far employed to this end by different authors, our single‐molecule methodology monitored marked differences in the conformational behaviors of the mutants with respect to the WT sequence. We found that all the mutants have a much higher propensity than the WT to adopt a monomeric compact conformation that is compatible with the acquiring of β structure. Mutants A30P and A53T show a similar conformational equilibrium that is significantly different from that of E46K. Another class of conformations, stabilized by mechanically weak interactions (MWI), shows a higher variety in the mutants than in the WT protein. In the A30P mutant these interactions are relatively stronger, and therefore the corresponding conformations are possibly more structured. The more structured and globular conformations of the mutants can explain their higher propensity to aggregate with respect to the WT.     

Role of Nitrate Species in the “NO2-SCR” Mechanism over a Commercial Fe-zeolite Catalyst for SCR Mobile Applications

The NO₂-SCR reaction is studied by transient reaction analysis over a Fe-zeolite commercial catalyst. It is proposed that the NO₂-SCR reaction occurs according to a mechanism wherein surface nitrates are first formed by NO₂ disproportionation, followed by their catalytic reduction to nitrogen by ammonia.     

Using PV and QV curves with the meaning of static contingency screening and planning

This paper investigates the use of the QV and PV curves in the planning scenario, when some system reinforcements and contingency screening are analyzed. The idea is to employ the continuation method to obtain the system load margin and the QV curve to calculate the reactive power reserve associated with each bus. Combining these approaches enables one to identify the system critical area, the actual operating conditions, the most severe contingencies and the most important reinforcements. The methodology proposed may provide important signals to system planners, since the planning is focused under the voltage security point of view. The ideas are tested with the help of some academic systems and two real (a Brazilians and a Paraguayan) systems with all the system limits considered.