Identification of new epidemiological molecular markers by comparative proteomics of serogroup A meningococcal isolates from three pandemic waves

We previously described the first reference map for the proteome of one strain of serogroup A Neisseria meningitidis (MenA), a major cause of epidemic meningitis in humans. As a preliminary finding, in that work we noted that 2‐DE protein maps of closely related MenA isolates from different epidemics spreads could be easily compared to detect minor differences and that 2‐DE phenotypes attributable to the well‐known epidemiological marker tbpB agreed with the genoclouds model of MenA epidemiological variation during pandemic waves. We explored here the possibility that an extended comparative study of 2‐DE maps of isolates representative of the nine genoclouds described by Achtman and collaborators could be used to discriminate between strains otherwise undistinguishable. We showed the example of 14 proteins with different 2‐DE spot patterns in different genoclouds that could be considered as putative tracers for alike‐strains discrimination. We introduce the novel concept that comparative proteomics can be useful in identifying new epidemiological markers for N. meningitidis.     

Modeling secondary electron images for linewidth measurement by critical dimension scanning electron microscopy

Modeling of critical dimensions scanning electron microscopy with sub-nanometer uncertainty is required to provide a metrics and to avoid yield loss in the processing of advanced CMOS technologies. In this paper, a new approach is proposed, which includes a new Monte Carlo scheme, a new Monte Carlo code, as well as the coupling with electrostatic fields to take into account self-charging effects.     

Citrus flavonoids: Molecular structure,biological activity and nutritional properties: A review

Epidemiological studies have shown an inverse relationship between dietary flavonoid intakes and cardiovascular diseases. Citrus fruits are the main winter fruits consumed in the Mediterranean diet, so they are the main source of dietary flavonoids. The possible beneficial effects are due, not only to the high amounts of vitamins and minerals, but also to the antioxidant properties of their flavonoids. Dietary flavonoids may help to supplement the body antioxidant defences against free radicals. These compounds’ possible beneficial effects are due to their antioxidant activity, which is related to the development of atherosclerosis and cancer, and to anti-inflammatory and antimicrobial activity. The present review summarizes the existing bibliography on biological and pharmacological studies of Citrus flavonoids, both in vitro and in vivo.     

Blame culture and defensive medicine

Introduction  

Defensive medicine takes place when healthcare personnel (doctors and nurses) order unnecessary treatments (positive defensive medicine) or avoid high-risk procedures or patients (negative defensive medicine) with the principle—though not exclusive—aim of reducing their expose to damages claims. This phenomenon is directly related to the significant growth in medical malpractice litigation over recent years. Defensive medicine increases the cost of healthcare and may expose patients to unnecessary risks. In fact, the large number of legal initiatives taken by patients have induced many doctors to set in place a defensive “strategy” so as to avoid placing their careers at risk. The threat of medical malpractice litigation constitutes a major obstacle to improving the reliability of healthcare organizations and patient safety.     

Optimal running and planning of a biomass-based energy production process

We propose mathematical programming models for solving problems arising from planning and running an energy production process based on burning biomasses. The models take into account different aspects of the problem: determination of the biomasses to produce and/or buy, transportation decisions to convey the materials to the respective plants, and plant site locations. Whereas the “running model” is linear, we propose two “planning models”, both of which are mixed-integer nonlinear programming problems. We show that a spatial branch-and-bound type algorithm applied to them is guaranteed to converge to an exact optimum in a finite number of steps.     

The antioxidant capacity of red wine in relationship with its polyphenolic constituents

The “antioxidant power” of a food is an expression of its capability both to defend the human organism from the action of the free radicals and to prevent degenerative disorders deriving from persistent oxidative stress. Purpose of this study is to analyse the antioxidant capacity (measured by means of the crocin bleaching method) of several samples of Sicilian red wines and to evaluate their dependency on the vintage and on the grape variety. Finally, the correlation between the single flavonoids compounds and the antioxidant capacity has been investigated. The analyses show that the antioxidant properties of red wine appear to be unequally influenced by the vintages for the different cultivars and that the correlation between antioxidant capacity and the total phenolic contents is weak. The latter can be explained by the fact that the wine’s antioxidant properties are influenced differently by each polyphenolic molecule.     

Photocatalytic oxidation of aliphatic and aromatic sulfides in the presence of silica adsorbed or zeolite-encapsulated 2,4,6-triphenyl(thia)pyrylium

Solid photocatalysts in which the 2,4,6-triphenylpyrylium (TP) or 2,4,6-triphenylthiapyrylium cation (TTP) are encapsulated within zeolite Y or deposited on mesoporous silica are used as photosensitizers for the oxidation of sulfides, both aromatic and aliphatic, in solvents of various polarity. Contrary to the same cations in solution, these solid sensitizers are not significantly degraded during operation. An effective oxygenation takes place leading to sulfoxides, disulfides, sulfinic and sulfenic esters as well as sulfonic acids. This large scope method shows a limited dependence on the substrate structure and on conditions and is suitable for the abatement of sulfur-containing pollutants.     

Identification of Aminoimidazole and Aminothiazole Derivatives as Src Family Kinase Inhibitors

Src family kinases (SFKs) are a family of non‐receptor tyrosine kinases (TKs) implicated in the regulation of many cellular processes. The aberrant activity of these TKs has been associated with the growth and progression of cancer. In particular, c‐Src is overexpressed or hyperactivated in a variety of solid tumors and is most likely a strong promoting factor for the development of metastasis. Herein, the synthesis of new 4‐aminoimidazole and 2‐aminothiazole derivatives and their in vitro biological evaluation are described for their potential use as SFK inhibitors. Initially, 2‐aminothiazole analogues of dasatinib and 4‐aminoimidazole derivatives were synthesized and tested against the SFKs Src, Fyn, Lyn, and Yes. Five hits were identified as the most promising compounds, with K_i values in the range of 90–480 nm . A combination of molecular docking, homology modeling, and molecular dynamics were then used to investigate the possible binding mode of such compounds within the ATP binding site of the SFKs. Finally, the antiproliferative activities of the best candidates were evaluated against SH‐SY5Y and K562 cell lines. Compound 3 b [2‐(4‐{2‐methyl‐6‐[(5‐phenylthiazol‐2‐yl)amino]pyrimidin‐4‐yl}piperazin‐1‐yl)ethanol] was found to be the most active inhibitor.     

Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation

HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents.