Barrage balloons against aircraft threat: A well proven concept revisited

Since the event of September 11, 2001 in New York City, many people started to speculate that the same type of attack could in future be brought against other installations. Indeed, the U.S. Nuclear Regulatory Commission decided to require for future plants to assess their resistance to the impact of a large civil airliner. Nuclear plant control authorities of other countries decided in a similar direction. The solutions to the technical problem is usually pursued in the direction of a reinforcement of external plant structures and, in some case, they may not be sufficient. Other solutions of more psychological nature have also been adopted. This paper aims at the demonstration that the use of barrage balloons, already adopted with success in both World Wars and also occasionally after these events, can afford a satisfactory solution to the protection problem at a reasonable cost. This solution is also applicable to existing plants. The history of barrage balloons is summarized. Modern technology offers electronic devices capable to detect in time an approaching threat and the paper describes a new barrage system based also on such new possibilities. If the aircraft crash problem is a real one or not for the next years, nobody knows for sure; however some considerations should be kept in mind:

•

The fact that an accident of this kind “anywhere” is an accident “everywhere” as usual;

•

The extremely uncertain political outlook worldwide, the peculiarities of the oil market and the possible nuclear renaissance.

     

The folding pathway of an engineered circularly permuted PDZ domain

To understand the role of sequence connectivity in the folding pathway of a multi-state protein, we have analysed the folding kinetics of an engineered circularly permuted PDZ domain. This variant has been designed with the specific aim of posing two of the strands participating in the stabilisation of an early folding nucleus as contiguous elements in the primary structure. Folding of the circularly permuted PDZ2 has been explored by a variety of different experimental approaches including stopped-flow and continuous-flow kinetics, as well as ligand-induced folding experiments. Data reveal that although circular permutation introduces a significant destabilisation of the native state, a folding intermediate is stabilised and accumulated prior folding. Furthermore, quantitative analysis of the observed kinetics indicates an acceleration of the early folding events by more than two orders of magnitude. The results support the importance of sequence connectivity both in the mechanism and the speed of protein folding.     

Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as HIV reverse transcriptase inhibitors

Previous studies aimed at exploring the SAR of C2-functionalized S-DABOs demonstrated that the substituent at this position plays a key role in the inhibition of both wild-type RT and drug-resistant enzymes, particularly the K103N mutant form. The introduction of a cyclopropyl group led us to the discovery of a potent inhibitor with picomolar activity against wild-type RT and nanomolar activity against many key mutant forms such as K103N. Despite its excellent antiviral profile, this compound suffers from a suboptimal ADME profile typical of many S-DABO analogues, but it could, however, represent a promising candidate as an anti-HIV microbicide. In the present work, a new series of S-DABO/N-DABO derivatives were synthesized to obtain additional SAR information on the C2-position and in particular to improve ADME properties while maintaining a good activity profile against HIV-1 RT. In vitro ADME properties (PAMPA permeation, water solubility, and metabolic stability) were also experimentally evaluated for the most interesting compounds to obtain a reliable indication of their plasma levels after oral administration.     

Emulsification of Simulated Gastric Fluids Protects Wheat α-Amylase Inhibitor 0.19 Epitopes from Digestion

Wheat α-amylase inhibitors (α-AIs) are known anti-nutritional factors, respiratory allergens, and they can sporadically cause food allergy. α-AIs are therefore expected to reach the enteric mucosae in an immunologically active form, but information on their stability to gastric digestion is not available. Resistance to pepsinolysis is nonetheless a key factor for any food allergen. We therefore investigated whether α-AIs could resist pepsin digestion in simulated gastric fluids (SGF) and in emulsified SGF, the latter simulating more realistically the multi-phase nature of stomach bolus. Since α-AIs comprise a huge family of proteins, we investigated 0.19 α-AI as a prominent member. The digestion patterns were analyzed by immunoblotting using anti-0.19 polyclonal antibodies and sera from wheat allergic patients sensitized to 0.19 α-AI. The results show that the immune epitopes of α-AI are detectable up to 120 min of digestion in emulsifying conditions. Intra-molecular disulfide bonds and, in particular, emulsification were found to be crucial factors for protein stability. The results show that 0.19 α-AI must be considered a potential food allergen.     

Evaluation of antioxidant capacity of some fruit and vegetable foods: efficiency of extraction of a sequence of solvents

All methods for assessing the total antioxidant capacity (TAC) of food samples are strongly affected by the solvents used during extraction. In recent years a sequential solvent extraction procedure utilising water and acetone has been widely used for TAC measurements of foods. To better understand the efficiency of this procedure in terms of the amount of extracted antioxidants and the subsequent measurement of TAC, two vegetables (onion and spinach) and two fruits (orange and tomato) were sequentially extracted with water, acetone and chloroform. Each extract fraction was analysed separately for its content of known antioxidant compounds by specific procedures and for its TAC by the Trolox equivalent antioxidant capacity assay. The results showed that the compounds in the water and acetone extracts were the main contributors to TAC. The chloroform extracts did not contribute to TAC, with the exception of the spinach extract, owing to the presence of low levels of carotenoids. In conclusion, the analysed extraction procedure was more effective for foods rich in water‐soluble antioxidants than for those rich in lipid‐soluble antioxidants. Copyright © 2006 Society of Chemical Industry     

Saccharomyces pastorianus: genomic insights inspiring innovation for industry

A combination of biological and non‐biological factors has led to the interspecific hybrid yeast species Saccharomyces pastorianus becoming one of the world's most important industrial organisms. This yeast is used in the production of lager‐style beers, the fermentation of which requires very low temperatures compared to other industrial fermentation processes. This group of organisms has benefited from both the whole‐genome duplication in its ancestral lineage and the subsequent hybridization event between S. cerevisiae and S. eubayanus, resulting in strong fermentative ability. The hybrid has key traits, such as cold tolerance and good maltose‐ and maltotriose‐utilizing ability, inherited either from the parental species or originating from genetic interactions between the parent genomes. Instability in the nascent allopolyploid hybrid genome may have contributed to rapid evolution of the yeast to tolerate conditions prevalent in the brewing environment. The recent discovery of S. eubayanus has provided new insights into the evolutionary history of S. pastorianus and may offer new opportunities for generating novel industrially‐beneficial lager yeast strains. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous Determination of 18 Bioactive Compounds in Italian Bitter Liqueurs by Reversed-Phase High-Performance Liquid Chromatography–Diode Array Detection

A simple, fast and accurate method has been developed to simultaneously determine 18 bioactive compounds in Italian bitter liqueurs containing gentian, cinchona, cinnamon, rhubarb, clove, star anise or orange, by reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with diode array detection (DAD). HPLC analysis was performed with a C18 column using methanol and aqueous phosphoric acid (pH 2.5) as mobile phase. Selected wavelengths, i.e. 210, 232, 275, 285, 291, 310 and 368 nm, were used for quantification of compounds. The column temperature was controlled at 30 °C. The correlation coefficients (R ²) of the calibration curves of the analysed compounds were ≥0.9999 in a relatively wide concentration range (0.5–50 μg/ml). The proposed method proved successful in simultaneously analysing 18 bitter liqueurs produced in Italy. The concentration of the most important bitter principles, gentiopicroside, amarogentin, quinine and naringin, ranged as follows: 1.17–299.20, 0.25–32.24, 1.44–6.93 and 0.28–39.99 μg/ml, respectively.     

Intercomparison campaign of spectroradiometers for a correct estimation of solar spectral irradiance: results and potential impact on photovoltaic devices calibration

This paper describes the results of an intercomparison of spectroradiometers for global and direct normal incidence irradiance in the visible and near‐infrared spectral regions together with an assessment of the impact these results may have on the estimation of the short‐circuit current (I_SC) calibration of photovoltaic devices and on the spectral mismatch calculation. The intercomparison was conducted in the framework of the European project Apollon with the additional participation of external partners from the Italian project for the long‐term monitoring of solar radiation for photovoltaics. Six institutions and six spectroradiometer systems, representing different technologies and manufacturers, were involved. Prior to the intercomparison, all participating partners calibrated their own instrument(s) according to their usual procedures in order to verify the entire measuring and traceability chain. The difference in measured spectra shape and amplitude showed to have an impact on I_SC calculation of less than 3% and less than 6% for single‐junction and multi‐junction devices, respectively. When only the shape of the spectra is considered, the spectral mismatch ranges from 1.7% to 4.7% depending on the spectral response of the device. Copyright © 2013 John Wiley & Sons, Ltd.     

Toward the discovery of novel anti-HIV drugs. Second-generation inhibitors of the cellular ATPase DDX3 with improved anti-HIV activity: synthesis, structure-activity relationship analysis, cytotoxicity studies, and target validation

A hit optimization protocol applied to the first nonnucleoside inhibitor of the ATPase activity of human DEAD-box RNA helicase DDX3 led to the design and synthesis of second-generation rhodanine derivatives with better inhibitory activity toward cellular DDX3 and HIV-1 replication. Additional DDX3 inhibitors were identified among triazine compounds. Biological data were rationalized in terms of structure-activity relationships and docking simulations. Antiviral activity and cytotoxicity of selected DDX3 inhibitors are reported and discussed. A thorough analysis confirmed human DDX3 as a valid anti-HIV target. The compounds described herein represent a significant advance in the pursuit of novel drugs that target HIV-1 host cofactors.